Pharmacological targeting of spreading depression in migraine
Eikermann-Haerter, Katharina; Can, Anil; Ayata, Cenk
2012-01-01
Migraine, particularly with aura, is a genetically heterogeneous disorder of ion channels, pumps or transporters associated with increased cortical excitability. Spreading depression, as one reflection of hyperexcitability, is the electrophysiological event underlying aura symptoms and a trigger for headache. Endogenous (e.g., genes and hormones) and exogenous factors (e.g., drugs) modulating migraine susceptibility have also been shown to modulate spreading depression susceptibility concordantly, suggesting that spreading depression can be a relevant therapeutic target in migraine. In support of this, several migraine prophylactic drugs used in clinical practice have been shown to suppress spreading depression susceptibility as a probable mechanism of action, despite belonging to widely different pharmacological classes. Hence, susceptibility to spreading depression can be a useful preclinical model with good positive and negative predictive value for drug screening. PMID:22364328
Cash, S; Dan, Y; Poo, M M; Zucker, R
1996-04-01
Synaptic activity is known to modulate neuronal connectivity in the nervous system. At developing Xenopus neuromuscular synapses in culture, repetitive postsynaptic application of ACh near the synapse leads to immediate and persistent synaptic depression, which was shown to be caused by reduction of presynaptic evoked transmitter release. However, little depression was found when ACh was applied to the muscle 20 microns or further from the synapse. Fluorescence imaging of cytosolic Ca2+ ([Ca2+]i) showed that each ACh pulse induced a transient elevation of myocyte [Ca2+]i that spread approximately 20 microns. Local photoactivated release of Ca2+ from the caged Ca2+ chelators nitr-5 or nitrophen in the postsynaptic cell was sufficient to induce persistent synaptic depression. These results support a model in which localized Ca2+ influx into the postsynaptic myocyte initiates transsynaptic retrograde modulation of presynaptic secretion mechanisms.
Mosca, Francesco; Narcisi, Valeria; Calzetta, Angela; Gioia, Luisa; Finoia, Maria G; Latini, Mario; Tiscar, Pietro G
2013-06-01
Hemocytes are a critical component of the mussel defense system and the present study aims at investigating their spreading and oxidative properties during phagocytosis under in vivo experimental stress conditions. The spreading ability was measured by an automated cell analyzer on the basis of the circularity, a parameter corresponding to the hemocyte roundness. The oxidative activity was investigated by micromethod assay, measuring the respiratory burst as expression of the fluorescence generated by the oxidation of specific probe. Following the application of high temperature and exposure to air, there was evidence of negative modulation of spreading and oxidative response, as revealed by a cell roundness increase and fluorescence generation decrease. Therefore, the fall of respiratory burst appeared as matched with the inhibition of hemocyte morphological activation, suggesting a potential depression of the phagocytosis process and confirming the application of the circularity parameter as potential stress marker, both in experimental and field studies. Copyright © 2012 Elsevier Ltd. All rights reserved.
Winkler, Maren Kl; Dengler, Nora; Hecht, Nils; Hartings, Jed A; Kang, Eun J; Major, Sebastian; Martus, Peter; Vajkoczy, Peter; Woitzik, Johannes; Dreier, Jens P
2017-05-01
Multimodal neuromonitoring in neurocritical care increasingly includes electrocorticography to measure epileptic events and spreading depolarizations. Spreading depolarization causes spreading depression of activity (=isoelectricity) in electrically active tissue. If the depression is long-lasting, further spreading depolarizations occur in still isoelectric tissue where no activity can be suppressed. Such spreading depolarizations are termed isoelectric and are assumed to indicate energy compromise. However, experimental and clinical recordings suggest that long-lasting spreading depolarization-induced depression and isoelectric spreading depolarizations are often recorded outside of the actual ischemic zones, allowing the remote diagnosis of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Here, we analyzed simultaneous electrocorticography and tissue partial pressure of oxygen recording in 33 aneurysmal subarachnoid hemorrhage patients. Multiple regression showed that both peak total depression duration per recording day and mean baseline tissue partial pressure of oxygen were independent predictors of outcome. Moreover, tissue partial pressure of oxygen preceding spreading depolarization was similar and differences in tissue partial pressure of oxygen responses to spreading depolarization were only subtle between isoelectric spreading depolarizations and spreading depressions. This further supports that, similar to clustering of spreading depolarizations, long spreading depolarization-induced periods of isoelectricity are useful to detect energy compromise remotely, which is valuable because the exact location of future developing pathology is unknown at the time when the neurosurgeon implants recording devices.
Increased Spreading Activation in Depression
ERIC Educational Resources Information Center
Foster, Paul S.; Yung, Raegan C.; Branch, Kaylei K.; Stringer, Kristi; Ferguson, Brad J.; Sullivan, William; Drago, Valeria
2011-01-01
The dopaminergic system is implicated in depressive disorders and research has also shown that dopamine constricts lexical/semantic networks by reducing spreading activation. Hence, depression, which is linked to reductions of dopamine, may be associated with increased spreading activation. However, research has generally found no effects of…
Migraine prophylaxis, ischemic depolarizations and stroke outcomes in mice
Eikermann-Haerter, Katharina; Lee, Jeong Hyun; Yalcin, Nilufer; Yu, Esther Sori; Daneshmand, Ali; Wei, Ying; Zheng, Yi; Can, Anil; Sengul, Buse; Ferrari, Michel D.; van den Maagdenberg, Arn M. J. M.; Ayata, Cenk
2014-01-01
Background and Purpose Migraine with aura is an established stroke risk factor, and excitatory mechanisms such as spreading depression are implicated in the pathogenesis of both migraine and stroke. Spontaneous spreading depression waves originate within the peri-infarct tissue and exacerbate the metabolic mismatch during focal cerebral ischemia. Genetically enhanced spreading depression susceptibility facilitates anoxic depolarizations and peri-infarct spreading depressions and accelerates infarct growth, suggesting that susceptibility to spreading depression is a critical determinant of vulnerability to ischemic injury. Because chronic treatment with migraine prophylactic drugs suppresses spreading depression susceptibility, we tested whether migraine prophylaxis can also suppress ischemic depolarizations and improve stroke outcome. Methods We measured the cortical susceptibility to spreading depression and ischemic depolarizations, and determined tissue and neurological outcome after middle cerebral artery occlusion in wild type and familial hemiplegic migraine type 1 knock-in mice treated with vehicle, topiramate or lamotrigine daily for 7 weeks or as a single dose shortly before testing. Results Chronic treatment with topiramate or lamotrigine reduces the susceptibility to KCl- or electrical stimulation-induced spreading depressions as well as ischemic depolarizations in both wild-type and familial hemiplegic migraine type 1 mutant mice. Consequently, both tissue and neurological outcomes are improved. Notably, treatment with a single dose of either drug is ineffective. Conclusions These data underscore the importance of hyperexcitability as a mechanism for increased stroke risk in migraineurs, and suggest that migraine prophylaxis may not only prevent migraine attacks but also protect migraineurs against ischemic injury. PMID:25424478
Kynurenine Metabolites and Migraine: Experimental Studies and Therapeutic Perspectives
Fejes, Annamária; Párdutz, Árpád; Toldi, József; Vécsei, László
2011-01-01
Migraine is one of the commonest neurological disorders. Despite intensive research, its exact pathomechanism is still not fully understood and effective therapy is not always available. One of the key molecules involved in migraine is glutamate, whose receptors are found on the first-, second- and third-order trigeminal neurones and are also present in the migraine generators, including the dorsal raphe nucleus, nucleus raphe magnus, locus coeruleus and periaqueductal grey matter. Glutamate receptors are important in cortical spreading depression, which may be the electrophysiological correlate of migraine aura. The kynurenine metabolites, endogenous tryptophan metabolites, include kynurenic acid (KYNA), which exerts a blocking effect on ionotropic glutamate and α7-nicotinic acetylcholine receptors. Thus, KYNA and its derivatives may act as modulators at various levels of the pathomechanism of migraine. They can give rise to antinociceptive effects at the periphery, in the trigeminal nucleus caudalis, and may also act on migraine generators and cortical spreading depression. The experimental data suggest that KYNA or its derivatives might offer a novel approach to migraine therapy. PMID:22131946
Kertesz, Szabolcs; Szabo, Geza; Udvari, Szabolcs; Levay, Gyorgy; Matyus, Peter; Harsing, Laszlo G
2013-01-25
We used isolated chicken retina to induce spreading depression by the glutamate receptor agonist N-methyl-d-aspartate. The N-methyl-d-aspartate-induced latency time of spreading depression was extended by the glycine(B) binding site competitive antagonist 7-chlorokynurenic acid. Addition of the glycine transporter type-1 inhibitors NFPS and Org-24461 reversed the inhibitory effect of 7-chlorokynurenic acid on N-methyl-d-aspartate-evoked spreading depression. The glycine uptake inhibitory activity of Org-24461, NFPS, and some newly synthesized analogs of NFPS was determined in CHO cells stably expressing human glycine transporter type-1b isoform. Compounds, which failed to inhibit glycine transporter type-1, also did not have effect on retinal spreading depression. These experiments indicate that the spreading depression model in chicken retina is a useful in vitro test to determine activity of glycine transporter type-1 inhibitors. In addition, our data serve further evidence for the role of glycine transporter type-1 in retinal neurotransmission and light processing. Copyright © 2012 Elsevier B.V. All rights reserved.
Kucharz, Krzysztof; Søndergaard Rasmussen, Ida; Bach, Anders; Strømgaard, Kristian; Lauritzen, Martin
2017-05-01
Cortical spreading depression is associated with activation of NMDA receptors, which interact with the postsynaptic density protein 95 (PSD-95) that binds to nitric oxide synthase (nNOS). Here, we tested whether inhibition of the nNOS/PSD-95/NMDA receptor complex formation by anti-ischemic compound, UCCB01-144 (Tat- N-dimer) ameliorates the persistent effects of cortical spreading depression on cortical function. Using in vivo two-photon microscopy in somatosensory cortex in mice, we show that fluorescently labelled Tat- N-dimer readily crosses blood-brain barrier and accumulates in nerve cells during the first hour after i.v. injection. The Tat- N-dimer suppressed stimulation-evoked synaptic activity by 2-20%, while cortical blood flow and cerebral oxygen metabolic (CMRO 2 ) responses were preserved. During cortical spreading depression, the Tat- N-dimer reduced the average amplitude of the negative shift in direct current potential by 33% (4.1 mV). Furthermore, the compound diminished the average depression of spontaneous electrocorticographic activity by 11% during first 40 min of post-cortical spreading depression recovery, but did not mitigate the suppressing effect of cortical spreading depression on cortical blood flow and CMRO 2 . We suggest that uncoupling of PSD-95 from NMDA receptors reduces overall neuronal excitability and the amplitude of the spreading depolarization wave. These findings may be of interest for understanding the neuroprotective effects of the nNOS/PSD-95 uncoupling in stroke.
Spreading of healthy mood in adolescent social networks
Hill, E. M.; Griffiths, F. E.; House, T.
2015-01-01
Depression is a major public health concern worldwide. There is evidence that social support and befriending influence mental health, and an improved understanding of the social processes that drive depression has the potential to bring significant public health benefits. We investigate transmission of mood on a social network of adolescents, allowing flexibility in our model by making no prior assumption as to whether it is low mood or healthy mood that spreads. Here, we show that while depression does not spread, healthy mood among friends is associated with significantly reduced risk of developing and increased chance of recovering from depression. We found that this spreading of healthy mood can be captured using a non-linear complex contagion model. Having sufficient friends with healthy mood can halve the probability of developing, or double the probability of recovering from, depression over a 6–12-month period on an adolescent social network. Our results suggest that promotion of friendship between adolescents can reduce both incidence and prevalence of depression. PMID:26290075
Spreading of healthy mood in adolescent social networks.
Hill, E M; Griffiths, F E; House, T
2015-08-22
Depression is a major public health concern worldwide. There is evidence that social support and befriending influence mental health, and an improved understanding of the social processes that drive depression has the potential to bring significant public health benefits. We investigate transmission of mood on a social network of adolescents, allowing flexibility in our model by making no prior assumption as to whether it is low mood or healthy mood that spreads. Here, we show that while depression does not spread, healthy mood among friends is associated with significantly reduced risk of developing and increased chance of recovering from depression. We found that this spreading of healthy mood can be captured using a non-linear complex contagion model. Having sufficient friends with healthy mood can halve the probability of developing, or double the probability of recovering from, depression over a 6-12-month period on an adolescent social network. Our results suggest that promotion of friendship between adolescents can reduce both incidence and prevalence of depression. © 2015 The Authors.
NR2A contributes to genesis and propagation of cortical spreading depression in rats.
Bu, Fan; Du, Ruoxing; Li, Yi; Quinn, John P; Wang, Minyan
2016-03-22
Cortical spreading depression (CSD) is a transient propagating excitation of synaptic activity followed by depression, which is implicated in migraine. Increasing evidence points to an essential role of NR2A-containing NMDA receptors in CSD propagation in vitro; however, whether these receptors mediate CSD genesis in vivo requires clarification and the role of NR2A on CSD propagation is still under debate. Using in vivo CSD in rats with electrophysiology and in vitro CSD in chick retina with intrinsic optical imaging, we addressed the role of NR2A in CSD. We demonstrated that NVP-AAM077, a potent antagonist for NR2A-containing receptors, perfused through microdialysis probes, markedly reduced cortex susceptibility to CSD, but also reduced magnitude of CSD genesis in rats. Additionally, NVP-AAM077 at 0.3 nmol perfused into the contralateral ventricle, considerably suppressed the magnitude of CSD propagation wave and propagation rate in rats. This reduction in CSD propagation was also observed with TCN-201, a negative allosteric modulator selective for NR2A, at 3 μM, in the chick retina. Our data provides strong evidence that NR2A subunit contributes to CSD genesis and propagation, suggesting drugs selectively antagonizing NR2A-containing receptors might constitute a highly specific strategy treating CSD associated migraine with a likely better safety profile.
NR2A contributes to genesis and propagation of cortical spreading depression in rats
Bu, Fan; Du, Ruoxing; Li, Yi; Quinn, John P; Wang, Minyan
2016-01-01
Cortical spreading depression (CSD) is a transient propagating excitation of synaptic activity followed by depression, which is implicated in migraine. Increasing evidence points to an essential role of NR2A-containing NMDA receptors in CSD propagation in vitro; however, whether these receptors mediate CSD genesis in vivo requires clarification and the role of NR2A on CSD propagation is still under debate. Using in vivo CSD in rats with electrophysiology and in vitro CSD in chick retina with intrinsic optical imaging, we addressed the role of NR2A in CSD. We demonstrated that NVP-AAM077, a potent antagonist for NR2A-containing receptors, perfused through microdialysis probes, markedly reduced cortex susceptibility to CSD, but also reduced magnitude of CSD genesis in rats. Additionally, NVP-AAM077 at 0.3 nmol perfused into the contralateral ventricle, considerably suppressed the magnitude of CSD propagation wave and propagation rate in rats. This reduction in CSD propagation was also observed with TCN-201, a negative allosteric modulator selective for NR2A, at 3 μM, in the chick retina. Our data provides strong evidence that NR2A subunit contributes to CSD genesis and propagation, suggesting drugs selectively antagonizing NR2A-containing receptors might constitute a highly specific strategy treating CSD associated migraine with a likely better safety profile. PMID:27001011
The Role of Cell Volume in the Dynamics of Seizure, Spreading Depression, and Anoxic Depolarization
Ullah, Ghanim; Wei, Yina; Dahlem, Markus A; Wechselberger, Martin; Schiff, Steven J
2015-01-01
Cell volume changes are ubiquitous in normal and pathological activity of the brain. Nevertheless, we know little of how cell volume affects neuronal dynamics. We here performed the first detailed study of the effects of cell volume on neuronal dynamics. By incorporating cell swelling together with dynamic ion concentrations and oxygen supply into Hodgkin-Huxley type spiking dynamics, we demonstrate the spontaneous transition between epileptic seizure and spreading depression states as the cell swells and contracts in response to changes in osmotic pressure. Our use of volume as an order parameter further revealed a dynamical definition for the experimentally described physiological ceiling that separates seizure from spreading depression, as well as predicted a second ceiling that demarcates spreading depression from anoxic depolarization. Our model highlights the neuroprotective role of glial K buffering against seizures and spreading depression, and provides novel insights into anoxic depolarization and the relevant cell swelling during ischemia. We argue that the dynamics of seizures, spreading depression, and anoxic depolarization lie along a continuum of the repertoire of the neuron membrane that can be understood only when the dynamic ion concentrations, oxygen homeostasis,and cell swelling in response to osmotic pressure are taken into consideration. Our results demonstrate the feasibility of a unified framework for a wide range of neuronal behaviors that may be of substantial importance in the understanding of and potentially developing universal intervention strategies for these pathological states. PMID:26273829
The effects of dynamical synapses on firing rate activity: a spiking neural network model.
Khalil, Radwa; Moftah, Marie Z; Moustafa, Ahmed A
2017-11-01
Accumulating evidence relates the fine-tuning of synaptic maturation and regulation of neural network activity to several key factors, including GABA A signaling and a lateral spread length between neighboring neurons (i.e., local connectivity). Furthermore, a number of studies consider short-term synaptic plasticity (STP) as an essential element in the instant modification of synaptic efficacy in the neuronal network and in modulating responses to sustained ranges of external Poisson input frequency (IF). Nevertheless, evaluating the firing activity in response to the dynamical interaction between STP (triggered by ranges of IF) and these key parameters in vitro remains elusive. Therefore, we designed a spiking neural network (SNN) model in which we incorporated the following parameters: local density of arbor essences and a lateral spread length between neighboring neurons. We also created several network scenarios based on these key parameters. Then, we implemented two classes of STP: (1) short-term synaptic depression (STD) and (2) short-term synaptic facilitation (STF). Each class has two differential forms based on the parametric value of its synaptic time constant (either for depressing or facilitating synapses). Lastly, we compared the neural firing responses before and after the treatment with STP. We found that dynamical synapses (STP) have a critical differential role on evaluating and modulating the firing rate activity in each network scenario. Moreover, we investigated the impact of changing the balance between excitation (E) and inhibition (I) on stabilizing this firing activity. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
Multicarrier orthogonal spread-spectrum (MOSS) data communications
Smith, Stephen F [London, TN; Dress, William B [Camas, WA
2008-01-01
Systems and methods are described for multicarrier orthogonal spread-spectrum (MOSS) data communication. A method includes individually spread-spectrum modulating at least two of a set of orthogonal frequency division multiplexed carriers, wherein the resulting individually spread-spectrum modulated at least two of a set of orthogonal frequency division multiplexed carriers are substantially mutually orthogonal with respect to both frequency division multiplexing and spread-spectrum modulation.
Turing-like structures in a functional model of cortical spreading depression
NASA Astrophysics Data System (ADS)
Verisokin, A. Yu.; Verveyko, D. V.; Postnov, D. E.
2017-12-01
Cortical spreading depression (CSD) along with migraine waves and spreading depolarization events with stroke or injures are the front-line examples of extreme physiological behaviors of the brain cortex which manifest themselves via the onset and spreading of localized areas of neuronal hyperactivity followed by their depression. While much is known about the physiological pathways involved, the dynamical mechanisms of the formation and evolution of complex spatiotemporal patterns during CSD are still poorly understood, in spite of the number of modeling studies that have been already performed. Recently we have proposed a relatively simple mathematical model of cortical spreading depression which counts the effects of neurovascular coupling and cerebral blood flow redistribution during CSD. In the present study, we address the main dynamical consequences of newly included pathways, namely, the changes in the formation and propagation speed of the CSD front and the pattern formation features in two dimensions. Our most notable finding is that the combination of vascular-mediated spatial coupling with local regulatory mechanisms results in the formation of stationary Turing-like patterns during a CSD event.
Bicarbonate and ammonia changes in brain during spreading depression1
Kraig, R. P.; Cooper, A. J. L.
2009-01-01
An alkaline, followed by an acid-going transient, characterizes acid–base changes in the interstitial space during spreading depression in a variety of brain structures. In rat, such changes are associated with a significant rise in brain lactate content. How brain proton buffers behave during spreading depression is unknown. Techniques to significantly improve the response time of gas permeable membrane semnimicroelectrodes for carbon dioxide and ammonia are reported. Measurements with such electrodes, when coupled to measurements of hydrogen ion concentration (from microelectrodes), permit rapid changes to be determined in bicarbonate concentration or ammonia and ammonium ion concentration, respectively. Bicarbonate concentration fell from 30 ± 1 (n = 16) to 14 ± 1 mM (n = 16) during spreading depression. On the other hand, ammonia concentration rose from 2.3 ± 0.1 to 4.4 ± 0.3 μM (n = 17) while ammonium ion concentration rose from 116 ± 11 (n = 17) to 382 ± 30 μM (n = 17) during spreading depression. Bicarbonate changes probably reflect titration of brain bicarbonate stores by accumulated lactic acid. Similar physicochemical changes do not explain the rise in ammonia and ammonium ion concentrations. Instead, elevation of the latter can only result from an increase in ammonia content of the interstitial space. PMID:3621035
Correlates of spreading depolarization in human scalp electroencephalography
Drenckhahn, Christoph; Winkler, Maren K. L.; Major, Sebastian; Scheel, Michael; Kang, Eun-Jeung; Pinczolits, Alexandra; Grozea, Cristian; Hartings, Jed A.; Woitzik, Johannes
2012-01-01
It has been known for decades that suppression of spontaneous scalp electroencephalographic activity occurs during ischaemia. Trend analysis for such suppression was found useful for intraoperative monitoring during carotid endarterectomy, or as a screening tool to detect delayed cerebral ischaemia after aneurismal subarachnoid haemorrhage. Nevertheless, pathogenesis of such suppression of activity has remained unclear. In five patients with aneurismal subarachnoid haemorrhage and four patients with decompressive hemicraniectomy after malignant hemispheric stroke due to middle cerebral artery occlusion, we here performed simultaneously full-band direct and alternating current electroencephalography at the scalp and direct and alternating current electrocorticography at the cortical surface. After subarachnoid haemorrhage, 275 slow potential changes, identifying spreading depolarizations, were recorded electrocorticographically over 694 h. Visual inspection of time-compressed scalp electroencephalography identified 193 (70.2%) slow potential changes [amplitude: −272 (−174, −375) µV (median quartiles), duration: 5.4 (4.0, 7.1) min, electrocorticography–electroencephalography delay: 1.8 (0.8, 3.5) min]. Intervals between successive spreading depolarizations were significantly shorter for depolarizations with electroencephalographically identified slow potential change [33.0 (27.0, 76.5) versus 53.0 (28.0, 130.5) min, P = 0.009]. Electroencephalography was thus more likely to display slow potential changes of clustered than isolated spreading depolarizations. In contrast to electrocorticography, no spread of electroencephalographic slow potential changes was seen, presumably due to superposition of volume-conducted electroencephalographic signals from widespread cortical generators. In two of five patients with subarachnoid haemorrhage, serial magnetic resonance imaging revealed large delayed infarcts at the recording site, while electrocorticography showed clusters of spreading depolarizations with persistent depression of spontaneous activity. Alternating current electroencephalography similarly displayed persistent depression of spontaneous activity, and direct current electroencephalography slow potential changes riding on a shallow negative ultraslow potential. Isolated spreading depolarizations with depression of both spontaneous electrocorticographic and electroencephalographic activity displayed significantly longer intervals between successive spreading depolarizations than isolated depolarizations with only depression of electrocorticographic activity [44.0 (28.0, 132.0) min, n = 96, versus 30.0 (26.5, 51.5) min, n = 109, P = 0.001]. This suggests fusion of electroencephalographic depression periods at high depolarization frequency. No propagation of electroencephalographic depression was seen between scalp electrodes. Durations/magnitudes of isolated electroencephalographic and corresponding electrocorticographic depression periods correlated significantly. Fewer spreading depolarizations were recorded in patients with malignant hemispheric stroke but characteristics were similar to those after subarachnoid haemorrhage. In conclusion, spreading depolarizations and depressions of spontaneous activity display correlates in time-compressed human scalp direct and alternating current electroencephalography that may serve for their non-invasive detection. PMID:22366798
Andreou, Anna P.; Holland, Philip R.; Akerman, Simon; Summ, Oliver; Fredrick, Joe
2016-01-01
Abstract A single pulse of transcranial magnetic stimulation has been shown to be effective for the acute treatment of migraine with and without aura. Here we aimed to investigate the potential mechanisms of action of transcranial magnetic stimulation, using a transcortical approach, in preclinical migraine models. We tested the susceptibility of cortical spreading depression, the experimental correlate of migraine aura, and further evaluated the response of spontaneous and evoked trigeminovascular activity of second order trigemontothalamic and third order thalamocortical neurons in rats. Single pulse transcranial magnetic stimulation significantly inhibited both mechanical and chemically-induced cortical spreading depression when administered immediately post-induction in rats, but not when administered preinduction, and when controlled by a sham stimulation. Additionally transcranial magnetic stimulation significantly inhibited the spontaneous and evoked firing rate of third order thalamocortical projection neurons, but not second order neurons in the trigeminocervical complex, suggesting a potential modulatory effect that may underlie its utility in migraine. In gyrencephalic cat cortices, when administered post-cortical spreading depression, transcranial magnetic stimulation blocked the propagation of cortical spreading depression in two of eight animals. These results are the first to demonstrate that cortical spreading depression can be blocked in vivo using single pulse transcranial magnetic stimulation and further highlight a novel thalamocortical modulatory capacity that may explain the efficacy of magnetic stimulation in the treatment of migraine with and without aura. PMID:27246325
Eising, Else; Shyti, Reinald; 't Hoen, Peter A C; Vijfhuizen, Lisanne S; Huisman, Sjoerd M H; Broos, Ludo A M; Mahfouz, Ahmed; Reinders, Marcel J T; Ferrari, Michel D; Tolner, Else A; de Vries, Boukje; van den Maagdenberg, Arn M J M
2017-05-01
Familial hemiplegic migraine type 1 (FHM1) is a rare monogenic subtype of migraine with aura caused by mutations in CACNA1A that encodes the α 1A subunit of voltage-gated Ca V 2.1 calcium channels. Transgenic knock-in mice that carry the human FHM1 R192Q missense mutation ('FHM1 R192Q mice') exhibit an increased susceptibility to cortical spreading depression (CSD), the mechanism underlying migraine aura. Here, we analysed gene expression profiles from isolated cortical tissue of FHM1 R192Q mice 24 h after experimentally induced CSD in order to identify molecular pathways affected by CSD. Gene expression profiles were generated using deep serial analysis of gene expression sequencing. Our data reveal a signature of inflammatory signalling upon CSD in the cortex of both mutant and wild-type mice. However, only in the brains of FHM1 R192Q mice specific genes are up-regulated in response to CSD that are implicated in interferon-related inflammatory signalling. Our findings show that CSD modulates inflammatory processes in both wild-type and mutant brains, but that an additional unique inflammatory signature becomes expressed after CSD in a relevant mouse model of migraine.
[Domino principle--monoamines in bottom-view].
Sümegi, András
2008-06-01
One of the first neurobiological theories of major depression was the monoamine deficiency hypothesis. The classic monoamine theory of depression suggested that a deficit in monoamine neurotransmitters in the synaptic cleft was the main and primary cause of depression. Recent and newer versions and modifications of the primary classic theory also mainly included this postulate, while other theories of depression preferred departing from the monoamine-based model altogether. Unfortunately, the clear neurobiology of major depression remains an elusive issue, despite intense research. It is clearly held that most, if not all, antidepressant pharmacotherapies treatments produce their therapeutic antidepressant effects, at least in part, by modulating monoamine systems (noradrenergic, serotonergic, and dopaminergic) by a selective or a multi-acting way; however, much less is known about the neurobiological pathology of these monoamine systems in depression. Much of the past 10-15 years of research in the biology of mood disorders has led to considerable evidence in depression implicating multiple system pathology, including abnormalities of monoamine as well as other neurotransmitter systems. These approaches and findings have led researchers to propose broader theories regarding the neurobiology of depression, just like a spreading disorder of specific neuronal networks in the brain. A model for the pathophysiology of depression ill be discussed in the next pages, after describing the main components of depression pathogenesis. Suggestion is that the primary defect emerges in the cross-regulation and vulnerability of special monoaminergic and non-monoaminergic neural networks, which leads to a decrease in the tonic release of neurotransmitters in their projection areas, altering postsynaptic sensitivity, and following, overexaggerated responses to acute increases in the presynaptic firing rate and transmitter release. It is proposed that the primary defect should be involved, in the noradrenergic innervation spreading from the locus coeruleus (LC). Dysregulation of the LC projection activities may lead in turn to malfunction of serotonergic and dopaminergic neurotransmission. Failure of the LC function could explain the basic impairments in the processing of novel information, intensive processing of irrational beliefs, and anxiety. Consecutive deficits in the serotonergic neurotransmission may contribute to the mood changes and reduction in the mesotelencephalic dopaminergic activity to loss of motivation, and anhedonia. Malfunction and dysregulation of CRF and other neuropeptides such as neuropeptide Y, galanin and substance P may reinforce the LC dysfunction and thus further weaken the adaptive ability to stressful stimuli. The new SNRI antidepressants seem to be more superior and effective in the treatment of major depression and in the prophylaxis of recurrent depressive episodes because of their coexistent noradrenergic activity.
Multidimensional signal modulation and/or demodulation for data communications
Smith, Stephen F [London, TN; Dress, William B [Camas, WA
2008-03-04
Systems and methods are described for multidimensional signal modulation and/or demodulation for data communications. A method includes modulating a carrier signal in a first domain selected from the group consisting of phase, frequency, amplitude, polarization and spread; modulating the carrier signal in a second domain selected from the group consisting of phase, frequency, amplitude, polarization and spread; and modulating the carrier signal in a third domain selected from the group consisting of phase, frequency, amplitude, polarization and spread.
Andreou, Anna P; Holland, Philip R; Akerman, Simon; Summ, Oliver; Fredrick, Joe; Goadsby, Peter J
2016-07-01
A single pulse of transcranial magnetic stimulation has been shown to be effective for the acute treatment of migraine with and without aura. Here we aimed to investigate the potential mechanisms of action of transcranial magnetic stimulation, using a transcortical approach, in preclinical migraine models. We tested the susceptibility of cortical spreading depression, the experimental correlate of migraine aura, and further evaluated the response of spontaneous and evoked trigeminovascular activity of second order trigemontothalamic and third order thalamocortical neurons in rats. Single pulse transcranial magnetic stimulation significantly inhibited both mechanical and chemically-induced cortical spreading depression when administered immediately post-induction in rats, but not when administered preinduction, and when controlled by a sham stimulation. Additionally transcranial magnetic stimulation significantly inhibited the spontaneous and evoked firing rate of third order thalamocortical projection neurons, but not second order neurons in the trigeminocervical complex, suggesting a potential modulatory effect that may underlie its utility in migraine. In gyrencephalic cat cortices, when administered post-cortical spreading depression, transcranial magnetic stimulation blocked the propagation of cortical spreading depression in two of eight animals. These results are the first to demonstrate that cortical spreading depression can be blocked in vivo using single pulse transcranial magnetic stimulation and further highlight a novel thalamocortical modulatory capacity that may explain the efficacy of magnetic stimulation in the treatment of migraine with and without aura. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.
Elicitation of spreading depression by rose bengal photodynamic action.
Netto, M; Martins-Ferreira, H
1989-08-01
Spreading depression refers to a slowly propagating depression of the ordinary electrical activity of the nervous tissue. It can be elicited by different types of physical or chemical non-specific stimuli. Various evidences suggest that transient alterations of cell membranes are involved. For this reason, and considering the action of free radicals on cell membranes, the elicitation of the reaction by dye photoactivation has been investigated. Isolated chick retina superfused in the dark with Ringer solution was able to regularly exhibit spreading depression when submitted to 1 microM rose bengal pulse of 5 min in duration, followed by 2.1 x 10(4) to 4.2 x 10(4) Jm-2 light pulse. The phenomenon was monitored either by visual inspection of the light-scattering milky wave that accompanies the reaction or by recording its characteristic slow voltage variation. The reaction was not triggered if the retina, superfused with the dye, was (a) maintained in the dark; (b) illuminated with red light (3.75 x 10(2) to 2.25 x 10(4) Jm-2), or (c) stimulated by white light but superfused with nitrogen-saturated solutions. It is concluded that, under the present conditions, the elicitation of spreading depression is contingent on the photoactivation of rose bengal in the presence of oxygen.
Spreading convulsions, spreading depolarization and epileptogenesis in human cerebral cortex
Major, Sebastian; Pannek, Heinz-Wolfgang; Woitzik, Johannes; Scheel, Michael; Wiesenthal, Dirk; Martus, Peter; Winkler, Maren K.L.; Hartings, Jed A.; Fabricius, Martin; Speckmann, Erwin-Josef; Gorji, Ali
2012-01-01
Spreading depolarization of cells in cerebral grey matter is characterized by massive ion translocation, neuronal swelling and large changes in direct current-coupled voltage recording. The near-complete sustained depolarization above the inactivation threshold for action potential generating channels initiates spreading depression of brain activity. In contrast, epileptic seizures show modest ion translocation and sustained depolarization below the inactivation threshold for action potential generating channels. Such modest sustained depolarization allows synchronous, highly frequent neuronal firing; ictal epileptic field potentials being its electrocorticographic and epileptic seizure its clinical correlate. Nevertheless, Leão in 1944 and Van Harreveld and Stamm in 1953 described in animals that silencing of brain activity induced by spreading depolarization changed during minimal electrical stimulations. Eventually, epileptic field potentials were recorded during the period that had originally seen spreading depression of activity. Such spreading convulsions are characterized by epileptic field potentials on the final shoulder of the large slow potential change of spreading depolarization. We here report on such spreading convulsions in monopolar subdural recordings in 2 of 25 consecutive aneurismal subarachnoid haemorrhage patients in vivo and neocortical slices from 12 patients with intractable temporal lobe epilepsy in vitro. The in vitro results suggest that γ-aminobutyric acid-mediated inhibition protects from spreading convulsions. Moreover, we describe arterial pulse artefacts mimicking epileptic field potentials in three patients with subarachnoid haemorrhage that ride on the slow potential peak. Twenty-one of the 25 subarachnoid haemorrhage patients (84%) had 656 spreading depolarizations in contrast to only three patients (12%) with 55 ictal epileptic events isolated from spreading depolarizations. Spreading depolarization frequency and depression periods per 24 h recording episodes showed an early and a delayed peak on Day 7. Patients surviving subarachnoid haemorrhage with poor outcome at 6 months showed significantly higher total and peak numbers of spreading depolarizations and significantly longer total and peak depression periods during the electrocorticographic monitoring than patients with good outcome. In a semi-structured telephone interview 3 years after the initial haemorrhage, 44% of the subarachnoid haemorrhage survivors had developed late post-haemorrhagic seizures requiring anti-convulsant medication. In those patients, peak spreading depolarization number had been significantly higher [15.1 (11.4–30.8) versus 7.0 (0.8–11.2) events per day, P = 0.045]. In summary, monopolar recordings here provided unequivocal evidence of spreading convulsions in patients. Hence, practically all major pathological cortical network events in animals have now been observed in people. Early spreading depolarizations may indicate a risk for late post-haemorrhagic seizures. PMID:22120143
ERIC Educational Resources Information Center
Boogaert, John
This competency-based preservice home economics teacher education module on resources for the economically depressed area family is the third in a set of three modules on human development in economically depressed areas. (This set is part of a larger set of sixty-seven modules on the Management Approach to Teaching Consumer and Homemaking…
ERIC Educational Resources Information Center
California State Univ., Fresno. Dept. of Home Economics.
This competency-based preservice home economics teacher education module on food availability in economically depressed areas (EDA) is the first in a set of three modules on foods and nutrition in economically depressed areas. (This set is part of a larger set of sixty-seven modules on the Management Approach to Teaching Consumer and Homemaking…
Dreier, Jens P; Fabricius, Martin; Ayata, Cenk; Sakowitz, Oliver W; William Shuttleworth, C; Dohmen, Christian; Graf, Rudolf; Vajkoczy, Peter; Helbok, Raimund; Suzuki, Michiyasu; Schiefecker, Alois J; Major, Sebastian; Winkler, Maren Kl; Kang, Eun-Jeung; Milakara, Denny; Oliveira-Ferreira, Ana I; Reiffurth, Clemens; Revankar, Gajanan S; Sugimoto, Kazutaka; Dengler, Nora F; Hecht, Nils; Foreman, Brandon; Feyen, Bart; Kondziella, Daniel; Friberg, Christian K; Piilgaard, Henning; Rosenthal, Eric S; Westover, M Brandon; Maslarova, Anna; Santos, Edgar; Hertle, Daniel; Sánchez-Porras, Renán; Jewell, Sharon L; Balança, Baptiste; Platz, Johannes; Hinzman, Jason M; Lückl, Janos; Schoknecht, Karl; Schöll, Michael; Drenckhahn, Christoph; Feuerstein, Delphine; Eriksen, Nina; Horst, Viktor; Bretz, Julia S; Jahnke, Paul; Scheel, Michael; Bohner, Georg; Rostrup, Egill; Pakkenberg, Bente; Heinemann, Uwe; Claassen, Jan; Carlson, Andrew P; Kowoll, Christina M; Lublinsky, Svetlana; Chassidim, Yoash; Shelef, Ilan; Friedman, Alon; Brinker, Gerrit; Reiner, Michael; Kirov, Sergei A; Andrew, R David; Farkas, Eszter; Güresir, Erdem; Vatter, Hartmut; Chung, Lee S; Brennan, K C; Lieutaud, Thomas; Marinesco, Stephane; Maas, Andrew Ir; Sahuquillo, Juan; Dahlem, Markus A; Richter, Frank; Herreras, Oscar; Boutelle, Martyn G; Okonkwo, David O; Bullock, M Ross; Witte, Otto W; Martus, Peter; van den Maagdenberg, Arn Mjm; Ferrari, Michel D; Dijkhuizen, Rick M; Shutter, Lori A; Andaluz, Norberto; Schulte, André P; MacVicar, Brian; Watanabe, Tomas; Woitzik, Johannes; Lauritzen, Martin; Strong, Anthony J; Hartings, Jed A
2017-05-01
Spreading depolarizations (SD) are waves of abrupt, near-complete breakdown of neuronal transmembrane ion gradients, are the largest possible pathophysiologic disruption of viable cerebral gray matter, and are a crucial mechanism of lesion development. Spreading depolarizations are increasingly recorded during multimodal neuromonitoring in neurocritical care as a causal biomarker providing a diagnostic summary measure of metabolic failure and excitotoxic injury. Focal ischemia causes spreading depolarization within minutes. Further spreading depolarizations arise for hours to days due to energy supply-demand mismatch in viable tissue. Spreading depolarizations exacerbate neuronal injury through prolonged ionic breakdown and spreading depolarization-related hypoperfusion (spreading ischemia). Local duration of the depolarization indicates local tissue energy status and risk of injury. Regional electrocorticographic monitoring affords even remote detection of injury because spreading depolarizations propagate widely from ischemic or metabolically stressed zones; characteristic patterns, including temporal clusters of spreading depolarizations and persistent depression of spontaneous cortical activity, can be recognized and quantified. Here, we describe the experimental basis for interpreting these patterns and illustrate their translation to human disease. We further provide consensus recommendations for electrocorticographic methods to record, classify, and score spreading depolarizations and associated spreading depressions. These methods offer distinct advantages over other neuromonitoring modalities and allow for future refinement through less invasive and more automated approaches.
Fabricius, Martin; Ayata, Cenk; Sakowitz, Oliver W; William Shuttleworth, C; Dohmen, Christian; Graf, Rudolf; Vajkoczy, Peter; Helbok, Raimund; Suzuki, Michiyasu; Schiefecker, Alois J; Major, Sebastian; Winkler, Maren KL; Kang, Eun-Jeung; Milakara, Denny; Oliveira-Ferreira, Ana I; Reiffurth, Clemens; Revankar, Gajanan S; Sugimoto, Kazutaka; Dengler, Nora F; Hecht, Nils; Foreman, Brandon; Feyen, Bart; Kondziella, Daniel; Friberg, Christian K; Piilgaard, Henning; Rosenthal, Eric S; Westover, M Brandon; Maslarova, Anna; Santos, Edgar; Hertle, Daniel; Sánchez-Porras, Renán; Jewell, Sharon L; Balança, Baptiste; Platz, Johannes; Hinzman, Jason M; Lückl, Janos; Schoknecht, Karl; Schöll, Michael; Drenckhahn, Christoph; Feuerstein, Delphine; Eriksen, Nina; Horst, Viktor; Bretz, Julia S; Jahnke, Paul; Scheel, Michael; Bohner, Georg; Rostrup, Egill; Pakkenberg, Bente; Heinemann, Uwe; Claassen, Jan; Carlson, Andrew P; Kowoll, Christina M; Lublinsky, Svetlana; Chassidim, Yoash; Shelef, Ilan; Friedman, Alon; Brinker, Gerrit; Reiner, Michael; Kirov, Sergei A; Andrew, R David; Farkas, Eszter; Güresir, Erdem; Vatter, Hartmut; Chung, Lee S; Brennan, KC; Lieutaud, Thomas; Marinesco, Stephane; Maas, Andrew IR; Sahuquillo, Juan; Dahlem, Markus A; Richter, Frank; Herreras, Oscar; Boutelle, Martyn G; Okonkwo, David O; Bullock, M Ross; Witte, Otto W; Martus, Peter; van den Maagdenberg, Arn MJM; Ferrari, Michel D; Dijkhuizen, Rick M; Shutter, Lori A; Andaluz, Norberto; Schulte, André P; MacVicar, Brian; Watanabe, Tomas; Woitzik, Johannes; Lauritzen, Martin; Strong, Anthony J; Hartings, Jed A
2016-01-01
Spreading depolarizations (SD) are waves of abrupt, near-complete breakdown of neuronal transmembrane ion gradients, are the largest possible pathophysiologic disruption of viable cerebral gray matter, and are a crucial mechanism of lesion development. Spreading depolarizations are increasingly recorded during multimodal neuromonitoring in neurocritical care as a causal biomarker providing a diagnostic summary measure of metabolic failure and excitotoxic injury. Focal ischemia causes spreading depolarization within minutes. Further spreading depolarizations arise for hours to days due to energy supply-demand mismatch in viable tissue. Spreading depolarizations exacerbate neuronal injury through prolonged ionic breakdown and spreading depolarization-related hypoperfusion (spreading ischemia). Local duration of the depolarization indicates local tissue energy status and risk of injury. Regional electrocorticographic monitoring affords even remote detection of injury because spreading depolarizations propagate widely from ischemic or metabolically stressed zones; characteristic patterns, including temporal clusters of spreading depolarizations and persistent depression of spontaneous cortical activity, can be recognized and quantified. Here, we describe the experimental basis for interpreting these patterns and illustrate their translation to human disease. We further provide consensus recommendations for electrocorticographic methods to record, classify, and score spreading depolarizations and associated spreading depressions. These methods offer distinct advantages over other neuromonitoring modalities and allow for future refinement through less invasive and more automated approaches. PMID:27317657
Direct sensorimotor corticospinal modulation of dorsal horn neuronal C-fiber responses in the rat.
Rojas-Piloni, Gerardo; Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Rodríguez-Jiménez, Javier
2010-09-10
Clinically, the stimulation of motor cortical areas has been used to alleviate certain pain conditions. However, the attempts to understand the mechanisms of cortical nociceptive modulation at the spinal cord level have yielded controversial results. The objectives of the present work were to: 1) determine the effects of activating and suppressing the activity of sensorimotor cortical neurons on the nociceptive electrophysiological responses of the segmental C-fibers, and 2) evaluate the contribution of direct and indirect corticospinal projections in segmental nociceptive modulation. By means of a bipolar matrix of stimulation electrodes we mapped the stimulation of cortical areas that modulate C-fiber evoked field potentials in the dorsal horn. In addition, suppressing the cortical activity by means of cortical spreading depression, we observed that the C-fiber evoked field potentials in the dorsal horn are facilitated when cortical activity is suppressed specifically in sensorimotor cortex. Moreover, the C-fiber evoked field potentials were inhibited during spontaneous activation of cortical projecting neurons. Furthermore, after a lesion of the pyramidal tract contralateral to the spinal cord recording sites, the cortical action was suppressed. Our results show that corticospinal tract fibers arising from the sensorimotor cortex modulate directly the nociceptive C-fiber evoked responses of the dorsal horn. 2010. Published by Elsevier B.V.
NASA Astrophysics Data System (ADS)
Lin, Ray-Ming; Lu, Yuan-Chieh; Chou, Yi-Lun; Chen, Guo-Hsing; Lin, Yung-Hsiang; Wu, Meng-Chyi
2008-06-01
We have studied the characteristics of blue InGaN /GaN multiquantum-well light-emitting diodes (LEDs) after reducing the length of the lateral current path through the transparent layer through formation of a peripheral high-resistance current-blocking region in the Mg-doped GaN layer. To study the mechanism of selective activation in the Mg-doped GaN layer, we deposited titanium (Ti), gold (Au), Ti /Au, silver, and copper individually onto the Mg-doped GaN layer and investigated their effects on the hole concentration in the p-GaN layer. The Mg-doped GaN layer capped with Ti effectively depressed the hole concentration in the p-GaN layer by over one order of magnitude relative to that of the as-grown layer. This may suggest that high resistive regions are formed by diffusion of Ti and depth of high resistive region from the p-GaN surface depends on the capped Ti film thickness. Selective activation of the Mg-doped GaN layer could be used to modulate the length of the lateral current path. Furthermore, the external quantum efficiency of the LEDs was improved significantly after reducing the lateral current spreading length. In our best result, the external quantum efficiency was 52.3% higher (at 100mA) than that of the as-grown blue LEDs.
Kemp, Mark A
2015-11-03
A high power RF device has an electron beam cavity, a modulator, and a circuit for feed-forward energy recovery from a multi-stage depressed collector to the modulator. The electron beam cavity include a cathode, an anode, and the multi-stage depressed collector, and the modulator is configured to provide pulses to the cathode. Voltages of the electrode stages of the multi-stage depressed collector are allowed to float as determined by fixed impedances seen by the electrode stages. The energy recovery circuit includes a storage capacitor that dynamically biases potentials of the electrode stages of the multi-stage depressed collector and provides recovered energy from the electrode stages of the multi-stage depressed collector to the modulator. The circuit may also include a step-down transformer, where the electrode stages of the multi-stage depressed collector are electrically connected to separate taps on the step-down transformer.
Piilgaard, Henning; Lauritzen, Martin
2009-09-01
Cortical spreading depression (CSD) is associated with a dramatic failure of brain ion homeostasis and increased energy metabolism. There is strong clinical and experimental evidence to suggest that CSD is the mechanism of migraine, and involved in progressive neuronal injury in stroke and head trauma. Here we tested the hypothesis that single episodes of CSD induced acute hypoxia, and prolonged impairment of neurovascular and neurometabolic coupling. Cortical spreading depression was induced in rat frontal cortex, whereas cortical electrical activity and local field potentials (LFPs) were recorded by glass microelectrodes, cerebral blood flow (CBF) by laser-Doppler flowmetry, and tissue oxygen tension (tpO(2)) with polarographic microelectrodes. Cortical spreading depression increased cerebral metabolic rate of oxygen (CMRO(2)) by 71%+/-6.7% and CBF by 238%+/-48.1% for 1 to 2 mins. For the following 2 h, basal tpO(2) and CBF were reduced whereas basal CMRO(2) was persistently elevated by 8.1%+/-2.9%. In addition, within first hour after CSD we found impaired neurovascular coupling (LFP versus CBF), whereas neurometabolic coupling (LFP versus CMRO(2)) remained unaffected. Impaired neurovascular coupling was explained by both reduced vascular reactivity and suppressed function of cortical inhibitory interneurons. The protracted effects of CSD on basal CMRO(2) and neurovascular coupling may contribute to cellular dysfunction in patients with migraine and acutely injured cerebral cortex.
Energy spectrum control for modulated proton beams.
Hsi, Wen C; Moyers, Michael F; Nichiporov, Dmitri; Anferov, Vladimir; Wolanski, Mark; Allgower, Chris E; Farr, Jonathan B; Mascia, Anthony E; Schreuder, Andries N
2009-06-01
In proton therapy delivered with range modulated beams, the energy spectrum of protons entering the delivery nozzle can affect the dose uniformity within the target region and the dose gradient around its periphery. For a cyclotron with a fixed extraction energy, a rangeshifter is used to change the energy but this produces increasing energy spreads for decreasing energies. This study investigated the magnitude of the effects of different energy spreads on dose uniformity and distal edge dose gradient and determined the limits for controlling the incident spectrum. A multilayer Faraday cup (MLFC) was calibrated against depth dose curves measured in water for nonmodulated beams with various incident spectra. Depth dose curves were measured in a water phantom and in a multilayer ionization chamber detector for modulated beams using different incident energy spreads. Some nozzle entrance energy spectra can produce unacceptable dose nonuniformities of up to +/-21% over the modulated region. For modulated beams and small beam ranges, the width of the distal penumbra can vary by a factor of 2.5. When the energy spread was controlled within the defined limits, the dose nonuniformity was less than +/-3%. To facilitate understanding of the results, the data were compared to the measured and Monte Carlo calculated data from a variable extraction energy synchrotron which has a narrow spectrum for all energies. Dose uniformity is only maintained within prescription limits when the energy spread is controlled. At low energies, a large spread can be beneficial for extending the energy range at which a single range modulator device can be used. An MLFC can be used as part of a feedback to provide specified energy spreads for different energies.
Direct-Sequence Spread Spectrum System
1990-06-01
by directly modulating a conventional narrowband frequency-modulated (FM) carrier by a high rate digital code. The direct modulation is binary phase ...specification of the DSSS system will not be developed. The results of the evaluation phase of this research will be compared against theoretical...spread spectrum is called binary phase -shift keying 19 (BPSK). BPSK is a modulation in which a binary Ŕ" represents a 0-degree relative phase
NASA Astrophysics Data System (ADS)
Zhou, Chao; Yu, Guoqiang; Furuya, Daisuke; Greenberg, Joel; Yodh, Arjun; Durduran, Turgut
2006-02-01
Diffuse optical correlation methods were adapted for three-dimensional (3D) tomography of cerebral blood flow (CBF) in small animal models. The image reconstruction was optimized using a noise model for diffuse correlation tomography which enabled better data selection and regularization. The tomographic approach was demonstrated with simulated data and during in-vivo cortical spreading depression (CSD) in rat brain. Three-dimensional images of CBF were obtained through intact skull in tissues(~4mm) deep below the cortex.
Cui, Yilong; Kataoka, Yosky; Inui, Takashi; Mochizuki, Takatoshi; Onoe, Hirotaka; Matsumura, Kiyoshi; Urade, Yoshihiro; Yamada, Hisao; Watanabe, Yasuyoshi
2008-03-01
Cortical spreading depression is an excitatory wave of depolarization spreading throughout cerebral cortex at a rate of 2-5 mm/min and has been implicated in various neurological disorders, such as epilepsy, migraine aura, and trauma. Although sleepiness or sleep is often induced by these neurological disorders, the cellular and molecular mechanism has remained unclear. To investigate whether and how the sleep-wake behavior is altered by such aberrant brain activity, we induced cortical spreading depression in freely moving rats, monitoring REM and non-REM (NREM) sleep and sleep-associated changes in cyclooxygenase (COX)-2 and prostaglandins (PGs). In such a model for aberrant neuronal excitation in the cerebral cortex, the amount of NREM sleep, but not of REM sleep, increased subsequently for several hours, with an up-regulated expression of COX-2 in cortical neurons and considerable production of PGs. A specific inhibitor of COX-2 completely arrested the increase in NREM sleep. These results indicate that up-regulated neuronal COX-2 would be involved in aberrant brain excitation-induced NREM sleep via production of PGs. (c) 2007 Wiley-Liss, Inc.
Sato, Shunichi; Kawauchi, Satoko; Okuda, Wataru; Nishidate, Izumi; Nawashiro, Hiroshi; Tsumatori, Gentaro
2014-01-01
Despite many efforts, the pathophysiology and mechanism of blast-induced traumatic brain injury (bTBI) have not yet been elucidated, partially due to the difficulty of real-time diagnosis and extremely complex factors determining the outcome. In this study, we topically applied a laser-induced shock wave (LISW) to the rat brain through the skull, for which real-time measurements of optical diffuse reflectance and electroencephalogram (EEG) were performed. Even under conditions showing no clear changes in systemic physiological parameters, the brain showed a drastic light scattering change accompanied by EEG suppression, which indicated the occurrence of spreading depression, long-lasting hypoxemia and signal change indicating mitochondrial energy impairment. Under the standard LISW conditions examined, hemorrhage and contusion were not apparent in the cortex. To investigate events associated with spreading depression, measurement of direct current (DC) potential, light scattering imaging and stereomicroscopic observation of blood vessels were also conducted for the brain. After LISW application, we observed a distinct negative shift in the DC potential, which temporally coincided with the transit of a light scattering wave, showing the occurrence of spreading depolarization and concomitant change in light scattering. Blood vessels in the brain surface initially showed vasodilatation for 3–4 min, which was followed by long-lasting vasoconstriction, corresponding to hypoxemia. Computer simulation based on the inverse Monte Carlo method showed that hemoglobin oxygen saturation declined to as low as ∼35% in the long-term hypoxemic phase. Overall, we found that topical application of a shock wave to the brain caused spreading depolarization/depression and prolonged severe hypoxemia-oligemia, which might lead to pathological conditions in the brain. Although further study is needed, our findings suggest that spreading depolarization/depression is one of the key events determining the outcome in bTBI. Furthermore, a rat exposed to an LISW(s) can be a reliable laboratory animal model for blast injury research. PMID:24416150
New Treatment Strategies of Depression: Based on Mechanisms Related to Neuroplasticity
Lane, Hsien-Yuan
2017-01-01
Major depressive disorder is a severe and complex mental disorder. Impaired neurotransmission and disrupted signalling pathways may influence neuroplasticity, which is involved in the brain dysfunction in depression. Traditional neurobiological theories of depression, such as monoamine hypothesis, cannot fully explain the whole picture of depressive disorders. In this review, we discussed new treatment directions of depression, including modulation of glutamatergic system and noninvasive brain stimulation. Dysfunction of glutamatergic neurotransmission plays an important role in the pathophysiology of depression. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has rapid and lasting antidepressive effects in previous studies. In addition to ketamine, other glutamatergic modulators, such as sarcosine, also show potential antidepressant effect in animal models or clinical trials. Noninvasive brain stimulation is another new treatment strategy beyond pharmacotherapy. Growing evidence has demonstrated that superficial brain stimulations, such as transcranial magnetic stimulation, transcranial direct current stimulation, cranial electrotherapy stimulation, and magnetic seizure therapy, can improve depressive symptoms. The antidepressive effect of these brain stimulations may be through modulating neuroplasticity. In conclusion, drugs that modulate neurotransmission via NMDA receptor and noninvasive brain stimulation may provide new directions of treatment for depression. Furthermore, exploring the underlying mechanisms will help in developing novel therapies for depression in the future. PMID:28491480
Predictors of adherence among community users of a cognitive behavior therapy website
Batterham, Philip J; Neil, Alison L; Bennett, Kylie; Griffiths, Kathleen M; Christensen, Helen
2008-01-01
Objective To investigate the predictors of early and late dropout among community users of the MoodGYM website, a five module online intervention for reducing the symptoms of depression. Method Approximately 82,000 users accessed the site in 2006, of which 27% completed one module and 10% completed two or more modules. Adherence was modeled as a trichotomous variable representing non-starters (0 modules), early dropouts (1 module) and late dropouts (2–5 modules). Predictor variables included age, gender, education, location, referral source, depression severity, anxiety severity, dysfunctional thinking, and change in symptom count. Results Better adherence was predicted by higher depression severity, higher anxiety severity, a greater level of dysfunctional thinking, younger age, higher education, being female, and being referred to the site by a mental health professional. In addition, users whose depression severity had improved or remained stable after the first intervention module had higher odds of completing subsequent modules. Conclusions While the effect of age and the null effect of location were in accordance with prior adherence research, the significant effects of gender, education and depression severity were not, and may reflect user characteristics, the content of the intervention and unique aspects of online interventions. Further research directions are suggested to investigate the elements of open access online interventions that facilitate adherence. PMID:19920949
Björkenstam, Charlotte; Björkenstam, Emma; Andersson, Gunnar; Cochran, Susan; Kosidou, Kyriaki
2017-03-01
Sexual minority individuals have a higher risk of anxiety and depression compared with heterosexuals. However, whether the higher risk is spread equally across the sexual minority population is not clear. To investigate the association between sexual orientation and self-reported current anxiety and a history of diagnosis of depression, paying particular attention to possible subgroup differences in risks within the sexual minority population, stratified by sex and to examine participants' history of medical care for anxiety disorders and depression. We conducted a population-based study of 874 lesbians and gays, 841 bisexuals, and 67,980 heterosexuals recruited in 2010 in Stockholm County. Data were obtained from self-administered surveys that were linked to nationwide registers. By using logistic regression, we compared risks of current anxiety, histories of diagnosed depression, and register-based medical care for anxiety and/or depression in lesbian and gay, bisexual, and heterosexual individuals. Bisexual women and gay men were more likely to report anxiety compared with their heterosexual peers. Bisexual individuals and gay men also were more likely to report a past diagnosis of depression. All sexual minority groups had an increased risk of having used medical care for anxiety and depression compared with heterosexuals, with bisexual women having the highest risk. Bisexual women appear to be a particularly vulnerable sexual minority group. Advocating for non-discrimination and protections for lesbian, gay, and bisexual people is a logical extension of the effort to lower the prevalence of mental illness. Björkenstam C, Björkenstam E, Andersson G, et al. Anxiety and Depression Among Sexual Minority Women and Men in Sweden: Is the Risk Equally Spread Within the Sexual Minority Population? J Sex Med 2017;14:396-403. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
Talwalkar, Jaideep S; Koff, Jonathan L; Lee, Hochang B; Britto, Clemente J; Mulenos, Arielle M; Georgiopoulos, Anna M
Individuals with cystic fibrosis (CF) are at high risk for depression and anxiety, which are associated with worse medical outcomes. Novel therapies for CF hold great promise for improving physical health, but the effects of these therapies on mental health remain poorly understood. This review aims to familiarize psychiatrists with the potential effect of novel CF therapies on depression and anxiety. We discuss novel therapies that directly target the mutant CF protein, the CF transmembrane regulator (CFTR), which are called CFTR modulators. We summarize depression and anxiety screening and treatment guidelines under implementation in accredited CF centers. Case vignettes highlight the complexities of caring for individuals with CF with comorbid depression and anxiety, including patients experiencing worsening depression and anxiety proximate to initiation of CFTR modulator therapy, and management of drug-drug interactions. Although CFTR modulator therapies provide hope for improving clinical outcomes, worsening depression and anxiety occurs in some patients when starting these novel agents. This phenomenon may be multifactorial, with hypothesized contributions from CFTR modulator-psychotropic medication interactions, direct effects of CFTR modulators on central nervous system function, the psychologic effect of starting a potentially life-altering drug, and typical triggers of depression and anxiety such as stress, pain, and inflammation. The medical and psychiatric complexity of many individuals with CF warrants more direct involvement of mental health specialists on the multidisciplinary CF team. Inclusion of mental health variables in patients with CF registries will facilitate further examination at an epidemiologic level. Copyright © 2017 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.
Pradhan, Amynah A; Smith, Monique L; Zyuzin, Jekaterina; Charles, Andrew
2014-01-01
Background and Purpose Migraine is an extraordinarily common brain disorder for which treatment options continue to be limited. Agonists that activate the δ-opioid receptor may be promising for the treatment of migraine as they are highly effective for the treatment of chronic rather than acute pain, do not induce hyperalgesia, have low abuse potential and have anxiolytic and antidepressant properties. The aim of this study was to investigate the therapeutic potential of δ-opioid receptor agonists for migraine by characterizing their effects in mouse migraine models. Experimental Approach Mechanical hypersensitivity was assessed in mice treated with acute and chronic doses of nitroglycerin (NTG), a known human migraine trigger. Conditioned place aversion to NTG was also measured as a model of migraine-associated negative affect. In addition, we assessed evoked cortical spreading depression (CSD), an established model of migraine aura, in a thinned skull preparation. Key Results NTG evoked acute and chronic mechanical and thermal hyperalgesia in mice, as well as conditioned place aversion. Three different δ-opioid receptor agonists, SNC80, ARM390 and JNJ20788560, significantly reduced NTG-evoked hyperalgesia. SNC80 also abolished NTG-induced conditioned place aversion, suggesting that δ-opioid receptor activation may also alleviate the negative emotional state associated with migraine. We also found that SNC80 significantly attenuated CSD, a model that is considered predictive of migraine preventive therapies. Conclusions and Implications These data show that δ-opioid receptor agonists modulate multiple basic mechanisms associated with migraine, indicating that δ-opioid receptors are a promising therapeutic target for this disorder. PMID:24467301
Luck, Jeff; Hagigi, Fred; Parker, Louise E; Yano, Elizabeth M; Rubenstein, Lisa V; Kirchner, JoAnn E
2009-09-28
Collaborative care models for depression in primary care are effective and cost-effective, but difficult to spread to new sites. Translating Initiatives for Depression into Effective Solutions (TIDES) is an initiative to promote evidence-based collaborative care in the U.S. Veterans Health Administration (VHA). Social marketing applies marketing techniques to promote positive behavior change. Described in this paper, TIDES used a social marketing approach to foster national spread of collaborative care models. The approach relied on a sequential model of behavior change and explicit attention to audience segmentation. Segments included VHA national leadership, Veterans Integrated Service Network (VISN) regional leadership, facility managers, frontline providers, and veterans. TIDES communications, materials and messages targeted each segment, guided by an overall marketing plan. Depression collaborative care based on the TIDES model was adopted by VHA as part of the new Primary Care Mental Health Initiative and associated policies. It is currently in use in more than 50 primary care practices across the United States, and continues to spread, suggesting success for its social marketing-based dissemination strategy. Development, execution and evaluation of the TIDES marketing effort shows that social marketing is a promising approach for promoting implementation of evidence-based interventions in integrated healthcare systems.
The negative ultraslow potential, electrophysiological correlate of infarction in the human cortex
Lückl, Janos; Lemale, Coline L; Kola, Vasilis; Horst, Viktor; Khojasteh, Uldus; Oliveira-Ferreira, Ana I; Major, Sebastian; Winkler, Maren K L; Kang, Eun-Jeung; Schoknecht, Karl; Martus, Peter; Hartings, Jed A; Woitzik, Johannes
2018-01-01
Abstract Spreading depolarizations are characterized by abrupt, near-complete breakdown of the transmembrane ion gradients, neuronal oedema, mitochondrial depolarization, glutamate excitotoxicity and activity loss (depression). Spreading depolarization induces either transient hyperperfusion in normal tissue; or hypoperfusion (inverse coupling = spreading ischaemia) in tissue at risk for progressive injury. The concept of the spreading depolarization continuum is critical since many spreading depolarizations have intermediate characteristics, as opposed to the two extremes of spreading depolarization in either severely ischaemic or normal tissue. In animals, the spreading depolarization extreme in ischaemic tissue is characterized by prolonged depolarization durations, in addition to a slow baseline variation termed the negative ultraslow potential. The negative ultraslow potential is initiated by spreading depolarization and similar to the negative direct current (DC) shift of prolonged spreading depolarization, but specifically refers to a negative potential component during progressive recruitment of neurons into cell death in the wake of spreading depolarization. We here first quantified the spreading depolarization-initiated negative ultraslow potential in the electrocorticographic DC range and the activity depression in the alternate current range after middle cerebral artery occlusion in rats. Relevance of these variables to the injury was supported by significant correlations with the cortical infarct volume and neurological outcome after 72 h of survival. We then identified negative ultraslow potential-containing clusters of spreading depolarizations in 11 patients with aneurysmal subarachnoid haemorrhage. The human platinum/iridium-recorded negative ultraslow potential showed a tent-like shape. Its amplitude of 45.0 (39.0, 69.4) mV [median (first, third quartile)] was 6.6 times larger and its duration of 3.7 (3.3, 5.3) h was 34.9 times longer than the negative DC shift of spreading depolarizations in less compromised tissue. Using Generalized Estimating Equations applied to a logistic regression model, we found that negative ultraslow potential displaying electrodes were significantly more likely to overlie a developing ischaemic lesion (90.0%, 27/30) than those not displaying a negative ultraslow potential (0.0%, 0/20) (P = 0.004). Based on serial neuroimages, the lesions under the electrodes developed within a time window of 72 (56, 134) h. The negative ultraslow potential occurred in this time window in 9/10 patients. It was often preceded by a spreading depolarization cluster with increasingly persistent spreading depressions and progressively prolonged DC shifts and spreading ischaemias. During the negative ultraslow potential, spreading ischaemia lasted for 40.0 (28.0, 76.5) min, cerebral blood flow fell from 57 (53, 65) % to 26 (16, 42) % (n = 4) and tissue partial pressure of oxygen from 12.5 (9.2, 15.2) to 3.3 (2.4, 7.4) mmHg (n = 5). Our data suggest that the negative ultraslow potential is the electrophysiological correlate of infarction in human cerebral cortex and a neuromonitoring-detected medical emergency. PMID:29668855
The negative ultraslow potential, electrophysiological correlate of infarction in the human cortex.
Lückl, Janos; Lemale, Coline L; Kola, Vasilis; Horst, Viktor; Khojasteh, Uldus; Oliveira-Ferreira, Ana I; Major, Sebastian; Winkler, Maren K L; Kang, Eun-Jeung; Schoknecht, Karl; Martus, Peter; Hartings, Jed A; Woitzik, Johannes; Dreier, Jens P
2018-06-01
Spreading depolarizations are characterized by abrupt, near-complete breakdown of the transmembrane ion gradients, neuronal oedema, mitochondrial depolarization, glutamate excitotoxicity and activity loss (depression). Spreading depolarization induces either transient hyperperfusion in normal tissue; or hypoperfusion (inverse coupling = spreading ischaemia) in tissue at risk for progressive injury. The concept of the spreading depolarization continuum is critical since many spreading depolarizations have intermediate characteristics, as opposed to the two extremes of spreading depolarization in either severely ischaemic or normal tissue. In animals, the spreading depolarization extreme in ischaemic tissue is characterized by prolonged depolarization durations, in addition to a slow baseline variation termed the negative ultraslow potential. The negative ultraslow potential is initiated by spreading depolarization and similar to the negative direct current (DC) shift of prolonged spreading depolarization, but specifically refers to a negative potential component during progressive recruitment of neurons into cell death in the wake of spreading depolarization. We here first quantified the spreading depolarization-initiated negative ultraslow potential in the electrocorticographic DC range and the activity depression in the alternate current range after middle cerebral artery occlusion in rats. Relevance of these variables to the injury was supported by significant correlations with the cortical infarct volume and neurological outcome after 72 h of survival. We then identified negative ultraslow potential-containing clusters of spreading depolarizations in 11 patients with aneurysmal subarachnoid haemorrhage. The human platinum/iridium-recorded negative ultraslow potential showed a tent-like shape. Its amplitude of 45.0 (39.0, 69.4) mV [median (first, third quartile)] was 6.6 times larger and its duration of 3.7 (3.3, 5.3) h was 34.9 times longer than the negative DC shift of spreading depolarizations in less compromised tissue. Using Generalized Estimating Equations applied to a logistic regression model, we found that negative ultraslow potential displaying electrodes were significantly more likely to overlie a developing ischaemic lesion (90.0%, 27/30) than those not displaying a negative ultraslow potential (0.0%, 0/20) (P = 0.004). Based on serial neuroimages, the lesions under the electrodes developed within a time window of 72 (56, 134) h. The negative ultraslow potential occurred in this time window in 9/10 patients. It was often preceded by a spreading depolarization cluster with increasingly persistent spreading depressions and progressively prolonged DC shifts and spreading ischaemias. During the negative ultraslow potential, spreading ischaemia lasted for 40.0 (28.0, 76.5) min, cerebral blood flow fell from 57 (53, 65) % to 26 (16, 42) % (n = 4) and tissue partial pressure of oxygen from 12.5 (9.2, 15.2) to 3.3 (2.4, 7.4) mmHg (n = 5). Our data suggest that the negative ultraslow potential is the electrophysiological correlate of infarction in human cerebral cortex and a neuromonitoring-detected medical emergency.awy102media15775596049001.
2009-01-01
Abstract Collaborative care models for depression in primary care are effective and cost-effective, but difficult to spread to new sites. Translating Initiatives for Depression into Effective Solutions (TIDES) is an initiative to promote evidence-based collaborative care in the U.S. Veterans Health Administration (VHA). Social marketing applies marketing techniques to promote positive behavior change. Described in this paper, TIDES used a social marketing approach to foster national spread of collaborative care models. TIDES social marketing approach The approach relied on a sequential model of behavior change and explicit attention to audience segmentation. Segments included VHA national leadership, Veterans Integrated Service Network (VISN) regional leadership, facility managers, frontline providers, and veterans. TIDES communications, materials and messages targeted each segment, guided by an overall marketing plan. Results Depression collaborative care based on the TIDES model was adopted by VHA as part of the new Primary Care Mental Health Initiative and associated policies. It is currently in use in more than 50 primary care practices across the United States, and continues to spread, suggesting success for its social marketing-based dissemination strategy. Discussion and conclusion Development, execution and evaluation of the TIDES marketing effort shows that social marketing is a promising approach for promoting implementation of evidence-based interventions in integrated healthcare systems. PMID:19785754
Li, Fan; Li, Xinying; Yu, Jianjun; Chen, Lin
2014-09-22
We experimentally demonstrated the transmission of 79.86-Gb/s discrete-Fourier-transform spread 32 QAM discrete multi-tone (DFT-spread 32 QAM-DMT) signal over 20-km standard single-mode fiber (SSMF) utilizing directly modulated laser (DML). The experimental results show DFT-spread effectively reduces Peak-to-Average Power Ratio (PAPR) of DMT signal, and also well overcomes narrowband interference and high frequencies power attenuation. We compared different types of training sequence (TS) symbols and found that the optimized TS for channel estimation is the symbol with digital BPSK/QPSK modulation format due to its best performance against optical link noise during channel estimation.
ERIC Educational Resources Information Center
California State Univ., Fresno. Dept. of Home Economics.
This competency-based preservice home economics teacher education module on marketing practices in relation to low income clientele is the third in a set of three modules on management in economically depressed areas (EDAs). (This set is part of a larger set of sixty-seven modules on the Management Approach to Teaching Consumer and Homemaking…
Rogers, Geoffrey
2018-06-01
The Yule-Nielsen effect is an influence on halftone color caused by the diffusion of light within the paper upon which the halftone ink is printed. The diffusion can be characterized by a point spread function. In this paper, a point spread function for paper is derived using the multiple-path model of reflection. This model treats the interaction of light with turbid media as a random walk. Using the multiple-path point spread function, a general expression is derived for the average reflectance of light from a frequency-modulated halftone, in which dot size is constant and the number of dots is varied, with the arrangement of dots random. It is also shown that the line spread function derived from the multiple-path model has the form of a Lorentzian function.
Chen, Yao; Liu, Xiaojie; Vickstrom, Casey R; Liu, Michelle J; Zhao, Li; Viader, Andreu; Cravatt, Benjamin F; Liu, Qing-Song
2016-01-01
Endocannabinoids are diffusible lipophilic molecules that may spread to neighboring synapses. Monoacylglycerol lipase (MAGL) is the principal enzyme that degrades the endocannabinoid 2-arachidonoylglycerol (2-AG). Using knock-out mice in which MAGL is deleted globally or selectively in neurons and astrocytes, we investigated the extent to which neuronal and astrocytic MAGL limit the spread of 2-AG-mediated retrograde synaptic depression in cerebellar slices. A brief tetanic stimulation of parallel fibers in the molecular layer induced synaptically evoked suppression of excitation (SSE) in Purkinje cells, and both neuronal and astrocytic MAGL contribute to the termination of this form of endocannabinoid-mediated synaptic depression. The spread of SSE among Purkinje cells occurred only after global knock-out of MAGL or pharmacological blockade of either MAGL or glutamate uptake, but no spread was detected following neuron- or astrocyte-specific deletion of MAGL. The spread of endocannabinoid signaling was also influenced by the spatial pattern of synaptic stimulation, because it did not occur at spatially dispersed parallel fiber synapses induced by stimulating the granular layer. The tetanic stimulation of parallel fibers did not induce endocannabinoid-mediated synaptic suppression in Golgi cells even after disruption of MAGL and glutamate uptake, suggesting that heightened release of 2-AG by Purkinje cells does not spread the retrograde signal to parallel fibers that innervate Golgi cells. These results suggest that both neuronal and astrocytic MAGL limit the spatial diffusion of 2-AG and confer synapse-specificity of endocannabinoid signaling.
Spreading Depressions as Secondary Insults After Traumatic Injury to the Human Brain
2010-09-01
meeting of the COSBID consortium took place on 6-8 May 2010 in Barcelona , Spain. Drs. Hartings and Wilson attended and made presentations on the topics...questions. 11 VI. REFERENCES aHartings JA, Strong AJ, Fabricius M, Manning A, Bhatia R, Dreier JP, Mazzeo AT, Tortella FC , Bullock MR. Spreading
Quah-Smith, Im; Suo, Chao; Williams, Mark A.
2013-01-01
Abstract Background It has been suggested that the antidepressant effect of laser acupuncture involves modulation of the default mode network (DMN) or resting state network (RSN). In this study, the authors investigated changes in the DMN during laser acupuncture in depressed and nondepressed participants. Objective To aim of this study was to determine if the modulation of the DMN effects by laser acupuncture in depressed participants are different from those of nondepressed participants. Design Randomized stimulation was performed with laser acupuncture on four putative antidepressant acupoints (LR 14, LR 8, CV 14, and HT 7) in a block on–off design, while the blood oxygenation level–dependent (BOLD) fMRI response was recorded from each subject's whole brain on a 3T scanner. DMN patterns of the participants were identified, using an independent component analysis. The identified DMN components from both the nondepressed group and the depressed group were then analytically compared using SPM5. Setting This study took place at a research institute. Subjects Ten nondepressed participants and 10 depressed participants (DS) as confirmed by the Hamilton Depression Rating Scale (HAM-D) participated in this study. Intervention Low Intensity Laser Acupuncture. Main outcome measures Significant DMN patterns in one group were greater than those in the other group. Results The nondepressed participants had significant modulation of DMN in the frontal region at the medial frontal gyrus (verum laser>rest, p<0.001) for three acupoints (LR 14, LR 8, and CV 14). For the depressive participants, the DMN modulation occurred at the inferior parietal cortex and the cerebellum (verum laser>rest, p<0.001). Conclusions Laser acupuncture on LR 8, LR 14, and CV 14 stimulated both the anterior and posterior DMN in both the nondepressed and depressed participants. However, in the nondepressed participants, there was consistently outstanding modulation of the anterior DMN at the medial frontal gyrus across all three acupoints. In the depressed participants, there was wider posterior DMN modulation at the parieto–temporal–limbic cortices. This is part of the antidepressant effect of laser acupuncture. PMID:24761169
NASA Astrophysics Data System (ADS)
Rowlett, Hugh; Forsyth, Donald W.
1984-07-01
New air gun reflection profiles, 3.5-kHz reflection profiles, and microearthquake data recorded by an array of ocean bottom seismographs form the basis for this study of the transition from a spreading center to a major transform fault. Disturbances of the thick, normally flat-lying, turbidite deposits provide indications of recent vertical motions. At the western intersection of the fracture zone with the median valley there is a depression in the sediments that represents the southerly extension of the median valley into the fracture zone valley. The depression is terminated abruptly on the south by the active transform fault, which acts as a locus for vertical as well as horizontal displacement. Flat-lying, undisturbed sediments terminate abruptly at the fault. The western boundary of the depression is much broader and is characterized by a series of slumplike steps. To the west, there is little or no evidence for uplift or tilting of sediments which might indicate vertical recovery of the crust as it spreads away from the depression. This suggests that uplift and recovery out of the depression is episodic in nature and has been inactive over the last million years along the western boundary. To the east there is clear evidence of uplift and tilting of sedimentary layers. A basement ridge emerging from the sediments is currently being uplifted and rotated in a manner analogous to processes responsible for the creation and cancellation of median valley relief. The transition between the spreading center and the transform fault appears to take place within 1-2 km. The width of the transform fault just east of the depression is less than a kilometer. Microearthquakes were located and displayed by new methods that directly account for nonlinearities associated with small arrays. Microearthquakes located by three or more ocean bottom seismometers show that the greatest seismic activity occurs along the eastern walls of the median valley, at the basement ridge, in the eastern portion of the depression and in the crestal mountains. Very little activity is associated with the western edge of the transform depression and the trace of the transform fault.
Ketamine and Beyond: Investigations into the Potential of Glutamatergic Agents to Treat Depression
Lener, Marc S.; Kadriu, Bashkim; Zarate, Carlos A.
2017-01-01
Clinical and preclinical studies suggest that dysfunction of the glutamatergic system is implicated in mood disorders such as major depressive disorder (MDD) and bipolar depression. In clinical studies of individuals with MDD and bipolar depression, rapid reductions in depressive symptoms have been observed in response to subanesthetic-dose ketamine, an agent whose mechanism of action involves the modulation of glutamatergic signaling. The findings from these studies have prompted the repurposing and/or development of other glutamatergic modulators for antidepressant efficacy, both as monotherapy or as an adjunct to conventional monoaminergic antidepressants. This review will highlight the evidence supporting the antidepressant effects of subanesthetic-dose ketamine as well as other glutamatergic modulators, such as D-cycloserine (DCS), riluzole, CP-101,606, CERC-301 (previously known as MK-0657), basimglurant, JNJ-40411813, dextromethorphan, nitrous oxide (N2O), GLYX-13, and esketamine. PMID:28194724
Spread spectrum phase modulation for coherent X-ray diffraction imaging.
Zhang, Xuesong; Jiang, Jing; Xiangli, Bin; Arce, Gonzalo R
2015-09-21
High dynamic range, phase ambiguity and radiation limited resolution are three challenging issues in coherent X-ray diffraction imaging (CXDI), which limit the achievable imaging resolution. This paper proposes a spread spectrum phase modulation (SSPM) method to address the aforementioned problems in a single strobe. The requirements on phase modulator parameters are presented, and a practical implementation of SSPM is discussed via ray optics analysis. Numerical experiments demonstrate the performance of SSPM under the constraint of available X-ray optics fabrication accuracy, showing its potential to real CXDI applications.
In vivo optical imaging of cortical spreading depression in rat
NASA Astrophysics Data System (ADS)
Chen, Shangbin; Li, Pengcheng; Luo, Weihua; Gong, Hui; Cheng, Haiying; Luo, Qingming
2003-12-01
Intrinsic optical signals imaging (IOSI) and laser speckle imaging (LSI) are both novel techniques for functional neuroimaging in vivo. Combining them to study cortical spreading depression (CSD) which is an important disease model for migraine and other neurological disorders. CSD were induced by pinprick in Sprague-Dawley rats. Intrinsic optical signals (IOS) at 540 nm showed CSD evolution happened in one hemisphere cortex at speeds of 3.7+/-0.4 mm/min, and the vasodilation closely correlated a four-phasic response. By LSI, we observed a transient and significant increase cerebral blood flow (CBF). In this paper, optical imaging would be showed as a powerful tool for describing the hemodynamic character during CSD in rat.
Spatio-temporal cerebral blood flow perfusion patterns in cortical spreading depression
NASA Astrophysics Data System (ADS)
Verisokin, Andrey Yu.; Verveyko, Darya V.; Postnov, Dmitry E.
2017-04-01
Cortical spreading depression (CSD) is an example of one of the most common abnormalities in biophysical brain functioning. Despite the fact that there are many mathematical models describing the cortical spreading depression (CSD), most of them do not take into consideration the role of redistribution of cerebral blood flow (CBF), that results in the formation of spatio-temporal patterns. The paper presents a mathematical model, which successfully explains the CBD role in the CSD process. Numerical study of this model has revealed the formation of stationary dissipative structures, visually analogous to Turing structures. However, the mechanism of their formation is not diffusion. We show these structures occur due to another type of spatial coupling, that is related to tissue perfusion rate. The proposed model predicts that at similar state of neurons the distribution of blood flow and oxygenation may by different. Currently, this effect is not taken into account when the Blood oxygen-level dependent (BOLD) contrast imaging used in functional magnetic resonance imaging (fMRI). Thus, the diagnosis on the BOLD signal can be ambiguous. We believe that our results can be used in the future for a more correct interpretation of the data obtained with fMRI, NIRS and other similar methods for research of the brain activity.
Cortical spreading depression: An enigma
NASA Astrophysics Data System (ADS)
Miura, R. M.; Huang, H.; Wylie, J. J.
2007-08-01
The brain is a complex organ with active components composed largely of neurons, glial cells, and blood vessels. There exists an enormous experimental and theoretical literature on the mechanisms involved in the functioning of the brain, but we still do not have a good understanding of how it works on a gross mechanistic level. In general, the brain maintains a homeostatic state with relatively small ion concentration changes, the major ions being sodium, potassium, and chloride. Calcium ions are present in smaller quantities but still play an important role in many phenomena. Cortical spreading depression (CSD for short) was discovered over 60 years ago by A.A.P. Leão, a Brazilian physiologist doing his doctoral research on epilepsy at Harvard University, “Spreading depression of activity in the cerebral cortex," J. Neurophysiol., 7 (1944), pp. 359-390. Cortical spreading depression is characterized by massive changes in ionic concentrations and slow nonlinear chemical waves, with speeds on the order of mm/min, in the cortex of different brain structures in various experimental animals. In humans, CSD is associated with migraine with aura, where a light scintillation in the visual field propagates, then disappears, and is followed by a sustained headache. To date, CSD remains an enigma, and further detailed experimental and theoretical investigations are needed to develop a comprehensive picture of the diverse mechanisms involved in producing CSD. A number of mechanisms have been hypothesized to be important for CSD wave propagation. In this paper, we briefly describe several characteristics of CSD wave propagation, and examine some of the mechanisms that are believed to be important, including ion diffusion, membrane ionic currents, osmotic effects, spatial buffering, neurotransmitter substances, gap junctions, metabolic pumps, and synaptic connections. Continuum models of CSD, consisting of coupled nonlinear diffusion equations for the ion concentrations, and a discrete lattice-Boltzmann method approach will be described. Also, we will describe some open problems and remaining challenges.
Smith, Kiersten S.; Rudolph, Uwe
2012-01-01
GABAA receptors mediate fast synaptic inhibitory neurotransmission throughout the central nervous system. Recent work indicates a role for GABAA receptors in physiologically modulating anxiety and depression levels. In this review, we summarize research that led to the identification of the essential role of GABAA receptors in counteracting trait anxiety and depression-related behaviors, and research aimed at identifying individual GABAA receptor subtypes involved in physiological and pharmacological modulation of emotions. PMID:21810433
[Prospective studies on dynamics of depression from preadolescence to early adolescence].
Bomba, Jacek; Modrzejewska, Renata
2006-01-01
The aim of the study is to evaluate the changes in prevalence and dynamics of depression during puberty. It was conducted in prospective studies in a representative group of large-town primary school students. A group of 1993, 10 year-old students were chosen in a two-stage draw. They were studied with the Karków Depression Inwentory (KID) in the subsequent years 2001, 2002, 2003. The point prevalence of depression was respectively 29%, 30% and 26% for 10, 11 and 12 year-olds. The spread-out rate of depressive disorder was relatively stable. Depression is more common in pre-adolescent boys than girls. The dynamics of the disorder, when studied in these three years show that depression is a disorder with a very unequivocal course amongst the preadolescents.
Hardin, Michael G; Schroth, Elizabeth; Pine, Daniel S; Ernst, Monique
2007-05-01
Developmental changes in cognitive and affective processes contribute to adolescent risk-taking behavior, emotional intensification, and psychopathology. The current study examined adolescent development of cognitive control processes and their modulation by incentive, in health and psychopathology. Predictions include 1) better cognitive control in adults than adolescents, and in healthy adolescents than anxious and depressed adolescents, and 2) a stronger influence of incentives in adolescents than adults, and in healthy adolescents than their depressed and anxious counterparts. Antisaccadic eye movement parameters, which provide a measure of cognitive control, were collected during a reward antisaccade task that included parameterized incentive levels. Participants were 20 healthy adults, 30 healthy adolescents, 16 adolescents with an anxiety disorder, and 11 adolescents with major depression. Performance accuracy and saccade latency were analyzed to test both developmental and psychopathology hypotheses. Development and psychopathology group differences in cognitive control were found. Specifically, adults performed better than healthy adolescents, and healthy adolescents than anxious and depressed adolescents. Incentive improved accuracy for all groups; however, incremental increases were not sufficiently large to further modulate performance. Incentives also affected saccade latencies, pushing healthy adolescent latencies to adult levels, while being less effective in adolescents with depression or anxiety. This latter effect was partially mediated by anxiety symptom severity. Current findings evidence the modulation of cognitive control processes by incentives. While seen in both healthy adults and healthy adolescents, this modulatory effect was stronger in youth. While anxious and depressed adolescents exhibited improved cognitive control under incentives, this effect was smaller than that in healthy adolescents. These findings suggest differential incentive and/or cognitive control processing in anxiety and depression, and across development. Differences could result from disorder specific, or combined developmental and pathological mechanisms.
Incentive-related modulation of cognitive control in healthy, anxious, and depressed adolescents
Hardin, Michael G.; Schroth, Elizabeth; Pine, Daniel S.; Ernst, Monique
2009-01-01
Background Developmental changes in cognitive and affective processes contribute to adolescent risk-taking behavior, emotional intensification, and psychopathology. The current study examined adolescent development of cognitive control processes and their modulation by incentive, in health and psychopathology. Predictions include 1) better cognitive control in adults than adolescents, and in healthy adolescents than anxious and depressed adolescents, and 2) a stronger influence of incentives in adolescents than adults, and in healthy adolescents than their depressed and anxious counterparts. Methods Antisaccadic eye movement parameters, which provide a measure of cognitive control, were collected during a reward antisaccade task that included parameterized incentive levels. Participants were 20 healthy adults, 30 healthy adolescents, 16 adolescents with an anxiety disorder, and 11 adolescents with major depression. Performance accuracy and saccade latency were analyzed to test both developmental and psychopathology hypotheses. Results Development and psychopathology group differences in cognitive control were found. Specifically, adults performed better than healthy adolescents, and healthy adolescents than anxious and depressed adolescents. Incentive improved accuracy for all groups; however, incremental increases were not sufficiently large to further modulate performance. Incentives also affected saccade latencies, pushing healthy adolescent latencies to adult levels, while being less effective in adolescents with depression or anxiety. This latter effect was partially mediated by anxiety symptom severity. Conclusions Current findings evidence the modulation of cognitive control processes by incentives. While seen in both healthy adults and healthy adolescents, this modulatory effect was stronger in youth. While anxious and depressed adolescents exhibited improved cognitive control under incentives, this effect was smaller than that in healthy adolescents. These findings suggest differential incentive and/or cognitive control processing in anxiety and depression, and across development. Differences could result from disorder specific, or combined developmental and pathological mechanisms. PMID:17501725
Kucharz, Krzysztof; Lauritzen, Martin
2018-04-01
Cortical spreading depolarization waves, the cause underlying migraine aura, are also the markers and mechanism of pathology in the acutely injured human brain. Propagation of spreading depolarization wave uniquely depends on the interaction between presynaptic and postsynaptic glutamate N-methyl-d-aspartate receptors (NMDARs). In the normally perfused brain, even a single wave causes a massive depolarization of neurons and glia, which results in transient loss of neuronal function and depression of the ongoing electrocorticographic activity. Endoplasmic reticulum is the cellular organelle of particular importance for modulation of neurotransmission. Neuronal endoplasmic reticulum structure is assumed to be persistently continuous in neurons, but is rapidly lost within 1 to 2 min of global cerebral ischaemia, i.e. the organelle disintegrates by fission. This phenomenon appears to be timed with the cardiac arrest-induced cortical spreading depolarizations, rather than ensuing cell death. To what extent NMDAR-dependent processes may trigger neuronal endoplasmic reticulum fission and whether fission is reversible in the normally perfused brain is unknown. We used two-photon microscopy to examine neuronal endoplasmic reticulum structural dynamics during whisker stimulation and cortical spreading depolarizations in vivo. Somatosensory stimulation triggered loss of endoplasmic reticulum continuity, a likely outcome of constriction and fission, in dendritic spines within less than 10 s of stimulation, which was spontaneously reversible and recovery to normal took 5 min. The endoplasmic reticulum fission was inhibited by blockade of NMDAR and Ca2+/calmodulin-dependent protein kinase II (CaMKII) activated downstream of the NMDARs, whereas inhibition of guanosine triphosphate hydrolases hindered regain of endoplasmic reticulum continuity, i.e. fusion. In contrast to somatosensory stimulation, endoplasmic reticulum fission during spreading depolarization was widespread and present in dendrites and spines, and was preceded by dramatic rise in intracellular Ca2+. The endoplasmic reticulum fission during spreading depolarization was more persistent, as 1 h after the depolarization cortical neurons still exhibited loss of endoplasmic reticulum continuity. Notably, endoplasmic reticulum fission was accompanied with loss of electrocorticographic activity, whereas subsequent regain of synaptic function paralleled the organelle fusion. Furthermore, blocking CaMKII activity partly rescued endoplasmic reticulum fission and markedly shortened the recovery time of brain spontaneous activity. Thus, prevention of endoplasmic reticulum fission with CaMKII inhibitors may be a novel strategy to rescue brain function in patients with migraine and a promising therapeutic avenue in the acutely injured brain.
Cheng, C Y; Pickler, R H
2014-01-01
Stress and fatigue are common complaints of pregnant and postpartum women as is depression. These symptoms may be related to immunomodulation. However, few studies have examined these relationships. The aim of this study was to examine the relationships among stress, fatigue, depression, and cytokines as markers of immune modulation in prenatal and postpartum women. Women completed questionnaires and gave blood samples during late pregnancy and again at 4-6 weeks postpartum. Blood was analyzed for cytokines as measures of immune modulation. Stress, fatigue, and depression were experienced at moderately high levels, with higher levels of fatigue and depression in the postpartum but higher stress in the prenatal period. Levels of several cytokines were increased in the postpartum over the prenatal period. Stress and depression were related in the prenatal period and stress, depression, and fatigue were related in the postpartum. While various cytokines were related to each other in both periods, only stress was related to MIP-1β, a cytokine that may be important for childbirth processes. More studies, especially longitudinal and interventional studies, are needed to increase our knowledge about etiology, patterns, symptoms, factors, and management of maternal distress. The search for reliable biomarkers for at-risk mothers remains a priority.
A four-year experience with a Web-based self-help intervention for depressive symptoms in Mexico.
Lara, María Asunción; Tiburcio, Marcela; Aguilar Abrego, Araceli; Sánchez-Solís, Alejandro
2014-01-01
To describe a four-year descriptive, naturalistic study monitoring the use of HDep (Help for Depression or Ayuda para depression (ADep)in Spanish), an open-access/free Web-based, psycho-education, cognitive-behavioral intervention program produced in Mexico consisting of seven self-help modules that include feedback-generating assessments of depressive symptoms, vignettes, recorded messages, a relaxation exercise, a personal workbook, blogs, and user discussion forums. Data were collected on all individuals who entered the HDep site since the program's launching in 2009. Those who entered the site two or more times and also registered as "users" or "participants." The user data consisted of 1) user profiles; 2) scores for the CES-D (Center for Epidemiological Studies Depression Scale), for users who completed the feedback-generating assessments of depressive symptoms; 3) user evaluations of the usefulness of HDep; and 4) transcripts of HDep discussion forum posts. The raw user data were obtained through Moodle (Modular Object-Oriented Dynamic Learning Environment, a free software e-learning platform) and analyzed quantitatively (using SPSS) and qualitatively (using ATLAS.ti). A total of 28 078 individuals accessed HDep and 17 318 of those (61.6%) qualified as users. Of all users, 84.4% were women, 64.6% used the workbook, and 60.9% entered the discussion forums (of whom 16.3% added a post). Depressive symptoms (CES-D score ≥ 16) were observed in 97.1% of the users who completed the feedback-generating assessment (n = 16 564). User retention dropped across the seven modules (from 12 366 users for Module 1 to 626 for Module 7). However, all seven modules were rated very high for "helpfulness/usefulness," with mean scores all above 4 on a 1 - 5 scale. The HDep discussion forums showed a rich social interaction. Predictors of entering at least one module (based on stepwise logistic regression analysis) included being a woman, being ≥ 30 years old, reporting disability, and having attempted suicide. Of the 72 participants who completed the final user evaluation of HDep, 97.5% said it had an enormous influence on helping them to identify and transform negative thoughts. Despite the high attrition among users, and the need for further structure adaptation, HDep can be considered a potentially useful mental health tool in Mexico for 1) detecting depression (via the CES-D assessments) and 2) providing a means of social support to those with depression. The high levels of depressive symptoms detected among users suggest that the role of free-access, self-help, Web-based interventions in public mental health programs should be further investigated. The effectiveness of HDep in reducing depressive symptoms and providing a support system has yet to be assessed and should be examined in future research.
Neural evidence for enhanced error detection in major depressive disorder.
Chiu, Pearl H; Deldin, Patricia J
2007-04-01
Anomalies in error processing have been implicated in the etiology and maintenance of major depressive disorder. In particular, depressed individuals exhibit heightened sensitivity to error-related information and negative environmental cues, along with reduced responsivity to positive reinforcers. The authors examined the neural activation associated with error processing in individuals diagnosed with and without major depression and the sensitivity of these processes to modulation by monetary task contingencies. The error-related negativity and error-related positivity components of the event-related potential were used to characterize error monitoring in individuals with major depressive disorder and the degree to which these processes are sensitive to modulation by monetary reinforcement. Nondepressed comparison subjects (N=17) and depressed individuals (N=18) performed a flanker task under two external motivation conditions (i.e., monetary reward for correct responses and monetary loss for incorrect responses) and a nonmonetary condition. After each response, accuracy feedback was provided. The error-related negativity component assessed the degree of anomaly in initial error detection, and the error positivity component indexed recognition of errors. Across all conditions, the depressed participants exhibited greater amplitude of the error-related negativity component, relative to the comparison subjects, and equivalent error positivity amplitude. In addition, the two groups showed differential modulation by task incentives in both components. These data implicate exaggerated early error-detection processes in the etiology and maintenance of major depressive disorder. Such processes may then recruit excessive neural and cognitive resources that manifest as symptoms of depression.
Spatial and spectral imaging of point-spread functions using a spatial light modulator
NASA Astrophysics Data System (ADS)
Munagavalasa, Sravan; Schroeder, Bryce; Hua, Xuanwen; Jia, Shu
2017-12-01
We develop a point-spread function (PSF) engineering approach to imaging the spatial and spectral information of molecular emissions using a spatial light modulator (SLM). We show that a dispersive grating pattern imposed upon the emission reveals spectral information. We also propose a deconvolution model that allows the decoupling of the spectral and 3D spatial information in engineered PSFs. The work is readily applicable to single-molecule measurements and fluorescent microscopy.
Mesnildrey, Quentin; Hilkhuysen, Gaston; Macherey, Olivier
2016-02-01
Noise- and sine-carrier vocoders are often used to acoustically simulate the information transmitted by a cochlear implant (CI). However, sine-waves fail to mimic the broad spread of excitation produced by a CI and noise-bands contain intrinsic modulations that are absent in CIs. The present study proposes pulse-spreading harmonic complexes (PSHCs) as an alternative acoustic carrier in vocoders. Sentence-in-noise recognition was measured in 12 normal-hearing subjects for noise-, sine-, and PSHC-vocoders. Consistent with the amount of intrinsic modulations present in each vocoder condition, the average speech reception threshold obtained with the PSHC-vocoder was higher than with sine-vocoding but lower than with noise-vocoding.
Tablet-Based Education to Reduce Depression-Related Stigma
ERIC Educational Resources Information Center
Lu, Catherine; Winkelman, Megan; Wong, Shane Shucheng
2016-01-01
Objectives: This study investigated the efficacy of a tablet-based multimedia education application, the Project Not Alone Depression Module, in improving depression literacy and reducing depression stigma among a community-based mental health clinic population. Methods: A total of 93 participants completed either a tablet-based multimedia…
[Prospective study on dynamics of depression in mid-adolescence].
Bomba, Jacek; Modrzejewska, Renata
2006-01-01
The aim of the study is an evaluation of the occurrence and dynamics of depression during mid-adolescence. It was conducted in prospective studies on a representative group of gymnasium school adolescents in large towns. In a two-stage draw, a representative group of 1737, 13 year-old adolescents was chosen. They were surveyed by the Krakow Depression Inventory (KID) subsequently in the years 2001, 2002, 2003. The point-prevalence of depression was respectively 24.6%, 24.5% and 26.6% for 13, 14 and 15 year-olds. The spread-out rate of depressive disorder in the studied group turned out to be relatively stable. Depression is more common amongst mid-adolescent girls than boys. Dynamics of the disorder, when studied throughout the three years show that amongst the mid-adolescent population, depression is a disorder of an unequivocal nature.
Hybrid spread spectrum radio system
Smith, Stephen F.; Dress, William B.
2010-02-02
Systems and methods are described for hybrid spread spectrum radio systems. A method includes modulating a signal by utilizing a subset of bits from a pseudo-random code generator to control an amplification circuit that provides a gain to the signal. Another method includes: modulating a signal by utilizing a subset of bits from a pseudo-random code generator to control a fast hopping frequency synthesizer; and fast frequency hopping the signal with the fast hopping frequency synthesizer, wherein multiple frequency hops occur within a single data-bit time.
Marine asset security and tracking (MAST) system
Hanson, Gregory Richard [Clinton, TN; Smith, Stephen Fulton [Loudon, TN; Moore, Michael Roy [Corryton, TN; Dobson, Eric Lesley [Charleston, SC; Blair, Jeffrey Scott [Charleston, SC; Duncan, Christopher Allen [Marietta, GA; Lenarduzzi, Roberto [Knoxville, TN
2008-07-01
Methods and apparatus are described for marine asset security and tracking (MAST). A method includes transmitting identification data, location data and environmental state sensor data from a radio frequency tag. An apparatus includes a radio frequency tag that transmits identification data, location data and environmental state sensor data. Another method includes transmitting identification data and location data from a radio frequency tag using hybrid spread-spectrum modulation. Another apparatus includes a radio frequency tag that transmits both identification data and location data using hybrid spread-spectrum modulation.
NASA Astrophysics Data System (ADS)
Vasil'ev, E. N.
2017-09-01
A mathematical model has been proposed for analyzing and optimizing thermoelectric cooling regimes for heat-loaded elements of engineering and electronic devices. The model based on analytic relations employs the working characteristics of thermoelectric modules as the initial data and makes it possible to determine the temperature regime and the optimal values of the feed current for the modules taking into account the thermal resistance of the heat-spreading system.
Altered brain network modules induce helplessness in major depressive disorder.
Peng, Daihui; Shi, Feng; Shen, Ting; Peng, Ziwen; Zhang, Chen; Liu, Xiaohua; Qiu, Meihui; Liu, Jun; Jiang, Kaida; Fang, Yiru; Shen, Dinggang
2014-10-01
The abnormal brain functional connectivity (FC) has been assumed to be a pathophysiological aspect of major depressive disorder (MDD). However, it is poorly understood, regarding the underlying patterns of global FC network and their relationships with the clinical characteristics of MDD. Resting-state functional magnetic resonance imaging data were acquired from 16 first episode, medication-naïve MDD patients and 16 healthy control subjects. The global FC network was constructed using 90 brain regions. The global topological patterns, e.g., small-worldness and modularity, and their relationships with depressive characteristics were investigated. Furthermore, the participant coefficient and module degree of MDD patients were measured to reflect the regional roles in module network, and the impairment of FC was examined by network based statistic. Small-world property was not altered in MDD. However, MDD patients exhibited 5 atypically reorganized modules compared to the controls. A positive relationship was also found among MDD patients between the intra-module I and helplessness factor evaluated via the Hamilton Depression Scale. Specifically, eight regions exhibited the abnormal participant coefficient or module degree, e.g., left superior orbital frontal cortex and right amygdala. The decreased FC was identified among the sub-network of 24 brain regions, e.g., frontal cortex, supplementary motor area, amygdala, thalamus, and hippocampus. The limited size of MDD samples precluded meaningful study of distinct clinical characteristics in relation to aberrant FC. The results revealed altered patterns of brain module network at the global level in MDD patients, which might contribute to the feelings of helplessness. Copyright © 2014 Elsevier B.V. All rights reserved.
Altered brain network modules induce helplessness in major depressive disorder
Peng, Daihui; Shi, Feng; Shen, Ting; Peng, Ziwen; Zhang, Chen; Liu, Xiaohua; Qiu, Meihui; Liu, Jun; Jiang, Kaida; Shen, Dinggang
2017-01-01
Objective The abnormal brain functional connectivity (FC) has been assumed to be a pathophysiological aspect of major depressive disorder (MDD). However, it is poorly understood, regarding the underlying patterns of global FC network and their relationships with the clinical characteristics of MDD. Methods Resting-state functional magnetic resonance imaging data were acquired from 16 first episode, medication-naïve MDD patients and 16 healthy control subjects. The global FC network was constructed using 90 brain regions. The global topological patterns, e.g., small-worldness and modularity, and their relationships with depressive characteristics were investigated. Furthermore, the participant coefficient and module degree of MDD patients were measured to reflect the regional roles in module network, and the impairment of FC was examined by network based statistic. Results Small-world property was not altered in MDD. However, MDD patients exhibited 5 atypically reorganized modules compared to the controls. A positive relationship was also found among MDD patients between the intra-module I and helplessness factor evaluated via the Hamilton Depression Scale. Specifically, eight regions exhibited the abnormal participant coefficient or module degree, e.g., left superior orbital frontal cortex and right amygdala. The decreased FC was identified among the sub-network of 24 brain regions, e.g., frontal cortex, supplementary motor area, amygdala, thalamus, and hippocampus. Limitation The limited size of MDD samples precluded meaningful study of distinct clinical characteristics in relation to aberrant FC. Conclusions The results revealed altered patterns of brain module network at the global level in MDD patients, which might contribute to the feelings of helplessness. PMID:25033474
2011-01-01
prognosis. Keywords: cortical spreading depression; electroencephalography; craniotomy ; signal processing; acute brain injury Introduction Cortical...Mannheim, Germany). Inclusion criteria were the clinical decision for craniotomy for lesion evacuation and/or decompression and age ~ 18 years...externalized through a burr hole in the skull (if the bone flap was replaced) and tu nne lied beneath the scalp to exit 2-3 em from the craniotomy
Sakadžić, Sava; Yuan, Shuai; Dilekoz, Ergin; Ruvinskaya, Svetlana; Vinogradov, Sergei A.; Ayata, Cenk; Boas, David A.
2009-01-01
We developed a novel imaging technique that provides real-time two-dimensional maps of the absolute partial pressure of oxygen and relative cerebral blood flow in rats by combining phosphorescence lifetime imaging with laser speckle contrast imaging. Direct measurement of blood oxygenation based on phosphorescence lifetime is not significantly affected by changes in the optical parameters of the tissue during the experiment. The potential of the system as a novel tool for quantitative analysis of the dynamic delivery of oxygen to support brain metabolism was demonstrated in rats by imaging cortical responses to forepaw stimulation and the propagation of cortical spreading depression waves. This new instrument will enable further study of neurovascular coupling in normal and diseased brain. PMID:19340106
Interoception in anxiety and depression
Stein, Murray B.
2010-01-01
We review the literature on interoception as it relates to depression and anxiety, with a focus on belief, and alliesthesia. The connection between increased but noisy afferent interoceptive input, self-referential and belief-based states, and top-down modulation of poorly predictive signals is integrated into a neuroanatomical and processing model for depression and anxiety. The advantage of this conceptualization is the ability to specifically examine the interface between basic interoception, self-referential belief-based states, and enhanced top-down modulation to attenuate poor predictability. We conclude that depression and anxiety are not simply interoceptive disorders but are altered interoceptive states as a consequence of noisily amplified self-referential interoceptive predictive belief states. PMID:20490545
Modulating speed-accuracy strategies in major depression.
Vallesi, Antonino; Canalaz, Francesca; Balestrieri, Matteo; Brambilla, Paolo
2015-01-01
Depression is associated with deficits in cognitive flexibility. The role of general slowing in modulating more specific cognitive deficits is however unclear. We assessed how depression affects the capacity to strategically adapt behavior between harsh and prudent response modalities and how general and specific processes may contribute to performance deficits. Patients suffering from major depression and age- and education-matched healthy controls were asked to randomly stress either speed or accuracy during perceptual decision-making. Diffusion models showed that patients with depression kept using a less conservative strategy after a trial with speed vs. accuracy instructions. Additionally, the depression group showed a slower rate of evidence accumulation as indicated by a generally lower drift rate. These data demonstrate that less efficient strategic regulation of behavior in depression is due not only to general slowing, but also to more specific deficits, such as a rigid dependence on past contextual instructions. Future studies should investigate the neuro-anatomical basis of this deficit. Copyright © 2014 Elsevier Ltd. All rights reserved.
Murphy, T M; Crawford, B; Dempster, E L; Hannon, E; Burrage, J; Turecki, G; Kaminsky, Z; Mill, J
2017-01-03
Major depressive disorder (MDD) represents a major social and economic health issue and constitutes a major risk factor for suicide. The molecular pathology of suicidal depression remains poorly understood, although it has been hypothesised that regulatory genomic processes are involved in the pathology of both MDD and suicidality. In this study, genome-wide patterns of DNA methylation were assessed in depressed suicide completers (n=20) and compared with non-psychiatric, sudden-death controls (n=20) using tissue from two cortical brain regions (Brodmann Area 11 (BA11) and Brodmann Area 25 (BA25)). Analyses focused on identifying differentially methylated regions (DMRs) associated with suicidal depression and epigenetic variation were explored in the context of polygenic risk scores for major depression and suicide. Weighted gene co-methylation network analysis was used to identify modules of co-methylated loci associated with depressed suicide completers and polygenic burden for MDD and suicide attempt. We identified a DMR upstream of the PSORS1C3 gene, subsequently validated using bisulfite pyrosequencing and replicated in a second set of suicide samples, which is characterised by significant hypomethylation in both cortical brain regions in MDD suicide cases. We also identified discrete modules of co-methylated loci associated with polygenic risk burden for suicide attempt, but not major depression. Suicide-associated co-methylation modules were enriched among gene networks implicating biological processes relevant to depression and suicidality, including nervous system development and mitochondria function. Our data suggest that there are coordinated changes in DNA methylation associated with suicide that may offer novel insights into the molecular pathology associated with depressed suicide completers.
Murphy, T M; Crawford, B; Dempster, E L; Hannon, E; Burrage, J; Turecki, G; Kaminsky, Z; Mill, J
2017-01-01
Major depressive disorder (MDD) represents a major social and economic health issue and constitutes a major risk factor for suicide. The molecular pathology of suicidal depression remains poorly understood, although it has been hypothesised that regulatory genomic processes are involved in the pathology of both MDD and suicidality. In this study, genome-wide patterns of DNA methylation were assessed in depressed suicide completers (n=20) and compared with non-psychiatric, sudden-death controls (n=20) using tissue from two cortical brain regions (Brodmann Area 11 (BA11) and Brodmann Area 25 (BA25)). Analyses focused on identifying differentially methylated regions (DMRs) associated with suicidal depression and epigenetic variation were explored in the context of polygenic risk scores for major depression and suicide. Weighted gene co-methylation network analysis was used to identify modules of co-methylated loci associated with depressed suicide completers and polygenic burden for MDD and suicide attempt. We identified a DMR upstream of the PSORS1C3 gene, subsequently validated using bisulfite pyrosequencing and replicated in a second set of suicide samples, which is characterised by significant hypomethylation in both cortical brain regions in MDD suicide cases. We also identified discrete modules of co-methylated loci associated with polygenic risk burden for suicide attempt, but not major depression. Suicide-associated co-methylation modules were enriched among gene networks implicating biological processes relevant to depression and suicidality, including nervous system development and mitochondria function. Our data suggest that there are coordinated changes in DNA methylation associated with suicide that may offer novel insights into the molecular pathology associated with depressed suicide completers. PMID:28045465
Monteiro, Heloísa Mirelle Costa; de Mendonça, Débora Carneiro; Sousa, Mariana Séfora Bezerra; Amancio-Dos-Santos, Angela
2018-06-01
This investigation studied whether physical exercise could modulate cortical spreading depression (CSD) propagation velocity in adult rat offspring from dams that had received a high-fat (HF) diet during lactation. Wistar male rats suckled by dams fed either control (C) or HF diet ad libitum. After weaning, pups received standard laboratory chow. From 40 to 60 days of life, half of the animals exercised on a treadmill (group E); the other half remained sedentary (group S). Two additional HF groups (E and S) received fluoxetine (F; 10 mg/kg/day, orogastrically) from 40 to 60 days of life (groups HF/EF and HF/F). At 40 days of life, rats from the maternal HF diet presented higher weight, thoracic circumference, and Lee Index than C animals and remained heavier at 60 days of life. Physical exercise decreased abdominal circumference. HF diet increased CSD propagation velocity (mean ± SD; mm/min) in sedentaries (HF/S 3.47 ± 0.31 versus C/S 3.24 ± 0.26). Treadmill exercise decelerated CSD propagation in both groups C/E (2.94 ± 0.28) and HF/E (2.97 ± 0.40). Fluoxetine alone decreased CSD propagation (HF/F 2.88 ± 0.45) compared with HF/S group. The combination of fluoxetine + exercise under HF condition (2.98 ± 0.27) was similar to HF/E group. Physical exercise is able to reduce CSD propagation velocity in rat adult brains even when they have suffered over-nourishing during lactation. The effects of exercise alone or fluoxetine alone on CSD were similar to the effects of fluoxetine + exercise, under the HF condition. Data reinforce malnutrition during lactation modifies cortical electrophysiology even when the HF condition no longer exists.
Dillon, Daniel Gerard; Pizzagalli, Diego Andrea
2013-05-30
Functional magnetic resonance imaging (fMRI) was used to examine cognitive regulation of negative emotion in 12 unmedicated patients with major depressive disorder (MDD) and 24 controls. The participants used reappraisal to increase (real condition) and reduce (photo condition) the personal relevance of negative and neutral pictures during fMRI as valence ratings were collected; passive viewing (look condition) served as a baseline. Reappraisal was not strongly affected by MDD. Ratings indicated that both groups successfully reappraised negative emotional experience. Both groups also showed better memory for negative vs. neutral pictures 2 weeks later. Across groups, increased brain activation was observed on negative/real vs. negative/look and negative/photo trials in left dorsolateral prefrontal cortex (DLPFC), rostral anterior cingulate, left parietal cortex, caudate, and right amygdala. Depressive severity was inversely correlated with activation modulation in the left DLPFC, right amygdala, and right cerebellum during negative reappraisal. The lack of group differences suggests that depressed adults can modulate the brain activation and subjective experience elicited by negative pictures when given clear instructions. However, the negative relationship between depression severity and effects of reappraisal on brain activation indicates that group differences may be detectable in larger samples of more severely depressed participants. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Hanke, Wolfgang; de Lima, Vera Maura Fernandes
2008-02-13
According to its physicochemical properties, neuronal tissue, including the central nervous system (CNS) and thus the human brain, is an excitable medium, which consequently exhibits, among other things, self-organization, pattern formation and propagating waves. Furthermore, such systems can be controlled by weak external forces. The spreading depression (SD), a propagating wave of excitation-depression, is such an event, which is additionally linked to a variety of medically important situations, classical migraine being just one example. Especially in retinal tissue, a true part of the CNS, the SD can be observed very easily with the naked eye and by video imaging techniques due to its big intrinsic optical signal. We have investigated the retinal SD and its control by external physical parameters such as gravity and temperature. Beyond this, especially due to its medical relevance, the control of CNS excitability by pharmacological tools is of specific interest, and we have studied this question in detail using the retinal SD as an experimental tool to collect information about the control of CNS tissue excitability.
Enríquez-Denton, M; Nielsen, J; Perreault, M-C; Morita, H; Petersen, N; Hultborn, H
2000-01-01
In cat lumbar motoneurones, disynaptic inhibitory postsynaptic potentials (IPSPs) evoked by stimulation of antagonist motor nerves were depressed for at least 150 ms following conditioning stimulation of flexor (1.7-2 times threshold (T)) and ankle extensor (5T) nerves. The aim of the present study was to investigate the possibility that this depression is caused by presynaptic inhibitory mechanisms acting at the terminals of group I afferent fibres projecting to the Ia inhibitory interneurones and/or the terminals of these interneurones to the target motoneurones. Conditioning stimulation of flexor, but not ankle extensor, nerves evoked a depression of the monosynaptic Ia excitatory postsynaptic potentials (EPSPs) recorded intracellularly in Ia inhibitory interneurones. This depression lasted between 200 and 700 ms and was not accompanied by a depression of the monosynaptic EPSPs evoked by stimulation of descending pathways. These results suggest that flexor, but not ankle extensor, group I afferent fibres can modulate sensory transmission at the synapse between Ia afferent fibres and Ia inhibitory interneurones. Conditioning stimulation of flexor muscle nerves, extensor muscle nerves and cutaneous nerves produced a long-lasting increase in excitability of the terminals of the Ia inhibitory interneurones. The increase in the excitability of the terminals was not secondary to an electrotonic spread of synaptic excitation at the soma. Indeed, concomitant with the excitability increase of the terminals there were signs of synaptic inhibition in the soma. The unitary IPSPs induced in target motoneurones following the spike activity of single Ia inhibitory interneurones were depressed by conditioning stimulation of muscle and cutaneous nerves. Since the conditioning stimulation also evoked compound IPSPs in those motoneurones, a firm conclusion as to whether unitary IPSP depression involved presynaptic inhibitory mechanism of the terminals of the interneurones could not be reached. The possibility that the changes in excitability of the Ia interneuronal terminals reflect the presence of a presynaptic inhibitory mechanism similar to that operating at the terminals of the afferent fibres (presynaptic inhibition) is discussed.1. In cat lumbar motoneurones, disynaptic inhibitory postsynaptic potentials (IPSPs) evoked by stimulation of antagonist motor nerves were depressed for at least 150 ms following conditioning stimulation of flexor (1.7-2 times threshold (T)) and ankle extensor (5T) nerves. The aim of the present study was to investigate the possibility that this depression is caused by presynaptic inhibitory mechanisms acting at the terminals of group I afferent fibres projecting to the Ia inhibitory interneurones and/or the terminals of these interneurones to the target motoneurones. PMID:10922013
Electrodermal reactivity and its association to substance use disorders.
Taylor, Jeanette
2004-11-01
Poor electrodermal response modulation is associated with substance use disorders, but the specificity of the relationship has not been tested. To test this, 112 college students were assessed for psychiatric symptoms using structured interviews and for ability to modulate skin conductance responses to 2-s 92- or 110-dB white noise blasts that varied in temporal predictability. Twenty-eight good and 28 poor modulators were compared on symptoms of alcohol and illicit drug use disorders, personality disorders (antisocial, borderline, histrionic, and narcissistic), social and specific phobia, and depression. As expected, poor modulators had significantly more symptoms of substance use disorders than good modulators. Groups did not differ in symptoms of anxiety disorder, depression, or personality disorders marked by disinhibition. Poor electrodermal response modulation may reflect a biological risk factor for substance use disorders in particular.
Sun, Yu; Narayan, Vaibhav A; Wittenberg, Gayle M
2016-10-21
Side effects, or the adverse effects of drugs, contain important clinical phenotypic information that may be useful in predicting novel or unknown targets of a drug. It has been suggested that drugs with similar side-effect profiles may share common targets. The diagnostic class, Major Depressive Disorder, is increasingly viewed as being comprised of multiple depression subtypes with different biological root causes. One 'type' of depression generating substantial interest today focuses on patients with high levels of inflammatory burden, indicated by elevated levels of C-reactive proteins (CRP) and pro-inflammatory cytokines such as interleukin 6 (IL-6). It has been suggested that drugs targeting the immune system may have beneficial effect on this subtype of depressed patients, and several studies are underway to test this hypothesis directly. However, patients have been treated with both anti-inflammatory and antidepressant compounds for decades. It may be possible to exploit similarities in clinical readouts to better understand the antidepressant effects of immune-related drugs. Here we explore the space of approved drugs by comparing the drug side effect profiles of known antidepressants and drugs targeting the immune system, and further examine the findings by comparing the human cell line expression profiles induced by them with those induced by antidepressants. We found 7 immune-modulators and 14 anti-inflammatory drugs sharing significant side effect profile similarities with antidepressants. Five of the 7 immune modulators share most similar side effect profiles with antidepressants that modulate dopamine release and/or uptake. In addition, the immunosuppressant rapamycin and the glucocorticoid alclometasone induces transcriptional changes similar to multiple antidepressants. These findings suggest that some antidepressants and some immune-related drugs may affect common molecular pathways. Our findings support the idea that certain medications aimed at the immune system may be helpful in relieving depressive symptoms, and suggest that it may be of value to test immune-modulators for antidepressant-like activity in future proof-of-concept studies.
NASA Astrophysics Data System (ADS)
Li, Pengcheng; Chen, Shangbin; Luo, Weihua; Luo, Qingming
2003-12-01
Cortical spreading depression (CSD) is an important disease model for migraine and cerebral ischemia. We investigated the spatio-temporal characteristics of the intrinsic optical signals (IOS) at 570 nm and the cerebral blood vessel responses during CSD simultaneously by optical reflectance imaging in vivo. The CSD were induced by pinprick in 10 α-chloralose/urethane anesthetized Sprague-Dawley rats. A four-phasic IOS response was observed at pial arteries and parenchymal sites in all experimental animals and an initial slight pial arteries dilation (21.5%+/-13.6%) and constriction (-4.2%+/-3.5%) precedes the dramatic dilation (69.2%+/-26.1%) of pial arterioles was recorded. Our experimental results show a high correlation (r = 0.89+/-0.025) between the IOS response and the diameter changes of the cerebral blood vessels during CSD in rats.
Carter, Russell E; Aiba, Isamu; Dietz, Robert M; Sheline, Christian T; Shuttleworth, C William
2011-01-01
Spreading depression (SD) involves coordinated depolarizations of neurons and glia that propagate through the brain tissue. Repetitive SD-like events are common following human ischemic strokes, and are believed to contribute to the enlargement of infarct volume. Accumulation of Zn2+ is also implicated in ischemic neuronal injury. Synaptic glutamate release contributes to SD propagation, and because Zn2+ is costored with glutamate in some synaptic vesicles, we examined whether Zn2+ is released by SD and may therefore provide a significant source of Zn2+ in the postischemic period. Spreading depression-like events were generated in acutely prepared murine hippocampal slices by deprivation of oxygen and glucose (OGD), and Zn2+ release was detected extracellularly by a Zn2+-selective indicator FluoZin-3. Deprivation of oxygen and glucose-SD produced large FluoZin-3 increases that propagated with the event, and signals were abolished in tissues from ZnT3 knockout animals lacking synaptic Zn2+. Synaptic Zn2+ release was also maintained with repetitive SDs generated by microinjections of KCl under normoxic conditions. Intracellular Zn2+ accumulation in CA1 neurons, assessed using microinjection of FluoZin-3, showed significant increases following SD that was attributed to synaptic Zn2+ release. These results suggest that Zn2+ is released during SDs and could provide a significant source of Zn2+ that contributes to neurodegeneration in the postischemic period. PMID:20978516
Formation of offshore tidal sand banks triggered by a gasmined bed subsidence
NASA Astrophysics Data System (ADS)
Roos, Pieter C.; Hulscher, Suzanne J. M. H.
2002-12-01
Offshore gasmining is an example of a human intervention with a morphological impact. On land, it is usually attended with a dish-like bed depression. We show that, if located at sea, such a bed depression can become morphodynamically active by triggering mechanisms related to tidal sand bank formation. To that end, a simple morphological model is considered which describes an erodible bed subject to a tidal wave in a shallow sea. The continuous subsidence is modelled by a sink term in the sediment balance. Then, a linear approximation is carried out to describe the bed evolution after the onset of subsidence. The results, presented in physical space, show that the subsidence triggers the formation of a sand bank pattern that gradually spreads around the centre of subsidence, at a rate that may go up to 160 m year -1, depending on the tidal transport rate and the tidal eccentricity. The dimension of the depression does not affect the spreading rate nor the orientation of the sand banks, but it does influence their spacing. The main conclusion is that the horizontal extent of the area influenced by the bed depression by far exceeds that of the direct subsidence, thus showing that bed depressions on land and at sea indeed behave in fundamentally different ways. The results suggest that nonlinear effects are worthwhile to be investigated in order to describe finite amplitude development of sand banks as well as the interaction between subsidence and bed forms.
Lunar Roving Vehicle parked in lunar depression on slope of Stone Mountain
1972-04-22
AS16-107-17473 (22 April 1972) --- The Lunar Roving Vehicle (LRV) appears to be parked in a deep lunar depression, on the slope of Stone Mountain. This photograph of the lunar scene at Station No. 4 was taken during the second Apollo 16 extravehicular activity (EVA) at the Descartes landing site. A sample collection bag is in the right foreground. Note field of small boulders at upper right. While astronauts John W. Young, commander, and Charles M. Duke Jr., lunar module pilot, descended in the Lunar Module (LM) "Orion" to explore the moon, astronaut Thomas K. Mattingly II, command module pilot, remained with the Command and Service Modules (CSM) in lunar orbit.
Gender differences in cardiac autonomic modulation during medical internship.
Lin, Yu-Hsuan; Chen, Ching-Yen; Lin, Sheng-Hsuan; Liu, Chun-Hao; Weng, Wei-Hung; Kuo, Terry B J; Yang, Cheryl C H
2013-06-01
Medical internship is known to be a time of high stress and long working hours, which increases the risk of depression and cardiovascular disease. Gender differences in medical interns' cardiovascular risk have not been reported previously. Thirty-eight medical interns (29 males) were repeatedly tested for depressive symptoms using the Hospital Anxiety and Depression Scale and 5-min spectral analysis of heart rate variability (HRV) at 3-month intervals during their internship. Among the male interns, the variance of the heart rate decreased at 6, 9, 12 months, and a reduced high frequency, which suggests reduced cardiac parasympathetic modulation, was found at 9 and 12 months into their internship. Increased depressive symptoms were also identified at 12 months in the male group. No significant differences in depression or any of the HRV indices were identified among the female interns during their internship. Copyright © 2013 Society for Psychophysiological Research.
Zhang, Zhen; Yan, Lixin; Du, Yingchao; ...
2017-05-01
We propose a method based on the slice energy spread modulation to generate strong subpicosecond density bunching in high-intensity relativistic electron beams. A laser pulse with periodic intensity envelope is used to modulate the slice energy spread of the electron beam, which can then be converted into density modulation after a dispersive section. It is found that the double-horn slice energy distribution of the electron beam induced by the laser modulation is very effective to increase the density bunching. Since the modulation is performed on a relativistic electron beam, the process does not suffer from strong space charge force ormore » coupling between phase spaces, so that it is straightforward to preserve the beam quality for terahertz (THz) radiation and other applications. We show in both theory and simulations that the tunable radiation from the beam can cover the frequency range of 1 - 10 THz with high power and narrow-band spectra.« less
Spreading Depression, Spreading Depolarizations, and the Cerebral Vasculature
Ayata, Cenk; Lauritzen, Martin
2015-01-01
Spreading depression (SD) is a transient wave of near-complete neuronal and glial depolarization associated with massive transmembrane ionic and water shifts. It is evolutionarily conserved in the central nervous systems of a wide variety of species from locust to human. The depolarization spreads slowly at a rate of only millimeters per minute by way of grey matter contiguity, irrespective of functional or vascular divisions, and lasts up to a minute in otherwise normal tissue. As such, SD is a radically different breed of electrophysiological activity compared with everyday neural activity, such as action potentials and synaptic transmission. Seventy years after its discovery by Leão, the mechanisms of SD and its profound metabolic and hemodynamic effects are still debated. What we did learn of consequence, however, is that SD plays a central role in the pathophysiology of a number of diseases including migraine, ischemic stroke, intracranial hemorrhage, and traumatic brain injury. An intriguing overlap among them is that they are all neurovascular disorders. Therefore, the interplay between neurons and vascular elements is critical for our understanding of the impact of this homeostatic breakdown in patients. The challenges of translating experimental data into human pathophysiology notwithstanding, this review provides a detailed account of bidirectional interactions between brain parenchyma and the cerebral vasculature during SD and puts this in the context of neurovascular diseases. PMID:26133935
Regan, R. Steve; LaFontaine, Jacob H.
2017-10-05
This report documents seven enhancements to the U.S. Geological Survey (USGS) Precipitation-Runoff Modeling System (PRMS) hydrologic simulation code: two time-series input options, two new output options, and three updates of existing capabilities. The enhancements are (1) new dynamic parameter module, (2) new water-use module, (3) new Hydrologic Response Unit (HRU) summary output module, (4) new basin variables summary output module, (5) new stream and lake flow routing module, (6) update to surface-depression storage and flow simulation, and (7) update to the initial-conditions specification. This report relies heavily upon U.S. Geological Survey Techniques and Methods, book 6, chapter B7, which documents PRMS version 4 (PRMS-IV). A brief description of PRMS is included in this report.
Traumatic Brain Injury: A Guide for Caregivers of Service Members and Veterans
2010-01-01
Fracture - Module 1, pages 2, 15, 22, 26...pages 6, 9, 13-16, 20, 22, 25, 27 Skull Fracture - Companion, page 9; Module 1, pages 14-15, 22, 26 Simple Fracture - Module 1, page 15 Compound... Fracture - Module 1, page 15 Depressed Skull Fracture - Module 1, page 15 Basal Skull Fracture - Module 1, page 15 Sleep Changes - Module 2, pages
Champagne, Tina
2011-01-01
The purpose of this article is to provide a brief overview of how Posttraumatic Stress Disorder (PTSD), Depression, and Sensory Processing patterns influence occupational engagement, including work performance. Interventions and outcomes of the Sensory Modulation Program and approaches from Cognitive Behavior Therapy (CBT) are reviewed through single case exploration with a 42 year-old woman in outpatient services. The marked increase in occupational engagement and improved work performance in this single case review demonstrates the need for more research on the use of the Sensory Modulation Program and approaches from CBT with populations with PTSD, Depression, and Sensory Processing disorder.
Sensorimotor Modulation of Mood and Depression: In Search of an Optimal Mode of Stimulation
Canbeyli, Resit
2013-01-01
Depression involves a dysfunction in an affective fronto-limbic circuitry including the prefrontal cortices, several limbic structures including the cingulate cortex, the amygdala, and the hippocampus as well as the basal ganglia. A major emphasis of research on the etiology and treatment of mood disorders has been to assess the impact of centrally generated (top-down) processes impacting the affective fronto-limbic circuitry. The present review shows that peripheral (bottom-up) unipolar stimulation via the visual and the auditory modalities as well as by physical exercise modulates mood and depressive symptoms in humans and animals and activates the same central affective neurocircuitry involved in depression. It is proposed that the amygdala serves as a gateway by articulating the mood regulatory sensorimotor stimulation with the central affective circuitry by emotionally labeling and mediating the storage of such emotional events in long-term memory. Since both amelioration and aggravation of mood is shown to be possible by unipolar stimulation, the review suggests that a psychophysical assessment of mood modulation by multimodal stimulation may uncover mood ameliorative synergisms and serve as adjunctive treatment for depression. Thus, the integrative review not only emphasizes the relevance of investigating the optimal levels of mood regulatory sensorimotor stimulation, but also provides a conceptual springboard for related future research. PMID:23908624
Effects of sciatic nerve stimulation on the propagation of cortical spreading depression
NASA Astrophysics Data System (ADS)
Sun, Xiaoli; Yu, Zhidong; Zeng, Shaoqun; Luo, Qingming; Li, Pengcheng
2008-02-01
Cortical spreading depression (CSD) is an important pathological model of migraine and is related to other neural disorders, such as cerebral ischemia and epilepsy. It has been reported that brain stimulation is a quite effective way to treat neural diseases. However, direct stimulation could cause harm to brain. If peripheral nerve stimulation could have the same treatment, it would be essential to investigate the mechanisms of peripheral nerve and the study of sciatic nerve stimulation would have profound clinical meaning. In this paper, we used optical intrinsic signal imaging (OISI) and extracellular electrophysiologic recording techniques to study the effects of sciatic nerve stimulation on the propagation of CSD. We found that: (1) continuous sciatic nerve stimulation on rats caused a decrease in light intensity on the whole cortex, which meant an increase in cerebral blood volume(CBV); (2) the spreading velocity of CSD declined from 3.63+/- 0.272 mm/min to 3.06+/-0.260 mm/min during sciatic nerve stimulation, compared with that without sciatic nerve stimulation. In summary, data suggests that sciatic nerve stimulation elicits a response of cortex and causes a slowdown in the propagation of CSD.
Takizawa, Tsubasa; Shibata, Mamoru; Kayama, Yohei; Shimizu, Toshihiko; Toriumi, Haruki; Ebine, Taeko; Unekawa, Miyuki; Koh, Anri; Yoshimura, Akihiko; Suzuki, Norihiro
2017-03-01
Single episodes of cortical spreading depression (CSD) are believed to cause typical migraine aura, whereas clusters of spreading depolarizations have been observed in cerebral ischemia and subarachnoid hemorrhage. We recently demonstrated that the release of high-mobility group box 1 (HMGB1) from cortical neurons after CSD in a rodent model is dependent on the number of CSD episodes, such that only multiple CSD episodes can induce significant HMGB1 release. Here, we report that only multiple CSD inductions caused microglial hypertrophy (activation) accompanied by a greater impact on the transcription activity of the HMGB1 receptor genes, TLR2 and TLR4, while the total number of cortical microglia was not affected. Both an HMGB1-neurtalizing antibody and the HMGB1 inhibitor glycyrrhizin abrogated multiple CSD-induced microglial hypertrophy. Moreover, multiple CSD inductions failed to induce microglial hypertrophy in TLR2/4 double knockout mice. These results strongly implicate the HMGB1-TLR2/4 axis in the activation of microglia following multiple CSD inductions. Increased expression of the lysosomal acid hydrolase cathepsin D was detected in activated microglia by immunostaining, suggesting that lysosomal phagocytic activity may be enhanced in multiple CSD-activated microglia.
The Role of Motivation in Cognitive Reappraisal for Depressed Patients
Wang, Xiaoxia; Zhou, Xiaoyan; Dai, Qin; Ji, Bing; Feng, Zhengzhi
2017-01-01
Background: People engage in emotion regulation in service of motive goals (typically, to approach a desired emotional goal or avoid an undesired emotional goal). However, how motives (goals) in emotion regulation operate to shape the regulation of emotion is rarely known. Furthermore, the modulatory role of motivation in the impaired reappraisal capacity and neural abnormalities typical of depressed patients is not clear. Our hypothesis was that (1) approach and avoidance motivation may modulate emotion regulation and the underlying neural substrates; (2) approach/avoidance motivation may modulate emotion regulation neural abnormalities in depressed patients. Methods: Twelve drug-free depressed patients and fifteen matched healthy controls reappraised emotional pictures with approach/avoidant strategies and self-rated their emotional intensities during fMRI scans. Approach/avoidance motivation was measured using Behavioral Inhibition System and Behavioral Activation System (BIS/BAS) Scale. We conducted whole-brain analyses and correlation analyses of regions of interest to identify alterations in regulatory prefrontal-amygdala circuits which were modulated by motivation. Results: Depressed patients had a higher level of BIS and lower levels of BAS-reward responsiveness and BAS-drive. BIS scores were positively correlated with depressive severity. We found the main effect of motivation as well as the interactive effect of motivation and group on the neural correlates of emotion regulation. Specifically, hypoactivation of IFG underlying the group differences in the motivation-related neural correlates during reappraisal may be partially explained by the interaction between group and reappraisal. Consistent with our prediction, dlPFC and vmPFC was differentially between groups which were modulated by motivation. Specifically, the avoidance motivation of depressed patients could predict the right dlPFC activation during decreasing positive emotion, while the approach motivation of normal individuals could predict the right vmPFC activation during decreasing negative emotion. Notably, striatal regions were observed when examining the neural substrates underlying the main effect of motivation (lentiform nucleus) and the interactive effect between motivation and group (midbrain). Conclusions: Our findings highlight the modulatory role of approach and avoidance motivation in cognitive reappraisal, which is dysfunctional in depressed patients. The results could enlighten the CBT directed at modifying the motivation deficits in cognitive regulation of emotion. PMID:29163097
The Role of Motivation in Cognitive Reappraisal for Depressed Patients.
Wang, Xiaoxia; Zhou, Xiaoyan; Dai, Qin; Ji, Bing; Feng, Zhengzhi
2017-01-01
Background: People engage in emotion regulation in service of motive goals (typically, to approach a desired emotional goal or avoid an undesired emotional goal). However, how motives (goals) in emotion regulation operate to shape the regulation of emotion is rarely known. Furthermore, the modulatory role of motivation in the impaired reappraisal capacity and neural abnormalities typical of depressed patients is not clear. Our hypothesis was that (1) approach and avoidance motivation may modulate emotion regulation and the underlying neural substrates; (2) approach/avoidance motivation may modulate emotion regulation neural abnormalities in depressed patients. Methods: Twelve drug-free depressed patients and fifteen matched healthy controls reappraised emotional pictures with approach/avoidant strategies and self-rated their emotional intensities during fMRI scans. Approach/avoidance motivation was measured using Behavioral Inhibition System and Behavioral Activation System (BIS/BAS) Scale. We conducted whole-brain analyses and correlation analyses of regions of interest to identify alterations in regulatory prefrontal-amygdala circuits which were modulated by motivation. Results: Depressed patients had a higher level of BIS and lower levels of BAS-reward responsiveness and BAS-drive. BIS scores were positively correlated with depressive severity. We found the main effect of motivation as well as the interactive effect of motivation and group on the neural correlates of emotion regulation. Specifically, hypoactivation of IFG underlying the group differences in the motivation-related neural correlates during reappraisal may be partially explained by the interaction between group and reappraisal. Consistent with our prediction, dlPFC and vmPFC was differentially between groups which were modulated by motivation. Specifically, the avoidance motivation of depressed patients could predict the right dlPFC activation during decreasing positive emotion, while the approach motivation of normal individuals could predict the right vmPFC activation during decreasing negative emotion. Notably, striatal regions were observed when examining the neural substrates underlying the main effect of motivation (lentiform nucleus) and the interactive effect between motivation and group (midbrain). Conclusions: Our findings highlight the modulatory role of approach and avoidance motivation in cognitive reappraisal, which is dysfunctional in depressed patients. The results could enlighten the CBT directed at modifying the motivation deficits in cognitive regulation of emotion.
Access of emotional information to visual awareness in patients with major depressive disorder.
Sterzer, P; Hilgenfeldt, T; Freudenberg, P; Bermpohl, F; Adli, M
2011-08-01
According to cognitive theories of depression, negative biases affect most cognitive processes including perception. Such depressive perception may result not only from biased cognitive appraisal but also from automatic processing biases that influence the access of sensory information to awareness. Twenty patients with major depressive disorder (MDD) and 20 healthy control participants underwent behavioural testing with a variant of binocular rivalry, continuous flash suppression (CFS), to investigate the potency of emotional visual stimuli to gain access to awareness. While a neutral, fearful, happy or sad emotional face was presented to one eye, high-contrast dynamic patterns were presented to the other eye, resulting in initial suppression of the face from awareness. Participants indicated the location of the face with a key press as soon as it became visible. The modulation of suppression time by emotional expression was taken as an index of unconscious emotion processing. We found a significant difference in the emotional modulation of suppression time between MDD patients and controls. This difference was due to relatively shorter suppression of sad faces and, to a lesser degree, to longer suppression of happy faces in MDD. Suppression time modulation by sad expression correlated with change in self-reported severity of depression after 4 weeks. Our finding of preferential access to awareness for mood-congruent stimuli supports the notion that depressive perception may be related to altered sensory information processing even at automatic processing stages. Such perceptual biases towards mood-congruent information may reinforce depressed mood and contribute to negative cognitive biases. © Cambridge University Press 2011
Ertürk, Korhan Levent; Şengül, Gökhan
2012-01-01
We developed 3D simulation software of human organs/tissues; we developed a database to store the related data, a data management system to manage the created data, and a metadata system for the management of data. This approach provides two benefits: first of all the developed system does not require to keep the patient's/subject's medical images on the system, providing less memory usage. Besides the system also provides 3D simulation and modification options, which will help clinicians to use necessary tools for visualization and modification operations. The developed system is tested in a case study, in which a 3D human brain model is created and simulated from 2D MRI images of a human brain, and we extended the 3D model to include the spreading cortical depression (SCD) wave front, which is an electrical phoneme that is believed to cause the migraine. PMID:23258956
V.M, Fernandes de Lima; W, Hanke
2014-01-01
In preclinical neuropharmacological research, molecular, cell-based, and systems using animals are well established. On the tissue level the situation is less comfortable, although during the last decades some effort went into establishing such systems, i.e. using slices of the vertebrate brain together with optical and electrophysiological techniques. However, these methods are neither fast, nor can they be automated or upscaled. By contrast, the chicken retina can be used as a suitable model. It is easy accessible and can be kept alive in vitro for hours up to days. Due to its structure, in addition the retina displays remarkable intrinsic optical signals, which can be easily used in experiments. Also to electrophysiological methods the retina is well accessible. In excitable tissue, to which the brain and the retina belong, propagating excitation waves can be expected, and the spreading depression is such a phenomenon. It has been first observed in the forties of the last century. Later, Martins-Ferreira established it in the chicken retina (retinal spreading depression or RSD). The electrophysiological characteristics of it are identical with those of the cortical SD. The metabolic differences are known and can be taken into account. The experimental advantage of the RSD compared to the cortical SD is the pronounced intrinsic optical signal (IOS) associated with the travelling wave. This is due to the maximum transparency of retinal tissue in the functional state; thus any physiological event will change it markedly and therefore can be easily seen even by naked eye. The theory can explain wave spread in one (action potentials), two (RSDs) and three dimensions (one heart beat). In this review we present the experimental and the excitable media context for the data interpretation using as example the cholinergic pharmacology in relation to functional syndromes. We also discuss the intrinsic optical signal and how to use it in pre-clinical research. PMID:25426010
Schoenberg, Poppy L A; Speckens, Anne E M
2014-10-01
Depressive severity has been associated with attenuated neocortical frontal midline theta (Fm-θ) power/evoked activity. Mindfulness-Based Cognitive Therapy (MBCT) has shown to be a successful novel intervention for Major Depressive Disorder (MDD), albeit precise working mechanisms remain elusive. We examined the hypothesis that MBCT would have modulating effects upon evoked Fm-θ power, in addition to investigating possible mediation of induced event-related de/synchronisation (ERD/ERS) dynamics. Fifty one patients with a primary diagnosis of MDD (26 exposed to MBCT vs. 25 wait-list/WL controls) undertook a Go/NoGo task consisting of positive, negative and neutral words, further stratified into abstract versus trait adjective matrices. Depressive symptom severity and rumination were also examined. A pattern of enhanced induced Fm-θ synchronisation during the latter 400-800 ms temporal-window pre-to-post MBCT was observed; the contrary in the WL. Modulated ERD/ERS dynamics correlated to amelioration in depressive and rumination symptoms in the MBCT group. We propose the primary action pathway alluded to a neural disengagement mechanism enacting upon tonic neuronal assemblies implicated in emotional and self-related processing. Due to the complexity and presently undiscovered complete unified scientific understanding of neuro-oscillatory-dynamics, and associated clinical interplays; we hypothesise that the electro-cortical and connected clinical working pathways of MBCT in depression are multi-levelled constituting nonlinear and interdependent mechanisms, represented by mediated EEG synchronisation dynamics.
Anderson, Ian M; Juhasz, Gabriella; Thomas, Emma; Downey, Darragh; McKie, Shane; Deakin, J F William; Elliott, Rebecca
2011-01-01
Both reduced serotonergic (5-HT) function and negative emotional biases have been associated with vulnerability to depression. In order to investigate whether these might be related we examined 5-HT modulation of affective processing in 14 remitted depressed subjects compared with 12 never depressed controls matched for age and sex. Participants underwent function magnetic resonance imaging (fMRI) during a covert face emotion task with and without intravenous citalopram (7.5mg) pretreatment. Compared with viewing neutral faces, and irrespective of group, citalopram enhanced left anterior cingulate blood oxygen level dependent (BOLD) response to happy faces, right posterior insula and right lateral orbitofrontal responses to sad faces, and reduced amygdala responses bilaterally to fearful faces. In controls, relative to remitted depressed subjects, citalopram increased bilateral hippocampal responses to happy faces and increased right anterior insula response to sad faces. These findings were not accounted for by changes in BOLD responses to viewing neutral faces. These results are consistent with previous findings showing 5-HT modulation of affective processing; differences found in previously depressed participants compared with controls may contribute to emotional processing biases underlying vulnerability to depressive relapse. Copyright © 2010 Elsevier B.V. and ECNP. All rights reserved.
Abrams, Robert C; Nathanson, Mark; Silver, Stephanie; Ramirez, Mildred; Toner, John A; Teresi, Jeanne A
2017-01-01
Low levels of symptom recognition by staff have been "gateway" barriers to the management of depression in long-term care. The study aims were to refine a depression training program for front-line staff in long-term care and provide evaluative knowledge outcome data. Three primary training modules provide an overview of depression symptoms; a review of causes and situational and environmental contributing factors; and communication strategies, medications, and clinical treatment strategies. McNemar's chi-square tests and paired t-tests were used to examine change in knowledge. Data were analyzed for up to 143 staff members, the majority from nursing. Significant changes (p < .001) in knowledge were observed for all modules, with an average change of between 2 and 3 points. Evidence was provided that participants acquired desired information in the recognition, detection, and differential diagnosis and treatment strategies for those persons at significant risk for a depressive disorder.
Specific emotion regulation impairments in major depression and anorexia nervosa.
Brockmeyer, Timo; Bents, Hinrich; Holtforth, Martin Grosse; Pfeiffer, Nils; Herzog, Wolfgang; Friederich, Hans-Christoph
2012-12-30
Emotion regulation (ER) difficulties have been considered to play an important role in the development and maintenance of various mental disorders such as depression and anorexia nervosa. However, previous research has failed to provide detailed insight into the disorder-specificity of ER difficulties. Therefore, the present study investigated specific ER difficulties in female samples of patients with major depression, patients with anorexia nervosa, and healthy controls (total sample: N=140). As compared to healthy controls, both clinical groups reported greater ER difficulties concerning both the experience and the differentiation as well as the attenuation and the modulation of emotions. Patients in both clinical groups reported comparably elevated ER difficulties regarding the experience and differentiation of emotions. However, depressed patients reported stronger ER difficulties regarding the attenuation and modulation of emotions as compared to patients with anorexia nervosa. These findings support the notion of ER difficulties as transdiagnostic phenomena, and suggest that depression may be characterized by broader and greater ER difficulties than anorexia nervosa. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
The Role of Neurotrophins in Major Depressive Disorder.
Jiang, Cheng; Salton, Stephen R
2013-03-01
Neurotrophins and other growth factors have been advanced as critical modulators of depressive behavior. Support for this model is based on analyses of knockout and transgenic mouse models, human genetic studies, and screens for gene products that are regulated by depressive behavior and/or antidepressants. Even subtle alteration in the regulated secretion of brain-derived neurotrophic factor (BDNF), for example, due to a single nucleotide polymorphism (SNP)-encoded Val-Met substitution in proBDNF that affects processing and sorting, impacts behavior and cognition. Alterations in growth factor expression result in changes in neurogenesis as well as structural changes in neuronal cytoarchitecture, including effects on dendritic length and spine density, in the hippocampus, nucleus accumbens, and prefrontal cortex. These changes have the potential to impact the plasticity and stability of synapses in the CNS, and the complex brain circuitry that regulates behavior. Here we review the role that neurotrophins play in the modulation of depressive behavior, and the downstream signaling targets they regulate that potentially mediate these behavioral pro-depressant and antidepressant effects.
The Role of Neurotrophins in Major Depressive Disorder
Jiang, Cheng; Salton, Stephen R.
2013-01-01
Neurotrophins and other growth factors have been advanced as critical modulators of depressive behavior. Support for this model is based on analyses of knockout and transgenic mouse models, human genetic studies, and screens for gene products that are regulated by depressive behavior and/or antidepressants. Even subtle alteration in the regulated secretion of brain-derived neurotrophic factor (BDNF), for example, due to a single nucleotide polymorphism (SNP)-encoded Val-Met substitution in proBDNF that affects processing and sorting, impacts behavior and cognition. Alterations in growth factor expression result in changes in neurogenesis as well as structural changes in neuronal cytoarchitecture, including effects on dendritic length and spine density, in the hippocampus, nucleus accumbens, and prefrontal cortex. These changes have the potential to impact the plasticity and stability of synapses in the CNS, and the complex brain circuitry that regulates behavior. Here we review the role that neurotrophins play in the modulation of depressive behavior, and the downstream signaling targets they regulate that potentially mediate these behavioral pro-depressant and antidepressant effects. PMID:23691270
Nonlinear modulation of interacting between COMT and depression on brain function.
Gong, L; He, C; Yin, Y; Ye, Q; Bai, F; Yuan, Y; Zhang, H; Lv, L; Zhang, H; Zhang, Z; Xie, C
2017-09-01
The catechol-O-methyltransferase (COMT) gene is related to dopamine degradation and has been suggested to be involved in the pathogenesis of major depressive disorder (MDD). However, how this gene affects brain function properties in MDD is still unclear. Fifty patients with MDD and 35 cognitively normal participants underwent a resting-state functional magnetic resonance imaging scan. A voxelwise and data-drive global functional connectivity density (gFCD) analysis was used to investigate the main effects and the interactions of disease states and COMT rs4680 gene polymorphism on brain function. We found significant group differences of the gFCD in bilateral fusiform area (FFA), post-central and pre-central cortex, left superior temporal gyrus (STG), rectal and superior temporal gyrus and right ventrolateral prefrontal cortex (vlPFC); abnormal gFCDs in left STG were positively correlated with severity of depression in MDD group. Significant disease×COMT interaction effects were found in the bilateral calcarine gyrus, right vlPFC, hippocampus and thalamus, and left SFG and FFA. Further post-hoc tests showed a nonlinear modulation effect of COMT on gFCD in the development of MDD. Interestingly, an inverted U-shaped modulation was found in the prefrontal cortex (control system) but U-shaped modulations were found in the hippocampus, thalamus and occipital cortex (processing system). Our study demonstrated nonlinear modulation of the interaction between COMT and depression on brain function. These findings expand our understanding of the COMT effect underlying the pathophysiology of MDD. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Hadjistavropoulos, Heather D; Pugh, Nicole E; Hesser, Hugo; Andersson, Gerhard
2016-03-01
Therapist-assisted Internet-delivered cognitive behavior therapy (ICBT) is efficacious for treating anxiety and depression, but predictors of response to treatment when delivered in clinical practice are not well understood. In this study, we explored demographic, clinical, and program variables that predicted modules started and symptom improvement (i.e., Generalized Anxiety Disorder-7 or Patient Health Questionnaire-9 total scores over pre-, mid-, and posttreatment) within a previously published open dissemination trial (Hadjistavropoulos et al., 2014). The sample consisted of 195 patients offered 12 modules of therapist-assisted ICBT for depression or generalized anxiety; ICBT was delivered by therapists working in six geographically dispersed clinics. Consistent across ICBT for depression or generalized anxiety, starting fewer modules was associated with more phone calls from therapists reflecting that therapists tended to call patients who did not start modules as scheduled. Also consistent for both ICBT programs, greater pretreatment condition severity and completion of more modules was associated with superior ICBT-derived benefit. Other predictors of response to treatment varied across the two programs. Younger age, lower education, taking psychotropic medication, being in receipt of psychiatric care and lower comfort with written communication were associated with either fewer program starts or lower symptom improvement in one of the two programs. It is concluded that monitoring response to ICBT may be particularly important in patients with these characteristics. Research directions for identifying patients who are less likely to benefit from ICBT are discussed. Copyright © 2015. Published by Elsevier Ltd.
Single molecular force across single integrins dictates cell spreading.
Chowdhury, Farhan; Li, Isaac T S; Leslie, Benjamin J; Doğanay, Sultan; Singh, Rishi; Wang, Xuefeng; Seong, Jihye; Lee, Sang-Hak; Park, Seongjin; Wang, Ning; Ha, Taekjip
2015-10-01
Cells' ability to sense and interpret mechanical signals from the extracellular milieu modulates the degree of cell spreading. Yet how cells detect such signals and activate downstream signaling at the molecular level remain elusive. Herein, we utilize tension gauge tether (TGT) platform to investigate the underlying molecular mechanism of cell spreading. Our data from both differentiated cells of cancerous and non-cancerous origin show that for the same stiff underlying glass substrates and for same ligand density it is the molecular forces across single integrins that ultimately determine cell spreading responses. Furthermore, by decoupling molecular stiffness and molecular tension we demonstrate that molecular stiffness has little influence on cell spreading. Our data provide strong evidence that links molecular forces at the cell-substrate interface to the degree of cell spreading.
Bonnet, U; Khalil-Boutros, Y
2014-01-01
Parotitis is a fairly uncommon adverse drug reaction of psychopharmacological treatment. Here, we report on an acute bilateral parotitis, which was associated with titration of venlafaxine in a 20-year-old female suffering from a severe depressive episode. The parotitis recovered quickly with oral penicillin and was most likely caused by bacteria assumed to spread from oral flora into Stensen's duct as a complication of pronounced venlafaxine-induced xerostomia. © Georg Thieme Verlag KG Stuttgart · New York.
DNA methylation and inflammation marker profiles associated with a history of depression.
Crawford, Bethany; Craig, Zoe; Mansell, Georgina; White, Isobel; Smith, Adam; Spaull, Steve; Imm, Jennifer; Hannon, Eilis; Wood, Andrew; Yaghootkar, Hanieh; Ji, Yingjie; Mullins, Niamh; Lewis, Cathryn M; Mill, Jonathan; Murphy, Therese M
2018-05-22
Depression is a common and disabling disorder, representing a major social and economic health issue. Moreover, depression is associated with the progression of diseases with an inflammatory etiology including many inflammatory-related disorders. At the molecular level, the mechanisms by which depression might promote the onset of these diseases and associated immune-dysfunction are not well understood. In this study we assessed genome-wide patterns of DNA methylation in whole blood-derived DNA obtained from individuals with a self-reported history of depression (n = 100) and individuals without a history of depression (n = 100) using the Illumina 450K microarray. Our analysis identified 6 significant (Sidak corrected P < 0.05) depression-associated differentially methylated regions (DMRs); the top-ranked DMR was located in exon 1 of the LTB4R2 gene (Sidak corrected P = 1.27 x 10-14). Polygenic risk scores (PRS) for depression were generated and known biological markers of inflammation, telomere length (TL) and IL-6, were measured in DNA and serum samples respectively. Next, we employed a systems-level approach to identify networks of co-methylated loci associated with a history of depression, in addition to depression PRS, TL and IL-6 levels. Our analysis identified one depression-associated co-methylation module (P = 0.04). Interestingly, the depression-associated module was highly enriched for pathways related to immune function and was also associated with TL and IL-6 cytokine levels. In summary, our genome-wide DNA methylation analysis of individuals with and without a self-reported history of depression identified several candidate DMRs of potential relevance to the pathogenesis of depression and its associated immune-dysfunction phenotype.
Suri, Rita; Stowe, Zachary N; Cohen, Lee S; Newport, D Jeffrey; Burt, Vivien K; Aquino-Elias, Ana R; Knight, Bettina T; Mintz, Jim; Altshuler, Lori L
Risk factors for postpartum depression in euthymic pregnant women with histories of major depressive disorder (MDD) were evaluated. From April 2003 to March 2009, 343 pregnant women with a history of Structured Clinical Interview for DSM-IV (SCID)-diagnosed major depressive disorder were prospectively assessed from the third trimester into the postpartum period using the SCID mood module and 17-item Hamilton Depression Rating Scale (HDRS). Data from 300 subjects who completed at least 2 mood module assessments (1 within 60 days before and the other within 60 days after delivery) were analyzed for predictive associations between variables assessed in the third trimester and the development of a postpartum depression. The majority of women were euthymic in pregnancy by SCID criteria. Women with third trimester SCID-diagnosed depression (n = 45) versus euthymia (n = 255) had a significantly higher risk for having depression after delivery (24% vs 11%, P = .013). For pregnant euthymic women, third trimester total HDRS scores significantly predicted postpartum depression (P < .0001); specifically, scores on 3 HDRS items alone-work activities, early insomnia, and suicidality-significantly predicted postpartum depression. Antidepressant use in the third trimester in euthymic women did not confer protection against the onset of postpartum depression. Among women with a history of MDD who are euthymic in the third trimester, 3 HDRS items-work activities, early insomnia, and suicidality-may be useful as screening items for clinicians working with pregnant women with histories of MDD to identify a group at risk for developing postpartum depression. Additionally, in euthymic women with a history of MDD, antidepressant use in the third trimester may not reduce the risk of developing postpartum depression. © Copyright 2017 Physicians Postgraduate Press, Inc.
A passerine spreads its tail to facilitate a rapid recovery of its body posture during hovering
Su, Jian-Yuan; Ting, Shang-Chieh; Chang, Yu-Hung; Yang, Jing-Tang
2012-01-01
We demonstrate experimentally that a passerine exploits tail spreading to intercept the downward flow induced by its wings to facilitate the recovery of its posture. The periodic spreading of its tail by the White-eye bird exhibits a phase correlation with both wingstroke motion and body oscillation during hovering flight. During a downstroke, a White-eye's body undergoes a remarkable pitch-down motion, with the tail undergoing an upward swing. This pitch-down motion becomes appropriately suppressed at the end of the downstroke; the bird's body posture then recovers gradually to its original status. Employing digital particle-image velocimetry, we show that the strong downward flow induced by downstroking the wings serves as an external jet flow impinging upon the tail, providing a depressing force on the tail to counteract the pitch-down motion of the bird's body. Spreading of the tail enhances a rapid recovery of the body posture because increased forces are experienced. The maximum force experienced by a spread tail is approximately 2.6 times that of a non-spread tail. PMID:22258552
A passerine spreads its tail to facilitate a rapid recovery of its body posture during hovering.
Su, Jian-Yuan; Ting, Shang-Chieh; Chang, Yu-Hung; Yang, Jing-Tang
2012-07-07
We demonstrate experimentally that a passerine exploits tail spreading to intercept the downward flow induced by its wings to facilitate the recovery of its posture. The periodic spreading of its tail by the White-eye bird exhibits a phase correlation with both wingstroke motion and body oscillation during hovering flight. During a downstroke, a White-eye's body undergoes a remarkable pitch-down motion, with the tail undergoing an upward swing. This pitch-down motion becomes appropriately suppressed at the end of the downstroke; the bird's body posture then recovers gradually to its original status. Employing digital particle-image velocimetry, we show that the strong downward flow induced by downstroking the wings serves as an external jet flow impinging upon the tail, providing a depressing force on the tail to counteract the pitch-down motion of the bird's body. Spreading of the tail enhances a rapid recovery of the body posture because increased forces are experienced. The maximum force experienced by a spread tail is approximately 2.6 times that of a non-spread tail.
The Gamma-Aminobutyric Acid B Receptor in Depression and Reward.
Jacobson, Laura H; Vlachou, Styliani; Slattery, David A; Li, Xia; Cryan, John F
2018-06-01
The metabotropic gamma-aminobutyric acid B (GABA B ) receptor was the first described obligate G protein-coupled receptor heterodimer and continues to set the stage for discoveries in G protein-coupled receptor signaling complexity. In this review, dedicated to the life and work of Athina Markou, we explore the role of GABA B receptors in depression, reward, and the convergence of these domains in anhedonia, a shared symptom of major depressive disorder and withdrawal from drugs of abuse. GABA B receptor expression and function are enhanced by antidepressants and reduced in animal models of depression. Generally, GABA B receptor antagonists are antidepressant-like and agonists are pro-depressive. Exceptions to this rule likely reflect the differential influence of GABA B1 isoforms in depression-related behavior and neurobiology, including the anhedonic effects of social stress. A wealth of data implicate GABA B receptors in the rewarding effects of drugs of abuse. We focus on nicotine as an example. GABA B receptor activation attenuates, and deactivation enhances, nicotine reward and associated neurobiological changes. In nicotine withdrawal, however, GABA B receptor agonists, antagonists, and positive allosteric modulators enhance anhedonia, perhaps owing to differential effects of GABA B1 isoforms on the dopaminergic system. Nicotine cue-induced reinstatement is more reliably attenuated by GABA B receptor activation. Separation of desirable and undesirable side effects of agonists is achievable with positive allosteric modulators, which are poised to enter clinical studies for drug abuse. GABA B1 isoforms are key to understanding the neurobiology of anhedonia, whereas allosteric modulators may offer a mechanism for targeting specific brain regions and processes associated with reward and depression. Copyright © 2018 Society of Biological Psychiatry. All rights reserved.
Normann, Claus; Frase, Sibylle; Haug, Verena; von Wolff, Gregor; Clark, Kristin; Münzer, Patrick; Dorner, Alexandra; Scholliers, Jonas; Horn, Max; Vo Van, Tanja; Seifert, Gabriel; Serchov, Tsvetan; Biber, Knut; Nissen, Christoph; Klugbauer, Norbert; Bischofberger, Josef
2017-10-19
Long-term synaptic plasticity is a basic ability of the brain to dynamically adapt to external stimuli and regulate synaptic strength and ultimately network function. It is dysregulated by behavioral stress in animal models of depression and in humans with major depressive disorder. Antidepressants have been shown to restore disrupted synaptic plasticity in both animal models and humans; however, the underlying mechanism is unclear. We examined modulation of synaptic plasticity by selective serotonin reuptake inhibitors (SSRIs) in hippocampal brain slices from wild-type rats and serotonin transporter (SERT) knockout mice. Recombinant voltage-gated calcium (Ca 2+ ) channels in heterologous expression systems were used to determine the modulation of Ca 2+ channels by SSRIs. We tested the behavioral effects of SSRIs in the chronic behavioral despair model of depression both in the presence and in the absence of SERT. SSRIs selectively inhibited hippocampal long-term depression. The inhibition of long-term depression by SSRIs was mediated by a direct block of voltage-activated L-type Ca 2+ channels and was independent of SERT. Furthermore, SSRIs protected both wild-type and SERT knockout mice from behavioral despair induced by chronic stress. Finally, long-term depression was facilitated in animals subjected to the behavioral despair model, which was prevented by SSRI treatment. These results showed that antidepressants protected synaptic plasticity and neuronal circuitry from the effects of stress via a modulation of Ca 2+ channels and synaptic plasticity independent of SERT. Thus, L-type Ca 2+ channels might constitute an important signaling hub for stress response and for pathophysiology and treatment of depression. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Cognitive control under contingencies in anxious and depressed adolescents: an antisaccade task.
Jazbec, Sandra; McClure, Erin; Hardin, Michael; Pine, Daniel S; Ernst, Monique
2005-10-15
Emotion-related perturbations in cognitive control characterize adult mood and anxiety disorders. Fewer data are available to confirm such deficits in youth. Studies of cognitive control and error processing can provide an ideal template to examine these perturbations. Antisaccade paradigms are particularly well suited for this endeavor because they provide exquisite behavioral measures of modulation of response errors. A new monetary reward antisaccade task was used with 28 healthy, 11 anxious, and 12 depressed adolescents. Performance accuracy, saccade latency, and peak velocity of incorrect responses were analyzed. Performance accuracy across all groups was improved by incentives (obtain reward, avoid punishment). However, modulation of saccade errors by incentives differed by groups. In incentive trials relative to neutral trials, inhibitory efficiency (saccade latency) was enhanced in healthy, unaffected in depressed, and diminished in anxious adolescents. Modulation of errant actions (saccade peak velocity) was improved in the healthy group and unchanged in both the anxious and depressed groups. These findings provide grounds for testing hypotheses related to the impact of motivation deficits and emotional interference on directed action in adolescents with mood and anxiety disorders. Furthermore, neural mechanisms can now be examined by using this task paired with functional neuroimaging.
A Season of Loss: Training Manual for the Prevention of Elderly Depression and Suicide.
ERIC Educational Resources Information Center
Praeger, Susan; And Others
This instructional module emphasizes that depression and suicide are real problems for elderly people, shows how depression and suicidal thoughts can arise in older people, and describes interventions that can be used. Chapter 1 presents an introduction and overview of elderly suicide and includes sections on the plight of the elderly, community…
Questions of Mind Over Immunity.
ERIC Educational Resources Information Center
Bower, Bruce
1991-01-01
Discussed is the possibility of disturbed immunity among people experiencing either clinical depression or some type of severe stress. Psychoneuroimmunology, the study of psychological treatment and its ability to shore up a person's immunity and slow the spread of infectious disease, is reviewed. (KR)
Leitl, Michael D.; Negus, Stevens
2015-01-01
Neuropathic pain is often associated with behavioral depression. Intraplantar formalin produces sustained, neuropathy-associated depression of intracranial self-stimulation (ICSS) in rats. This study evaluated pharmacological modulation of formalin-induced ICSS depression. Rats with intracranial electrodes targeting the medial forebrain bundle responded for electrical brain stimulation in an ICSS procedure. Bilateral intraplantar formalin administration depressed ICSS for 14 days. Morphine (0.32–3.2 mg/kg), ketoprofen (0.1–10 mg/kg), bupropion (3.2–32 mg/kg), and Δ9-tetrahydrocannabinol (THC; 0.32–3.2 mg/kg) were evaluated for their effectiveness to reverse formalin-induced depression of ICSS. Drug effects on formalin-induced mechanical allodynia were evaluated for comparison. Morphine and bupropion reversed both formalin-induced ICSS depression and mechanical allodynia, and effects on ICSS were sustained during repeated treatment. Ketoprofen failed to reverse either formalin effect. THC blocked mechanical allodynia, but decreased ICSS in control rats and exacerbated formalin-induced depression of ICSS. The failure of ketoprofen to alter formalin effects suggests that formalin effects result from neuropathy rather than inflammation. The effectiveness of morphine and bupropion to reverse formalin effects agrees with other evidence that these drugs block pain-depressed behavior in rats and relieve neuropathic pain in humans. The effects of THC suggest general behavioral suppression and do not support the use of THC to treat neuropathic pain. PMID:26588213
Santafe, M M; Priego, M; Obis, T; Garcia, N; Tomàs, M; Lanuza, M A; Tomàs, J
2015-07-01
Adenosine receptors (ARs) are present in the motor terminals at the mouse neuromuscular junction. ARs and the presynaptic muscarinic acetylcholine receptors (mAChRs) share the functional control of the neuromuscular junction. We analysed their mutual interaction in transmitter release modulation. In electrophysiological experiments with unaltered synaptic transmission (muscles paralysed by blocking the voltage-dependent sodium channel of the muscle cells with μ-conotoxin GIIIB), we found that: (i) a collaborative action between different AR subtypes reduced synaptic depression at a moderate activity level (40 Hz); (ii) at high activity levels (100 Hz), endogenous adenosine production in the synaptic cleft was sufficient to reduce depression through A1 -type receptors (A1 Rs) and A2 A-type receptors (A2 A Rs); (iii) when the non-metabolizable 2-chloroadenosine (CADO) agonist was used, both the quantal content and depression were reduced; (iv) the protective effect of CADO on depression was mediated by A1 Rs, whereas A2 A Rs seemed to modulate A1 Rs; (v) ARs and mAChRs absolutely depended upon each other for the modulation of evoked and spontaneous acetylcholine release in basal conditions and in experimental conditions with CADO stimulation; (vi) the purinergic and muscarinic mechanisms cooperated in the control of depression by sharing a common pathway although the purinergic control was more powerful than the muscarinic control; and (vii) the imbalance of the ARs created by using subtype-selective and non-selective inhibitory and stimulatory agents uncoupled protein kinase C from evoked transmitter release. In summary, ARs (A1 Rs, A2 A Rs) and mAChRs (M1 , M2 ) cooperated in the control of activity-dependent synaptic depression and may share a common protein kinase C pathway. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
NASA Technical Reports Server (NTRS)
Kulis, Michael J.; Perry, David S.; Miller, Fletcher; Piltch, Nancy
2003-01-01
A diode laser diagnostic is being developed for use in an ongoing investigation of flame spread in microgravity at NASA Glenn Research Center. Flame spread rates through non-homogenous gas mixtures are significantly different in a microgravity environment because of buoyancy and possibly hydrostatic pressure effects. These effects contribute to the fuel vapor concentration ahead of the flame being altered so that flame spread is more rapid in microgravity. This paper describes spectral transmission measurements made through mixtures of alcohol, water vapor, and nitrogen in a gas cell that was designed and built to allow measurements at temperatures up to 500 C. The alcohols considered are methanol, ethanol, and n-propanol. The basic technique of wavelength modulation spectroscopy for gas species measurements in microgravity was developed by Silver et al. For this technique to be applicable, one must carefully choose the spectral features over which the diode laser is modulated to provide good sensitivity and minimize interference from other molecular lines such as those in water. Because the methanol spectrum was not known with sufficient resolution in the wavelength region of interest, our first task was to perform high-resolution transmission measurements with an FTIR spectrometer for methanol vapor in nitrogen, followed recently by ethanol and n-propanol. A computer program was written to generate synthesized data to mimic that expected from the experiment using the laser diode, and results from that simulation are also presented.
Modulation of intrinsic brain activity by electroconvulsive therapy in major depression
Leaver, Amber M.; Espinoza, Randall; Pirnia, Tara; Joshi, Shantanu H.; Woods, Roger P.; Narr, Katherine L.
2015-01-01
Introduction One of the most effective interventions for intractable major depressive episodes is electroconvulsive therapy (ECT). Because ECT is also relatively fast-acting, longitudinal study of its neurobiological effects offers critical insight into the mechanisms underlying depression and antidepressant response. Here we assessed modulation of intrinsic brain activity in corticolimbic networks associated with ECT and clinical response. Methods We measured resting-state functional connectivity (RSFC) in patients with treatment-resistant depression (n=30), using functional magnetic resonance imaging (fMRI) acquired before and after completing a treatment series with right-unilateral ECT. Using independent component analysis, we assessed changes in RSFC with 1) symptom improvement and 2) ECT regardless of treatment outcome in patients, with reference to healthy controls (n=33, also scanned twice). Results After ECT, consistent changes in RSFC within targeted depression-relevant functional networks were observed in the dorsal anterior cingulate (ACC), mediodorsal thalamus (mdTh), hippocampus, and right anterior temporal, medial parietal, and posterior cingulate cortex in all patients. In a separate analysis, changes in depressive symptoms were associated with RSFC changes in the dorsal ACC, mdTh, putamen, medial prefrontal, and lateral parietal cortex. RSFC of these regions did not change in healthy controls. Conclusions Neuroplasticity underlying clinical change was in part separable from changes associated with the effects of ECT observed in all patients. However, both ECT and clinical change were associated with RSFC modulation in dorsal ACC, mdTh and hippocampus, which may indicate that these regions underlie the mechanisms of clinical outcome in ECT and may be effective targets for future neurostimulation therapies. PMID:26878070
Group Combustion Module (GCM) Installation
2016-09-27
ISS049e011638 (09/27/2016) --- Expedition 49 crewmember Takuya Onishi of JAXA works on the setup of the Group Combustion Module (GCM) inside the Japanese Experiment Module. The GCM will be used to house the Group Combustion experiment from the Japan Aerospace Exploration Agency (JAXA) to test a theory that fuel sprays change from partial to group combustion as flames spread across a cloud of droplets.
Bakare, Muideen O; Okoye, Jane O; Obindo, James T
2014-01-01
This study investigates the possibility of introducing depression and developmental screening tools into the National Programme on Immunization (NPI) in southeast Nigeria. The specific objectives were to determine the prevalence of postpartum depression (PPD) among mothers attending immunization clinics and to assess the association of maternal PPD and infant growth in relation to World Health Organization (WHO) recommendations. Four hundred and eight (408) mothers completed the sociodemographic questionnaire and the self-report Edinburgh Postnatal Depression Scale (EPDS). The weights, lengths and head circumferences of their infants were recorded, while the WHO recommended equivalents at 50th percentiles were also recorded for each child. The mothers were then interviewed with the major depressive episode module of Mini International Neuropsychiatric Interview (M.I.N.I.) to make diagnosis of depression. About 24.8% and 15.2% of the mothers were found to be depressed using EPDS and major depressive episode module of M.I.N.I., respectively. It was found that maternal PPD is significantly associated with the growth parameters of weights and lengths of the infants studied but not their head circumference. NPI may provide appropriate forum for early screening of mothers for PPD and interventions in Nigeria. The NPI would also serve a useful avenue of screening for developmental concerns in Nigerian children. © 2014.
In-situ seismic record of potential sill intrusion at the ultraslow spreading Southwest Indian Ridge
NASA Astrophysics Data System (ADS)
Meier, M.; Schlindwein, V. S. N.
2017-12-01
Ultraslow spreading mid-ocean ridges with full spreading rates up to 15 mm/yr are described as the melt poor endmember of the entire mid-ocean ridge system. The melt supply along ultraslow spreading ridges is uneven resulting in the formation of volcanic centres and amagmatic segments. Amagmatic segments show thicker brittle lithosphere of up to 30 km, whereas magmatic segments have much thinner lithosphere of up to less than 15 km. It is supposed that melt travels along the lithosphere asthenosphere boundary from amagmatic segments to magmatic segments, where it can reach the seafloor and erupt. These spreading events are rare at ultraslow spreading ridges compared to faster spreading ridges and insitu observations hardly exist. During an ocean bottom seismometer (OBS) experiment at the eastern Southwest Indian Ridge two earthquake swarms were accidentally recorded. The swarms occurred in January and April 2013 and both lasted for a few days. The events of the earthquake swarms were relatively located with HypoDD for better spatial resolution. This unique dataset allowed for studying active spreading processes at an ultraslow spreading ridge. The earthquakes occurred in depths, where the magma chamber of the nearby Segment-8 volcano is located. This magma chamber potentially fed a sill intrusion, which was recorded as earthquake swarms. During the first hours of the first earthquake swarm a migration pattern was identified. The hypocentres migrated away from the Segment-8 volcanic centre and slightly downwards. Later events occurred more randomly in the active area. Simultaneously seismic tremor was recorded at the station closest to the swarm locations. The tremor lasted longer for the shorter earthquake swarm in April. During both tremor phases the signal was modulated with a 12 hour period. We speculate that a hydrothermal system was affected by the intrusion and fluid flow modulated by the tides produced the tremor signal.
Pharmacological modulation of spreading depolarizations.
Sánchez-Porras, Renán; Zheng, Zelong; Sakowitz, Oliver W
2015-01-01
Spreading depolarization (SD) is a wave of almost complete depolarization of the neuronal and glial cells. Nowadays there is sufficient evidence demonstrating its pathophysiological effect in migraine with aura, transient global amnesia, stroke, subarachnoid hemorrhage, intracerebral hemorrhage, and traumatic brain injury. In these cases, occurrence of SD has been associated with functional neuronal damage, neuronal necrosis, neurological degeneration, and poor clinical outcome. Animal models show that SD can be modulated by drugs that interfere with its initiation and propagation. There are many pharmacological targets that may help to suppress SD occurrence, such as Na⁺, K⁺, Cl⁻, and Ca²⁺ channels; Na⁺/K⁺ -ATPase; gap junctions; and ligand-based receptors, for example, adrenergic, serotonin, sigma-1, calcitonin gene-related peptide, GABAA, and glutamate receptors. In this regard, N-methyl-d-aspartate (NMDA) receptor blockers, in particular, ketamine, have shown promising results. Therefore, theoretically pharmacologic modulation of SD could help diminish its pathological effects.
Solberg, Leif I; Crain, A Lauren; Maciosek, Michael V; Unützer, Jürgen; Ohnsorg, Kris A; Beck, Arne; Rubenstein, Lisa; Whitebird, Robin R; Rossom, Rebecca C; Pietruszewski, Pamela B; Crabtree, Benjamin F; Joslyn, Kenneth; Van de Ven, Andrew; Glasgow, Russell E
2015-09-01
Scale-up and spread of evidence-based practices is one of the most important challenges facing health care. We tested whether a statewide initiative, Depression Improvement Across Minnesota-Offering a New Direction (DIAMOND), to implement the collaborative care model for depression in 75 primary care clinics resulted in patient outcome improvements corresponding to those reported in randomized controlled trials. Health plans provided a new monthly payment to participating clinics after a 6-month intensive training program with ongoing data submission, networking, and consultation. Implementation was staggered, with 5 sequences of 10 to 40 clinics every 6 months. Payers provided weekly contact information for members from participating clinics who were filling antidepressant prescriptions, and we conducted baseline and 6-month surveys of 1,578 patients about their care and outcomes. There were 466 patients in DIAMOND clinics who received usual care before implementation (UCB), 559 who received usual care in DIAMOND clinics after implementation (UCA), 245 who received DIAMOND care after implementation (DCA), and 308 who received usual care in comparison clinics (UC). Patients who received DIAMOND care after implementation reported more collaborative care depression services than the 3 comparison groups (10.9 vs 6.4-6.7, on a scale of 0 of 14, where higher numbers indicate more services; P <.001) and more satisfaction with their care (4.0 vs 3.4 on a scale 1 to 5, in which higher scores indicate higher satisfaction; P ≤.001). Depression remission rates, however, were not significantly different among the 4 groups (36.4% DCA vs 35.8% UCB, 35.0% UCA, 33.9% UC; P = .94). Despite the incentive of a supporting payment change and intensive training and support for clinics volunteering to participate, no difference in depression outcomes was documented. Specific unmeasured actions present in trials but not present in these clinics may be critical for successful outcome improvement. © 2015 Annals of Family Medicine, Inc.
Yıldırım, Timur; Eylen, Alpaslan; Lule, Sevda; Erdener, Sefik Evren; Vural, Atay; Karatas, Hulya; Ozveren, Mehmet Faik; Dalkara, Turgay; Gursoy-Ozdemir, Yasemin
2015-01-01
Under pathological conditions such as brain trauma, subarachnoid hemorrhage and stroke, cortical spreading depression (CSD) or peri-infarct depolarizations contribute to brain damage in animal models of neurological disorders as well as in human neurological diseases. CSD causes transient megachannel opening on the neuronal membrane, which may compromise neuronal survival under pathological conditions. Poloxamer-188 (P-188) and citicoline are neuroprotectants with membrane sealing properties. The aim of this study is to investigate the effect of P-188 and citicoline on the neuronal megachannel opening induced by CSD in the mouse brain. We have monitored megachannel opening with propidium iodide, a membrane impermeable fluorescent dye and, demonstrate that P-188 and citicoline strikingly decreased CSD-induced neuronal PI influx in cortex and hippocampal dentate gyrus. Therefore, these agents may be providing neuroprotection by blocking megachannel opening, which may be related to their membrane sealing action and warrant further investigation for treatment of traumatic brain injury and ischemic stroke.
Santos, Laura M.; Mattiace, Linda A.; Costa, Manoel L.; Ferreira, Luciano C.; Benabou, Kelly; Kim, Ana H.; Abrahams, John; Bennett, Michael V. L.; Rozental, Renato
2012-01-01
Spreading depression (SD), a slow diffusion-mediated self-sustained wave of depolarization that severely disrupts neuronal function, has been implicated as a cause of cellular injury in a number of central nervous system pathologies, including blind spots in the retina. Here we show that in the hypoglycemic chicken retina, spontaneous episodes of SD can occur, resulting in irreversible punctate lesions in the macula, the region of highest visual acuity in the central region of the retina. These lesions in turn can act as sites of origin for secondary self-sustained reentrant spiral waves of SD that progressively enlarge the lesions. Furthermore, we show that the degeneration of the macula under hypoglycemic conditions can be prevented by blocking reentrant spiral SDs or by blocking caspases. The observation that spontaneous formation of reentrant spiral SD waves leads to the development of progressive retinal lesions under conditions of hypoglycemia establishes a potential role of SD in initiation and progression of macular degeneration, one of the leading causes of visual disability worldwide. PMID:22308470
Osmotic forces and gap junctions in spreading depression: a computational model
NASA Technical Reports Server (NTRS)
Shapiro, B. E.
2001-01-01
In a computational model of spreading depression (SD), ionic movement through a neuronal syncytium of cells connected by gap junctions is described electrodiffusively. Simulations predict that SD will not occur unless cells are allowed to expand in response to osmotic pressure gradients and K+ is allowed to move through gap junctions. SD waves of [K+]out approximately 25 to approximately 60 mM moving at approximately 2 to approximately 18 mm/min are predicted over the range of parametric values reported in gray matter, with extracellular space decreasing up to approximately 50%. Predicted waveform shape is qualitatively similar to laboratory reports. The delayed-rectifier, NMDA, BK, and Na+ currents are predicted to facilitate SD, while SK and A-type K+ currents and glial activity impede SD. These predictions are consonant with recent findings that gap junction poisons block SD and support the theories that cytosolic diffusion via gap junctions and osmotic forces are important mechanisms underlying SD.
Spread-spectrum multiple access using wideband noncoherent MFSK
NASA Technical Reports Server (NTRS)
Ha, Tri T.; Pratt, Timothy; Maggenti, Mark A.
1987-01-01
Two spread-spectrum multiple access systems which use wideband M-ary frequency shift keying (FSK) (MFSK) as the primary modulation are presented. A bit error rate performance analysis is presented and system throughput is calculated for sample C band and Ku band satellite systems. Sample link analyses are included to illustrate power and adjacent satellite interference considerations in practical multiple access systems.
Smolders, I
2005-01-01
Several researchers are currently trying to unravel neurobiological relationships between epilepsy and depression. After all, these disorders often develop in the same vulnerable brain regions and the importance of comorbid depression and epilepsy is still underscored. Facilitation of central serotonin (5-HT), dopamine (DA) and noradrenaline (NAD) release seems to be associated with both anticonvulsant and antidepressant effects. We show that selective ionotropic and metabotropic glutamate receptor ligands with anticonvulsant properties differentially modulate NAD, DA and 5-HT in rat limbic lobe structures.
Expanding the Interactome of TES by Exploiting TES Modules with Different Subcellular Localizations.
Sala, Stefano; Van Troys, Marleen; Medves, Sandrine; Catillon, Marie; Timmerman, Evy; Staes, An; Schaffner-Reckinger, Elisabeth; Gevaert, Kris; Ampe, Christophe
2017-05-05
The multimodular nature of many eukaryotic proteins underlies their temporal or spatial engagement in a range of protein cocomplexes. Using the multimodule protein testin (TES), we here report a proteomics approach to increase insight in cocomplex diversity. The LIM-domain containing and tumor suppressor protein TES is present at different actin cytoskeleton adhesion structures in cells and influences cell migration, adhesion and spreading. TES module accessibility has been proposed to vary due to conformational switching and variants of TES lacking specific domains target to different subcellular locations. By applying iMixPro AP-MS ("intelligent Mixing of Proteomes"-affinity purification-mass spectrometry) to a set of tagged-TES modular variants, we identified proteins residing in module-specific cocomplexes. The obtained distinct module-specific interactomes combine to a global TES interactome that becomes more extensive and richer in information. Applying pathway analysis to the module interactomes revealed expected actin-related canonical pathways and also less expected pathways. We validated two new TES cocomplex partners: TGFB1I1 and a short form of the glucocorticoid receptor. TES and TGFB1I1 are shown to oppositely affect cell spreading providing biological validity for their copresence in complexes since they act in similar processes.
Gao, Chong; Du, Qiaohui; Li, Wenting; Deng, Ruixia; Wang, Qi; Xu, Aimin; Shen, Jiangang
2018-04-19
Olfactory dysfunction is often accompanied with anxiety- and depressive-like behaviors in depressive patients. Impaired neurogenesis in hippocampus and subventricular zone (SVZ)-olfactory bulb (OB) contribute to anxiety- and depressive-like behaviors and olfactory dysfunctions. However, the underlying mechanisms of olfactory dysfunction remain unclear. Our previous study indicates that adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2), could affect the activity and sensitivity of glucocorticoid receptor (GR) and mediate impaired hippocampal neurogenesis, which contribute the development of depression. In the present study, we further identified the roles of APPL2 in olfactory functions. APPL2 Tg mice displayed higher GR activity and less capacity of neurogenesis at olfactory system with less olfactory sensitivity than WT mice, indicating that APPL2 could be a potential therapeutic target for depression and olfactory deficits. We then studied the effects of baicalin, a medicinal herbal compound, on modulating APPL2/GR signaling pathway for promoting neurogenesis and antidepressant as well as improving olfactory functions. Baicalin treatment inhibited APPL2/GR signaling pathway and improved neurogenesis at SVZ, OB, and hippocampus in APPL2 Tg mice and chronic corticosterone-induced depression mouse model. Behavioral tests revealed that baicalin attenuated depressive- and anxiety-like behaviors and improve olfactory functions in the chronic depression mouse model and APPL2 Tg mice. Taken together, APPL2 could be a novel therapeutic target for improving depressant-related olfactory dysfunctions and baicalin could inhibit APPL2-mediated GR hyperactivity and promote adult neurogenesis, subsequently releasing depressive and anxiety symptoms and improving olfactory functions for antidepressant therapy.
Valente, Maria Maddalena; Bortolotto, Valeria; Cuccurazzu, Bruna; Ubezio, Federica; Meneghini, Vasco; Francese, Maria Teresa; Canonico, Pier Luigi; Grilli, Mariagrazia
2012-08-01
Although the role of adult hippocampal neurogenesis remains to be fully elucidated, several studies suggested that the process is involved in cognitive and emotional functions and is deregulated in various neuropsychiatric disorders, including major depression. Several psychoactive drugs, including antidepressants, can modulate adult neurogenesis. Here we show for the first time that the α2δ ligands gabapentin [1-(aminomethyl)cyclohexaneacetic acid] and pregabalin (PGB) [(S)-(+)-3-isobutyl-GABA or (S)-3-(aminomethyl)-5-methylhexanoic acid] can produce concentration-dependent increases in the numbers of newborn mature and immature neurons generated in vitro from adult hippocampal neural progenitor cells and, in parallel, a decrease in the number of undifferentiated precursor cells. These effects were confirmed in vivo, because significantly increased numbers of adult cell-generated neurons were observed in the hippocampal region of mice receiving prolonged treatment with PGB (10 mg/kg i.p. for 21 days), compared with vehicle-treated mice. We demonstrated that PGB administration prevented the appearance of depression-like behaviors induced by chronic restraint stress and, in parallel, promoted hippocampal neurogenesis in adult stressed mice. Finally, we provided data suggesting involvement of the α2δ1 subunit and the nuclear factor-κB signaling pathway in drug-mediated proneurogenic effects. The new pharmacological activities of α2δ ligands may help explain their therapeutic activity as supplemental therapy for major depression and depressive symptoms in post-traumatic stress disorder and generalized anxiety disorders. These data contribute to the identification of novel molecular pathways that may represent potential targets for pharmacological modulation in depression.
Autonomic dysregulation in burnout and depression: evidence for the central role of exhaustion.
Kanthak, Magdalena K; Stalder, Tobias; Hill, LaBarron K; Thayer, Julian F; Penz, Marlene; Kirschbaum, Clemens
2017-09-01
Objectives Given the important role of the autonomic nervous system (ANS) in stress regulation, astonishingly little is known about ANS functioning in burnout, a condition arising after prolonged exposure to work-related stress. The current study sought to investigate ANS modulation, as indexed by vagally-mediated heart rate variability (HRV), in relation to burnout symptomatology to (i) distinguish associations between the three dimensions of burnout [emotional exhaustion (EE), cynicism, reduced personal accomplishment] and (ii) investigate overlap in associations with depressive symptomatology. Methods Assessments of vagally-mediated HRV (ie, root mean square of successive differences, RMSSD) were conducted in a large population-based sample from the Dresden Burnout Study [N=410, mean age 42.2, standard deviation (SD) 11.2 years; 33.4% male]. Vagally-mediated HRV was assessed for 90 seconds during an emotionally-arousing situation (venipuncture, recumbent), a 335-second recumbent recovery period, and a 335-second seated resting condition. Results Results from multiple linear regression analyses revealed that EE was negatively related to RMSSD during venipuncture (=β -0.11, P=0.03) and the seated rest (β= -0.09, P=0.04) even after accounting for established ANS modulators (eg, age, body mass index). This pattern was not observed for the other dimensions of burnout. Exploratory analyses of depressive symptomatology further revealed that RMSSD was significantly and inversely associated with burnout-related symptoms but not with the core criteria of depression (eg, depressed mood). Conclusions This study presents evidence for a link between exhaustion and reduced vagal function, both in burnout and depression, suggesting that ANS modulations may not be disorder-specific but rather a psychophysiological correlate of an underlying feature shared by both conditions.
Novel animal model defines genetic contributions for neuron-to-neuron transfer of α-synuclein.
Tyson, Trevor; Senchuk, Megan; Cooper, Jason F; George, Sonia; Van Raamsdonk, Jeremy M; Brundin, Patrik
2017-08-08
Cell-to-cell spreading of misfolded α-synuclein (α-syn) is suggested to contribute to the progression of neuropathology in Parkinson's disease (PD). Compelling evidence supports the hypothesis that misfolded α-syn transmits from neuron-to-neuron and seeds aggregation of the protein in the recipient cells. Furthermore, α-syn frequently appears to propagate in the brains of PD patients following a stereotypic pattern consistent with progressive spreading along anatomical pathways. We have generated a C. elegans model that mirrors this progression and allows us to monitor α-syn neuron-to-neuron transmission in a live animal over its lifespan. We found that modulation of autophagy or exo/endocytosis, affects α-syn transfer. Furthermore, we demonstrate that silencing C. elegans orthologs of PD-related genes also increases the accumulation of α-syn. This novel worm model is ideal for screening molecules and genes to identify those that modulate prion-like spreading of α-syn in order to target novel strategies for disease modification in PD and other synucleinopathies.
Modelling of a spread of hazardous substances in a Floreon+ system
NASA Astrophysics Data System (ADS)
Ronovsky, Ales; Brzobohaty, Tomas; Kuchar, Stepan; Vojtek, David
2017-07-01
This paper is focused on a module of an automatized numerical modelling of a spread of hazardous substances developed for the Floreon+ system on demand of the Fire Brigade of Moravian-Silesian. The main purpose of the module is to provide more accurate prediction for smog situations that are frequent problems in the region. It can be operated by non-scientific user through the Floreon+ client and can be used as a short term prediction model of an evolution of concentrations of dangerous substances (SO2, PMx) from stable sources, such as heavy industry factories, local furnaces or highways or as fast prediction of spread of hazardous substances in case of crash of mobile source of contamination (transport of dangerous substances) or in case of a leakage in a local chemical factory. The process of automatic gathering of atmospheric data, connection of Floreon+ system with an HPC infrastructure necessary for computing of such an advantageous model and the model itself are described bellow.
Serotonin modulates a depression-like state in Drosophila responsive to lithium treatment
Ries, Ariane-Saskia; Hermanns, Tim; Poeck, Burkhard; Strauss, Roland
2017-01-01
Major depressive disorder (MDD) affects millions of patients; however, the pathophysiology is poorly understood. Rodent models have been developed using chronic mild stress or unavoidable punishment (learned helplessness) to induce features of depression, like general inactivity and anhedonia. Here we report a three-day vibration-stress protocol for Drosophila that reduces voluntary behavioural activity. As in many MDD patients, lithium-chloride treatment can suppress this depression-like state in flies. The behavioural changes correlate with reduced serotonin (5-HT) release at the mushroom body (MB) and can be relieved by feeding the antidepressant 5-hydroxy-L-tryptophan or sucrose, which results in elevated 5-HT levels in the brain. This relief is mediated by 5-HT-1A receptors in the α-/β-lobes of the MB, whereas 5-HT-1B receptors in the γ-lobes control behavioural inactivity. The central role of serotonin in modulating stress responses in flies and mammals indicates evolutionary conserved pathways that can provide targets for treatment and strategies to induce resilience. PMID:28585544
Toschi-Dias, Edgar; Tobaldini, Eleonora; Solbiati, Monica; Costantino, Giorgio; Sanlorenzo, Roberto; Doria, Stefania; Irtelli, Floriana; Mencacci, Claudio; Montano, Nicola
2017-05-01
Several studies have demonstrated that adjuvant therapies as exercise and breathing training are effective in improving cardiac autonomic control (CAC) in patients with affective spectrum disorders. However, the effects of Sudarshan Kriya Yoga (SKY) on autonomic function in this population is unknown. Our objective was to test the hypothesis that SKY training improves CAC and cardiorespiratory coupling in patients with anxiety and/or depression disorders. Forty-six patients with a diagnosis of anxiety and/or depression disorders (DSM-IV) were consecutively enrolled and divided in two groups: 1) conventional therapy (Control) and 2) conventional therapy associated with SKY (Treatment) for 15 days. Anxiety and depression levels were determined using quantitative questionnaires. For the assessment of CAC and cardiorespiratory coupling, cardiorespiratory traces were analyzed using monovariate and bivariate autoregressive spectral analysis, respectively. After 15-days, we observed a reduction of anxiety and depression levels only in Treatment group. Moreover, sympathetic modulation and CAC were significantly lower while parasympathetic modulation and cardiorespiratory coupling were significantly higher in the Treatment compared to Control group. Intensive breathing training using SKY approach improves anxiety and/or depressive disorders as well as CAC and cardiorespiratory coupling. These finding suggest that the SKY training may be a useful non-pharmacological intervention to improve symptoms and reduce cardiovascular risk in patients with anxiety/depression disorders. Copyright © 2017 Elsevier B.V. All rights reserved.
Continental Break-up Above A Mantle Plume: Opening of The Southern Red Sea
NASA Astrophysics Data System (ADS)
Ebinger, C.; Eagles, G.; Elders, C.; Gloaguen, R.; McClay, K.; Tiberi, C.; Wolfenden, E.
Initial rifting in the Red Sea occurred concurrent with, or soon after flood basaltic mag- matism at~31 Ma in the Ethiopia-Yemen plume province. Yet, the development of the ca. 400 km-wide extensional province of the southern Red Sea between 31 Ma and the onset of seafloor spreading at ~4 Ma has been poorly understood, in large part owing to inaccessibility in the Afar depression. The Afar depression is a diffuse extensional province marking a triple point zone between plate boundaries in the Red Sea (Arabia Nubia), the Gulf of Aden (Arabia Somalia); and the Main Ethiopian Rift (Somalia Nu- bia). Complicating this setting, the Danakil horst is a microplate lying between oceanic provinces in the southernmost Red Sea and incipient seafloor spreading in the northern Afar depression. We have integrated exploration seismic, gravity, well, and magnetic data from offshore regions with remote sensing, geological and geophysical data from Ethiopia, Eritrea, and Yemen to evaluate models for continental break-up above mantle plumes. Plate kinematic reconstructions using a pole of rotation within the error ellipse of the Chu and Gordon (1999) pole predict real features in remote sensing and gravity data; these reconstructions provide a general framework for our interpretations. Field and geochronology studies along the western margin of Afar show a southward prop- agation of rifting since about 25 Ma when extension commenced offshore Red Sea and in Yemen. We also see an eastward migration of strain from the western border fault to narrow zones of primarily basaltic magmatism since mid-Miocene time. These magmatic sequences, where not onlapped by Pliocene-Recent sedimentary strata, dip steeply seaward and define a regional eastward flexure into transitional oceanic crust, as suggested by gravity models constrained by existing seismic data. Our synthesis suggests that the southern Afar depression, assumed to be most proximal to the plume, was the site of incipient seafloor spreading in Miocene time, but that this has ceased or stalled during plate reorganisation as the Aden rift propagated into Afar to make the Danakil a microplate.
Receiver Statistics for Cognitive Radios in Dynamic Spectrum Access Networks
2012-02-28
SNR) are employed by many protocols and processes in direct-sequence ( DS ) spread-spectrum packet radio networks, including soft-decision decoding...adaptive modulation protocols, and power adjustment protocols. For DS spread spectrum, we have introduced and evaluated SNR estimators that employ...obtained during demodulation in a binary CDMA receiver. We investigated several methods to apply the proposed metric to the demodulator’s soft-decision
Nie, Lulin; Wei, Gang; Peng, Shengming; Qu, Zhongsen; Yang, Ying; Yang, Qian; Huang, Xinfeng; Liu, Jianjun; Zhuang, Zhixiong; Yang, Xifei
2017-07-08
Alzheimer's disease (AD) is a devastating neurodegenerative disease accompanied by neuropsychiatric symptoms, such as anxiety and depression. The levels of melatonin decrease in brains of AD patients. The potential effect of melatonin on anxiety and depression behaviors in AD and the underlying mechanisms remain unclear. In this study, we treated 10-month-old triple transgenic mice of AD (3xTg-AD) with melatonin (10 mg/kg body weight/day) for 1 month and explored the effects of melatonin on anxiety and depression-like behaviors in 3xTg-AD mice and the protein expression of hippocampal tissues. The behavioral test showed that melatonin ameliorated anxiety and depression-like behaviors of 3xTg-AD mice as measured by open field test, elevated plus maze test, forced swimming test, and tail suspension test. By carrying out two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry, we revealed a total of 46 differentially expressed proteins in hippocampus between the wild-type (WT) mice and non-treated 3xTg-AD mice. A total of 21 differentially expressed proteins were revealed in hippocampus between melatonin-treated and non-treated 3xTg-AD mice. Among these differentially expressed proteins, glutathione S-transferase P 1 (GSTP1) (an anxiety-associated protein) and complexin-1 (CPLX1) (a depression-associated protein) were significantly down-regulated in hippocampus of 3xTg-AD mice compared with the WT mice. The expression of these two proteins was modulated by melatonin treatment. Our study suggested that melatonin could be used as a potential candidate drug to improve the neuropsychiatric behaviors in AD via modulating the expression of the proteins (i.e. GSTP1 and CPLX1) involved in anxiety and depression behaviors. © 2017 BioFactors, 43(4):593-611, 2017. © 2017 International Union of Biochemistry and Molecular Biology.
Nair, A; Vaidya, V A
2008-01-01
Depression is the major psychiatric ailment of our times, afflicting ~20% of the population. Despite its prevalence, the pathophysiology of this complex disorder is not well understood. In addition, although antidepressants have been in existence for the past several decades, the mechanisms that underlie their therapeutic effects remain elusive. Building evidence implicates a role for the plasticity of specific neuro-circuitry in both the pathophysiology and treatment of depression. Damage to limbic regions is thought to contribute to the etiology of depression and antidepressants have been reported to reverse such damage and promote adaptive plasticity. The molecular pathways that contribute to the damage associated with depression and antidepressant-mediated plasticity are a major focus of scientific enquiry. The transcription factor cyclic AMP response element binding protein (CREB) and the neurotrophin brain-derived neurotrophic factor (BDNF) are targets of diverse classes of antidepressants and are known to be regulated in animal models and in patients suffering from depression. Given their role in neuronal plasticity, CREB and BDNF have emerged as molecules that may play an important role in modulating mood. The purpose of this review is to discuss the role of CREB and BDNF in depression and as targets/mediators of antidepressant action. PMID:17006024
A pilot study of modified cognitive-behavioral therapy for childhood traumatic grief (CBT-CTG).
Cohen, Judith A; Mannarino, Anthony P; Staron, Virginia R
2006-12-01
This pilot study evaluated outcomes for a modified 12-session protocol of cognitive-behavioral therapy for childhood traumatic grief (CBT-CTG) conducted between March 2004 and October 2005. CTG is an emerging condition characterized by a combination of posttraumatic stress and unresolved grief symptoms. This two-module treatment model consisting of sequential trauma- and grief-focused components was shortened from a previously presented 16-session protocol. Thirty-nine children ages 6 to 17 years old with CTG and their parents received the modified 12-session protocol of CBT-CTG. CTG and posttraumatic stress disorder (PTSD) symptoms were assessed at pretreatment, after the trauma-focused module, and after the grief-focused module (at posttreatment). Child depression, anxiety, and behavioral symptoms, as well as parental depression and PTSD symptoms, were assessed at pre- and posttreatment. Children reported significant improvement in CTG, PTSD, depression, and anxiety, and parents reported significant improvement in children's PTSD, internalizing and total behavior problems, and their personal PTSD symptoms. Although PTSD significantly improved only during the trauma-focused module of treatment, CTG improved significantly during both trauma- and grief-focused modules of treatment. Child satisfaction and parent satisfaction for this treatment protocol were also high. These findings suggest that the shortened CBT-CTG protocol, which is similar in the number of sessions to what many community child bereavement programs offer, may be acceptable and efficacious for this population. The CBT-CTG model requires further evaluation in randomized, controlled treatment trials.
Proper Analytic Point Spread Function for Lateral Modulation
NASA Astrophysics Data System (ADS)
Chikayoshi Sumi,; Kunio Shimizu,; Norihiko Matsui,
2010-07-01
For ultrasonic lateral modulation for the imaging and measurement of tissue motion, better envelope shapes of the point spread function (PSF) than of a parabolic function are searched for within analytic functions or windows on the basis of the knowledge of the ideal shape of PSF previously obtained, i.e., having a large full width at half maximum and short feet. Through simulation of displacement vector measurement, better shapes are determined. As a better shape, a new window is obtained from a Turkey window by changing Hanning windows by power functions with an order larger than the second order. The order of measurement accuracies obtained is as follows, the new window > rectangular window > power function with a higher order > parabolic function > Akaike window.
Acetylcholine-modulated plasticity in reward-driven navigation: a computational study.
Zannone, Sara; Brzosko, Zuzanna; Paulsen, Ole; Clopath, Claudia
2018-06-21
Neuromodulation plays a fundamental role in the acquisition of new behaviours. In previous experimental work, we showed that acetylcholine biases hippocampal synaptic plasticity towards depression, and the subsequent application of dopamine can retroactively convert depression into potentiation. We also demonstrated that incorporating this sequentially neuromodulated Spike-Timing-Dependent Plasticity (STDP) rule in a network model of navigation yields effective learning of changing reward locations. Here, we employ computational modelling to further characterize the effects of cholinergic depression on behaviour. We find that acetylcholine, by allowing learning from negative outcomes, enhances exploration over the action space. We show that this results in a variety of effects, depending on the structure of the model, the environment and the task. Interestingly, sequentially neuromodulated STDP also yields flexible learning, surpassing the performance of other reward-modulated plasticity rules.
Spreading activation in nonverbal memory networks.
Foster, Paul S; Wakefield, Candias; Pryjmak, Scott; Roosa, Katelyn M; Branch, Kaylei K; Drago, Valeria; Harrison, David W; Ruff, Ronald
2017-09-01
Theories of spreading activation primarily involve semantic memory networks. However, the existence of separate verbal and visuospatial memory networks suggests that spreading activation may also occur in visuospatial memory networks. The purpose of the present investigation was to explore this possibility. Specifically, this study sought to create and describe the design frequency corpus and to determine whether this measure of visuospatial spreading activation was related to right hemisphere functioning and spreading activation in verbal memory networks. We used word frequencies taken from the Controlled Oral Word Association Test and design frequencies taken from the Ruff Figural Fluency Test as measures of verbal and visuospatial spreading activation, respectively. Average word and design frequencies were then correlated with measures of left and right cerebral functioning. The results indicated that a significant relationship exists between performance on a test of right posterior functioning (Block Design) and design frequency. A significant negative relationship also exists between spreading activation in semantic memory networks and design frequency. Based on our findings, the hypotheses were supported. Further research will need to be conducted to examine whether spreading activation exists in visuospatial memory networks as well as the parameters that might modulate this spreading activation, such as the influence of neurotransmitters.
Chang, Lun-Ching; Jamain, Stephane; Lin, Chien-Wei; Rujescu, Dan; Tseng, George C; Sibille, Etienne
2014-01-01
Large scale gene expression (transcriptome) analysis and genome-wide association studies (GWAS) for single nucleotide polymorphisms have generated a considerable amount of gene- and disease-related information, but heterogeneity and various sources of noise have limited the discovery of disease mechanisms. As systematic dataset integration is becoming essential, we developed methods and performed meta-clustering of gene coexpression links in 11 transcriptome studies from postmortem brains of human subjects with major depressive disorder (MDD) and non-psychiatric control subjects. We next sought enrichment in the top 50 meta-analyzed coexpression modules for genes otherwise identified by GWAS for various sets of disorders. One coexpression module of 88 genes was consistently and significantly associated with GWAS for MDD, other neuropsychiatric disorders and brain functions, and for medical illnesses with elevated clinical risk of depression, but not for other diseases. In support of the superior discriminative power of this novel approach, we observed no significant enrichment for GWAS-related genes in coexpression modules extracted from single studies or in meta-modules using gene expression data from non-psychiatric control subjects. Genes in the identified module encode proteins implicated in neuronal signaling and structure, including glutamate metabotropic receptors (GRM1, GRM7), GABA receptors (GABRA2, GABRA4), and neurotrophic and development-related proteins [BDNF, reelin (RELN), Ephrin receptors (EPHA3, EPHA5)]. These results are consistent with the current understanding of molecular mechanisms of MDD and provide a set of putative interacting molecular partners, potentially reflecting components of a functional module across cells and biological pathways that are synchronously recruited in MDD, other brain disorders and MDD-related illnesses. Collectively, this study demonstrates the importance of integrating transcriptome data, gene coexpression modules and GWAS results for providing novel and complementary approaches to investigate the molecular pathology of MDD and other complex brain disorders.
Odorant receptor modulation: Ternary paradigm for mode of action of insect repellents
USDA-ARS?s Scientific Manuscript database
The modulation of insect behavior for the purpose of controlling the spread of infectious diseases has been the task of a few insect repellents for which the mechanistic modes of action on odorant receptors (ORs) are unclear. Here, we study the effects of the repellents DEET and IR3535, and a novel ...
An intraorganizational model for developing and spreading quality improvement innovations.
Kellogg, Katherine C; Gainer, Lindsay A; Allen, Adrienne S; OʼSullivan, Tatum; Singer, Sara J
Recent policy reforms encourage quality improvement (QI) innovations in primary care, but practitioners lack clear guidance regarding spread inside organizations. We designed this study to identify how large organizations can facilitate intraorganizational spread of QI innovations. We conducted ethnographic observation and interviews in a large, multispecialty, community-based medical group that implemented three QI innovations across 10 primary care sites using a new method for intraorganizational process development and spread. We compared quantitative outcomes achieved through the group's traditional versus new method, created a process model describing the steps in the new method, and identified barriers and facilitators at each step. The medical group achieved substantial improvement using its new method of intraorganizational process development and spread of QI innovations: standard work for rooming and depression screening, vaccine error rates and order compliance, and Pap smear error rates. Our model details nine critical steps for successful intraorganizational process development (set priorities, assess the current state, develop the new process, and measure and refine) and spread (develop support, disseminate information, facilitate peer-to-peer training, reinforce, and learn and adapt). Our results highlight the importance of utilizing preexisting organizational structures such as established communication channels, standardized roles, common workflows, formal authority, and performance measurement and feedback systems when developing and spreading QI processes inside an organization. In particular, we detail how formal process advocate positions in each site for each role can facilitate the spread of new processes. Successful intraorganizational spread is possible and sustainable. Developing and spreading new QI processes across sites inside an organization requires creating a shared understanding of the necessary process steps, considering the barriers that may arise at each step, and leveraging preexisting organizational structures to facilitate intraorganizational process development and spread.
An intraorganizational model for developing and spreading quality improvement innovations
Kellogg, Katherine C.; Gainer, Lindsay A.; Allen, Adrienne S.; O'Sullivan, Tatum; Singer, Sara J.
2017-01-01
Background: Recent policy reforms encourage quality improvement (QI) innovations in primary care, but practitioners lack clear guidance regarding spread inside organizations. Purpose: We designed this study to identify how large organizations can facilitate intraorganizational spread of QI innovations. Methodology/Approach: We conducted ethnographic observation and interviews in a large, multispecialty, community-based medical group that implemented three QI innovations across 10 primary care sites using a new method for intraorganizational process development and spread. We compared quantitative outcomes achieved through the group’s traditional versus new method, created a process model describing the steps in the new method, and identified barriers and facilitators at each step. Findings: The medical group achieved substantial improvement using its new method of intraorganizational process development and spread of QI innovations: standard work for rooming and depression screening, vaccine error rates and order compliance, and Pap smear error rates. Our model details nine critical steps for successful intraorganizational process development (set priorities, assess the current state, develop the new process, and measure and refine) and spread (develop support, disseminate information, facilitate peer-to-peer training, reinforce, and learn and adapt). Our results highlight the importance of utilizing preexisting organizational structures such as established communication channels, standardized roles, common workflows, formal authority, and performance measurement and feedback systems when developing and spreading QI processes inside an organization. In particular, we detail how formal process advocate positions in each site for each role can facilitate the spread of new processes. Practice Implications: Successful intraorganizational spread is possible and sustainable. Developing and spreading new QI processes across sites inside an organization requires creating a shared understanding of the necessary process steps, considering the barriers that may arise at each step, and leveraging preexisting organizational structures to facilitate intraorganizational process development and spread. PMID:27428788
Diffraction leveraged modulation of X-ray pulses using MEMS-based X-ray optics
Lopez, Daniel; Shenoy, Gopal; Wang, Jin; Walko, Donald A.; Jung, Il-Woong; Mukhopadhyay, Deepkishore
2016-08-09
A method and apparatus are provided for implementing Bragg-diffraction leveraged modulation of X-ray pulses using MicroElectroMechanical systems (MEMS) based diffractive optics. An oscillating crystalline MEMS device generates a controllable time-window for diffraction of the incident X-ray radiation. The Bragg-diffraction leveraged modulation of X-ray pulses includes isolating a particular pulse, spatially separating individual pulses, and spreading a single pulse from an X-ray pulse-train.
Influence of GRIK4 genetic variants on the electroconvulsive therapy response.
Minelli, Alessandra; Congiu, Chiara; Ventriglia, Mariacarla; Bortolomasi, Marco; Bonvicini, Cristian; Abate, Maria; Sartori, Riccardo; Gainelli, Giulio; Gennarelli, Massimo
2016-07-28
Several lines of evidence have shown the involvement of the glutamatergic system in the function of electroconvulsive therapy (ECT). In particular, patients with treatment resistant depression (TRD) and chronic depression have lower levels of glutamate/glutamine than controls, and ECT can reverse this deficit. Genetic factors might contribute to modulating the mechanisms underlying ECT. This study aimed to evaluate the relationship between three polymorphisms (rs1954787, rs4936554 and rs11218030) of the glutamate receptor ionotropic kainate 4 (GRIK4) gene and responsiveness to ECT treatment in a sample of one hundred individuals, TRD or depressive Bipolar Disorder patients resistant to pharmacological treatments. The results revealed that GRIK4 variants were significantly associated with the response to ECT. In particular, we found that patients carrying the G allele of the GRIK4 rs11218030 had a significantly poorer response to ECT (p=2.71×10(-4)), showing five times the risk of relapse after ECT compared to the AA homozygotes. Analogously, patients carrying the GG rs1954787 genotype and rs4936554A allele carriers presented a double risk of lack of response after ECT (p=0.013 and p=0.040, respectively). In conclusion, the current study provides new evidence, indicating that some GRIK4 variants modulate the response to ECT in patients with depression resistant to treatment, suggesting a role for kainate receptor modulation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Spread-Spectrum Carrier Estimation With Unknown Doppler Shift
NASA Technical Reports Server (NTRS)
DeLeon, Phillip L.; Scaife, Bradley J.
1998-01-01
We present a method for the frequency estimation of a BPSK modulated, spread-spectrum carrier with unknown Doppler shift. The approach relies on a classic periodogram in conjunction with a spectral matched filter. Simulation results indicate accurate carrier estimation with processing gains near 40. A DSP-based prototype has been implemented for real-time carrier estimation for use in New Mexico State University's proposal for NASA's Demand Assignment Multiple Access service.
NASA Astrophysics Data System (ADS)
Wu, Jheng-Syong; Chung, Yung-Chin; Chien, Jun-Jei; Chou, Chien
2018-01-01
A two-frequency laser scanning confocal fluorescence microscope (TF-LSCFM) based on intensity modulated fluorescence signal detection was proposed. The specimen-induced spherical aberration and scattering effect were suppressed intrinsically, and high image contrast was presented due to heterodyne interference. An improved axial point spread function in a TF-LSCFM compared with a conventional laser scanning confocal fluorescence microscope was demonstrated and discussed.
Kumar, Poornima; Slavich, George M.; Berghorst, Lisa H.; Treadway, Michael T.; Brooks, Nancy H.; Dutra, Sunny J.; Greve, Douglas N.; O'Donovan, Aoife; Bleil, Maria E.; Maninger, Nicole; Pizzagalli, Diego A.
2015-01-01
Introduction Major depressive disorder (MDD) is often precipitated by life stress and growing evidence suggests that stress-induced alterations in reward processing may contribute to such risk. However, no human imaging studies have examined how recent life stress exposure modulates the neural systems that underlie reward processing in depressed and healthy individuals. Methods In this proof-of-concept study, 12 MDD and 10 psychiatrically healthy individuals were interviewed using the Life Events and Difficulties Schedule (LEDS) to assess their perceived levels of recent acute and chronic life stress exposure. Additionally, each participant performed a monetary incentive delay task under baseline (no-stress) and stress (social-evaluative) conditions during functional MRI. Results Across groups, medial prefrontal cortex (mPFC) activation to reward feedback was greater during acute stress versus no-stress conditions in individuals with greater perceived stressor severity. Under acute stress, depressed individuals showed a positive correlation between perceived stressor severity levels and reward-related mPFC activation (r = 0.79, p = 0.004), whereas no effect was found in healthy controls. Moreover, for depressed (but not healthy) individuals, the correlations between the stress (r = 0.79) and no-stress (r = −0.48) conditions were significantly different. Finally, relative to controls, depressed participants showed significantly reduced mPFC grey matter, but functional findings remained when accounting for structural differences. Limitation Small sample size, which warrants replication. Conclusion Depressed individuals experiencing greater recent life stress recruited the mPFC more under stress when processing rewards. Our results represent an initial step toward elucidating mechanisms underlying stress sensitization and recurrence in depression. PMID:25898329
Newcomb, Michael E; Bedoya, C Andres; Blashill, Aaron J; Lerner, Jonathan A; O'Cleirigh, Conall; Pinkston, Megan M; Safren, Steven A
2015-11-01
There are an estimated 1.1 million individuals living with HIV/AIDS in the United States. In addition to the various medical comorbidities of HIV infection, depression is one of the most frequently co-occurring psychiatric conditions among HIV-infected individuals. Furthermore, depression has been found to be associated with nonadherence to antiretroviral therapy (ART), as well as HIV disease progression. Cognitive behavioral therapy (CBT) has repeatedly been found to effectively treat depression in adult populations, and CBT for adherence and depression (CBT-AD) is an effective treatment for improving depressive symptoms and medication adherence in the context of various chronic health conditions, including diabetes and HIV-infection. This paper provides a description of the CBT-AD approach to treat depression and ART adherence in HIV-infected adults, which we have developed and tested in our clinic, and for which detailed therapist and client guides exist. To augment the description of treatment, the present article provides video component demonstrations of several core modules that highlight important aspects of this treatment, including Life-Steps for medication adherence, orientation to CBT-AD and psychoeducation, and suggestions for adaptation of core CBT modules for HIV-infected adults. Discussion of video demonstrations highlights differences in patient presentations and course of treatment between HIV-infected adults receiving CBT-AD and HIV-uninfected adults receiving traditional CBT for depression. This description and the accompanying demonstrations are intended as a practical guide to assist therapists wishing to conduct such a treatment in the outpatient setting.
Default Mode Network Mechanisms of Transcranial Magnetic Stimulation in Depression
Liston, Conor; Chen, Ashley C.; Zebley, Benjamin D.; Drysdale, Andrew T.; Gordon, Rebecca; Leuchter, Bruce; Voss, Henning U.; Casey, B.J.; Etkin, Amit; Dubin, Marc J.
2014-01-01
Background Repetitive transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) is an established treatment for depression, but its underlying mechanism of action remains unknown. Abnormalities in two large-scale neuronal networks—the frontoparietal central executive network (CEN) and the medial prefrontal-medial parietal default mode network (DMN)—are consistent findings in depression and potential therapeutic targets for TMS. Here, we assessed the impact of TMS on activity in these networks and their relation to treatment response. Methods We used resting state functional magnetic resonance imaging (rs-fMRI) to measure functional connectivity within and between the DMN and CEN in 17 depressed patients, before and after a five-week course of TMS. Motivated by prior reports, we focused on connectivity seeded from the DLPFC and the subgenual cingulate, a key region closely aligned with the DMN in depression. Connectivity was also compared to a cohort of 35 healthy controls. Results Prior to treatment, functional connectivity in depressed patients was abnormally elevated within the DMN and diminished within the CEN, and connectivity between these two networks was altered. TMS normalized depression-related subgenual hyperconnectivity in the DMN but did not alter connectivity in the CEN. TMS also induced anticorrelated connectivity between the DLPFC and medial prefrontal DMN nodes. Baseline subgenual connectivity predicted subsequent clinical improvement. Conclusions TMS selectively modulates functional connectivity both within and between the CEN and DMN, and modulation of subgenual cingulate connectivity may play an important mechanistic role in alleviating depression. The results also highlight potential neuroimaging biomarkers for predicting treatment response. PMID:24629537
Zhang, Fan; Luo, Jie; Min, Su; Ren, Li; Qin, Peipei
2016-07-01
This study investigated the effects of propofol and electroconvulsive shock (ECS), the analogue of electroconvulsive therapy (ECT) in animals, on tissue plasminogen activator (tPA) and its inhibitor (PAI-1) as well as the precursor of brain-derived neurotrophic factor (proBDNF)/mature BDNF (mBDNF) ratio in depressive rats. ECT is an effective treatment for depression, but can cause cognitive deficit. Some studies have indicated that propofol can ameliorate cognitive decline induced by ECT, but the underlying molecular mechanism is still unclear. Recent evidence has found that mBDNF and its precursor proBDNF are related to depression and cognitive function; they elicit opposite effects on cellular functions. Chronic unpredicted mild stress is widely used to induce depressive behaviors in rodents. This study found that the depression resulted in an increased expression of PAI-1 and upregulation of the proBDNF/mBDNF ratio, together with a decreased level of tPA, long-term potentiation (LTP) impairment, and cognitive decline. The proBDNF/mBDNF ratio was further upregulated after the ECS treatment in depressive rats, resulting in the deterioration of cognitive function and hippocampal LTP. Propofol alone did not reverse the changes in depressive rats, but when co-administered with ECS, it improved the cognitive function, alleviated the impairment of LTP, downregulated the proBDNF/mBDNF ratio, and increased the tPA expression. The results of this study suggest that propofol ameliorates cognitive decline induced by ECT, which was partly by modulating the proBDNF/mBDNF ratio and reversing the excessive changes in hippocampal synaptic plasticity, providing a new evidence for involving the proBDNF/mBDNF system in the progression and treatment of depression. Copyright © 2016 Elsevier B.V. All rights reserved.
Wang, Yanqing; Burrell, Brian D
2016-08-01
Endocannabinoids can elicit persistent depression of excitatory and inhibitory synapses, reducing or enhancing (disinhibiting) neural circuit output, respectively. In this study, we examined whether differences in Cl(-) gradients can regulate which synapses undergo endocannabinoid-mediated synaptic depression vs. disinhibition using the well-characterized central nervous system (CNS) of the medicinal leech, Hirudo verbana Exogenous application of endocannabinoids or capsaicin elicits potentiation of pressure (P) cell synapses and depression of both polymodal (Npoly) and mechanical (Nmech) nociceptive synapses. In P synapses, blocking Cl(-) export prevented endocannabinoid-mediated potentiation, consistent with a disinhibition process that has been indicated by previous experiments. In Nmech neurons, which are depolarized by GABA due to an elevated Cl(-) equilibrium potentials (ECl), endocannabinoid-mediated depression was prevented by blocking Cl(-) import, indicating that this decrease in synaptic signaling was due to depression of excitatory GABAergic input (disexcitation). Npoly neurons are also depolarized by GABA, but endocannabinoids elicit depression in these synapses directly and were only weakly affected by disruption of Cl(-) import. Consequently, the primary role of elevated ECl may be to protect Npoly synapses from disinhibition. All forms of endocannabinoid-mediated plasticity required activation of transient potential receptor vanilloid (TRPV) channels. Endocannabinoid/TRPV-dependent synaptic plasticity could also be elicited by distinct patterns of afferent stimulation with low-frequency stimulation (LFS) eliciting endocannabinoid-mediated depression of Npoly synapses and high-frequency stimulus (HFS) eliciting endocannabinoid-mediated potentiation of P synapses and depression of Nmech synapses. These findings demonstrate a critical role of differences in Cl(-) gradients between neurons in determining the sign, potentiation vs. depression, of synaptic modulation under normal physiological conditions. Copyright © 2016 the American Physiological Society.
Wang, Yanqing
2016-01-01
Endocannabinoids can elicit persistent depression of excitatory and inhibitory synapses, reducing or enhancing (disinhibiting) neural circuit output, respectively. In this study, we examined whether differences in Cl− gradients can regulate which synapses undergo endocannabinoid-mediated synaptic depression vs. disinhibition using the well-characterized central nervous system (CNS) of the medicinal leech, Hirudo verbana. Exogenous application of endocannabinoids or capsaicin elicits potentiation of pressure (P) cell synapses and depression of both polymodal (Npoly) and mechanical (Nmech) nociceptive synapses. In P synapses, blocking Cl− export prevented endocannabinoid-mediated potentiation, consistent with a disinhibition process that has been indicated by previous experiments. In Nmech neurons, which are depolarized by GABA due to an elevated Cl− equilibrium potentials (ECl), endocannabinoid-mediated depression was prevented by blocking Cl− import, indicating that this decrease in synaptic signaling was due to depression of excitatory GABAergic input (disexcitation). Npoly neurons are also depolarized by GABA, but endocannabinoids elicit depression in these synapses directly and were only weakly affected by disruption of Cl− import. Consequently, the primary role of elevated ECl may be to protect Npoly synapses from disinhibition. All forms of endocannabinoid-mediated plasticity required activation of transient potential receptor vanilloid (TRPV) channels. Endocannabinoid/TRPV-dependent synaptic plasticity could also be elicited by distinct patterns of afferent stimulation with low-frequency stimulation (LFS) eliciting endocannabinoid-mediated depression of Npoly synapses and high-frequency stimulus (HFS) eliciting endocannabinoid-mediated potentiation of P synapses and depression of Nmech synapses. These findings demonstrate a critical role of differences in Cl− gradients between neurons in determining the sign, potentiation vs. depression, of synaptic modulation under normal physiological conditions. PMID:27226449
Burnout and Depression: Two Entities or One?
Schonfeld, Irvin Sam; Bianchi, Renzo
2016-01-01
The purpose of this study was to examine the overlap in burnout and depression. The sample comprised 1,386 schoolteachers (mean [M]age = 43; Myears taught = 15; 77% women) from 18 different U.S. states. We assessed burnout, using the Shirom-Melamed Burnout Measure, and depression, using the depression module of the Patient Health Questionnaire. Treated dimensionally, burnout and depressive symptoms were strongly correlated (.77; disattenuated correlation, .84). Burnout and depressive symptoms were similarly correlated with each of 3 stress-related factors, stressful life events, job adversity, and workplace support. In categorical analyses, 86% of the teachers identified as burned out met criteria for a provisional diagnosis of depression. Exploratory analyses revealed a link between burnout and anxiety. This study provides evidence that past research has underestimated burnout-depression overlap. The state of burnout is likely to be a form of depression. Given the magnitude of burnout-depression overlap, treatments for depression may help workers identified as "burned out." © 2015 Wiley Periodicals, Inc.
Development and testing of advanced fire-resistant photovoltaic modules
NASA Technical Reports Server (NTRS)
Sugimura, R. S.; Otth, D. H.; Ross, R. G., Jr.
1985-01-01
The evaluation of back-surface materials flammability in order to identify fire resistant module designs is examined. The fire test apparatus, burning-brand test sequence, and spread-of-flame test sequence are described. Video recordings and time-temperature profiles of module back surfaces are utilized to study the flammability failure mechanism and identify high-temperature materials. A table of flammability test results for various module designs is provided. The data reveals that 2-mil kapton, fiberglass cloth coated or impregnated with a material to plug pores, and metal foil back-surface materials achieve class A and B fire-resistance levels, and are applicable for photovoltaic module designs.
Small-scale ionospheric troughs detected over a range of mid-latitude locations
NASA Astrophysics Data System (ADS)
Bowman, G. G.
1991-07-01
Spread-F structures at three spaced midlatitude stations (Canberra, 45 deg CGlat; Bribie Island, 36 deg CGlat; Townsville, 28 deg CGlat) obtained by N(h) analyses reveal modulated ionospheric height rises, electron-density depletions with spread-F recorded during the recovery stage of these ionospheric structure changes. At Bribie Island, fixed-frequency phase-path measurements (at 1.98 MHz) reveal a traveling ionospheric disturbance wavetrain of several cycles (periodicity 25 m) before and during the height rise associated with the spread-F event. When these midlatitude spread-F characteristics (including speeds of movement) are compared with those related to the daytime trough in high-latitude regions, the two phenomena are found to be similar. However, the magnitudes of the high-latitude changes are much greater than for the midlatitude spread-F events. It is suggested that both phenomena may result from the breaking of atmospheric gravity waves.
Spreading of triboelectrically charged granular matter
NASA Astrophysics Data System (ADS)
Kumar, Deepak; Sane, A.; Gohil, Smita.; Bandaru, P. R.; Bhattacharya, S.; Ghosh, Shankar
2014-06-01
We report on the spreading of triboelectrically charged glass particles on an oppositely charged surface of a plastic cylindrical container in the presence of a constant mechanical agitation. The particles spread via sticking, as a monolayer on the cylinder's surface. Continued agitation initiates a sequence of instabilities of this monolayer, which first forms periodic wavy-stripe-shaped transverse density modulation in the monolayer and then ejects narrow and long particle-jets from the tips of these stripes. These jets finally coalesce laterally to form a homogeneous spreading front that is layered along the spreading direction. These remarkable growth patterns are related to a time evolving frictional drag between the moving charged glass particles and the countercharges on the plastic container. The results provide insight into the multiscale time-dependent tribolelectric processes and motivates further investigation into the microscopic causes of these macroscopic dynamical instabilities and spatial structures.
Theoretical and numerical analyses of a slit-masked chicane for modulated bunch generation
Zhu, Xiaofang; Broemmelsiek, Daniel R.; Shin, Young -Min; ...
2015-10-28
Density modulations on electron beams can improve machine performance of beam-driven accelerators and FELs with resonance beam-wave coupling. The beam modulation is studied with a masked chicane by the analytic model and simulations with the beam parameters of the Fermilab Accelerator Science and Technology (FAST) facility. With the chicane design parameters (bending angle of 18o, bending radius of 0.95 m and R 56 ~ –0.19 m) and a nominal beam of 3 ps bunch length, the analytic model showed that a slit-mask with slit period 900 μ m and aperture width 300 μ m induces a modulation of bunch-to-bunch spacingmore » ~ 100 μ m to the bunch with 2.4% correlated energy spread. With the designed slit mask and a 3 ps bunch, particle-in-cell (PIC) simulations, including nonlinear energy distributions, space charge force, and coherent synchrotron radiation (CSR) effect, also result in beam modulation with bunch-to-bunch distance around 100 μ m and a corresponding modulation frequency of 3 THz. The beam modulation has been extensively examined with three different beam conditions, 2.25 ps (0.25 nC), 3.25 ps (1 nC), and 4.75 ps (3.2 nC), by tracking code Elegant. The simulation analysis indicates that the sliced beam by the slit-mask with 3 ~ 6% correlated energy spread has modulation lengths about 187 μ m (0.25 nC), 270 μ m (1 nC) and 325 μ m (3.2 nC). As a result, the theoretical and numerical data proved the capability of the designed masked chicane in producing modulated bunch train with micro-bunch length around 100 fs.« less
Theoretical and numerical analyses of a slit-masked chicane for modulated bunch generation
NASA Astrophysics Data System (ADS)
Zhu, X.; Broemmelsiek, D. R.; Shin, Y.-M.
2015-10-01
Density modulations on electron beams can improve machine performance of beam-driven accelerators and FELs with resonance beam-wave coupling. The beam modulation is studied with a masked chicane by the analytic model and simulations with the beam parameters of the Fermilab Accelerator Science and Technology (FAST) facility. With the chicane design parameters (bending angle of 18o, bending radius of 0.95 m and R56 ~ -0.19 m) and a nominal beam of 3 ps bunch length, the analytic model showed that a slit-mask with slit period 900 μ m and aperture width 300 μ m induces a modulation of bunch-to-bunch spacing ~ 100 μ m to the bunch with 2.4% correlated energy spread. With the designed slit mask and a 3 ps bunch, particle-in-cell (PIC) simulations, including nonlinear energy distributions, space charge force, and coherent synchrotron radiation (CSR) effect, also result in beam modulation with bunch-to-bunch distance around 100 μ m and a corresponding modulation frequency of 3 THz. The beam modulation has been extensively examined with three different beam conditions, 2.25 ps (0.25 nC), 3.25 ps (1 nC), and 4.75 ps (3.2 nC), by tracking code Elegant. The simulation analysis indicates that the sliced beam by the slit-mask with 3 ~ 6% correlated energy spread has modulation lengths about 187 μ m (0.25 nC), 270 μ m (1 nC) and 325 μ m (3.2 nC). The theoretical and numerical data proved the capability of the designed masked chicane in producing modulated bunch train with micro-bunch length around 100 fs.
Day, Victor; McGrath, Patrick J; Wojtowicz, Magdalena
2013-07-01
Anxiety, depression and stress, often co-occurring, are the psychological problems for which university students most often seek help. Moreover there are many distressed students who cannot, or choose not to, access professional help. The present study evaluated the efficacy of an internet-based guided self-help program for moderate anxiety, depression and stress. The program was based on standard cognitive behavior therapy principles and included 5 core modules, some of which involved options for focusing on anxiety and/or depression and/or stress. Trained student coaches provided encouragement and advice about using the program via e-mail or brief weekly phone calls. Sixty-six distressed university students were randomly assigned to either Immediate Access or a 6-week Delayed Access condition. Sixty-one percent of Immediate Access participants completed all 5 core modules, and 80% of all participants completed the second assessment. On the Depression, Anxiety and Stress Scales-21, Immediate Access participants reported significantly greater reductions in depression (ηp(2)=. 07), anxiety (ηp(2)=. 08) and stress (ηp(2)=. 12) in comparison to participants waiting to do the program, and these improvements were maintained at a six month follow-up. The results suggest that the provision of individually-adaptable, internet-based, self-help programs can reduce psychological distress in university students. Copyright © 2013 Elsevier Ltd. All rights reserved.
The roosting spatial network of a bird-predator bat.
Fortuna, Miguel A; Popa-Lisseanu, Ana G; Ibáñez, Carlos; Bascompte, Jordi
2009-04-01
The use of roosting sites by animal societies is important in conservation biology, animal behavior, and epidemiology. The giant noctule bat (Nyctalus lasiopterus) constitutes fission-fusion societies whose members spread every day in multiple trees for shelter. To assess how the pattern of roosting use determines the potential for information exchange or disease spreading, we applied the framework of complex networks. We found a social and spatial segregation of the population in well-defined modules or compartments, formed by groups of bats sharing the same trees. Inside each module, we revealed an asymmetric use of trees by bats representative of a nested pattern. By applying a simple epidemiological model, we show that there is a strong correlation between network structure and the rate and shape of infection dynamics. This modular structure slows down the spread of diseases and the exchange of information through the entire network. The implication for management is complex, affecting differently the cohesion inside and among colonies and the transmission of parasites and diseases. Network analysis can hence be applied to quantifying the conservation status of individual trees used by species depending on hollows for shelter.
Shrink that frown! Botulinum toxin therapy is lifting the face of psychiatry.
Wollmer, M Axel; Neumann, Insa; Magid, Michelle; Kruger, Tillmann H
2018-08-01
Treating glabellar frown lines with injections of botulinum toxin is the most frequently applied procedure in aesthetic medicine. In addition to its cosmetic effect, botulinum toxin may also positively modulate mood and affect, which may contribute to its popularity. A series of clinical studies has shown that this modulation can be used in the treatment of major depression. After a single glabellar treatment with botulinum toxin, patients suffering from unipolar depression experienced a quick, strong and sustained improvement in the symptoms of depression. Preliminary data suggest that botulinum toxin therapy may also be effective in the treatment of other mental disorders characterized by an excess of negative emotions, such as borderline personality disorder. Thus, the extreme bottom-up approach of paralyzing the facial muscles to influence the emotional brain via proprioceptive feedback mechanisms may represent a paradigm shift in psychiatric therapy.
Can home-monitoring of sleep predict depressive episodes in bipolar patients?
Migliorini, M; Mariani, S; Bertschy, G; Kosel, M; Bianchi, A M
2015-08-01
The aim of this study is the evaluation of the autonomic regulations during depressive stages in bipolar patients in order to test new quantitative and objective measures to detect such events. A sensorized T-shirt was used to record ECG signal and body movements during the night, from which HRV data and sleep macrostructure were estimated and analyzed. 9 out of 20 features extracted resulted to be significant (p<;0.05) in discriminating among depressive and non-depressive states. Such features are representation of HRV dynamics in both linear and non-linear domain and parameters linked to sleep modulations.
Melo-Carrillo, Agustin; Strassman, Andrew M.
2017-01-01
Functioning of the glymphatic system, a network of paravascular tunnels through which cortical interstitial solutes are cleared from the brain, has recently been linked to sleep and traumatic brain injury, both of which can affect the progression of migraine. This led us to investigate the connection between migraine and the glymphatic system. Taking advantage of a novel in vivo method we developed using two-photon microscopy to visualize the paravascular space (PVS) in naive uninjected mice, we show that a single wave of cortical spreading depression (CSD), an animal model of migraine aura, induces a rapid and nearly complete closure of the PVS around surface as well as penetrating cortical arteries and veins lasting several minutes, and gradually recovering over 30 min. A temporal mismatch between the constriction or dilation of the blood vessel lumen and the closure of the PVS suggests that this closure is not likely to result from changes in vessel diameter. We also show that CSD impairs glymphatic flow, as indicated by the reduced rate at which intraparenchymally injected dye was cleared from the cortex to the PVS. This is the first observation of a PVS closure in connection with an abnormal cortical event that underlies a neurological disorder. More specifically, the findings demonstrate a link between the glymphatic system and migraine, and suggest a novel mechanism for regulation of glymphatic flow. SIGNIFICANCE STATEMENT Impairment of brain solute clearance through the recently described glymphatic system has been linked with traumatic brain injury, prolonged wakefulness, and aging. This paper shows that cortical spreading depression, the neural correlate of migraine aura, closes the paravascular space and impairs glymphatic flow. This closure holds the potential to define a novel mechanism for regulation of glymphatic flow. It also implicates the glymphatic system in the altered cortical and endothelial functioning of the migraine brain. PMID:28193695
Schain, Aaron J; Melo-Carrillo, Agustin; Strassman, Andrew M; Burstein, Rami
2017-03-15
Functioning of the glymphatic system, a network of paravascular tunnels through which cortical interstitial solutes are cleared from the brain, has recently been linked to sleep and traumatic brain injury, both of which can affect the progression of migraine. This led us to investigate the connection between migraine and the glymphatic system. Taking advantage of a novel in vivo method we developed using two-photon microscopy to visualize the paravascular space (PVS) in naive uninjected mice, we show that a single wave of cortical spreading depression (CSD), an animal model of migraine aura, induces a rapid and nearly complete closure of the PVS around surface as well as penetrating cortical arteries and veins lasting several minutes, and gradually recovering over 30 min. A temporal mismatch between the constriction or dilation of the blood vessel lumen and the closure of the PVS suggests that this closure is not likely to result from changes in vessel diameter. We also show that CSD impairs glymphatic flow, as indicated by the reduced rate at which intraparenchymally injected dye was cleared from the cortex to the PVS. This is the first observation of a PVS closure in connection with an abnormal cortical event that underlies a neurological disorder. More specifically, the findings demonstrate a link between the glymphatic system and migraine, and suggest a novel mechanism for regulation of glymphatic flow. SIGNIFICANCE STATEMENT Impairment of brain solute clearance through the recently described glymphatic system has been linked with traumatic brain injury, prolonged wakefulness, and aging. This paper shows that cortical spreading depression, the neural correlate of migraine aura, closes the paravascular space and impairs glymphatic flow. This closure holds the potential to define a novel mechanism for regulation of glymphatic flow. It also implicates the glymphatic system in the altered cortical and endothelial functioning of the migraine brain. Copyright © 2017 the authors 0270-6474/17/372904-12$15.00/0.
One-Hundred-km-Scale Basins on Enceladus: Evidence for an Active Ice Shell
NASA Technical Reports Server (NTRS)
Schenk, Paul M.; McKinnon, William B.
2009-01-01
Stereo-derived topographic mapping of 50% of Enceladus reveals at least 6 large-scale, ovoid depressions (basins) 90-175 km across and 800-to-1500 m deep and uncorrelated with geologic boundaries. Their shape and scale are inconsistent with impact, geoid deflection, or with dynamically supported topography. Isostatic thinning of Enceladus ice shell associated with upwellings (and tidally-driven ice melting) can plausibly account for the basins. Thinning implies upwarping of the base of the shell of 10-20 km beneath the depressions, depending on total shell thickness; loss of near-surface porosity due to enhanced heat flow may also contribute to basin lows. Alternatively, the basins may overly cold, inactive, and hence denser ice, but thermal isostasy alone requires thermal expansion more consistent with clathrate hydrate than water ice. In contrast to the basins, the south polar depression (SPD) is larger (350 wide) and shallower (0.4-to-0.8 km deep) and correlates with the area of tectonic deformation and active resurfacing. The SPD also differs in that the floor is relatively flat (i.e., conforms roughly to the global triaxial shape, or geoid) with broad, gently sloping flanks. The relative flatness across the SPD suggests that it is in or near isostatic equilibrium, and underlain by denser material, supporting the polar sea hypothesis of Collins and Goodman. Near flatness is also predicted by a crustal spreading origin for the "tiger stripes (McKinnon and Barr 2007, Barr 2008); the extraordinary, high CIRS heat flows imply half-spreading rates in excess of 10 cm/yr, a very young surface age (250,000 yr), and a rather thin lithosphere (hence modest thermal topography). Topographic rises in places along the outer margin of the SPD correlate with parallel ridges and deformation along the edge of the resurfaced terrain, consistent with a compressional, imbricate thrust origin for these ridges, driven by the spreading.
Yary, Teymoor
2013-01-01
Depression in students is a major public health problem. Although several risk factors associated with depression have been identified, the cause of depression is still not clear. Several studies have demonstrated that physical activity and nutrient intake, such as increased levels of B vitamins in serum, decrease symptoms of depression. The aim of this study was to investigate the association between physical activity and dietary intake of vitamins B₆, B₉, and B₁₂ and symptoms of depression among postgraduate students. The results of this study suggest that intake of vitamin B9 may modulate the total score of Center for Epidemiological Studies Depression Scale (CES-D) and two subscales of the CES-D including depressive affect and interpersonal difficulties. This study also showed that moderate/high levels of physical activity were inversely and significantly associated with symptoms of depression (total scores) and three subscales of the CES-D including depressive affect, positive affect, and somatic complaints.
Gawali, Nitin B; Bulani, Vipin D; Gursahani, Malvika S; Deshpande, Padmini S; Kothavade, Pankaj S; Juvekar, Archana R
2017-05-15
Agmatine, a neurotransmitter/neuromodulator, has shown to exert numerous effects on the CNS. Chronic stress is a risk factor for development of depression, anxiety and deterioration of cognitive performance. Compelling evidences indicate an involvement of nitric oxide (NO) pathway in these disorders. Hence, investigation of the beneficial effects of agmatine on chronic unpredictable mild stress (CUMS)-induced depression, anxiety and cognitive performance with the involvement of nitrergic pathway was undertaken. Mice were subjected to a battery of stressors for 28days. Agmatine (20 and 40mg/kg, i.p.) alone and in combination with NO modulators like L-NAME (15mg/kg, i.p.) and l-arginine (400mg/kg i.p.) were administered daily. The results showed that 4-weeks CUMS produces significant depression and anxiety-like behaviour. Stressed mice have also shown a significant high serum corticosterone (CORT) and low BDNF level. Chronic treatment with agmatine produced significant antidepressant-like behaviour in forced swim test (FST) and sucrose preference test, whereas, anxiolytic-like behaviour in elevated plus maze (EPM) and open field test (OFT) with improved cognitive impairment in Morris water maze (MWM). Furthermore, agmatine administration reduced the levels of acetylcholinesterase and oxidative stress markers. In addition, agmatine treatment significantly increased the BDNF level and inhibited serum CORT level in stressed mice. Treatment with L-NAME (15mg/kg) potentiated the effect of agmatine whereas l-arginine abolished the anxiolytic, antidepressant and neuroprotective effects of agmatine. Agmatine showed marked effect on depression and anxiety-like behaviour in mice through nitrergic pathway, which may be related to modulation of oxidative-nitrergic stress, CORT and BDNF levels. Copyright © 2017 Elsevier B.V. All rights reserved.
Glutamate and Its Receptors as Therapeutic Targets for Migraine.
Hoffmann, Jan; Charles, Andrew
2018-04-01
There is substantial evidence indicating a role for glutamate in migraine. Levels of glutamate are higher in the brain and possibly also in the peripheral circulation in migraine patients, particularly during attacks. Altered blood levels of kynurenines, endogenous modulators of glutamate receptors, have been reported in migraine patients. Population genetic studies implicate genes that are involved with glutamate signaling in migraine, and gene mutations responsible for familial hemiplegic migraine and other familial migraine syndromes may influence glutamate signaling. Animal studies indicate that glutamate plays a key role in pain transmission, central sensitization, and cortical spreading depression. Multiple therapies that target glutamate receptors including magnesium, topiramate, memantine, and ketamine have been reported to have efficacy in the treatment of migraine, although with the exception of topiramate, the evidence for the efficacy of these therapies is not strong. Also, because all of these therapies have other mechanisms of action, it is not possible to conclude that the efficacy of these drugs is entirely due to their effects on glutamate receptors. Further studies are needed to more clearly delineate the possible roles of glutamate and its specific receptor subtypes in migraine and to identify new ways of targeting glutamate for migraine therapy.
Photoperiodic and circadian bifurcation theories of depression and mania
Kripke, Daniel F.; Elliott, Jeffrey A.; Welsh, David K.; Youngstedt, Shawn D.
2015-01-01
Seasonal effects on mood have been observed throughout much of human history. Seasonal changes in animals and plants are largely mediated through the changing photoperiod (i.e., the photophase or duration of daylight). We review that in mammals, daylight specifically regulates SCN (suprachiasmatic nucleus) circadian organization and its control of melatonin secretion. The timing of melatonin secretion interacts with gene transcription in the pituitary pars tuberalis to modulate production of TSH (thyrotropin), hypothalamic T3 (triiodothyronine), and tuberalin peptides which modulate pituitary production of regulatory gonadotropins and other hormones. Pituitary hormones largely mediate seasonal physiologic and behavioral variations. As a result of long winter nights or inadequate illumination, we propose that delayed morning offset of nocturnal melatonin secretion, suppressing pars tuberalis function, could be the main cause for winter depression and even cause depressions at other times of year. Irregularities of circadian sleep timing and thyroid homeostasis contribute to depression. Bright light and sleep restriction are antidepressant and conversely, sometimes trigger mania. We propose that internal desynchronization or bifurcation of SCN circadian rhythms may underlie rapid-cycling manic-depressive disorders and perhaps most mania. Much further research will be needed to add substance to these theories. PMID:26180634
Maternal Weaning Modulates Emotional Behavior and Regulates the Gut-Brain Axis
Farshim, Pamela; Walton, Gemma; Chakrabarti, Bhismadev; Givens, Ian; Saddy, Doug; Kitchen, Ian; R. Swann, Jonathan; Bailey, Alexis
2016-01-01
Evidence shows that nutritional and environmental stress stimuli during postnatal period influence brain development and interactions between gut and brain. In this study we show that in rats, prevention of weaning from maternal milk results in depressive-like behavior, which is accompanied by changes in the gut bacteria and host metabolism. Depressive-like behavior was studied using the forced-swim test on postnatal day (PND) 25 in rats either weaned on PND 21, or left with their mother until PND 25 (non-weaned). Non-weaned rats showed an increased immobility time consistent with a depressive phenotype. Fluorescence in situ hybridization showed non-weaned rats to harbor significantly lowered Clostridium histolyticum bacterial groups but exhibit marked stress-induced increases. Metabonomic analysis of urine from these animals revealed significant differences in the metabolic profiles, with biochemical phenotypes indicative of depression in the non-weaned animals. In addition, non-weaned rats showed resistance to stress-induced modulation of oxytocin receptors in amygdala nuclei, which is indicative of passive stress-coping mechanism. We conclude that delaying weaning results in alterations to the gut microbiota and global metabolic profiles which may contribute to a depressive phenotype and raise the issue that mood disorders at early developmental ages may reflect interplay between mammalian host and resident bacteria. PMID:26903212
Liu, Xuemei; Qian, Xin; Xing, Jing; Wang, Jinhua; Sun, Yixuan; Wang, Qin'geng; Li, Huiming
2018-04-23
Particulate matter (PM) exposure may contribute to depressive-like response in mice. However, few studies have evaluated the adaptive impacts of long-term PM exposure on depressive-like response associated with systemic inflammation and brain-derived neurotrophic factor (BDNF) signaling pathway. We studied the association among depressive-like behaviors, mRNA levels of pro- and anti-inflammatory cytokines, and the expression of BDNF signaling pathway in mice by long-term PM exposure. C57BL/6 male mice were exposed to ambient air alongside control mice breathing air filtered through a high-efficiency air PM (HEPA) filter. Depressive-like behaviors were assessed together with pro-inflammatory, anti-inflammatory cytokine mRNA levels and the modulation of BDNF pathway in hippocampus and olfactory-bulb of mice exposed to PM for 4, 8, and 12 weeks. Exposure to HEPA filtered air for 4 weeks may exert antidepressant like effects in mice. Pro-inflammatory cytokines were up-regulated while the expression of BDNF, its high-affinity receptor tropomyosin-related kinase B (TrkB), and the transcription factor cAMP-response-element binding protein (CREB) were down-regulated in ambient air mice. However, after 8 weeks, there was no significant difference in the rate of depressive-like behaviors between the two groups. After 12 weeks, mice exposed to ambient air again had a higher rate of depressive-like behaviors, significant up-regulation of pro-inflammatory cytokines, down-regulation of interleukin-10 (IL-10), BDNF, TrkB, and CREB than HEPA mice. Ultrafine PM in brain tissues of mice exposed to ambient air was observed. Our results suggest continuous high-level PM exposure alters the depressive-like response in mice and induces a damage-repair-imbalance reaction.
Kumar, Poornima; Slavich, George M; Berghorst, Lisa H; Treadway, Michael T; Brooks, Nancy H; Dutra, Sunny J; Greve, Douglas N; O'Donovan, Aoife; Bleil, Maria E; Maninger, Nicole; Pizzagalli, Diego A
2015-07-15
Major depressive disorder (MDD) is often precipitated by life stress and growing evidence suggests that stress-induced alterations in reward processing may contribute to such risk. However, no human imaging studies have examined how recent life stress exposure modulates the neural systems that underlie reward processing in depressed and healthy individuals. In this proof-of-concept study, 12 MDD and 10 psychiatrically healthy individuals were interviewed using the Life Events and Difficulties Schedule (LEDS) to assess their perceived levels of recent acute and chronic life stress exposure. Additionally, each participant performed a monetary incentive delay task under baseline (no-stress) and stress (social-evaluative) conditions during functional MRI. Across groups, medial prefrontal cortex (mPFC) activation to reward feedback was greater during acute stress versus no-stress conditions in individuals with greater perceived stressor severity. Under acute stress, depressed individuals showed a positive correlation between perceived stressor severity levels and reward-related mPFC activation (r=0.79, p=0.004), whereas no effect was found in healthy controls. Moreover, for depressed (but not healthy) individuals, the correlations between the stress (r=0.79) and no-stress (r=-0.48) conditions were significantly different. Finally, relative to controls, depressed participants showed significantly reduced mPFC gray matter, but functional findings remained robust while accounting for structural differences. Small sample size, which warrants replication. Depressed individuals experiencing greater recent life stress recruited the mPFC more under stress when processing rewards. Our results represent an initial step toward elucidating mechanisms underlying stress sensitization and recurrence in depression. Copyright © 2015 Elsevier B.V. All rights reserved.
ERIC Educational Resources Information Center
Hardin, Michael G.; Schroth, Elizabeth; Pine, Daniel S.; Ernst, Monique
2007-01-01
Background: Developmental changes in cognitive and affective processes contribute to adolescent risk-taking behavior, emotional intensification, and psychopathology. The current study examined adolescent development of cognitive control processes and their modulation by incentive, in health and psychopathology. Predictions include 1) better…
Hergueta, Thierry; Weiller, Emmanuelle
2013-01-01
The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), includes a new 'With Mixed Features' specifier for mood episodes. In (hypo-)manic episodes, the specifier is given if three or more depressive symptoms are present nearly every day during the episode. A new module of the Mini International Neuropsychiatric Interview (M.I.N.I.) has been developed as a patient-completed questionnaire to evaluate the DSM-5 specifier for (hypo-)manic episodes. The objective of this study was to validate this new module. In Phase I, patients with a manic episode in the past 6 months completed the module and were asked whether the wording was clear, understandable, relevant and specific. Based on their feedback, the module was refined and finalised. In Phase II, psychiatrists each invited five patients to complete the module. The psychiatrists completed record forms for these five patients, which included their diagnoses, made according to DSM-5 criteria during clinical interviewing. The module was validated by comparing depressive symptoms reported by the patients themselves using the M.I.N.I. module with those evaluated by their psychiatrist using DSM-5 criteria during clinical interviewing. In Phase I, a few changes were made to the M.I.N.I. module based on feedback from 20 patients (60% of whom had mixed features). In Phase II, 23 psychiatrists completed record forms for 115 patients, 99 (86.1%) of whom completed the M.I.N.I. module. Agreement between psychiatrists' DSM-5 diagnoses and patients' M.I.N.I. responses was substantial (Cohen's kappa coefficient, 0.60). The overall sensitivity of the M.I.N.I. was 0.91 and its specificity was 0.70. Sensitivity ranged from 0.63 for psychomotor retardation to 0.90 for suicidal thoughts. Specificity ranged from 0.63 for diminished interest/pleasure to 0.90 for suicidal thoughts. The module's positive and negative predictive values were 0.72 and 0.90, respectively. In summary, the M.I.N.I. module demonstrated good concurrent validity with psychiatrists' evaluation of DSM-5 mixed features in manic patients, accurately detecting mixed features with limited risk of over-diagnosis. Due to its simplicity, the M.I.N.I. module could be incorporated into routine psychiatric evaluation of patients with manic episodes. It could also provide a valuable standardised tool for clinical and epidemiological research.
Cognitive Radio for Tactical Wireless Communication Networks
2011-10-09
Pursley. Demodulator Statistics for Enhanced Soft-Decision Decoding in CDMA Packet Radio Systems, ICC 2010 - 2010 IEEE International Conference on...likelihood ratio (LLR) metrics and distance metrics. In [BPR08], [BoP09], and [BPR11], we investigated direct-sequence spread-spectrum ( DS -SS...modulation formats, which are among the most robust formats for tactical cognitive radio networks. DS -SS modulation with adaptive soft-decision decoding is
Yang, Ya-Chin; Hu, Chun-Chang; Huang, Chen-Syuan; Chou, Pei-Yu
2014-03-01
The thalamic synapses relay peripheral sensory information to the cortex, and constitute an important part of the thalamocortical network that generates oscillatory activities responsible for different vigilance (sleep and wakefulness) states. However, the modulation of thalamic synaptic transmission by potential sleep regulators, especially by combination of regulators in physiological scenarios, is not fully characterized. We found that somnogen adenosine itself acts similar to wake-promoting serotonin, both decreasing synaptic strength as well as short-term depression, at the retinothalamic synapse. We then combined the two modulators considering the coexistence of them in the hypnagogic (sleep-onset) state. Adenosine plus serotonin results in robust synergistic inhibition of synaptic strength and dramatic transformation of short-term synaptic depression to facilitation. These synaptic effects are not achievable with a single modulator, and are consistent with a high signal-to-noise ratio but a low level of signal transmission through the thalamus appropriate for slow-wave sleep. This study for the first time demonstrates that the sleep-regulatory modulators may work differently when present in combination than present singly in terms of shaping information flow in the thalamocortical network. The major synaptic characters such as the strength and short-term plasticity can be profoundly altered by combination of modulators based on physiological considerations. © 2013 International Society for Neurochemistry.
Martínez-López, B; Ivorra, B; Fernández-Carrión, E; Perez, A M; Medel-Herrero, A; Sánchez-Vizcaíno, F; Gortázar, C; Ramos, A M; Sánchez-Vizcaíno, J M
2014-04-01
This study presents a multi-disciplinary decision-support tool, which integrates geo-statistics, social network analysis (SNA), spatial-stochastic spread model, economic analysis and mapping/visualization capabilities for the evaluation of the sanitary and socio-economic impact of livestock diseases under diverse epidemiologic scenarios. We illustrate the applicability of this tool using foot-and-mouth disease (FMD) in Peru as an example. The approach consisted on a flexible, multistep process that may be easily adapted based on data availability. The first module (mI) uses a geo-statistical approach for the estimation (if needed) of the distribution and abundance of susceptible population (in the example here, cattle, swine, sheep, goats, and camelids) at farm-level in the region or country of interest (Peru). The second module (mII) applies SNA for evaluating the farm-to-farm contact patterns and for exploring the structure and frequency of between-farm animal movements as a proxy for potential disease introduction or spread. The third module (mIII) integrates mI-II outputs into a spatial-stochastic model that simulates within- and between-farm FMD-transmission. The economic module (mIV) connects outputs from mI-III to provide an estimate of associated direct and indirect costs. A visualization module (mV) is also implemented to graph and map the outputs of module I-IV. After 1000 simulated epidemics, the mean (95% probability interval) number of outbreaks, infected animals, epidemic duration, and direct costs were 37 (1, 1164), 2152 (1, 13, 250), 63 days (0, 442), and US$ 1.2 million (1072, 9.5 million), respectively. Spread of disease was primarily local (<4.5km), but geolocation and type of index farm strongly influenced the extent and spatial patterns of an epidemic. The approach is intended to support decisions in the last phase of the FMD eradication program in Peru, in particular to inform and support the implementation of risk-based surveillance and livestock insurance systems that may help to prevent and control potential FMD virus incursions into Peru. Copyright © 2014 Elsevier B.V. All rights reserved.
Diagnostic overlap of depressive, anxiety, stress and somatoform disorders in primary care.
Bener, Abdulbari; Al-Kazaz, Mohammed; Ftouni, Darine; Al-Harthy, Munjid; Dafeeah, Elnour E
2013-03-01
The aim of the present study was to determine the prevalence of somatization, anxiety, depression and stress in a primary care population, explore their association to psychosocial stressors and determine the diagnostic overlap of these four mental disorders. This is a prospective cross-sectional study. A representative sample of 2,150 patients was approached, of whom 1,762 patients agreed to participate and responded to the questionnaire (81.9%). Anxiety was assessed with the Generalized Anxiety Disorder Scale (GAD-7). Depression was assessed with the depression module Patients Health Questionnaire-8. Somatization was measured with the somatic symptom module PHQ-15. The Perceived Stress Scale (PSS) instrument was used to identify the stress cases. Of the study sample, 23.8% of the total cases were identified as probable cases. The prevalence of somatization, depression, anxiety and stress was 11.7%, 11.3%, 8.3% and 18.6%, respectively. The specific gender prevalence of these four psychological disorders was very similar in men and women: depression (11.3% versus 11.3%), anxiety (7.7% versus 8.9%), somatization (12.5% versus 10.7%) and stress disorders (19.3% versus 17.8%). A significant difference was observed in nationality and marital status for depression and anxiety (P < 0.05). The age-specific prevalence rate showed a higher prevalence in the age group 45-54 years: depression (13.3%), anxiety (9.5%), somatization (12.8%) and stress (20.4%). Unable to control worries (69.2%) was the worst symptom for anxiety disorders, while the majority of the depressed patients wanted to hurt themselves (71.9%). Stomach pain (46.1%) was the most common symptom in somatic patients. Most of the patients experiencing stress could not cope with their daily duties (65.9%). There was a high comorbidity rate of depression, anxiety, somatization and stress observed in the studied population (9.3%). The prevalence of somatization and depression was similar, but the prevalence of stress was higher in inpatient patients. Somatization, depression, anxiety and stress disorders co-occurred at higher rate in the study sample. Copyright © 2012 Blackwell Publishing Asia Pty Ltd.
Adjibade, Moufidath; Andreeva, Valentina A; Lemogne, Cédric; Touvier, Mathilde; Shivappa, Nitin; Hébert, James R; Wirth, Michael D; Hercberg, Serge; Galan, Pilar; Julia, Chantal; Assmann, Karen E; Kesse-Guyot, Emmanuelle
2017-05-01
Background: Low-grade chronic inflammation, which can be modulated by diet, has been suggested as an important risk factor for depression, but few studies have investigated the association between the inflammatory potential of the diet and depression. Objective: We investigated the prospective association between the inflammatory potential of the diet, measured by the Dietary Inflammatory Index (DII), and incident depressive symptoms and tested the potential modulating effect of sex, age, physical activity, and smoking status. Methods: This study included 3523 participants (aged 35-60 y) from the SU.VI.MAX (Supplémentation en Vitamines et Minéraux Antioxydants) cohort, who were initially free of depressive symptoms. Baseline DII (1994-1996) was computed by using repeated 24-h dietary records. Incident depressive symptoms were defined by a Center for Epidemiologic Studies-Depression Scale score ≥17 for men and ≥23 for women in 2007-2009. We used multivariable logistic regression models to estimate ORs and 95% CIs, and modeled the DII as a continuous variable and as sex-specific quartiles. Results: A total of 172 cases of incident depressive symptoms were identified over a mean follow-up of 12.6 y. The DII was not associated with incident depressive symptoms in the full sample. In sex-specific models, men with a higher DII had a higher risk of incident depressive symptoms (quartile 4 compared with quartile 1-OR: 2.32; 95% CI: 1.01, 5.35), but the association was only marginally significant ( P -trend = 0.06). When analyses were performed across smoking status, current and former smokers with a higher DII had a higher risk of incident depressive symptoms (quartile 4 compared with quartile 1-OR: 2.21; 95% CI: 1.08, 4.52). A positive association was also observed among less physically active participants (quartile 4 compared with quartile 1-OR: 2.07; 95% CI: 1.05, 4.07). Conclusion: The promotion of a healthy diet with anti-inflammatory properties may help to prevent depressive symptoms, particularly among men, smokers, or physically inactive individuals. This trial was registered at clinicaltrials.gov as NCT0027242. © 2017 American Society for Nutrition.
Economic Hardship and Depression Among Women in Latino Farmworker Families.
Pulgar, Camila A; Trejo, Grisel; Suerken, Cynthia; Ip, Edward H; Arcury, Thomas A; Quandt, Sara A
2016-06-01
Farmworker family members risk poor mental health due to stressors including poverty, relocation, and documentation status. This paper explores the relationship between farm-work related stressors and depressive symptoms in women of Latino farmworker families. 248 mothers of young children completed fixed-response interviews in Spanish. Measures included the Center for Epidemiologic Studies-Depression Scale, Migrant Farmworker Stress Inventory, and USDA Household Food Security Survey Module. Bivariate analyses indicated greater depressive symptoms with more economic hardship, more farm work-related stressors, greater age, and being unmarried. In multivariable logistic regression, economic hardship remained the only factor associated with depressive symptoms. Greater economic hardship, but not general farm work-related stress, is a main factor associated with depression in women of Latino farmworker families. Maternal depression can have consequences for both mothers and families. Mental health services for women in farmworker families should be targeted to those with the greatest economic challenges.
Phillips, Mary L.; Chase, Henry W.; Sheline, Yvette I.; Etkin, Amit; Almeida, Jorge R.C.; Deckersbach, Thilo; Trivedi, Madhukar H.
2015-01-01
Objective Despite significant advances in neuroscience and treatment development, no widely accepted biomarkers are available to inform diagnostics or identify preferred treatments for individuals with major depressive disorder. Method In this critical review, the authors examine the extent to which multimodal neuroimaging techniques can identify biomarkers reflecting key pathophysiologic processes in depression and whether such biomarkers may act as predictors, moderators, and mediators of treatment response that might facilitate development of personalized treatments based on a better understanding of these processes. Results The authors first highlight the most consistent findings from neuroimaging studies using different techniques in depression, including structural and functional abnormalities in two parallel neural circuits: serotonergically modulated implicit emotion regulation circuitry, centered on the amygdala and different regions in the medial prefrontal cortex; and dopaminergically modulated reward neural circuitry, centered on the ventral striatum and medial prefrontal cortex. They then describe key findings from the relatively small number of studies indicating that specific measures of regional function and, to a lesser extent, structure in these neural circuits predict treatment response in depression. Conclusions Limitations of existing studies include small sample sizes, use of only one neuroimaging modality, and a focus on identifying predictors rather than moderators and mediators of differential treatment response. By addressing these limitations and, most importantly, capitalizing on the benefits of multimodal neuroimaging, future studies can yield moderators and mediators of treatment response in depression to facilitate significant improvements in shorter- and longer-term clinical and functional outcomes. PMID:25640931
Perlman, Greg; Simmons, Alan N.; Wu, Jing; Hahn, Kevin S.; Tapert, Susan F.; Max, Jeffrey E.; Paulus, Martin P.; Brown, Gregory G.; Frank, Guido K.; Campbell-Sills, Laura; Yang, Tony T.
2012-01-01
Background Ineffective emotion regulation and abnormal amygdala activation have each been found in adolescent-onset major depressive disorder. However, amygdala activation during emotion regulation has not been studied in adolescent-onset major depressive disorder. Method Fourteen unmedicated adolescents diagnosed with current depression without comorbid psychiatric disorders and fourteen well-matched controls ages 13 to 17 years underwent an emotional regulation task during functional magnetic resonance imaging. During this task, participants viewed negatively-valence images and were asked to notice how they were feeling without trying to change it and maintain their emotional reaction (“Maintain”) or to interpret the image in such a way as minimize their emotional response (“Reduce”). Results Imaging analyses demonstrated that adolescents with depression showed: (1) greater right amygdala activation during the maintain condition relative to controls, (2) less connectivity during the maintain condition between the amygdala and both the insula and medial prefrontal cortex than controls, and (3) a significant positive correlation between amygdala-seeded connectivity during maintenance of emotion and psychosocial functioning. Limitations The current study is cross-sectional comparison and longitudinal investigations with larger sample sizes are needed to examine the association between amygdala reactivity and emotion regulation over time in adolescent MDD. Conclusions During the maintain condition, adolescents with depression showed a heightened amygdala response and less reciprocal activation in brain regions that may modulate the amygdala. A poorly modulated, overreactive amygdala may contribute to poor emotion regulation. PMID:22401827
Rosenberger, Christina; Thürling, Markus; Forsting, Michael; Elsenbruch, Sigrid; Timmann, Dagmar; Gizewski, Elke R
2013-04-01
There is evidence to support that the cerebellum contributes to the neural processing of both emotions and painful stimuli. This could be particularly relevant in conditions associated with chronic abdominal pain, such as the irritable bowel syndrome (IBS), which are often also characterized by affective disturbances. We aimed to test the hypothesis that in IBS, symptoms of anxiety and depression modulate brain activation during visceral stimulation within the cerebellum. We reanalyzed a previous data set from N = 15 female IBS patients and N = 12 healthy women with a specific focus on the cerebellum using advanced normalization methods. Rectal distension-induced brain activation was measured with functional magnetic resonance imaging using non-painful and painful rectal distensions. Symptoms of anxiety and depression, assessed with the Hospital Anxiety and Depression scale, were correlated with cerebellar activation within IBS patients. Within IBS, depression scores were associated with non-painful distension-induced activation in the right cerebellum primarily in Crus II and lobule VIIIb, and additionally in Crus I. Depression scores were also associated with painful distension-induced activation predominantly in vermal lobule V with some extension to the intermediate cerebellum. Anxiety scores correlated significantly with non-painful induced activation in Crus II. Symptoms of anxiety and depression, which are frequently found in chronic pain conditions like IBS, modulate activation during visceral sensory signals not only in cortical and subcortical brain areas but also in the cerebellum.
A Multi-agent Simulation Tool for Micro-scale Contagion Spread Studies
DOE Office of Scientific and Technical Information (OSTI.GOV)
Koch, Daniel B
2016-01-01
Within the disaster preparedness and emergency response community, there is interest in how contagions spread person-to-person at large gatherings and if mitigation strategies can be employed to reduce new infections. A contagion spread simulation module was developed for the Incident Management Preparedness and Coordination Toolkit that allows a user to see how a geographically accurate layout of the gathering space helps or hinders the spread of a contagion. The results can inform mitigation strategies based on changing the physical layout of an event space. A case study was conducted for a particular event to calibrate the underlying simulation model. Thismore » paper presents implementation details of the simulation code that incorporates agent movement and disease propagation. Elements of the case study are presented to show how the tool can be used.« less
3D Indoor Positioning of UAVs with Spread Spectrum Ultrasound and Time-of-Flight Cameras
Aguilera, Teodoro
2017-01-01
This work proposes the use of a hybrid acoustic and optical indoor positioning system for the accurate 3D positioning of Unmanned Aerial Vehicles (UAVs). The acoustic module of this system is based on a Time-Code Division Multiple Access (T-CDMA) scheme, where the sequential emission of five spread spectrum ultrasonic codes is performed to compute the horizontal vehicle position following a 2D multilateration procedure. The optical module is based on a Time-Of-Flight (TOF) camera that provides an initial estimation for the vehicle height. A recursive algorithm programmed on an external computer is then proposed to refine the estimated position. Experimental results show that the proposed system can increase the accuracy of a solely acoustic system by 70–80% in terms of positioning mean square error. PMID:29301211
Blanks, Deidra A.; Buss, Emily; Grose, John H.; Fitzpatrick, Douglas C.; Hall, Joseph W.
2009-01-01
Objectives The present study investigated interaural time discrimination for binaurally mismatched carrier frequencies in listeners with normal hearing. One goal of the investigation was to gain insights into binaural hearing in patients with bilateral cochlear implants, where the coding of interaural time differences may be limited by mismatches in the neural populations receiving stimulation on each side. Design Temporal envelopes were manipulated to present low frequency timing cues to high frequency auditory channels. Carrier frequencies near 4 kHz were amplitude modulated at 128 Hz via multiplication with a half-wave rectified sinusoid, and that modulation was either in-phase across ears or delayed to one ear. Detection thresholds for non-zero interaural time differences were measured for a range of stimulus levels and a range of carrier frequency mismatches. Data were also collected under conditions designed to limit cues based on stimulus spectral spread, including masking and truncation of sidebands associated with modulation. Results Listeners with normal hearing can detect interaural time differences in the face of substantial mismatches in carrier frequency across ears. Conclusions The processing of interaural time differences in listeners with normal hearing is likely based on spread of excitation into binaurally matched auditory channels. Sensitivity to interaural time differences in listeners with cochlear implants may depend upon spread of current that results in the stimulation of neural populations that share common tonotopic space bilaterally. PMID:18596646
Involvement of Cellular Prion Protein in α-Synuclein Transport in Neurons.
Urrea, Laura; Segura-Feliu, Miriam; Masuda-Suzukake, Masami; Hervera, Arnau; Pedraz, Lucas; García Aznar, José Manuel; Vila, Miquel; Samitier, Josep; Torrents, Eduard; Ferrer, Isidro; Gavín, Rosalina; Hagesawa, Masato; Del Río, José Antonio
2018-03-01
The cellular prion protein, encoded by the gene Prnp, has been reported to be a receptor of β-amyloid. Their interaction is mandatory for neurotoxic effects of β-amyloid oligomers. In this study, we aimed to explore whether the cellular prion protein participates in the spreading of α-synuclein. Results demonstrate that Prnp expression is not mandatory for α-synuclein spreading. However, although the pathological spreading of α-synuclein can take place in the absence of Prnp, α-synuclein expanded faster in PrP C -overexpressing mice. In addition, α-synuclein binds strongly on PrP C -expressing cells, suggesting a role in modulating the effect of α-synuclein fibrils.
Hindcasting of Equatorial Spread F Using Seasonal Empirical Models
NASA Astrophysics Data System (ADS)
Aswathy, R. P.; Manju, G.
2018-02-01
The role of gravity waves in modulating equatorial spread F (ESF) day-to-day variability is investigated using ionosonde data at Trivandrum (geographic coordinates, 8.5°N, 77°E; mean geomagnetic latitude -0.3°N) a magnetic equatorial location. A novel empirical model that incorporates the combined effects of electrodynamics and gravity waves in modulating ESF occurrence during autumnal equinox season was presented by Aswathy and Manju (2017). In the present study, the height variations of the requisite gravity wave seed perturbations for ESF are examined for the vernal equinoxes, summer solstices, and winter solstices of different years. Subsequently, the empirical model, incorporating the electrodynamical effects and the gravity wave modulation, valid for each of the seasons is developed. Accordingly, for each season, the threshold curve may be demarcated provided the solar flux index (F10.7) is known. The empirical models are validated using the data for high, moderate, and low solar activity years corresponding to each season. In the next stage, this model is to be fine tuned to facilitate the prediction of ESF well before its onset.
Changes in Soleus H-Reflex Modulation after Treadmill Training in Children with Cerebral Palsy
ERIC Educational Resources Information Center
Hodapp, Maike; Vry, Julia; Mall, Volker; Faist, Michael
2009-01-01
In healthy children, short latency leg muscle reflexes are profoundly modulated throughout the step cycle in a functionally meaningful way and contribute to the electromyographic (EMG) pattern observed during gait. With maturation of the corticospinal tract, the reflex amplitudes are depressed via supraspinal inhibitory mechanisms. In the soleus…
Involvement of Brain-Derived Neurotrophic Factor in Late-Life Depression
Dwivedi, Yogesh
2013-01-01
Brain-derived neurotrophic factor (BDNF), one of the major neurotrophic factors, plays an important role in the maintenance and survival of neurons, synaptic integrity, and synaptic plasticity. Evidence suggests that BDNF is involved in major depression, such that the level of BDNF is decreased in depressed patients and that antidepressants reverse this decrease. Stress, a major factor in depression, also modulates BDNF expression. These studies have led to the proposal of the neurotrophin hypothesis of depression. Late-life depression is associated with disturbances in structural and neural plasticity as well as impairments in cognitive behavior. Stress and aging also play a crucial role in late-life depression. Many recent studies have suggested that not only expression of BDNF is decreased in the serum/plasma of patients with late-life depression, but structural abnormalities in the brain of these patients may be associated with a polymorphism in the BDNF gene, and that there is a relationship between a BDNF polymorphism and antidepressant remission rates. This review provides a critical review of the involvement of BDNF in major depression, in general, and in late-life depression, in particular. PMID:23570887
Modular Multi-Function Multi-Band Airborne Radio System (MFBARS). Volume II. Detailed Report.
1981-06-01
Three Platforms in a Field of Hyperbolic LOP’s.......................... 187 76 Comparison, MFBARS Versus Baseline .......... 190 77 Program Flow Chart...configure, from a set of common modules, a given total CNI capability on specific platforms for a given mission " the ability to take advantage of...X Comm/Nav GPS L-Band; Spread Spectrum Nay X X SEEK TALK UHF Spread; Spectrum Comm X X SINCGARS VHF; Freq. Hop Comm (some platforms ) AFSATCOM UHF
Association of adverse childhood environment and 5-HTTLPR Genotype with late-life depression.
Ritchie, Karen; Jaussent, Isabelle; Stewart, Robert; Dupuy, Anne-Marie; Courtet, Philippe; Ancelin, Marie-Laure; Malafosse, Alain
2009-09-01
Neurobiological and clinical studies suggest that childhood maltreatment may result in functional and structural nervous system changes that predispose the individual to depression. This vulnerability appears to be modulated by a polymorphism in the serotonin gene-linked promoter region (5-HTTLPR). Little is known, however, about the persistence of this vulnerability across the life span, although clinical studies of adult populations suggest that gene-environment interaction may diminish with aging. Depressive symptomatology and adverse and protective childhood events were examined in a population of 942 persons aged 65 years and older, taking into account sociodemographic characteristics and proximal competing causes of depression (widowhood, recent life events, vascular and neurologic disorder, and disability). Subjects were recruited between March 1999 and February 2001 and were diagnosed as depressed if they met 1 of 3 criteria: a diagnosis of major depression on the Mini-International Neuropsychiatric Interview, a score higher than 16 on the Center for Epidemiologic Studies-Depression Scale, or current treatment with an antidepressant. Exposure to traumatic events in childhood doubled the risk of late-life depression and increased the risk of repeated episodes. Not all events were found to be pathogenic; significant risk was associated with excessive sharing of parental problems, poverty or financial difficulties, mental disorder in parents, excessive physical punishment, verbal abuse from parents, humiliation, and mistreatment by an adult outside the family. Interactions were observed between the 5-HTTLPR long (L) allele, poverty, and excessive sharing of parental problems. Certain types of childhood trauma continue to constitute risk factors for depression in old age, outweighing more proximal causes. Gene environment vulnerability interaction is linked in older age to the L-carrying genotype, modulating the effects of general environmental conditions rather than aggressive acts on the individual, perhaps due to increased cardiac reactivity. Copyright 2009 Physicians Postgraduate Press, Inc.
Shuttleworth, C William; Kirov, Sergei A; Ayata, Cenk; Hinzman, Jason M; Foreman, Brandon; Andrew, R David; Boutelle, Martyn G; Brennan, KC; Carlson, Andrew P; Dahlem, Markus A; Drenckhahn, Christoph; Dohmen, Christian; Fabricius, Martin; Farkas, Eszter; Feuerstein, Delphine; Graf, Rudolf; Helbok, Raimund; Lauritzen, Martin; Major, Sebastian; Oliveira-Ferreira, Ana I; Richter, Frank; Rosenthal, Eric S; Sakowitz, Oliver W; Sánchez-Porras, Renán; Santos, Edgar; Schöll, Michael; Strong, Anthony J; Urbach, Anja; Westover, M Brandon; Winkler, Maren KL; Witte, Otto W; Woitzik, Johannes; Dreier, Jens P
2016-01-01
A modern understanding of how cerebral cortical lesions develop after acute brain injury is based on Aristides Leão’s historic discoveries of spreading depression and asphyxial/anoxic depolarization. Treated as separate entities for decades, we now appreciate that these events define a continuum of spreading mass depolarizations, a concept that is central to understanding their pathologic effects. Within minutes of acute severe ischemia, the onset of persistent depolarization triggers the breakdown of ion homeostasis and development of cytotoxic edema. These persistent changes are diagnosed as diffusion restriction in magnetic resonance imaging and define the ischemic core. In delayed lesion growth, transient spreading depolarizations arise spontaneously in the ischemic penumbra and induce further persistent depolarization and excitotoxic damage, progressively expanding the ischemic core. The causal role of these waves in lesion development has been proven by real-time monitoring of electrophysiology, blood flow, and cytotoxic edema. The spreading depolarization continuum further applies to other models of acute cortical lesions, suggesting that it is a universal principle of cortical lesion development. These pathophysiologic concepts establish a working hypothesis for translation to human disease, where complex patterns of depolarizations are observed in acute brain injury and appear to mediate and signal ongoing secondary damage. PMID:27328690
Severns, Paul M; Liston, Aaron; Wilson, Mark V
2011-01-01
Small population size, genetic diversity, and spatial patterns of vegetative spread are important aspects to consider when managing populations of rare clonal plant species. We used 5 variable nuclear simple sequence repeat nDNA loci to determine the extent of genet rhizome spread, examine the possibility of very small population sizes, and project how Bombus spp. (bumblebee) foraging may impact selfing (through geitonogamy) for a threatened lupine (Lupinus oreganus Heller) that sprawls through nonadventitious rhizomes. Genotyping identified 1 genet (27 × 13 m) that dominated about 30% of a study site, whereas 15 genets spread a maximum average distance of about 5.5 m (range 1.6 -27.1 m) and appeared to be well integrated with intervening genets. We found unexpectedly high genotype diversity, no evidence of a recent genetic bottleneck, and 5 of 6 patches had mean fixation index values that were near Hardy-Weinberg Equilibrium expectations. If the median maximum Bombus foraging distance observed in lupine patches (1.2 m) occurred within genotyped populations, a typical foraging flight would have >80% chance of occurring between different genets. Our study demonstrates that inferences associated with clonality, small population size, and inbreeding depression should be directly evaluated for rare vegetatively spreading plants.
Thakare, Vishnu N; Dhakane, Valmik D; Patel, Bhoomika M
2017-04-01
Protocatechuic acid ethyl ester (PCA), a phenolic compound, exhibits neuroprotective effects through improving endogenous antioxidant enzymatic and nonezymatic system. Based on the role of oxidative stress in modulating depressive disorders and the relationship between neuroprotective and antioxidant potential of PCA, we studied if its antidepressant like effect is associated by modulation of cerebral cortex and hippocampal antioxidant alterations. Acute restraint stress (ARS) is known to induce depressive like behavior by neuronal oxidative damage in mice. Swiss albino mice subjected to ARS exhibited an increased immobility time in forced swim test, elevated serum corticosterone and produced oxidative stress dependent alterations in cerebral cortex and hippocampus mainly increased thiobarbituric acid reactive substances and reduced catalase (CAT), superoxide dismutase (SOD) activity. Treatment with PCA was able to prevent stress induced immobility time in forced swim test without altering locomotor activity in mice. Further, PCA treatment attenuated the elevation of serum corticosterone, lipid peroxidation and restored enzymatic antioxidants in cerebral cortex and hippocampus in ARS mice. Altogether, the experimental findings demonstrate the notion that PCA exhibit antidepressant like activity might be related, at least in part, to its capability of modulating antioxidant defense system and oxidative damage induced by ARS in cerebral cortex and hippocampus in mice and thus maintain the pro-/anti-oxidative homeostasis.
dos Santos Palazzo, L; Humberto Béria, J; Alonso-Fernández, F; Tomasi, E
2001-11-15
To investigate the prevalence of depression and its relationship to the reason for the consultation and to the medical diagnosis. Descriptive, cross-sectional design. Primary care units of a community in Brazil. Individuals between 13 and 19 years old, who attended 10 primary care units to consult with a non-psychiatric doctor between October 1997 and January 1998 (n = 463). The CET-DE (Alonso-Fernández, 1986) was used to measure depression, jointly with a questionnaire for evaluating social and demographic details and data pertinent to the consultation. Prevalence ran at 26.5% (95% CI: 22.6-30.4%). 99.2% cases of depression had not been identified. Complaints were spread over the somatic field (61.1%), or were sex-related (49.5%), mainly pregnancy (31.7%), especially among the cases of depression (p < 0.001). There were few psychiatric-social complaints (1.5%). Diagnoses often coincided with complaints: 59.9% somatic, 38.4% sex-related (pregnancy = 21.6%) and 1.7% psychiatric-social. Adolescent depression is common in primary care, but is not usually identified. The reason for this may be the kind of depression, which is usually light or focused on just one dimension of human vitality; the doctors tendency to centre his/her attention on the complaint without broadening the clinical spectrum; or even because the adolescent expresses his/her emotional problems poorly, which often contributes to the depression not being diagnosed.
Teacher Unions, (Neo) Liberalism and the State: The Perth County Conspiracy of 1885
ERIC Educational Resources Information Center
Smaller, Harry
2004-01-01
In 1885, following a period of severe economic depression and social unrest in colonial Canada, state teachers in rural Perth County, Ontario met and formed the nucleus of what could clearly be described as a teachers' union. The idea spread quickly, and within six months the founding convention of a province-wide union was held in Toronto.…
Interpersonal Psychotherapy: Past, Present and Future
Markowitz, John C.; Weissman, Myrna M.
2012-01-01
The authors briefly describe the origins, theory, and development of interpersonal psychotherapy: its roots in clinical outcome research, its spread from major depression to other psychiatric disorders and its increasing dissemination as an empirically validated clinical intervention included in treatment guidelines. They attempt to forecast research, organizational and training issues the growing interpersonal psychotherapy community may face in the future. PMID:22331561
In vivo cerebral blood flow autoregulation studies using rheoencephalography
NASA Astrophysics Data System (ADS)
Bodo, M.; Pearce, F.; Garcia, A.; Van Albert, S.; Settle, T.; Szebeni, J.; Baranyi, L.; Hartings, J.; Armonda, R.
2010-04-01
Acute management of patients with traumatic brain/blast injury is a challenge. To minimize secondary injury and improve outcome, it is critical to detect neurological deterioration early, when it is potentially reversible. One potential monitoring method is cerebral electrical impedance (rheoencephalography-REG) because of its non-invasiveness and good time resolution. Reported here are the results of cerebral blood flow (CBF) manipulations comparing electroencephalogram (EEG) with REG (both intra-cerebral) and measuring with surface and skull REG electrodes. Our hypothesis was that REG would reflect spreading depression and CBF autoregulation. Animal experiments were performed using one rat (four trials with intracerebral electrodes), monkeys (n=8, with surface electrodes) and pigs (n = 24 pigs with skull electrodes; 57 trials, 19 types of liposomes). Challenges included intracranial pressure (ICP) elevation, liposome infusion, and hemorrhage. Data were stored on a PC and evaluated off line. CBF autoregulation was evaluated both by visual inspection and by a Matlab script. These studies confirmed that REG reflects CBF autoregulation and that REG is useful for detecting spreading depression (SD), vasospasm and the lower limit of CBF autoregulation. These findings have clinical relevance for use in noninvasive neuro-monitoring in the neurosurgery intensive care and during transportation of patients with brain injury.
Electrophysiological and optical changes in slices of rat hippocampus during spreading depression.
Snow, R W; Taylor, C P; Dudek, F E
1983-09-01
Spreading depression (SD) was studied with intracellular and extracellular recordings and with photometry in slices of rat hippocampus. Repetitive electrical stimulation could initiate SD in either normal medium or in low-Ca2+ medium containing Mn2+, especially during transient hypoxia. The extracellular voltage near CA1 pyramidal somata and dendrites became negative by approximately 18 mV during SD. This negativity peaked more slowly in low-Ca2+ medium containing Mn2+. The wave of negativity propagated across the slice in both media at approximately 6 mm/min. Input resistance of pyramidal neurons became undetectable during SD, and differential voltage recording between neurons and adjacent extracellular space demonstrated that transmembrane potential approached zero. Slices became more opaque during SD. Photometry revealed approximately 10% increase in reflectance and a similar decrease in transmittance of white light, which occurred with a time course similar to the extracellularly recorded voltage shift. These data support the hypothesis that SD represents a large increase in membrane permeability associated with substantial movements of water. The persistance of SD in a bathing solution that blocked electrically evoked postsynaptic potentials suggests that the contribution of synaptic transmitter release to the propagation of SD should be reappraised.
NASA Astrophysics Data System (ADS)
Ding, Hongxia; Chen, Shangbin; Zeng, Shuai; Zeng, Shaoqun; Liu, Qian; Luo, Qingming
2008-12-01
Spreading depression (SD) shows as propagating suppression of electrical activity, which relates with migraine and focal cerebral ischaemia. The putative mechanism of SD is the reaction-diffusion hypothesis involving potassium ions. In part inspired by optical imaging of two SD waves collision, we aimed to show the merged and large wavefront but not annihilation during collision by experimental and computational study. This paper modified Reggia et al established bistable equation with recovery to compute and visualize SD. Firstly, the media tissue of SD was assumed as one-dimensional continuum. The Crank-Nicholson method was used to solve the modified equations with recovery term. Then, the computation results were extended to two-dimensional space by symmetry. One individual SD was visualized as a concentric wave initiating from the stimulation point. The mergence but not annihilation of two colliding waves of SD was demonstrated. In addition, the dynamics of SD depending on the parameters was studied and presented. The results allied SD with the emerging concepts of volume transmission. This work not only supplied a paradigm to compute and visualize SD but also became a tool to explore the mechanisms of SD.
Computational model of cerebral blood flow redistribution during cortical spreading depression
NASA Astrophysics Data System (ADS)
Verisokin, Andrey Y.; Verveyko, Darya V.; Postnov, Dmitry E.
2016-04-01
In recent decades modelling studies on cortical spreading depression (CSD) and migraine waves successfully contributed to formation of modern view on these fundamental phenomena of brain physiology. However, due to the extreme complexity of object under study (brain cortex) and the diversity of involved physiological pathways, the development of new mathematical models of CSD is still a very relevant and challenging research problem. In our study we follow the functional modelling approach aimed to map the action of known physiological pathways to the specific nonlinear mechanisms that govern formation and evolution of CSD wave patterns. Specifically, we address the role of cerebral blood flow (CBF) redistribution that is caused by excessive neuronal activity by means of neurovascular coupling and mediates a spatial pattern of oxygen and glucose delivery. This in turn changes the local metabolic status of neural tissue. To build the model we simplify the web of known cell-to-cell interactions within a neurovascular unit by selecting the most relevant ones, such as local neuron-induced elevation of extracellular potassium concentration and biphasic response of arteriole radius. We propose the lumped description of distance-dependent hemodynamic coupling that fits the most recent experimental findings.
Huang, Qin; Liu, Rui; Gui, Shen; Lu, Jinling; Li, Pengcheng
2018-03-07
Cortical spreading depression (CSD), a propagation wave of transient neuronal and glial depolarization followed by suppression of spontaneous brain activity, has been hypothesized to be the underlying mechanism of migraine aura and triggers the headache attack. Evidence from various animal models accumulates since its first discovery in 1944 and provides support for this hypothesis. In this paper, alterations of bilateral cortical responses are investigated in a mice migrainous model of CSD using voltage-sensitive dye imaging under hindlimb and cortical stimulation. After CSD induction in the right hemisphere, bilateral sensory responses evoked by left hindlimb stimulation dramatically decreases, whereas right hindlimb stimulation can still activate bilateral responses with an increased response of the left hemisphere and a well-preserved response of the right hemisphere. In addition, cortical neural excitability remains after CSD assessed by direct activation of the right hemisphere in spite of the sensory deficit under contralateral hindlimb stimulation. These results depict the sensory disturbance of bilateral hemispheres after CSD, which may be helpful in understanding how sensory disturbance occur during migraine aura. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Camfield, David A.; Mills, Jessica; Kornfeld, Emma J.; Croft, Rodney J.
2016-01-01
Recent studies have suggested that classical conditioning may be capable of modulating early sensory processing in the human brain, and that there may be differences in the magnitude of the conditioned changes for individuals with major depressive disorder. The effect of conditioning on the N170 event-related potential was investigated using neutral faces as conditioned stimuli (CS+) and emotional imagery and acoustic startle as unconditioned stimuli (UCS). In the first experiment, electroencephalogram was recorded from 24 undergraduate students (M = 21.07 years, SD = 3.38 years) under the following conditions: (i) CS+/aversive imagery, (ii) CS+/aversive imagery and acoustic startle, (iii) CS+/acoustic startle, and (iv) CS+/pleasant imagery. The amplitude of the N170 was enhanced following conditioning with aversive imagery as well as acoustic startle. In the second experiment, 26 healthy control participants were tested (17 females and 9 males, age M = 25.97 years, SD = 9.42) together with 18 depressed participants (13 females and 5 males, age M = 23.26 years, SD = 4.01) and three conditions were used: CS+/aversive imagery, CS+/pleasant imagery, and CS-. N170 amplitude at P7 was increased for the CS+/aversive condition in comparison to CS- in the conditioning blocks versus baseline. No differences between depressed and healthy participants were found. Across both experiments, evaluative conditioning was absent. It was concluded that aversive UCS are capable of modulating early sensory processing of faces, although further research is also warranted in regards to positive UCS. PMID:27445773
Inflammasome signaling affects anxiety- and depressive-like behavior and gut microbiome composition
Wong, M-L; Inserra, A; Lewis, M D; Mastronardi, C A; Leong, L; Choo, J; Kentish, S; Xie, P; Morrison, M; Wesselingh, S L; Rogers, G B; Licinio, J
2016-01-01
The inflammasome is hypothesized to be a key mediator of the response to physiological and psychological stressors, and its dysregulation may be implicated in major depressive disorder. Inflammasome activation causes the maturation of caspase-1 and activation of interleukin (IL)-1β and IL-18, two proinflammatory cytokines involved in neuroimmunomodulation, neuroinflammation and neurodegeneration. In this study, C57BL/6 mice with genetic deficiency or pharmacological inhibition of caspase-1 were screened for anxiety- and depressive-like behaviors, and locomotion at baseline and after chronic stress. We found that genetic deficiency of caspase-1 decreased depressive- and anxiety-like behaviors, and conversely increased locomotor activity and skills. Caspase-1 deficiency also prevented the exacerbation of depressive-like behaviors following chronic stress. Furthermore, pharmacological caspase-1 antagonism with minocycline ameliorated stress-induced depressive-like behavior in wild-type mice. Interestingly, chronic stress or pharmacological inhibition of caspase-1 per se altered the fecal microbiome in a very similar manner. When stressed mice were treated with minocycline, the observed gut microbiota changes included increase in relative abundance of Akkermansia spp. and Blautia spp., which are compatible with beneficial effects of attenuated inflammation and rebalance of gut microbiota, respectively, and the increment in Lachnospiracea abundance was consistent with microbiota changes of caspase-1 deficiency. Our results suggest that the protective effect of caspase-1 inhibition involves the modulation of the relationship between stress and gut microbiota composition, and establishes the basis for a gut microbiota–inflammasome–brain axis, whereby the gut microbiota via inflammasome signaling modulate pathways that will alter brain function, and affect depressive- and anxiety-like behaviors. Our data also suggest that further elucidation of the gut microbiota–inflammasome–brain axis may offer novel therapeutic targets for psychiatric disorders. PMID:27090302
Inflammasome signaling affects anxiety- and depressive-like behavior and gut microbiome composition.
Wong, M-L; Inserra, A; Lewis, M D; Mastronardi, C A; Leong, L; Choo, J; Kentish, S; Xie, P; Morrison, M; Wesselingh, S L; Rogers, G B; Licinio, J
2016-06-01
The inflammasome is hypothesized to be a key mediator of the response to physiological and psychological stressors, and its dysregulation may be implicated in major depressive disorder. Inflammasome activation causes the maturation of caspase-1 and activation of interleukin (IL)-1β and IL-18, two proinflammatory cytokines involved in neuroimmunomodulation, neuroinflammation and neurodegeneration. In this study, C57BL/6 mice with genetic deficiency or pharmacological inhibition of caspase-1 were screened for anxiety- and depressive-like behaviors, and locomotion at baseline and after chronic stress. We found that genetic deficiency of caspase-1 decreased depressive- and anxiety-like behaviors, and conversely increased locomotor activity and skills. Caspase-1 deficiency also prevented the exacerbation of depressive-like behaviors following chronic stress. Furthermore, pharmacological caspase-1 antagonism with minocycline ameliorated stress-induced depressive-like behavior in wild-type mice. Interestingly, chronic stress or pharmacological inhibition of caspase-1 per se altered the fecal microbiome in a very similar manner. When stressed mice were treated with minocycline, the observed gut microbiota changes included increase in relative abundance of Akkermansia spp. and Blautia spp., which are compatible with beneficial effects of attenuated inflammation and rebalance of gut microbiota, respectively, and the increment in Lachnospiracea abundance was consistent with microbiota changes of caspase-1 deficiency. Our results suggest that the protective effect of caspase-1 inhibition involves the modulation of the relationship between stress and gut microbiota composition, and establishes the basis for a gut microbiota-inflammasome-brain axis, whereby the gut microbiota via inflammasome signaling modulate pathways that will alter brain function, and affect depressive- and anxiety-like behaviors. Our data also suggest that further elucidation of the gut microbiota-inflammasome-brain axis may offer novel therapeutic targets for psychiatric disorders.
Designing a range modulator wheel to spread-out the Bragg peak for a passive proton therapy facility
NASA Astrophysics Data System (ADS)
Jia, S. Bijan; Romano, F.; Cirrone, Giuseppe A. P.; Cuttone, G.; Hadizadeh, M. H.; Mowlavi, A. A.; Raffaele, L.
2016-01-01
In proton beam therapy, a Spread-Out Bragg peak (SOBP) is used to establish a uniform dose distribution in the target volume. In order to create a SOBP, several Bragg peaks of different ranges, corresponding to different entrance energies, with certain intensities (weights) should be combined each other. In a passive beam scattering system, the beam is usually extracted from a cyclotron at a constant energy throughout a treatment. Therefore, a SOBP is produced by a range modulator wheel, which is basically a rotating wheel with steps of variable thicknesses, or by using the ridge filters. In this study, we used the Geant4 toolkit to simulate a typical passive scattering beam line. In particular, the CATANA transport beam line of INFN Laboratori Nazionali del Sud (LNS) in Catania has been reproduced in this work. Some initial properties of the entrance beam have been checked by benchmarking simulations with experimental data. A class dedicated to the simulation of the wheel modulators has been implemented. It has been designed in order to be easily modified for simulating any desired modulator wheel and, hence, any suitable beam modulation. By using some auxiliary range-shifters, a set of pristine Bragg peaks was obtained from the simulations. A mathematical algorithm was developed, using the simulated pristine dose profiles as its input, to calculate the weight of each pristine peak, reproduce the SOBP, and finally generate a flat dose distribution. Therefore, once the designed modulator has been realized, it has been tested at CATANA facility, comparing the experimental data with the simulation results.
Impinging Water Droplets on Inclined Glass Surfaces
DOE Office of Scientific and Technical Information (OSTI.GOV)
Armijo, Kenneth Miguel; Lance, Blake; Ho, Clifford K.
Multiphase computational models and tests of falling water droplets on inclined glass surfaces were developed to investigate the physics of impingement and potential of these droplets to self-clean glass surfaces for photovoltaic modules and heliostats. A multiphase volume-of-fluid model was developed in ANSYS Fluent to simulate the impinging droplets. The simulations considered different droplet sizes (1 mm and 3 mm), tilt angles (0°, 10°, and 45°), droplet velocities (1 m/s and 3 m/s), and wetting characteristics (wetting=47° contact angle and non-wetting = 93° contact angle). Results showed that the spread factor (maximum droplet diameter during impact divided by the initialmore » droplet diameter) decreased with increasing inclination angle due to the reduced normal force on the surface. The hydrophilic surface yielded greater spread factors than the hydrophobic surface in all cases. With regard to impact forces, the greater surface tilt angles yielded lower normal forces, but higher shear forces. Experiments showed that the experimentally observed spread factor (maximum droplet diameter during impact divided by the initial droplet diameter) was significantly larger than the simulated spread factor. Observed spread factors were on the order of 5 - 6 for droplet velocities of ~3 m/s, whereas the simulated spread factors were on the order of 2. Droplets were observed to be mobile following impact only for the cases with 45° tilt angle, which matched the simulations. An interesting phenomenon that was observed was that shortly after being released from the nozzle, the water droplet oscillated (like a trampoline) due to the "snapback" caused by the surface tension of the water droplet being released from the nozzle. This oscillation impacted the velocity immediately after the release. Future work should evaluate the impact of parameters such as tilt angle and surface wettability on the impact of particle/soiling uptake and removal to investigate ways that photovoltaic modules and heliostats can be designed to maximize self-cleaning.« less
Burnout does not help predict depression among French school teachers.
Bianchi, Renzo; Schonfeld, Irvin Sam; Laurent, Eric
2015-11-01
Burnout has been viewed as a phase in the development of depression. However, supportive research is scarce. We examined whether burnout predicted depression among French school teachers. We conducted a 2-wave, 21-month study involving 627 teachers (73% female) working in French primary and secondary schools. Burnout was assessed with the Maslach Burnout Inventory and depression with the 9-item depression module of the Patient Health Questionnaire (PHQ-9). The PHQ-9 grades depressive symptom severity and provides a provisional diagnosis of major depression. Depression was treated both as a continuous and categorical variable using linear and logistic regression analyses. We controlled for gender, age, and length of employment. Controlling for baseline depressive symptoms, linear regression analysis showed that burnout symptoms at time 1 (T1) did not predict depressive symptoms at time 2 (T2). Baseline depressive symptoms accounted for about 88% of the association between T1 burnout and T2 depressive symptoms. Only baseline depressive symptoms predicted depressive symptoms at follow-up. Similarly, logistic regression analysis revealed that burnout symptoms at T1 did not predict incident cases of major depression at T2 when depressive symptoms at T1 were included in the predictive model. Only baseline depressive symptoms predicted cases of major depression at follow-up. This study does not support the view that burnout is a phase in the development of depression. Assessing burnout symptoms in addition to "classical" depressive symptoms may not always improve our ability to predict future depression.
Beyond network structure: How heterogeneous susceptibility modulates the spread of epidemics.
Smilkov, Daniel; Hidalgo, Cesar A; Kocarev, Ljupco
2014-04-25
The compartmental models used to study epidemic spreading often assume the same susceptibility for all individuals, and are therefore, agnostic about the effects that differences in susceptibility can have on epidemic spreading. Here we show that-for the SIS model-differential susceptibility can make networks more vulnerable to the spread of diseases when the correlation between a node's degree and susceptibility are positive, and less vulnerable when this correlation is negative. Moreover, we show that networks become more likely to contain a pocket of infection when individuals are more likely to connect with others that have similar susceptibility (the network is segregated). These results show that the failure to include differential susceptibility to epidemic models can lead to a systematic over/under estimation of fundamental epidemic parameters when the structure of the networks is not independent from the susceptibility of the nodes or when there are correlations between the susceptibility of connected individuals.
Methods and apparatuses using filter banks for multi-carrier spread-spectrum signals
Moradi, Hussein; Farhang, Behrouz; Kutsche, Carl A
2014-10-14
A transmitter includes a synthesis filter bank to spread a data symbol to a plurality of frequencies by encoding the data symbol on each frequency, apply a common pulse-shaping filter, and apply gains to the frequencies such that a power level of each frequency is less than a noise level of other communication signals within the spectrum. Each frequency is modulated onto a different evenly spaced subcarrier. A demodulator in a receiver converts a radio frequency input to a spread-spectrum signal in a baseband. A matched filter filters the spread-spectrum signal with a common filter having characteristics matched to the synthesis filter bank in the transmitter by filtering each frequency to generate a sequence of narrow pulses. A carrier recovery unit generates control signals responsive to the sequence of narrow pulses suitable for generating a phase-locked loop between the demodulator, the matched filter, and the carrier recovery unit.
Methods and apparatuses using filter banks for multi-carrier spread-spectrum signals
Moradi, Hussein; Farhang, Behrouz; Kutsche, Carl A
2014-05-20
A transmitter includes a synthesis filter bank to spread a data symbol to a plurality of frequencies by encoding the data symbol on each frequency, apply a common pulse-shaping filter, and apply gains to the frequencies such that a power level of each frequency is less than a noise level of other communication signals within the spectrum. Each frequency is modulated onto a different evenly spaced subcarrier. A demodulator in a receiver converts a radio frequency input to a spread-spectrum signal in a baseband. A matched filter filters the spread-spectrum signal with a common filter having characteristics matched to the synthesis filter bank in the transmitter by filtering each frequency to generate a sequence of narrow pulses. A carrier recovery unit generates control signals responsive to the sequence of narrow pulses suitable for generating a phase-locked loop between the demodulator, the matched filter, and the carrier recovery unit.
Beyond network structure: How heterogeneous susceptibility modulates the spread of epidemics
Smilkov, Daniel; Hidalgo, Cesar A.; Kocarev, Ljupco
2014-01-01
The compartmental models used to study epidemic spreading often assume the same susceptibility for all individuals, and are therefore, agnostic about the effects that differences in susceptibility can have on epidemic spreading. Here we show that–for the SIS model–differential susceptibility can make networks more vulnerable to the spread of diseases when the correlation between a node's degree and susceptibility are positive, and less vulnerable when this correlation is negative. Moreover, we show that networks become more likely to contain a pocket of infection when individuals are more likely to connect with others that have similar susceptibility (the network is segregated). These results show that the failure to include differential susceptibility to epidemic models can lead to a systematic over/under estimation of fundamental epidemic parameters when the structure of the networks is not independent from the susceptibility of the nodes or when there are correlations between the susceptibility of connected individuals. PMID:24762621
An in vivo evaluation of the antiseizure activity and acute neurotoxicity of agmatine.
Bence, Aimee K; Worthen, David R; Stables, James P; Crooks, Peter A
2003-02-01
Agmatine, an endogenous cationic amine, exerts a wide range of biological effects, including modulation of glutamate-activated N-methyl-D-aspartate (NMDA) receptor function in the central nervous system (CNS). Since glutamate and the NMDA receptor have been implicated in the initiation and spread of seizure activity, the capacity of agmatine to inhibit seizure spread was evaluated in vivo. Orally administered agmatine (30 mg/kg) protected against maximal electroshock seizure (MES)-induced seizure spread in rats as rapidly as 15 min and for as long as 6 h after administration. Inhibition of MES-induced seizure spread was also observed when agmatine was administered intraperitoneally. Agmatine's antiseizure activity did not appear to be dose-dependent. An in vivo neurotoxicity screen indicated that agmatine was devoid of any acute neurological toxicity at the doses tested. These preliminary data suggest that agmatine has promising anticonvulsant activity.
Everaert, Jonas; Grahek, Ivan; Koster, Ernst H W
2017-06-01
Deficient cognitive control over emotional material and cognitive biases are important mechanisms underlying depression, but the interplay between these emotionally distorted cognitive processes in relation to depressive symptoms is not well understood. This study investigated the relations among deficient cognitive control of emotional information (i.e. inhibition, shifting, and updating difficulties), cognitive biases (i.e. negative attention and interpretation biases), and depressive symptoms. Theory-driven indirect effect models were constructed, hypothesising that deficient cognitive control over emotional material predicts depressive symptoms through negative attention and interpretation biases. Bootstrapping analyses demonstrated that deficient inhibitory control over negative material was related to negative attention bias which in turn predicted a congruent bias in interpretation and subsequently depressive symptoms. Both shifting and updating impairments in response to negative material had an indirect effect on depression severity through negative interpretation bias. No evidence was found for direct effects of deficient cognitive control over emotional material on depressive symptoms. These findings may help to formulate an integrated understanding of the cognitive foundations of depressive symptoms.
Kaplan, Peter S.; Danko, Christina M.; Kalinka, Christina J.; Cejka, Anna M.
2014-01-01
Infants of mothers who varied in symptoms of depression were tested at 4 and 12 months of age for their ability to associate a segment of an unfamiliar non-depressed mother’s infant-directed speech (IDS) with a face. At 4 months, all infants learned the voice-face association. At 12 months, despite the fact that none of the mothers were still clinically depressed, infants of mothers with chronically elevated self-reported depressive symptoms, and infants of mothers with elevated self-reported depressive symptoms at 4 months but not 12 months, on average did not learn the association. For infants of mothers diagnosed with depression in remission, learning at 12 months was negatively correlated with the postpartum duration of the mother’s depressive episode. At neither age did extent of pitch modulation in the IDS segments correlate with infant learning. However, learning scores at 12 months correlated significantly with concurrent maternal reports of infant receptive language development. The roles of the duration and timing of maternal depressive symptoms are discussed. PMID:22721737
Aquaporin-4 Regulates the Velocity and Frequency of Cortical Spreading Depression in Mice
Yao, Xiaoming; Smith, Alex J.; Jin, Byung-Ju; Zador, Zsolt; Manley, Geoffrey T.; Verkman, A.S.
2016-01-01
The astrocyte water channel aquaporin-4 (AQP4) regulates extracellular space (ECS) K+ concentration ([K+]e) and volume dynamics following neuronal activation. Here, we investigated how AQP4-mediated changes in [K+]e and ECS volume affect the velocity, frequency and amplitude of cortical spreading depression (CSD) depolarizations produced by surface KCl application in wild-type (AQP4+/+) and AQP4-deficient (AQP4−/−) mice. Contrary to initial expectations, both the velocity and frequency of CSD were significantly reduced in AQP4−/− mice when compared to AQP4+/+ mice, by 22% and 32%, respectively. Measurement of [K+]e with K+-selective microelectrodes demonstrated an increase to ~35 mM during spreading depolarizations in both AQP4+/+ and AQP4−/− mice, but the rates of [K+]e increase (3.5 vs. 1.5 mM/s) and reuptake (t1/2 33 vs. 61 s) were significantly reduced in AQP4−/− mice. ECS volume fraction measured by trimethylammonium iontophoresis was greatly reduced during depolarizations from 0.18 to 0.053 in AQP4+/+ mice, and 0.23 to 0.063 in AQP4−/− mice. Analysis of the experimental data using a mathematical model of CSD propagation suggested that the reduced velocity of CSD depolarizations in AQP4−/− mice was primarily a consequence of the slowed increase in [K+]e during neuronal depolarization. These results demonstrate that AQP4 effects on [K+]e and ECS volume dynamics accelerate CSD propagation. PMID:25944186
Cell swelling increases the severity of spreading depression in Locusta migratoria
Chin, Brittany; Witiuk, Kelsey L. M.
2015-01-01
Progressive accumulation of extracellular potassium ions can trigger propagating waves of spreading depression (SD), which are associated with dramatic increases in extracellular potassium levels ([K+]o) and arrest in neural activity. In the central nervous system the restricted nature of the extracellular compartment creates an environment that is vulnerable to disturbances in ionic homeostasis. Here we investigate how changes in the size of the extracellular space induced by alterations in extracellular osmolarity affect locust SD. We found that hypotonic exposure increased susceptibility to experimentally induced SD evidenced by a decrease in the latency to onset and period between individual events. Hypertonic exposure was observed to delay the onset of SD or prevent the occurrence altogether. Additionally, the magnitude of extracellular K+ concentration ([K+]o) disturbance during individual SD events was significantly greater and they were observed to propagate more quickly under hypotonic conditions compared with hypertonic conditions. Our results are consistent with a conclusion that hypotonic exposure reduced the size of the extracellular compartment by causing cell swelling and thus facilitated the accumulation of K+ ions. Lastly, we found that pharmacologically reducing the accumulation of extracellular K+ using the K+ channel blocker tetraethylammonium slowed the rate of SD propagation while increasing [K+]o through inhibition of the Na-K-2Cl cotransporter increased propagation rates. Overall our findings indicate that treatments or conditions that act to reduce the accumulation of extracellular K+ help to protect against the development of SD and attenuate the spread of ionic disturbance adding to the evidence that diffusion of K+ is a leading event during locust SD. PMID:26378209
Characterization of pain, disability, and psychological burden in Marfan syndrome.
Speed, Traci J; Mathur, Vani A; Hand, Matthew; Christensen, Bryt; Sponseller, Paul D; Williams, Kayode A; Campbell, Claudia M
2017-02-01
The clinical manifestations of Marfan syndrome frequently cause pain. This study aimed to characterize pain in a cohort of adults with Marfan syndrome and investigate demographic, physical, and psychological factors associated with pain and pain-related disability. Two hundred and forty-five participants (73% female, 89% non-Hispanic white, 90% North American) completed an online questionnaire assessing clinical features of Marfan syndrome, pain severity, pain-related disability, physical and mental health, depressive symptoms, pain catastrophizing, and insomnia. Eighty-nine percent of respondents reported having pain with 28% of individuals reporting pain as a presenting symptom of Marfan syndrome. Almost half of individuals reported that pain has spread from its initial site. Participants in our study reported poor physical and mental health functioning, moderate pain-related disability, and mild levels of depressive symptoms, sleep disturbances, and pain catastrophizing. Those who identified pain as an initial symptom of Marfan syndrome and those who reported that pain had spread from its initial site reported greater psychological burden compared with those without pain as an initial symptom or pain spreading. Physical health is the largest predictor of pain severity and pain-related disability. While pain catastrophizing and worse mental health functioning are significant correlates of pain severity and pain-related disability, respectively. Pain is a significant and persistent problem in Marfan syndrome and is associated with profound disability and psychological burden. Further studies are indicated to better characterize the directionality of pain, pain-related disability, and psychological burden in Marfan syndrome. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Kwangju, K-57, Korea. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.
1974-03-06
JtTHER I 5fU -17 o CLSS HOURS (L S T. SPEED Mi..EAN (KNTS) 1 -3 4 6 7. 10 11 16 17 - 21 22 - 27 28 33 34 - 40 41 47 48- 55 56 % WIND DIR. S _ _ PEED E .3...the summary consists of a bivariate percentage frequency distribution of wet-bulb depression in 17 classes spread horizontally; by 2-degree intervals...AC 4)25f. K4{bNC() ILIA K-57 3-59,A 4 .72 ALL N STATION NAME YEARS., PArF I ~R ALL-- T5 L .T. WET BULB TEMPERATURE DEPRESSION (F) I_ TOTAL TOTAL (F
Progesterone After Estradiol Modulates Shuttle-Cage Escape by Facilitating Volition
Mayeaux, Darryl J.; Tandle, Sarah M.; Cilano, Sean M.; Fitzharris, Matthew J.
2015-01-01
In animal models of depression, depression is defined as performance on a learning task. That task is typically escaping a mild electric shock in a shuttle cage by moving from one side of the cage to the other. Ovarian hormones influence learning in other kinds of tasks, and these hormones are associated with depressive symptoms in humans. The role of these hormones in shuttle-cage escape learning, however, is less clear. This study manipulated estradiol and progesterone in ovariectomized female rats to examine their performance in shuttle-cage escape learning without intentionally inducing a depressive-like state. Progesterone, not estradiol, within four hours of testing affected latencies to escape. The improvement produced by progesterone was in the decision to act, not in the speed of learning or speed of escaping. This parallels depression in humans in that depressed people are slower in volition, in their decisions to take action. PMID:26823653
Depressive symptoms, antidepressant medication use, and insulin resistance: the PPP-Botnia Study.
Pyykkönen, Antti-Jussi; Räikkönen, Katri; Tuomi, Tiinamaija; Eriksson, Johan G; Groop, Leif; Isomaa, Bo
2011-12-01
Although insulin resistance (IR) may underlie associations between depressive symptoms and diabetes, previous findings have been contradictory. We examined whether depressive symptoms associate with IR and insulin secretion, and, additionally, whether antidepressant medication use may modulate such associations. A total of 4,419 individuals underwent an oral glucose tolerance test (OGTT). Participants with previously or newly diagnosed diabetes are excluded from this sample. The homeostasis model assessment of IR (HOMA-IR) and corrected insulin response (CIR) were calculated. Depressive symptoms and antidepressant medication use were self-reported. After controlling for confounding factors, depressive symptoms were associated with higher fasting and 30-min insulin during the OGTT and higher HOMA-IR but not CIR. Antidepressant medication use failed to modify these associations. Depressive symptoms are associated with IR but not with changes in insulin response when corrected for IR in individuals without previously or newly diagnosed diabetes.
Structure of Kinetic Alfvén Waves of Small Transverse Scale
NASA Astrophysics Data System (ADS)
Morales, G. J.; Maggs, J. E.
1996-11-01
This analytical study illustrates the spatial pattern of kinetic Alfvén waves excited by a current-modulating disk whose dimension R transverse to the confining magnetic field is comparable to cs / Ω_i. The radial structure of the wave azimuthal magnetic field consists of 3 regions: a Bessel function behavior for r < R, a near null at r ~ R, and a driven Airy pattern for r >> R. The pattern spreads at an angle given by tan θ = (ω/Ω_i)(c_s/V_A)/(2 \\cdot 6), where ω is the modulation frequency and VA the Alfvén speed. This arises because there is a maximum value at finite k_⊥ for the ratio of the perpendicular to parallel group velocity, which differs from the cone spreading(G.J. Morales, R.S. Loritsch, and J.E. Maggs, Phys. Plasmas) 1, 3765 (1994) associated with inertial Alfvén waves. Sponsored by ONR
Golay sequences coded coherent optical OFDM for long-haul transmission
NASA Astrophysics Data System (ADS)
Qin, Cui; Ma, Xiangrong; Hua, Tao; Zhao, Jing; Yu, Huilong; Zhang, Jian
2017-09-01
We propose to use binary Golay sequences in coherent optical orthogonal frequency division multiplexing (CO-OFDM) to improve the long-haul transmission performance. The Golay sequences are generated by binary Reed-Muller codes, which have low peak-to-average power ratio and certain error correction capability. A low-complexity decoding algorithm for the Golay sequences is then proposed to recover the signal. Under same spectral efficiency, the QPSK modulated OFDM with binary Golay sequences coding with and without discrete Fourier transform (DFT) spreading (DFTS-QPSK-GOFDM and QPSK-GOFDM) are compared with the normal BPSK modulated OFDM with and without DFT spreading (DFTS-BPSK-OFDM and BPSK-OFDM) after long-haul transmission. At a 7% forward error correction code threshold (Q2 factor of 8.5 dB), it is shown that DFTS-QPSK-GOFDM outperforms DFTS-BPSK-OFDM by extending the transmission distance by 29% and 18%, in non-dispersion managed and dispersion managed links, respectively.
Christensen, Helen; Griffiths, Kathy; Groves, Chloe; Korten, Ailsa
2006-01-01
Little is known about the predictors of symptom change or the methods that might increase user 'compliance' on websites designed to improve mental health outcomes. The present paper: (i) examines predictors of expected final depression and anxiety scores on the MoodGYM website as a function of user characteristics; and (ii) compares the compliance rates of the original site with the new public version of the site (MoodGYM Mark II). The latter site requires compulsory completion of 'core' online assessments and may increase completion of site questionnaires. MoodGYM Mark I participants were 19,607 visitors (public registrants) between April 2001 and September 2003 plus 182 participants who had been randomly assigned to MoodGYM in an earlier trial (The BlueMood Trial). MoodGYM Mark II participants were 38,791 public registrants of the MoodGYM Mark II site collected between September 2003 and October 2004. Symptom assessments are repeated within the website intervention to allow the examination of change in symptoms. Outcome variables were gender, initial depression severity scores, number of assessments completed and final anxiety and depression scores. Men are predicted to be 0.19 units (SE=0.095) higher than women on depression, controlling for the initial depression level and number of modules completed. For initial depression scores above 2, it is predicted that the final score will indicate improvement relative to the initial score, the magnitude of the improvement increasing as a function of the number of modules attempted. For initial anxiety scores above 2, it is predicted that the final score will indicate improvement relative to the initial score, the magnitude of the improvement increasing as a function of the number of modules attempted. Mark II registrants were more likely than to Mark I registrants to complete onsite assessments. Visitors to the MoodGYM site are likely to have better psychological outcomes if they complete more of the site material. Compulsory completion of core sections increases assessment completion. There is a need to examine further the significance of attrition from online interventions, to develop methods of handling missing data, and to investigate strategies to improve visitor dropout.
Self-Encoded Spread Spectrum Modulation for Robust Anti-Jamming Communication
2009-06-30
experience in both theoretical and experimental aspects of RF and optical communications, multi-user CDMA systems, transmitter precoding and code...the performance of DS - and FH-SESS modulation in the presence of worst-case jamming, develop innovative SESS schemes that further exploit time and...Determine BER and AJ performance of the feedback and iterative detectors in DS -SESS under pulsed-noise and multi-tone jamming • Task 2: Develop a scheme
Yang, Jingyan; Latkin, Carl A.; Davey-Rothwell, Melissa
2015-01-01
BACKGROUND The prevalence of depression among drug users is high. It has been recognized that drug use behaviors can be influenced and spread through social networks. OBJECTIVES We investigated the directional relationship between social network factors and depressive symptoms among a sample of inner-city residents in Baltimore, MD. METHODS We performed a longitudinal study of four-wave data collected from a network-based HIV/STI prevention intervention for women and network members, consisting of both men and women. Our primary outcome and exposure were depression using CESD scale and social network characteristics, respectively. Linear mixed model with clustering adjustment was used to account for both repeated measurement and network design. RESULTS Of the 746 participants, those who had high levels of depression tended to be female, less educated, homeless, smokers, and did not have a main partner. In the univariate longitudinal model, larger size of drug network was significantly associated with depression (OR=1.38, p<0.001). This relationship held after controlling for age, gender, homeless in the past six months, college education, having a main partner, cigarette smoking, perceived health, and social support network (aOR=1.19, p=0.001). In the univariate mixed model using depression to predict size of drug network, the data suggested that depression was associated with larger size of drug network (coef.=1.23, p<0.001) and the same relation held in multivariate model (adjusted coef.=1.08, p=0.001). CONCLUSIONS The results suggest that larger size of drug network is a risk factor for depression, and vice versa. Further intervention strategies to reduce depression should address social networks factors. PMID:26584046
Fang, Zhuo; Zhu, Senhua; Gillihan, Seth J.; Korczykowski, Marc; Detre, John A.; Rao, Hengyi
2013-01-01
The short (S) allele of the serotonin transporter-linked polymorphic region (5-HTTLPR) has been associated with increased susceptibility to depression. Previous neuroimaging studies have consistently showed increased amygdala activity during the presentation of negative stimuli or regulation of negative emotion in the homozygous short allele carriers, suggesting the key role of amygdala response in mediating increased risk for depression. The brain default mode network (DMN) has also been shown to modulate amygdala activity. However, it remains unclear whether 5-HTTLPR genetic variation modulates functional connectivity (FC) between the amygdala and regions of DMN. In this study, we re-analyzed our previous imaging dataset and examined the effects of 5-HTTLPR genetic variation on amygdala connectivity. A total of 15 homozygous short (S/S) and 15 homozygous long individuals (L/L) were scanned in functional magnetic resonance imaging (fMRI) during four blocks: baseline, sad mood, mood recovery, and return to baseline. The S/S and L/L groups showed a similar pattern of FC and no differences were found between the two groups during baseline and sad mood scans. However, during mood recovery, the S/S group showed significantly reduced anti-correlation between amygdala and posterior cingulate cortex/precuneus (PCC/PCu) compared to the L/L group. Moreover, PCC/PCu-amygdala connectivity correlated with amygdala activity in the S/S group but not the L/L group. These results suggest that 5-HTTLPR genetic variation modulates amygdala connectivity which subsequently affects its activity during mood regulation, providing an additional mechanism by which the S allele confers depression risk. PMID:24198772
Bunch modulation in LWFA blowout regime
NASA Astrophysics Data System (ADS)
Vyskočil, Jiří; Klimo, Ondřej; Vieira, Jorge; Korn, Georg
2015-05-01
Laser wakefield acceleration (LWFA) is able to produce high quality electron bunches interesting for many applications ranging from coherent light sources to high energy physics. The blow-out regime of LWFA provides excellent accelerating structure able to maintain small transverse emittance and energy spread of the accelerating electron beam if combined with localised injection. A modulation of the back of a self-injected electron bunch in the blowout regime of Laser Wakefield Acceleration appears 3D Particle-in-Cell simulations with the code OSIRIS. The shape of the modulation is connected to the polarization of the driving laser pulse, although the wavelength of the modulation is longer than that of the pulse. Nevertheless a circularly polarized laser pulse leads to a corkscrew-like modulation, while in the case of linear polarization, the modulation lies in the polarization plane.
NASA Technical Reports Server (NTRS)
Ha, Tri T.; Pratt, Timothy
1989-01-01
The feasibility of using spread spectrum techniques to provide a low-cost multiple access system for a very large number of low data terminals was investigated. Two applications of spread spectrum technology to very small aperture terminal (VSAT) satellite communication networks are presented. Two spread spectrum multiple access systems which use a form of noncoherent M-ary FSK (MFSK) as the primary modulation are described and the throughput analyzed. The analysis considers such factors as satellite power constraints and adjacent satellite interference. Also considered is the effect of on-board processing on the multiple access efficiency and the feasibility of overlaying low data rate spread spectrum signals on existing satellite traffic as a form of frequency reuse is investigated. The use of chirp is examined for spread spectrum communications. In a chirp communication system, each data bit is converted into one or more up or down sweeps of frequency, which spread the RF energy across a broad range of frequencies. Several different forms of chirp communication systems are considered, and a multiple-chirp coded system is proposed for overlay service. The mutual interference problem is examined in detail and a performance analysis undertaken for the case of a chirp data channel overlaid on a video channel.
NASA Technical Reports Server (NTRS)
Bickler, D. B.
1979-01-01
The paper describes a 'test case' manufacturing process sequence for solar photovoltaic modules which will cost 50 cents/watt in 1986. The process, which starts with the purification of silicon grown into 75-mm-wide thin ribbons, is discussed, and the plant layout is depicted; each department is sized to produce 250 MW of modules/per year. The cost of this process sequence is compared to present technology at various companies showing considerable spread for each process; data are tabulated in a composite state-of-the-art cell processing cost summary for these processes.
The spread of attention across features of a surface
Ernst, Zachary Raymond; Jazayeri, Mehrdad
2013-01-01
Contrasting theories of visual attention have emphasized selection by spatial location, individual features, and whole objects. We used functional magnetic resonance imaging to ask whether and how attention to one feature of an object spreads to other features of the same object. Subjects viewed two spatially superimposed surfaces of random dots that were segregated by distinct color-motion conjunctions. The color and direction of motion of each surface changed smoothly and in a cyclical fashion. Subjects were required to track one feature (e.g., color) of one of the two surfaces and detect brief moments when the attended feature diverged from its smooth trajectory. To tease apart the effect of attention to individual features on the hemodynamic response, we used a frequency-tagging scheme. In this scheme, the stimulus features (color and direction of motion) are modulated periodically at distinct frequencies so that the contribution of each feature to the hemodynamics can be inferred from the harmonic response at the corresponding frequency. We found that attention to one feature (e.g., color) of one surface increased the response modulation not only to the attended feature but also to the other feature (e.g., motion) of the same surface. This attentional modulation was evident in multiple visual areas and was present as early as V1. The spread of attention to the behaviorally irrelevant features of a surface suggests that attention may automatically select all features of a single object. Thus object-based attention may be supported by an enhancement of feature-specific sensory signals in the visual cortex. PMID:23883860
Interacting effect of BDNF Val66Met polymorphism and stressful life events on adolescent depression.
Chen, J; Li, X; McGue, M
2012-11-01
There is a strong etiological link between brain-derived neurotrophic factor and depression, but the neurocellular mechanisms and gene-environment interactions remain obscure. This study investigated whether one functional polymorphism in the brain-derived neurotrophic factor gene (BDNF Val66Met) modulates the influence of stressful life events on adolescent depressive symptoms. A total of 780 pairs of ethnic Han Chinese adolescent twins, 11-17 years of age, were randomly assigned to one of two subgroups (twin1 and twin2). All subjects were genotyped as Val/Val, Val/Met or Met/Met, and assessed for depressive symptoms using the Children's Depression Inventory. The level of environmental stress was estimated by the frequency of stressful life events using the Life Events Checklist. The frequency of stressful life events was significantly correlated with depressive symptoms (twin1: β = 0.21, P = 0.01; twin2: β = 0.27, P < 0.01), but there was no significant main effect of the BDNF Val66Met genotype on depressive symptoms. In both subgroups, however, the interaction between the BDNF Val66Met genotype and stressful life event frequency was significant (twin1: β = 0.19, P = 0.01; twin2: β = 0.15, P = 0.04); individuals with one or two Val alleles demonstrated a greater susceptibility to both the detrimental effects of higher stress and the beneficial effects of lower stress compared to the Met/Met genotype. These findings support the 'differential-susceptibility' hypothesis, whereby the BDNF Val allele modulates the influence of environmental stress on depression by enhancing the neuroplastic response to all life events. © 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.
Heartbeat Complexity Modulation in Bipolar Disorder during Daytime and Nighttime.
Nardelli, Mimma; Lanata, Antonio; Bertschy, Gilles; Scilingo, Enzo Pasquale; Valenza, Gaetano
2017-12-20
This study reports on the complexity modulation of heartbeat dynamics in patients affected by bipolar disorder. In particular, a multiscale entropy analysis was applied to the R-R interval series, that were derived from electrocardiographic (ECG) signals for a group of nineteen subjects comprised of eight patients and eleven healthy control subjects. They were monitored using a textile-based sensorized t-shirt during the day and overnight for a total of 47 diurnal and 27 nocturnal recordings. Patients showed three different mood states: depression, hypomania and euthymia. Results show a clear loss of complexity during depressive and hypomanic states as compared to euthymic and healthy control states. In addition, we observed that a more significant complexity modulation among healthy and pathological mood states occurs during the night. These findings suggest that bipolar disorder is associated with an enhanced sleep-related dysregulation of the Autonomic Nervous System (ANS) activity, and that heartbeat complex dynamics may serve as a viable marker of pathological conditions in mental health.
Effect of wet bulb depression on heat sterilization time of slash pine lumber
William T. Simpson
For international trade, heat sterilization of wood products is often required to prevent the spread of insects and pathogens. Application of heat sterilization requires estimates of the time necessary to heat the center of the wood configuration to the temperature required to kill the insect or other pest. The nature of the heating medium was found to have a...
Novel Therapeutic Targets for Chronic Migraine
2012-09-01
investigation of amiloride and related drugs as treatments for chronic migraine. We have also found that the drug memantine inhibits cortical...spreading depression, but acute treatment with memantine does not inhibit nociceptive signaling in the brainstem. These results are consistent with the...potential efficacy of memantine as a preventive therapy, but not as an acute therapy for migraine. We have also found that delta opioid receptor
Ichikawa, Yasushi; Nagashima, Yoji; Morioka, Kaori; Akimoto, Kazunori; Kojima, Yasuyuki; Ishikawa, Takashi; Goto, Ayumu; Kobayashi, Noritoshi; Watanabe, Kazuteru; Ota, Mitsuyoshi; Fujii, Shoichi; Kawamata, Mayumi; Takagawa, Ryo; Kunizaki, Chikara; Takahashi, Hirokazu; Nakajima, Atsushi; Maeda, Shin; Shimada, Hiroshi; Inayama, Yoshiaki; Ohno, Shigeo; Endo, Itaru
2014-09-01
Colorectal flat-type tumors include laterally spreading tumors (LSTs) and flat depressed-type tumors. The former of which shows a predominant lateral spreading growth rather than an invasive growth. The present study examined the morphological characteristics of LSTs, in comparison with polypoid- or flat depressed-type tumors, along with the expression of atypical protein kinase C (aPKC) λ/ι, a pivotal cell polarity regulator, and the hallmarks of cell polarity, as well as with type IV collagen, β-catenin and E-cadherin. In total, 37 flat-type (24 LSTs and 13 flat depressed-type tumors) and 20 polypoid-type colorectal tumors were examined. The LSTs were classified as 15 LST adenoma (LST-A) and nine LST cancer in adenoma (LST-CA). An immunohistochemical examination was performed on aPKC λ/ι, type IV collagen, β-catenin and E-cadherin. The LST-A and -CA showed a superficial replacing growth pattern, with expression of β-catenin and E-cadherin in the basolateral membrane and type IV collagen along the basement membrane. In addition, 86.6% of LST-A and 55.6% of LST-CA showed aPKC λ/ι expression of 1+ (weak to normal intensity staining in the cytoplasm compared with the normal epithelium). Furthermore, ~45% of the polypoid-type adenomas showed 2+ (moderate intensity staining in the cytoplasm and/or nucleus) and 66.7% of the polypoid-type cancer in adenoma were 3+ (strong intensity staining in the cytoplasm and nucleus). A statistically significant positive correlation was observed between the expression of aPKC λ/ι and β-catenin (r=0.842; P<0.001), or type IV collagen (r=0.823; P<0.001). The LSTs showed a unique growth pattern, different from the expanding growth pattern presented by a polypoid tumor and invasive cancer. The growth characteristics of LST appear to be caused by adequate coexpression of β-catenin, type IV collagen and aPKC λ/ι.
Optical integration of SPO mirror modules in the ATHENA telescope
NASA Astrophysics Data System (ADS)
Valsecchi, G.; Marioni, F.; Bianucci, G.; Zocchi, F. E.; Gallieni, D.; Parodi, G.; Ottolini, M.; Collon, M.; Civitani, M.; Pareschi, G.; Spiga, D.; Bavdaz, M.; Wille, E.
2017-08-01
ATHENA (Advanced Telescope for High-ENergy Astrophysics) is the next high-energy astrophysical mission selected by the European Space Agency for launch in 2028. The X-ray telescope consists of 1062 silicon pore optics mirror modules with a target angular resolution of 5 arcsec. Each module must be integrated on a 3 m structure with an accuracy of 1.5 arcsec for alignment and assembly. This industrial and scientific team is developing the alignment and integration process of the SPO mirror modules based on ultra-violet imaging at the 12 m focal plane. This technique promises to meet the accuracy requirement while, at the same time, allowing arbitrary integration sequence and mirror module exchangeability. Moreover, it enables monitoring the telescope point spread function during the planned 3-year integration phase.
Spread spectrum communications. Volume 1, 2 & 3
NASA Technical Reports Server (NTRS)
Simon, M. K.; Levitt, B. K.; Omura, J. K.; Scholtz, R. A.
1985-01-01
The design and operation of spread-spectrum (SS) communication systems are examined in an introductory text intended for graduate engineering students and practicing engineers. Chapters are devoted to an overview of SS systems, the historical origins of SS, basic concepts and system models, antijam communication systems, pseudonoise generators, coherent direct-sequence systems, noncoherent frequency-hopped systems, coherent and differentially coherent modulation techniques, pseudonoise acquisition and tracking in direct-sequence receivers, time and frequency synchronization of frequency-hopped receivers, low-probability-of-intercept communication, and multiple-access communication. Graphs, diagrams, and photographs are provided.
Fattahian, Ehsan; Hajhashemi, Valiollah; Rabbani, Mohammad; Minaiyan, Mohsen; Mahzouni, Parvin
2016-01-01
Depressive disorders are more common among persons with chronic diseases such as inflammatory bowel disease and anti-inflammatory effect of some antidepressants such as amitriptyline has been reported. Acetic acid colitis was induced in both reserpinised (depressed) and non-reserpinised (normal) rats. Reserpinised groups received reserpine (6 mg/kg, i.p.) one hour prior to colitis induction. Then Amitriptyline (5, 10, 20 mg/kg, i.p.) was administered to separate groups of male Wistar rats. All treatments were carried out two hours after colitis induction and continued daily for four days. Dexamethasone (1 mg/kg) and normal saline (1 mL/kg) were used in reference and control groups, respectively. At day five, animals were euthanized and colonic tissue injuries were assessed macroscopically and pathologically. Myeloperoxidase activity as a marker of neutrophil infiltration was also measured in colonic tissues. Results showed that reserpine (6 mg/kg, i.p.) intensified colitic condition. Compared to control, amitriptyline (10, 20 mg/kg) and dexamethasone significantly decreased weight of colon and ulcer index in normal and reserpine-induced depressed rats. Myeloperoxidase activity and pathological assessments also proved anti-inflammatory effect of amitriptyline. Our results suggest that amitriptyline, a tricyclic antidepressant, could reduce inflammatory and ulcerative injuries of colon both in normal and depressed rats. So among the wide spread anti-depressant drugs, amitriptyline is a good choice to treat depression comorbidities in patients with IBD. PMID:28228811
Kaplan, Peter S; Danko, Christina M; Cejka, Anna M; Everhart, Kevin D
2015-11-01
The hypothesis that the associative learning-promoting effects of infant-directed speech (IDS) depend on infants' social experience was tested in a conditioned-attention paradigm with a cumulative sample of 4- to 14-month-old infants. Following six forward pairings of a brief IDS segment and a photographic slide of a smiling female face, infants of clinically depressed mothers exhibited evidence of having acquired significantly weaker voice-face associations than infants of non-depressed mothers. Regression analyses revealed that maternal depression was significantly related to infant learning even after demographic correlates of depression, antidepressant medication use, and extent of pitch modulation in maternal IDS had been taken into account. However, after maternal depression had been accounted for, maternal emotional availability, coded by blind raters from separate play interactions, accounted for significant further increments in the proportion of variance accounted for in infant learning scores. Both maternal depression and maternal insensitivity negatively, and additively, predicted poor learning. Copyright © 2015 Elsevier Inc. All rights reserved.
Cano, Marta; Cardoner, Narcís; Urretavizcaya, Mikel; Martínez-Zalacaín, Ignacio; Goldberg, Ximena; Via, Esther; Contreras-Rodríguez, Oren; Camprodon, Joan; de Arriba-Arnau, Aida; Hernández-Ribas, Rosa; Pujol, Jesús; Soriano-Mas, Carles; Menchón, José M
2016-01-01
Although current models of depression suggest that a sequential modulation of limbic and prefrontal connectivity is needed for illness recovery, neuroimaging studies of electroconvulsive therapy (ECT) have focused on assessing functional connectivity (FC) before and after an ECT course, without characterizing functional changes occurring at early treatment phases. To assess sequential changes in limbic and prefrontal FC during the course of ECT and their impact on clinical response. Longitudinal intralimbic and limbic-prefrontal networks connectivity study. We assessed 15 patients with treatment-resistant depression at four different time-points throughout the entire course of an ECT protocol and 10 healthy participants at two functional neuroimaging examinations. Furthermore, a path analysis to test direct and indirect predictive effects of limbic and prefrontal FC changes on clinical response measured with the Hamilton Rating Scale for Depression was also performed. An early significant intralimbic FC decrease significantly predicted a later increase in limbic-prefrontal FC, which in turn significantly predicted clinical improvement at the end of an ECT course. Our data support that treatment response involves sequential changes in FC within regions of the intralimbic and limbic-prefrontal networks. This approach may help in identifying potential early biomarkers of treatment response. Copyright © 2015 Elsevier Inc. All rights reserved.
Greening, Steven G.; Osuch, Elizabeth A.; Williamson, Peter C.
2014-01-01
Depressive cognitive schemas play an important role in the emergence and persistence of major depressive disorder (MDD). The current study adapted emotion regulation techniques to reflect elements of cognitive behavioural therapy (CBT) and related psychotherapies to delineate neurocognitive abnormalities associated with modulating the negative cognitive style in MDD. Nineteen non-medicated patients with MDD and 19 matched controls reduced negative or enhanced positive feelings elicited by emotional scenes while undergoing functional magnetic resonance imaging. Although both groups showed significant emotion regulation success as measured by subjective ratings of affect, the controls were significantly better at modulating both negative and positive emotion. Both groups recruited regions of dorsolateral prefrontal cortex and ventrolateral prefrontal cortex (VLPFC) when regulating negative emotions. Only in controls was this accompanied by reduced activity in sensory cortices and amygdala. Similarly, both groups showed enhanced activity in VLPFC and ventral striatum when enhancing positive affect; however, only in controls was ventral striatum activity correlated with regulation efficacy. The results suggest that depression is associated with both a reduced capacity to achieve relief from negative affect despite recruitment of ventral and dorsal prefrontal cortical regions implicated in emotion regulation, coupled with a disconnect between activity in reward-related regions and subjective positive affect. PMID:23482626
Rehabilitation after amputation: psychotherapeutic intervention module in Indian scenario.
Srivastava, Kalpana; Chaudhury, Suprakash
2014-01-01
Psychological aspects of adjustment to amputation are varied and not addressed in the present treatment regime. There is no research evidence available of psychological intervention and outcome in Indian scenario. One hundred and seventy-three consecutive patients with limb amputations were randomly assigned to psychotherapeutic intervention module (PIM, study group) (n = 90) and treatment as usual group (TAU, control group) (n = 83). Patients with psychotic disorder were excluded from the study. Carroll Rating Scale for Depression (CRSD), State-Trait Anxiety Inventory (STAI), Amputees Body Image Scale (ABIS), and Impact of Event Scale (IES) along with specially designed information schedule were administered individually. Structured psychotherapeutic module was developed for the intervention. Patients in PIM group were given six therapy sessions, addressing the specific areas of concern. All patients were evaluated on the same tools after two months of therapy. Analysis showed that after treatment a significant reduction in scores was noted on CRSD, STAI, ABIS, and IES in the PIM group. On the TAU group a significant reduction was seen only in the ABIS. The psychological intervention module proposed by authors was efficacious in alleviating the psychological distress, depression, and anxiety and thus was vastly superior to the conventional method of management of amputees.
Ummavathy, P; Sherina, M S; Rampal, L; Siti Irma Fadhilah, I
2015-06-01
Chemotherapy is the most common form of treatment among cancer patients. It is also known to cause many physical and psychological side-effects. This study developed, implemented and evaluated the outcome of a chemotherapy counseling module among oncology patients by pharmacists based on their psychological effects (depression, anxiety) and selfesteem. A randomized, single blind, placebo controlled study was conducted among 162 patients undergoing chemotherapy in a government hospital in Malaysia. Counseling sessions were conducted using the 'Managing Patients on Chemotherapy' module for oncology patients undergoing chemotherapy at each treatment cycle. The outcome of repetitive chemotherapy counseling using the module was determined at baseline, first follow-up, second follow-up and third follow-up. The findings revealed that there was significant improvement in the intervention group as compared to the control group with large effect size on depression (p = 0.001, partial η(2) = 0.394), anxiety (p = 0.001, partial η(2) = 0.232) and self-esteem (p = 0.001, partial η(2) = 0.541). Repetitive counseling using the 'Managing Patients on Chemotherapy' module was found to be effective in improving psychological effects and self-esteem among patients undergoing chemotherapy.
Ho, Pei-Shen; Yeh, Yi-Wei; Huang, San-Yuan; Liang, Chih-Sung
2015-03-01
Depression is hypothesized to involve inflammatory processes, and identifying the key cytokines targeted by antidepressant drugs is critical for tailoring treatment to specific cases. However, investigating a limited number of cytokines at one time cannot provide a broad picture of antidepressant-associated immunomodulation. Cytokines act in a network where one could demonstrate pleiotropism, redundancy, synergy, and antagonism with other cytokine functions. This study was aimed at determining whether escitalopram functions as an anti-inflammatory agent and, if so, how it influences cytokine networks. A total of 24 healthy controls and 26 patients with clinical depression requiring inpatient treatment were recruited. A multiplex assay, an efficient tool to simultaneously measure 27 cytokines, was applied in patients with depression before and after 4-week escitalopram treatment. Healthy controls did not take escitalopram and completed cytokine analyses once. We demonstrated that escitalopram increased the levels of interleukin (IL)-1 receptor antagonist and IL-2. Moreover, escitalopram contributed to a shift toward T helper 2 responses and an increase in modulators of innate immunity, leading to a decrease of immune system activation, both innate and adaptive. We suggest that escitalopram modulates the balance of IL-1 and IL-1 receptor antagonist and improves the function and number of T regulatory cells. However, diverse conclusions could be drawn if only a few cytokines were assessed or different significance levels were used. Further studies should investigate a wide range of cytokines in a reliable and valid way, which is key to disentangling the effects of different antidepressants on inflammatory processes. Copyright © 2015 Elsevier Ltd. All rights reserved.
Convergent mechanisms underlying rapid antidepressant action
Zanos, Panos; Thompson, Scott M.; Duman, Ronald S.; Zarate, Carlos A.; Gould, Todd D.
2018-01-01
Traditional pharmacological treatments for depression have a delayed therapeutic onset, ranging from several weeks to months, and there is a high percentage of individuals who never respond to treatment. In contrast, ketamine produces rapid-onset antidepressant, anti-suicidal and anti-anhedonic actions following a single administration to depressed patients. Proposed mechanisms of ketamine’s antidepressant action include N-methyl-D-aspartate receptor (NMDAR) modulation, GABAergic interneuron disinhibition, and direct actions of its hydroxynorketamine (HNK) metabolites. Downstream actions include activation of mechanistic target of rapamycin (mTOR), deactivation of glycogen synthase kinase-3 and eukaryotic elongation factor 2 (eEF2), enhanced brain-derived neurotrophic factor (BDNF) signaling, and activation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs). These putative mechanisms of ketamine action are not mutually exclusive and may complement each other to induce potentiation of excitatory synapses in affective-regulating brain circuits, which results in amelioration of depression symptoms. We review these proposed mechanisms of ketamine action in the context of how such mechanisms are informing the development of novel putative rapid-acting antidepressant drugs. Such drugs that have undergoing pre-clinical, and in some cases clinical, testing include the muscarinic acetylcholine receptor antagonist scopolamine, GluN2B-NMDAR antagonists (i.e., CP-101,606, MK-0657), (2R,6R)-HNK, NMDAR glycine site modulators (i.e., 4-chlorokynurenine - pro-drug of the glycineB NMDAR antagonist 7-chlorokynurenic acid), NMDAR agonists (i.e. GLYX-13 (rapastinel)), metabotropic glutamate receptor 2/3 (mGluR2/3) antagonists, GABAA receptor modulators, and drugs acting on various serotonin receptor subtypes. These ongoing studies suggest that the future acute treatment of depression will typically occur within hours, rather than months, of treatment initiation. PMID:29516301
Disruption of amygdala-entorhinal-hippocampal network in late-life depression.
Leal, Stephanie L; Noche, Jessica A; Murray, Elizabeth A; Yassa, Michael A
2017-04-01
Episodic memory deficits are evident in late-life depression (LLD) and are associated with subtle synaptic and neurochemical changes in the medial temporal lobes (MTL). However, the particular mechanisms by which memory impairment occurs in LLD are currently unknown. We tested older adults with (DS+) and without (DS-) depressive symptoms using high-resolution fMRI that is capable of discerning signals in hippocampal subfields and amygdala nuclei. Scanning was conducted during performance of an emotional discrimination task used previously to examine the relationship between depressive symptoms and amygdala-mediated emotional modulation of hippocampal pattern separation in young adults. We found that hippocampal dentate gyrus (DG)/CA3 activity was reduced during correct discrimination of negative stimuli and increased during correct discrimination of neutral items in DS+ compared to DS- adults. The extent of the latter increase was correlated with symptom severity. Furthermore, DG/CA3 and basolateral amygdala (BLA) activity predicted discrimination performance on negative trials, a relationship that depended on symptom severity. The impact of the BLA on depressive symptom severity was mediated by the DG/CA3 during discrimination of neutral items, and by the lateral entorhinal cortex (LEC) during false recognition of positive items. These results shed light on a novel mechanistic account for amygdala-hippocampal network changes and concurrent alterations in emotional episodic memory in LLD. The BLA-LEC-DG/CA3 network, which comprises a key pathway by which emotion modulates memory, is specifically implicated in LLD. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Changes in personality traits during treatment with sertraline or citalopram.
Ekselius, L; Von Knorring, L
1999-05-01
Recent studies indicate that selective serotonin re-uptake inhibitors (SSRIs) reduce the symptoms accompanying personality disorders and modulate a normal personality. To examine the effect of two SSRIs, sertraline and citalopram, on personality traits in major depressed patients. Personality traits were evaluated at baseline and after six months using the Karolinska Scales of Personality (KSP). After treatment, significant changes in the direction of normalisation were seen in all scales. To determine whether the observed changes could be explained by improved depressive symptoms, multiple stepwise regressions with the separate KSP as dependent variables were performed. Improvements in depressive symptoms only accounted for 0-8.4% of the observed variance. In depressed patients treated with SSRIs significant effects are seen on personality traits measured by the KSP.
Scorza, Pamela; Masyn, Katherine; Salomon, Joshua A; Betancourt, Theresa S
2018-01-01
Depression is currently the second largest contributor to non-fatal disease burden globally. For that reason, economic evaluations are increasingly being conducted using data from depression prevalence estimates to analyze return on investments for services that target mental health. Psychiatric epidemiology studies have reported large cross-national differences in the prevalence of depression. These differences may impact the cost-effectiveness assessments of mental health interventions, thereby affecting decisions regarding government and multi-lateral investment in mental health services. Some portion of the differences in prevalence estimates across countries may be due to true discrepancies in depression prevalence, resulting from differential levels of risk in environmental and demographic factors. However, some portion of those differences may reflect non-invariance in the way standard tools measure depression across countries. This paper attempts to discern the extent to which measurement differences are responsible for reported differences in the prevalence of depression across countries. This analysis uses data from the World Mental Health Surveys, a coordinated series of psychiatric epidemiology studies in 27 countries using multistage household probability samples to assess prevalence and correlates of mental disorders. Data in the current study include responses to the depression module of the World Mental Health Composite International Diagnostic Interview (CIDI) in four countries: Two high-income, western countries-the United States (n = 20, 015) and New Zealand (n = 12,992)-an upper-middle income sub-Saharan African country, South Africa (n = 4,351), and a lower-middle income sub-Saharan African country, Nigeria (n = 6,752). Latent class analysis, a type of finite mixture modeling, was used to categorize respondents into underlying categories based on the variation in their responses to questions in each of three sequential parts of the CIDI depression module: 1) The initial screening items, 2) Additional duration and severity exclusion criteria, and 3) The core symptom questions. After each of these parts, exclusion criteria expel respondents from the remainder of the diagnostic interview, rendering a diagnosis of "not depressed". Latent class models were fit to each of the three parts in each of the four countries, and model fit was assessed using overall chi-square values and Pearson standardized residuals. Latent transition analysis was then applied in order to model participants' progression through the CIDI depression module. Proportion of individuals falling into each latent class and probabilities of transitioning into subsequent classes were used to estimate the percentage in each country that ultimately fell into the more symptomatic class, i.e. classified as "depressed". This latent variable design allows for a non-zero probability that individuals were incorrectly excluded from or retained in the diagnostic interview at any of the three exclusion points and therefore incorrectly diagnosed. Prevalence estimates based on the latent transition model reversed the order of depression prevalence across countries. Based on the latent transition model in this analysis, Nigeria has the highest prevalence (21.6%), followed by New Zealand (17.4%), then South Africa (15.0%), and finally the US (12.5%). That is compared to the estimates in the World Mental Health Surveys that do not allow for measurement differences, in which Nigeria had by far the lowest prevalence (3.1%), followed by South Africa (9.8%), then the United States (13.5%) and finally New Zealand (17.8%). Individuals endorsing the screening questions in Nigeria and South Africa were more likely to endorse more severe depression symptomology later in the module (i.e. they had higher transition probabilities), suggesting that individuals in the two Western countries may be more likely to endorse screening questions even when they don't have as severe symptoms. These differences narrow the range of depression prevalence between countries 14 percentage points in the original estimates to 6 percentage points in the estimate taking account of measurement differences. These data suggest fewer differences in cross-national prevalence of depression than previous estimates. Given that prevalence data are used to support key decisions regarding resource-allocation for mental health services, more critical attention should be paid to differences in the functioning of measurement across contexts and the impact these differences have on prevalence estimates. Future research should include qualitative methods as well as external measures of disease severity, such as impairment, to assess how the latent classes predict these external variables, to better understand the way that standard tools estimate depression prevalence across contexts. Adjustments could then be made to prevalence estimates used in cost-effectiveness analyses.
Evidence for a vagal pathophysiology for bulimia nervosa and the accompanying depressive symptoms.
Faris, Patricia L; Eckert, Elke D; Kim, Suck-Won; Meller, William H; Pardo, Jose V; Goodale, Robert L; Hartman, Boyd K
2006-05-01
The bilateral vagus nerves (Cranial X) provide both afferent and efferent connections between the viscera and the caudal medulla. The afferent branches increasingly are being recognized as providing significant input to the central nervous system for modulation of complex behaviors. In this paper, we review evidence from our laboratory that increases in vagal afferent activity are involved in perpetuating binge-eating and vomiting in bulimia nervosa. Preliminary findings are also presented which suggest that a subgroup of depressions may have a similar pathophysiology. Two main approaches were used to study the role of vagal afferents. Ondansetron (ONDAN), a 5-HT3 antagonist, was used as a pharmacological tool for inhibiting or reducing vagal afferent neurotransmission. Second, somatic pain detection thresholds were assessed for monitoring a physiological process known to be modulated by vagal afferents, including the gastric branches involved in meal termination and satiety. High levels of vagal activity result in an increase in pain detection thresholds. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). Positron Emission Tomography (PET) was used to identify higher cortical brain areas activated by vagal stimulation produced by proximal gastric distention in normal eating subjects. Double-blind treatment of severe bulimia nervosa subjects with ONDAN resulted in a rapid and significant decrease in binge-eating and vomiting compared to placebo controls. The decrease in abnormal eating episodes was accompanied by a return of normal satiety. Pain detection thresholds measured weekly over the course of the treatment protocol were found to dynamically fluctuate in association with bulimic episodes. Thresholds were the most elevated during periods of short-term abstinence from the behaviors, suggesting that not engaging in a binge/vomit episode is accompanied by an increase in vagal activity. ONDAN also resulted in abolition of the fluctuations in pain thresholds. Depressive symptoms in these subjects also were reduced by ONDAN. Like pain thresholds, depressive symptoms varied dynamically with the bulimic behaviors, with BDI scores increasing (more depressed) as more time elapsed since the last bulimic episode. PET studies indicated that mechanical distention of the stomach with a balloon (a non-nutritive stimulus) was associated with the activation of several brain loci, including those associated with vagal activation (parabrachial nucleus), emotive aspects of eating (lateral inferior frontal and orbitofrontal), and depressive symptoms (anterior cingulate). The results of the ONDAN study in bulimia nervosa subjects suggest that cyclic increases in vagal activity drive the urge to binge-eat and vomit. The alterations in vagal firing patterns are possibly a physiological adaptation to the high levels of vagal stimulation initially provided by voluntarily binge-eating and vomiting for weight control. The depressive symptoms that occur in association with the urge to binge-eat are also likely due to the cyclic increase in vagal activity. This suggestion is supported by the reduction of depressive symptoms during ONDAN treatment in bulimia subjects and PET imaging studies in normal eating subjects showing that brain loci classically involved in depression are activated by vagal stimulation administered by mechanical gastric distention. In normal eating individuals, depressions accompanying visceral diseases may also be vagally mediated. Ondansetron and other drugs known to modulate vagal activity may be helpful in treating depressions of this origin.
PPAR-γ agonism as a modulator of mood: proof-of-concept for pioglitazone in bipolar depression.
Kemp, David E; Schinagle, Martha; Gao, Keming; Conroy, Carla; Ganocy, Stephen J; Ismail-Beigi, Faramarz; Calabrese, Joseph R
2014-06-01
Insulin resistance and other cardio-metabolic risk factors predict increased risk of depression and decreased response to antidepressant and mood stabilizer treatments. This proof-of-concept study tested whether administration of an insulin-sensitizing peroxisome proliferator-activated receptor (PPAR)-γ agonist could reduce bipolar depression symptom severity. A secondary objective was to determine whether levels of highly sensitive C-reactive protein and interleukin (IL)-6 predicted treatment outcome. Patients (n = 34) with bipolar disorder (I, II, or not otherwise specified) and metabolic syndrome/insulin resistance who were currently depressed (Quick Inventory of Depressive Symptoms [QIDS] total score ≥11) despite an adequate trial of a mood stabilizer received open-label, adjunctive treatment with the PPAR-γ agonist pioglitazone (15-30 mg/day) for 8 weeks. The majority of participants (76 %, n = 26) were experiencing treatment-resistant bipolar depression, having already failed two mood stabilizers or the combination of a mood stabilizer and a conventional antidepressant. Supporting an association between insulin sensitization and depression severity, pioglitazone treatment was associated with a decrease in the total Inventory of Depressive Symptomatology (IDS-C30) score from 38.7 ± 8.2 at baseline to 21.2 ± 9.2 at week 8 (p < 0.001). Self-reported depressive symptom severity and clinician-rated anxiety symptom severity significantly improved over 8 weeks as measured by the QIDS (p < 0.001) and Structured Interview Guide for the Hamilton Anxiety Scale (p < 0.001), respectively. Functional improvement also occurred as measured by the change in total score on the Sheehan Disability Scale (-17.9 ± 3.6; p < 0.001). Insulin sensitivity increased from baseline to week 8 as measured by the Insulin Sensitivity Index derived from an oral glucose tolerance test (0.98 ± 0.3; p < 0.001). Higher baseline levels of IL-6 were associated with greater decrease in depression severity (parameter estimate β = -3.89, standard error [SE] = 1.47, p = 0.015). A positive correlation was observed between improvement in IDS-C30 score and change in IL-6 (r = 0.44, p < 0.01). Open-label administration of the PPAR-γ agonist pioglitazone was associated with improvement in depressive symptoms and reduced cardio-metabolic risk. Reduction in inflammation may represent a novel mechanism by which pioglitazone modulates mood. (ClinicalTrials.gov Identifier: NCT00835120).
Object-based spatial attention when objects have sufficient depth cues.
Takeya, Ryuji; Kasai, Tetsuko
2015-01-01
Attention directed to a part of an object tends to obligatorily spread over all of the spatial regions that belong to the object, which may be critical for rapid object-recognition in cluttered visual scenes. Previous studies have generally used simple rectangles as objects and have shown that attention spreading is reflected by amplitude modulation in the posterior N1 component (150-200 ms poststimulus) of event-related potentials, while other interpretations (i.e., rectangular holes) may arise implicitly in early visual processing stages. By using modified Kanizsa-type stimuli that provided less ambiguity of depth ordering, the present study examined early event-related potential spatial-attention effects for connected and separated objects, both of which were perceived in front of (Experiment 1) and in back of (Experiment 2) the surroundings. Typical P1 (100-140 ms) and N1 (150-220 ms) attention effects of ERP in response to unilateral probes were observed in both experiments. Importantly, the P1 attention effect was decreased for connected objects compared to separated objects only in Experiment 1, and the typical object-based modulations of N1 were not observed in either experiment. These results suggest that spatial attention spreads over a figural object at earlier stages of processing than previously indicated, in three-dimensional visual scenes with multiple depth cues.
A three-dimensional gravity study of the 95.5°W propagating rift in the Galapagos spreading center
NASA Astrophysics Data System (ADS)
Phipps Morgan, Jason; Parmentier, E. M.
1987-01-01
Seafloor at the Galapagos 95.5°W propagating rift (PR) has a varied morphological expression that can be spatially correlated with the predicted kinematic history of the PR. A median valley-like depression occurs near the tip of the growing ridge axis. To test if this bathymetry is a dynamic feature supported by mantle or lithosphere strength or if it is due to isostatically compensated crustal thickness variations, we use three-dimensional gravity modelling to constrain the crustal structure in this region, from data collected by Hey in 1979 and 1982. The gravity anomaly at the PR tip depression suggests that the tip depression is not caused by crustal thinning. The data are consistent with a stress-supported PR tip depression caused by asthenospheric along-axis flow into the growing ridge axis (Phipps Morgan and Parmentier [1]). In contrast to the tip depression, seafloor in the sheared zone of material transferred through transform migration from the Cocos to Nazca plate is anomalously shallow and has a pronounced regional 300-400 m tilt towards the growing ridge axis over the 20 km width of the sheared zone. The gravity data also suggest that the sheared zone is not compensated by crustal thickening.
Forkmann, Thomas; Boecker, Maren; Norra, Christine; Eberle, Nicole; Kircher, Tilo; Schauerte, Patrick; Mischke, Karl; Westhofen, Martin; Gauggel, Siegfried; Wirtz, Markus
2009-05-01
The calibration of item banks provides the basis for computerized adaptive testing that ensures high diagnostic precision and minimizes participants' test burden. The present study aimed at developing a new item bank that allows for assessing depression in persons with mental and persons with somatic diseases. The sample consisted of 161 participants treated for a depressive syndrome, and 206 participants with somatic illnesses (103 cardiologic, 103 otorhinolaryngologic; overall mean age = 44.1 years, SD =14.0; 44.7% women) to allow for validation of the item bank in both groups. Persons answered a pool of 182 depression items on a 5-point Likert scale. Evaluation of Rasch model fit (infit < 1.3), differential item functioning, dimensionality, local independence, item spread, item and person separation (>2.0), and reliability (>.80) resulted in a bank of 79 items with good psychometric properties. The bank provides items with a wide range of content coverage and may serve as a sound basis for computerized adaptive testing applications. It might also be useful for researchers who wish to develop new fixed-length scales for the assessment of depression in specific rehabilitation settings. (PsycINFO Database Record (c) 2009 APA, all rights reserved).
Organizational Cost of Quality Improvement for Depression Care
Liu, Chuan-Fen; Rubenstein, Lisa V; Kirchner, JoAnn E; Fortney, John C; Perkins, Mark W; Ober, Scott K; Pyne, Jeffrey M; Chaney, Edmund F
2009-01-01
Objective We documented organizational costs for depression care quality improvement (QI) to develop an evidence-based, Veterans Health Administration (VA) adapted depression care model for primary care practices that performed well for patients, was sustained over time, and could be spread nationally in VA. Data Sources and Study Setting Project records and surveys from three multistate VA administrative regions and seven of their primary care practices. Study Design Descriptive analysis. Data Collection We documented project time commitments and expenses for 86 clinical QI and 42 technical expert support team participants for 4 years from initial contact through care model design, Plan–Do–Study–Act cycles, and achievement of stable workloads in which models functioned as routine care. We assessed time, salary costs, and costs for conference calls, meetings, e-mails, and other activities. Principle Findings Over an average of 27 months, all clinics began referring patients to care managers. Clinical participants spent 1,086 hours at a cost of $84,438. Technical experts spent 2,147 hours costing $197,787. Eighty-five percent of costs derived from initial regional engagement activities and care model design. Conclusions Organizational costs of the QI process for depression care in a large health care system were significant, and should be accounted for when planning for implementation of evidence-based depression care. PMID:19146566
Long-term prognosis of depression in primary care.
Simon, G. E.
2000-01-01
This article uses longitudinal data from a primary care sample to examine long-term prognosis of depression. A sample of 225 patients initiating antidepressant treatment in primary care completed assessments of clinical outcome (Hamilton Depression Rating Scale and the mood module of the Structured Clinical Interview for DSM-IIIR) 1, 3, 6, 9, 12, 18 and 24 months after initiating treatment. The proportion of patients continuing to meet criteria for major depression fell rapidly to approximately 10% and remained at approximately that level throughout follow-up. The proportion meeting criteria for remission (Hamilton Depression score of 7 or less) rose gradually to approximately 45%. Long-term prognosis (i.e. probability of remission at 6 months and beyond) was strongly related to remission status at 3 months (odds ratio 3.65; 95% confidence interval, 2.81-4.76) and only modestly related to various clinical characteristics assessed at baseline (e.g. prior history of recurrent depression, medical comorbidity, comorbid anxiety symptoms). The findings indicate that potentially modifiable risk factors influence the long-term prognosis of depression. This suggests that more systematic and effective depression treatment programmes might have an important effect on long-term course and reduce the overall burden of chronic and recurrent depression. PMID:10885162
Cerenkov emissions of ion acoustic-like waves generated by electron beams emitted during TSS 1R
NASA Astrophysics Data System (ADS)
Huang, C. Y.; Burke, W. J.; Hardy, D. A.; Gough, M. P.; Olson, D. G.; Gentile, L. C.; Gilchrist, B. E.; Bonifazi, C.; Raitt, W. J.; Thompson, D. C.
During the Tethered Satellite System reflight the Spacecraft Particle Correlation Experiment detected fluxes of energetic electrons and ions that were simultaneously modulated at low frequencies during firings of both the fast pulsed electron gun (FPEG) and the electron generator assembly (EGA). The modulations have been interpreted as signatures of large-amplitude, ion acoustic-like waves excited in Cerenkov interactions between electron beams and ambient plasmas as the shuttle moved at supersonic speeds across the ionospheric magnetic field. We present examples of particle modulations observed during steady beam emissions. Measurements show that (1) most electron modulations were at frequencies of several hundred Hertz and (2) ions modulated at similar frequencies appeared at spectral energy peaks during shuttle negative charging events. Detection of modulated ion fluxes confirms the Cerenkov emission hypothesis. Observed frequency variations indicate that the EGA beam underwent more spatial spreading than the FPEG beam.
Galvão, Ana C. de Menezes; de Almeida, Raíssa N.; Silva, Erick A. dos Santos; Freire, Fúlvio A. M.; Palhano-Fontes, Fernanda; Onias, Heloisa; Arcoverde, Emerson; Maia-de-Oliveira, João P.; de Araújo, Dráulio B.; Lobão-Soares, Bruno; Galvão-Coelho, Nicole L.
2018-01-01
Major depression is a highly prevalent mood disorder, affecting about 350 million people, and around 30% of the patients are resistant to currently available antidepressant medications. Recent evidence from a randomized controlled trial (RCT) supports the rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression. The aim of this study was to explore the effect of ayahuasca on plasma cortisol and awakening salivary cortisol response, in the same group of treatment-resistant patients (MD) and in healthy volunteers (C). Subjects received a single dose of ayahuasca or placebo (dosing session), and both plasma and awakening salivary cortisol response were measured at baseline (before dosing session) and 48 h after the dosing session. Baseline assessment (D0) showed blunted awakening salivary cortisol response and hypocortisolemia in patients, with respect to healthy controls. Salivary cortisol was also measured during dosing session, and we observed higher increases for both C and MD that ingested ayahuasca than placebo. After 48 h from the dosing session with ayahuasca, patients' awakening salivary cortisol response is similar to the ones detected in controls. No significant changes in plasma cortisol levels were observed 48 h after the sessions. Therefore, these findings point to new evidence on the modulation of salivary cortisol levels as a result of an ayahuasca session, both in healthy and depressive volunteers. Considering that cortisol acts in regulation of distinct physiological pathways, emotional and cognitive processes, it is assumed to be critically involved to the etiology of depression and its regulation seems to be important for the treatment and remission of major depression, ayahuasca use as antidepressant should be further investigated. Moreover, this study highlights the importance of psychedelics in the treatment of human mental disorders. PMID:29867608
War exposure, 5-HTTLPR genotype and lifetime risk of depression
Artero, Sylvaine; Touchon, Jacques; Dupuy, Anne-Marie; Malafosse, Alain; Ritchie, Karen
2011-01-01
Background in 1962, during the Algerian war, approximately one and a half million French people living in Algeria were repatriated to France in very poor and often life-threatening conditions. These subjects constitute a cohort for the study of the long term impact of gene-environment interaction on depression. Aims To examine the interaction between a highly stressful life event and subsequent depression, and its modulation by the serotonin transporter gene (5-HTTLPR). Method A community sample of elderly persons aged 65 years and over residing in the Montpellier region of the South of France was randomly recruited from electoral rolls. Genotyping was performed on 248 repatriated persons and 632 controls. Current and lifetime major and minor depressions were assessed according to DSM-IV criteria. Results A significant relationship was observed between exposure to repatriation and subsequent depression (p<0.002), but there was no significant effect of gene alone (p=0.62). After controlling for age, gender, education, disability, recent life events and cognitive function, the gene-environment interaction (Repatriation X 5-HTTLPR) was globally significant (p<0.002; OR= 3.21 [2.48–5.12]). Subjects carrying the two short ( S ) alleles of 5-HTTLPR were observed to be at higher risk (p<0.005; OR=2.34 [1.24–4.32]) and particularly when the repatriation occurred before the age of 35 (p<0.002; OR=2.91 [1.44–5.88]) but did not reach significance in subjects who were older at the time of the event (p=0.067). Conclusion The association between depression and war repatriation is significantly modulated by 5-HTTLPR genotype but this appears to occur only in persons who were younger at the time of exposure. PMID:21593514
2010-01-01
Background Recent projections suggest that by the year 2030 depression will be the primary cause of disease burden among developed countries. Delivery of accessible consumer-focused evidenced-based services may be an important element in reducing this burden. Many consumers report a preference for self-help modes of delivery. The Internet offers a promising modality for delivering such services and there is now evidence that automated professionally developed self-help psychological interventions can be effective. By contrast, despite their popularity, there is little evidence as to the effectiveness of Internet support groups which provide peer-to-peer mutual support. Methods/Design Members of the community with elevated psychological distress were randomised to receive one of the following: (1) Internet Support Group (ISG) intervention, (2) a multi-module automated psychoeducational and skills Internet Training Program (ITP), (3) a combination of the ISG and ITP, or (4) an Internet Attention Control website (IAC) comprising health and wellbeing information and question and answer modules. Each intervention was 12 weeks long. Assessments were conducted at baseline, post-intervention, 6 and 12 months to examine depressive symptoms, social support, self-esteem, quality of life, depression literacy, stigma and help-seeking for depression. Participants were recruited through a screening postal survey sent to 70,000 Australians aged 18 to 65 years randomly selected from four rural and four metropolitan regions in Australia. Discussion To our knowledge this study is the first randomised controlled trial of the effectiveness of a depression ISG. Trial registration Current Controlled Trials ISRCTN65657330. PMID:20211025
War exposure, 5-HTTLPR genotype and lifetime risk of depression.
Artero, Sylvaine; Touchon, Jacques; Dupuy, Anne-Marie; Malafosse, Alain; Ritchie, Karen
2011-07-01
In 1962 approximately 1.5 million French people living in Algeria were repatriated to France in very poor and often life-threatening conditions. These people constitute a cohort for the study of the long-term impact of gene-environment interaction on depression. To examine the interaction between a highly stressful life event and subsequent depression, and its modulation by a length polymorphism of the serotonin transporter gene (5-HTTLPR). A community sample of people aged 65 years and over residing in the Montpellier region of the south of France was randomly recruited from electoral rolls. Genotyping was performed on 248 repatriated persons and 632 controls. Current and lifetime major and minor depressive disorders were assessed according to DSM-IV criteria. A significant relationship was observed between exposure to repatriation and subsequent depression (P<0.002), but there was no significant effect of gene alone (P = 0.62). After controlling for age, gender, education, disability, recent life events and cognitive function, the gene-environment interaction (repatriation × 5-HTTLPR) was globally significant (P<0.002; OR = 3.21, 95% CI 2.48-5.12). Individuals carrying the two short (s) alleles of 5-HTTLPR were observed to be at higher risk (P<0.005; OR = 2.34, 95% CI 1.24-4.32), particularly when repatriation occurred before age 35 years (P<0.002; OR = 2.91, 95% CI 1.44-5.88), but this did not reach significance in those who were older at the time of the event (P = 0.067). The association between depression and war repatriation was significantly modulated by 5-HTTLPR genotype but this appeared to occur only in people who were younger at the time of exposure.
[The prevalence of generalized anxiety disorder and comorbidity among psychiatric outpatients].
Ozcan, Murat; Uğuz, Faruk; Cilli, Ali Savaş
2006-01-01
In this study, we aimed to investigate the prevalence, association with sociodemographic characteristics, and comorbidity with other anxiety and depressive disorders of generalized anxiety disorder (GAD) among psychiatric outpatients. In the first phase of the study, outpatient psychiatry clinic physician interviewed with consecutive 950 patients who applied to psychiatry outpatient clinic of an university hospital by using GAD module of CIDI (Composite International Diagnostic Interview, version 2.1) during 4-month. Ninety-nine patients with diagnosis of GAD in the first phase were referred to the researcher physician for further evaluation. In the second phase, patients were interviewed by using CIDI anxiety and mood (major depression, dysthymic disorder) disorder modules. By this way, 12-month additional diagnoses were examined, and diagnosis of GAD was confirmed. One patient was excluded, because did not meet the GAD criteria during reexamination by the researcher physician. Ninety-eight patients (10.3%) met DSM-IV criteria for GAD. Eighty-nine (90.8%) of the cases had comorbid any anxiety or depressive disorder. The rates of comorbidity with any of depressive disorders and anxiety disorders were found 84.7% and 56.1%, respectively. The most common comorbid diagnosis was major depression (83.7%). The most common anxiety disorders were social phobia (30.6%), OCD (19.4%) and specific phobia (17.4%). The prevalence of GAD was observed significantly higher in women, married ones, housewives, unworking girls, subjects with history of medical illness and lower educational status. Our results show that among psychiatric outpatients, GAD has high comorbidity rates with depressive and other anxiety disorders, and it is associate with some sociodemographic characteristics such as gender, and marital, working and educational status.
Electro-optic modulation for high-speed characterization of entangled photon pairs
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lukens, Joseph M.; Odele, Ogaga D.; Leaird, Daniel E.
In this study, we demonstrate a new biphoton manipulation and characterization technique based on electro-optic intensity modulation and time shifting. By applying fast modulation signals with a sharply peaked cross-correlation to each photon from an entangled pair, it is possible to measure temporal correlations with significantly higher precision than that attainable using standard single-photon detection. Low-duty-cycle pulses and maximal-length sequences are considered as modulation functions, reducing the time spread in our correlation measurement by a factor of five compared to our detector jitter. With state-of-the-art electro-optic components, we expect the potential to surpass the speed of any single-photon detectors currentlymore » available.« less
Electro-optic modulation for high-speed characterization of entangled photon pairs
Lukens, Joseph M.; Odele, Ogaga D.; Leaird, Daniel E.; ...
2015-11-10
In this study, we demonstrate a new biphoton manipulation and characterization technique based on electro-optic intensity modulation and time shifting. By applying fast modulation signals with a sharply peaked cross-correlation to each photon from an entangled pair, it is possible to measure temporal correlations with significantly higher precision than that attainable using standard single-photon detection. Low-duty-cycle pulses and maximal-length sequences are considered as modulation functions, reducing the time spread in our correlation measurement by a factor of five compared to our detector jitter. With state-of-the-art electro-optic components, we expect the potential to surpass the speed of any single-photon detectors currentlymore » available.« less
Cortical organization of inhibition-related functions and modulation by psychopathology
Warren, Stacie L.; Crocker, Laura D.; Spielberg, Jeffery M.; Engels, Anna S.; Banich, Marie T.; Sutton, Bradley P.; Miller, Gregory A.; Heller, Wendy
2013-01-01
Individual differences in inhibition-related functions have been implicated as risk factors for a broad range of psychopathology, including anxiety and depression. Delineating neural mechanisms of distinct inhibition-related functions may clarify their role in the development and maintenance of psychopathology. The present study tested the hypothesis that activity in common and distinct brain regions would be associated with an ecologically sensitive, self-report measure of inhibition and a laboratory performance measure of prepotent response inhibition. Results indicated that sub-regions of DLPFC distinguished measures of inhibition, whereas left inferior frontal gyrus and bilateral inferior parietal cortex were associated with both types of inhibition. Additionally, co-occurring anxiety and depression modulated neural activity in select brain regions associated with response inhibition. Results imply that specific combinations of anxiety and depression dimensions are associated with failure to implement top-down attentional control as reflected in inefficient recruitment of posterior DLPFC and increased activation in regions associated with threat (MTG) and worry (BA10). Present findings elucidate possible neural mechanisms of interference that could help explain executive control deficits in psychopathology. PMID:23781192
Cortical organization of inhibition-related functions and modulation by psychopathology.
Warren, Stacie L; Crocker, Laura D; Spielberg, Jeffery M; Engels, Anna S; Banich, Marie T; Sutton, Bradley P; Miller, Gregory A; Heller, Wendy
2013-01-01
Individual differences in inhibition-related functions have been implicated as risk factors for a broad range of psychopathology, including anxiety and depression. Delineating neural mechanisms of distinct inhibition-related functions may clarify their role in the development and maintenance of psychopathology. The present study tested the hypothesis that activity in common and distinct brain regions would be associated with an ecologically sensitive, self-report measure of inhibition and a laboratory performance measure of prepotent response inhibition. Results indicated that sub-regions of DLPFC distinguished measures of inhibition, whereas left inferior frontal gyrus and bilateral inferior parietal cortex were associated with both types of inhibition. Additionally, co-occurring anxiety and depression modulated neural activity in select brain regions associated with response inhibition. Results imply that specific combinations of anxiety and depression dimensions are associated with failure to implement top-down attentional control as reflected in inefficient recruitment of posterior DLPFC and increased activation in regions associated with threat (MTG) and worry (BA10). Present findings elucidate possible neural mechanisms of interference that could help explain executive control deficits in psychopathology.
Is burnout separable from depression in cluster analysis? A longitudinal study.
Bianchi, Renzo; Schonfeld, Irvin Sam; Laurent, Eric
2015-06-01
Whether burnout and depression represent distinct pathologies is unclear. The aim of this study was to examine whether burnout and depressive symptoms manifest themselves separately from each other or are so closely intertwined as to reflect the same phenomenon. A two-wave longitudinal study involving 627 French schoolteachers (73 % female) was conducted. Burnout was assessed with the Maslach Burnout Inventory and depression with the 9-item depression module of the Patient Health Questionnaire. Burnout and depressive symptoms clustered both at baseline and follow-up. Cluster membership at time 1 (T1) predicted cases of burnout and depression at time 2 (T2), controlling for gender, age, length of employment, lifetime history of depression, and antidepressant intake. Changes in burnout and depressive symptoms from T1 to T2 were found to overlap. Teachers with increasing burnout experienced increases in depression and teachers with decreasing burnout experienced decreases in depression. In addition, emotional exhaustion, the core of burnout, was more strongly associated with depression than with depersonalization, the second dimension of burnout, underlining an inconsistency in the conceptualization of the burnout syndrome. Our results are consistent with recent findings showing qualitative and quantitative symptom overlap of burnout with depression. The close interconnection of burnout and depression questions the relevance of a nosological distinction between the two entities. Emotional exhaustion and depersonalization, the two main dimensions of burnout, may be better conceptualized as depressive responses to adverse occupational environments than as components of a separate entity.
On the benefit of DMT modulation in nonlinear VLC systems.
Qian, Hua; Cai, Sunzeng; Yao, Saijie; Zhou, Ting; Yang, Yang; Wang, Xudong
2015-02-09
In a visible light communication (VLC) system, the nonlinear characteristic of the light emitting diode (LED) in transmitter is a limiting factor of system performance. Modern modulation signals with large peak-to-power-ratio (PAPR) suffers uneven distortion. The nonlinear response directly impacts the intensity modulation and direct detection VLC system with pulse-amplitude modulation (PAM). The amplitude of the PAM signal is distorted unevenly and large signal is vulnerable to noise. Orthogonal linear transformations, such as discrete multi-tone (DMT) modulation, can spread the nonlinear effects evenly to each data symbol, thus perform better than PAM signals. In this paper, we provide theoretical analysis on the benefit of DMT modulation in nonlinear VLC system. We show that the DMT modulation is a better choice than the PAM modulation for the VLC system as the DMT modulation is more robust against nonlinearity. We also show that the post-distortion nonlinear elimination method, which is applied at the receiver, can be a reliable solution to the nonlinear VLC system. Simulation results show that the post-distortion greatly improves the system performance for the DMT modulation.
Effect of Alcohol on the Spreading Ability of Sodium Hypochlorite Endodontic Irrigant
1982-09-01
Research Progress Sodium Hypochlorite Endodontic Irrigant Report (Interim) 6. PERFORMING ORG. REPORT NUMBER 7. AU THOR(s) 8. CONTRACT OR GRANT NUMBER(s...neceewary and Identify by block nam.ber) Alcohol Sodium hypochlorite Endodontics Root canal 20, ABSTRACT (Continue on reveree side If neceeseay and...depressant significantly increased the ability of the sodium hypochlorite endodontic irrigant to penetrate in vitro. A freshly mixed solution containing 30
William T. Simpson
2003-01-01
Heat sterilization is often required to prevent spread of insects and pathogens in wood products in international trade. Heat sterilization requires estimating the time necessary for the center of the wood configuration to reach the temperature required to kill insects or pathogens. In these experiments on 1.0- and 1.8-in.- (25- and 46-mm-) thick slash pine, heating...
Martens-Mantai, Tanja; Speckmann, Erwin-Josef; Gorji, Ali
2014-07-22
Propagation of cortical spreading depression (CSD) to the subcortical structures could be the underlying mechanism of some neurological deficits in migraine with aura. The entorhinal cortex (EC) as a gray matter bridge between the neocortex and subcortical regions plays an important role in this propagation. In vitro combined neocortex-hippocampus brain slices were used to study the propagation pattern of CSD between the neocortex and the hippocampus. The effects of different compounds as well as tetanic electrical stimulations in the EC on propagation of CSD to the hippocampus were investigated. Repetitive induction of CSD by KCl injection in the somatosensory cortex enhanced the probability of CSD entrance to the hippocampus via EC. Local application of AMPA receptor blocker CNQX and cannabinoid receptor agonist WIN 55212-2 in EC facilitated the propagation of CSD to the hippocampus, whereas application of NMDA receptor blocker APV and GABA A receptor blocker bicuculline in this region reduced the probability of CSD penetration to the hippocampus. Application of tetanic stimulation in EC also facilitated the propagation of CSD entrance to the hippocampus. Our data suggest the importance of synaptic plasticity of EC in filtering the propagation of CSD into subcortical structures and possibly the occurrence of concomitant neurological deficits. Synapse, 2014. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.
Lauritzen, Martin; Dreier, Jens Peter; Fabricius, Martin; Hartings, Jed A; Graf, Rudolf; Strong, Anthony John
2011-01-01
Cortical spreading depression (CSD) and depolarization waves are associated with dramatic failure of brain ion homeostasis, efflux of excitatory amino acids from nerve cells, increased energy metabolism and changes in cerebral blood flow (CBF). There is strong clinical and experimental evidence to suggest that CSD is involved in the mechanism of migraine, stroke, subarachnoid hemorrhage and traumatic brain injury. The implications of these findings are widespread and suggest that intrinsic brain mechanisms have the potential to worsen the outcome of cerebrovascular episodes or brain trauma. The consequences of these intrinsic mechanisms are intimately linked to the composition of the brain extracellular microenvironment and to the level of brain perfusion and in consequence brain energy supply. This paper summarizes the evidence provided by novel invasive techniques, which implicates CSD as a pathophysiological mechanism for this group of acute neurological disorders. The findings have implications for monitoring and treatment of patients with acute brain disorders in the intensive care unit. Drawing on the large body of experimental findings from animal studies of CSD obtained during decades we suggest treatment strategies, which may be used to prevent or attenuate secondary neuronal damage in acutely injured human brain cortex caused by depolarization waves. PMID:21045864
Exploring the role of microglia in cortical spreading depression in neurological disease
Suzuki, Norihiro
2017-01-01
Microglia play a pivotal role in innate immunity in the brain. During development, they mature from myeloerythroid progenitor cells in the yolk sac and colonize the brain to establish a resident population of tissue macrophages. In the postnatal brain, they exert phagocytosis and induce inflammatory response against invading pathogens. Microglia also act as guardians of brain homeostasis by surveying the microenvironment using motile processes. Cortical spreading depression (CSD) is a slowly propagating (2–5 mm/min) wave of rapid, near-complete depolarization of neurons and astrocytes followed by a period of electrical suppression of a distinct population of cortical neurons. Not only has CSD been implicated in brain migraine aura, but CSD-like events have also been detected in stroke and traumatic injury. CSD causes a considerable perturbation of the ionic environment in the brain, which may be readily detected by microglia. Although CSD is known to activate microglia, the role of microglial activation in CSD-related neurological disorders remains poorly understood. In this article, we first provide an overview of microglial development and the multiple functions of microglia. Then, we review existing data on the relationship between microglia and CSD and discuss the relevance of CSD-induced microglial activation in neurological disease. PMID:28155572
Aiba, Isamu; Carlson, Andrew P.; Sheline, Christian T.
2012-01-01
Cortical spreading depression (CSD) is a consequence of a slowly propagating wave of neuronal and glial depolarization (spreading depolarization; SD). Massive release of glutamate contributes to SD propagation, and it was recently shown that Zn2+ is also released from synaptic vesicles during SD. The present study examined consequences of extracellular Zn2+ accumulation on the propagation of SD. SD mechanisms were studied first in murine brain slices, using focal KCl applications as stimuli and making electrical and optical recordings in hippocampal area CA1. Elevating extracellular Zn2+ concentrations with exogenous ZnCl2 reduced SD propagation rates. Selective chelation of endogenous Zn2+ (using TPEN or CaEDTA) increased SD propagation rates, and these effects appeared due to chelation of Zn2+ derived from synaptic vesicles. Thus, in tissues where synaptic Zn2+ release was absent [knockout (KO) of vesicular Zn2+ transporter ZnT-3], SD propagation rates were increased, and no additional increase was observed following chelation of endogenous Zn2+ in these tissues. The role of synaptic Zn2+ was then examined on CSD in vivo. ZnT-3 KO animals had higher susceptibility to CSD than wild-type controls as evidenced by significantly higher propagation rates and frequencies. Studies of candidate mechanisms excluded changes in neuronal excitability, presynaptic release, and GABA receptors but left open a possible contribution of N-methyl-d-aspartate (NMDA) receptor inhibition. These results suggest the extracellular accumulation of synaptically released Zn2+ can serve as an intrinsic inhibitor to limit SD events. The inhibitory action of extracellular Zn2+ on SD may counteract to some extent the neurotoxic effects of intracellular Zn2+ accumulation in acute brain injury models. PMID:22131381
Aiba, Isamu; Carlson, Andrew P; Sheline, Christian T; Shuttleworth, C William
2012-02-01
Cortical spreading depression (CSD) is a consequence of a slowly propagating wave of neuronal and glial depolarization (spreading depolarization; SD). Massive release of glutamate contributes to SD propagation, and it was recently shown that Zn(2+) is also released from synaptic vesicles during SD. The present study examined consequences of extracellular Zn(2+) accumulation on the propagation of SD. SD mechanisms were studied first in murine brain slices, using focal KCl applications as stimuli and making electrical and optical recordings in hippocampal area CA1. Elevating extracellular Zn(2+) concentrations with exogenous ZnCl(2) reduced SD propagation rates. Selective chelation of endogenous Zn(2+) (using TPEN or CaEDTA) increased SD propagation rates, and these effects appeared due to chelation of Zn(2+) derived from synaptic vesicles. Thus, in tissues where synaptic Zn(2+) release was absent [knockout (KO) of vesicular Zn(2+) transporter ZnT-3], SD propagation rates were increased, and no additional increase was observed following chelation of endogenous Zn(2+) in these tissues. The role of synaptic Zn(2+) was then examined on CSD in vivo. ZnT-3 KO animals had higher susceptibility to CSD than wild-type controls as evidenced by significantly higher propagation rates and frequencies. Studies of candidate mechanisms excluded changes in neuronal excitability, presynaptic release, and GABA receptors but left open a possible contribution of N-methyl-d-aspartate (NMDA) receptor inhibition. These results suggest the extracellular accumulation of synaptically released Zn(2+) can serve as an intrinsic inhibitor to limit SD events. The inhibitory action of extracellular Zn(2+) on SD may counteract to some extent the neurotoxic effects of intracellular Zn(2+) accumulation in acute brain injury models.
Barnes, Samuel A; Sheffler, Douglas J; Semenova, Svetlana; Cosford, Nicholas D P; Bespalov, Anton
2018-06-01
The ability of novel pharmacological compounds to improve outcomes in preclinical models is often not translated into clinical efficacy. Psychiatric disorders do not have biological boundaries, and identifying mechanisms to improve the translational bottleneck between preclinical and clinical research domains is an important and challenging task. Glutamate transmission is disrupted in several neuropsychiatric disorders. Metabotropic glutamate (mGlu) receptors represent a diverse class of receptors that contribute to excitatory neurotransmission. Given the wide, yet region-specific manner of expression, developing pharmacological compounds to modulate mGlu receptor activity provides an opportunity to subtly and selectively modulate excitatory neurotransmission. This review focuses on the potential involvement of mGlu5 receptor disruption in major depressive disorder and substance and/or alcohol use disorders. We provide an overview of the justification of targeting mGlu5 receptors in the treatment of these disorders, summarize the preclinical evidence for negatively modulating mGlu5 receptors as a therapeutic target for major depressive disorders and nicotine dependence, and highlight the outcomes of recent clinical trials. While the evidence of mGlu5 receptor negative allosteric modulation has been promising in preclinical investigations, these beneficial effects have not translated into clinical efficacy. In this review, we identify key challenges that may contribute to poor clinical translation and provide suggested approaches moving forward to potentially improve the translation from preclinical to clinical domains. Such approaches may increase the success of clinical trials and may reduce the translational bottleneck that exists in drug discovery for psychiatric disorders. Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Mohd-Sidik, Sherina; Akhtari-Zavare, Mehrnoosh; Periasamy, Ummavathy; Rampal, Lekhraj; Fadhilah, Siti Irma; Mahmud, Rozi
2018-05-01
The aim of this study was to implement and evaluate the outcomes of chemotherapy counselling based on the "Managing Patients on Chemotherapy" module on self-esteem and psychological affect (anxiety, depression) of cancer patients by pharmacists in ten selected government hospitals in Peninsular Malaysia. A randomized control trial was conducted among 2120 cancer patients from April 2016 to January 2017 in ten selected government hospitals in Peninsular Malaysia. Cancer patients were randomly assigned to intervention and control groups. The intervention group received chemotherapy counselling by pharmacists based on the "Managing Patients on Chemotherapy" module. The outcomes were assessed at baseline, 1st, 2nd and 3rd follow-ups after counselling. In the course of data analysis; independent sample t-test, chi-square and two-way repeated measures ANOVA were conducted. Mean scores of self-esteem in the intervention group had significant difference in comparison with those of the control group in the 1st, 2nd and 3rd follow-ups after counselling (P < 0.0001). Also, among those with depression and anxiety at baseline, there was reduction in depression and anxiety scores after the 1st, 2nd and 3rd follow-ups after counselling (p < 0.05). Repetitive counselling by pharmacists based on the "Managing Patients on Chemotherapy" module had positive effect on improving self-esteem and psychological affect of cancer patients undergoing chemotherapy in Peninsular Malaysia. This module can be used for all Malaysian cancer patients undergoing chemotherapy to improving self-esteem and psychological affect. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
Nursing students' alternative beliefs regarding care for patients suffering from depression.
Arrue, Marta; Zarandona, Jagoba; Hoyos Cillero, Itziar
2018-03-01
Depression is an illness that constitutes a major challenge for Public Health worldwide. Therefore, there is a clear need to receive training to care for this type of patient. This study sets out to identify alternative non-scientific beliefs among nursing students regarding the topic of depression after studying the module of Psychopathology. This study enrolled 102 third year undergraduate nursing students. The students resolved a case on an individual basis in written form which was analysed qualitatively. In this study, we have found that, despite having undergone information-transfer educational training in relation to the physiopathology of depression, nursing students persist in holding unscientific beliefs about this condition. On the basis that the opinions of nurses about depression can influence the care of their future patients, it is important to consider these alternative beliefs as learning difficulties in order to design an effective teaching instruction. Copyright © 2018. Published by Elsevier Ltd.
Duan, Dongmei; Yang, Xiuyan; Ya, Tu; Chen, Liping
2014-01-01
Preliminary basic research and clinical findings have demonstrated that electroacupuncture therapy exhibits positive effects in ameliorating depression. However, most studies of the underlying mechanism are at the single gene level; there are few reports regarding the mechanism at the whole-genome level. Using a rat genomic gene-chip, we profiled hippocampal gene expression changes in rats after electroacupuncture therapy. Electroacupuncture therapy alleviated depression-related manifestations in the model rats. Using gene-chip analysis, we demonstrated that electroacupuncture at Baihui (DU20) and Yintang (EX-HN3) regulates the expression of 21 genes. Real-time PCR showed that the genes Vgf, Igf2, Tmp32, Loc500373, Hif1a, Folr1, Nmb, and Rtn were upregulated or downregulated in depression and that their expression tended to normalize after electroacupuncture therapy. These results indicate that electroacupuncture at Baihui and Yintang modulates depression by regulating the expression of particular genes. PMID:25206746
The “Depressive” Attributional Style Is Not That Depressive for Buddhists
Liu, Michelle T.; Wang, Fei; Peng, Kaiping
2017-01-01
Numerous studies have shown that depression-prone people are characterized by a chronic style of attributing failures to internal, stable, and global causes, sometimes labeled as the “depressive attributional style.” Much less is known, however, about how social-cultural factors such as religious beliefs might modulate these processes. In the current study, we hypothesized that Buddhism’s view of ultimate internal controllability plays a buffering role against the depressive attributional style and reduces its negative impacts. We administrated measures of attributional styles and psychological adjustments to a sample of Chinese Buddhists as well as a control group recruited in China. Data analyses showed that Buddhists were more likely to attribute bad outcomes to internal, stable, and global causes, but their well-being was less affected by it. Thus, these results indicate that the “depressive” attributional style is not that depressive for Buddhists, after all. PMID:28701970
Cao, Longlong; Guo, Shuixia; Xue, Zhimin; Hu, Yong; Liu, Haihong; Mwansisya, Tumbwene E; Pu, Weidan; Yang, Bo; Liu, Chang; Feng, Jianfeng; Chen, Eric Y H; Liu, Zhening
2014-02-01
Aberrant brain functional connectivity patterns have been reported in major depressive disorder (MDD). It is unknown whether they can be used in discriminant analysis for diagnosis of MDD. In the present study we examined the efficiency of discriminant analysis of MDD by individualized computer-assisted diagnosis. Based on resting-state functional magnetic resonance imaging data, a new approach was adopted to investigate functional connectivity changes in 39 MDD patients and 37 well-matched healthy controls. By using the proposed feature selection method, we identified significant altered functional connections in patients. They were subsequently applied to our analysis as discriminant features using a support vector machine classification method. Furthermore, the relative contribution of functional connectivity was estimated. After subset selection of high-dimension features, the support vector machine classifier reached up to approximately 84% with leave-one-out training during the discrimination process. Through summarizing the classification contribution of functional connectivities, we obtained four obvious contribution modules: inferior orbitofrontal module, supramarginal gyrus module, inferior parietal lobule-posterior cingulated gyrus module and middle temporal gyrus-inferior temporal gyrus module. The experimental results demonstrated that the proposed method is effective in discriminating MDD patients from healthy controls. Functional connectivities might be useful as new biomarkers to assist clinicians in computer auxiliary diagnosis of MDD. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.
Oldham, Mark A.; Ciraulo, Domenic A.
2017-01-01
Bright light therapy (BLT) is considered among the first-line treatments for seasonal affective disorder (SAD), yet a growing body of literature supports its use in other neuropsychiatric conditions including non-seasonal depression. Despite evidence of its antidepressant efficacy, clinical use of BLT remains highly variable internationally. In this article, we explore the autonomic effects of BLT and suggest that such effects may play a role in its antidepressant and chronotherapeutic properties. After providing a brief introduction on the clinical application of BLT, we review the chronobiological effects of BLT on depression and on the autonomic nervous system in depressed and non-depressed individuals with an emphasis on non-seasonal depression. Such a theory of autonomic modulation via BLT could serve to integrate aspects of recent work centered on alleviating allostatic load, the polyvagal theory, the neurovisceral integration model and emerging evidence on the roles of glutamate and gamma-hydroxybutyric acid (GABA). PMID:24397276
Beckley, Ethan H.; Scibelli, Angela C.; Finn, Deborah A.
2010-01-01
Progesterone withdrawal has been proposed as an underlying factor in premenstrual syndrome and postpartum depression. Progesterone withdrawal induces forced swim test (FST) immobility in mice, a depression-like behavior, but the contribution of specific receptors to this effect is unclear. The role of progesterone’s GABAA receptor-modulating metabolite allopregnanolone in depression- and anxiety-related behaviors has been extensively documented, but little attention has been paid to the role of progesterone receptors. We administered the classic progesterone receptor antagonist mifepristone (RU-38486) and the specific progesterone receptor antagonist CDB-4124 to mice that had been primed with progesterone for five days, and found that both compounds induced FST immobility reliably, robustly, and in a dose-dependent fashion. Although CDB-4124 increased FST immobility, it did not suppress initial activity in a locomotor test. These findings suggest that decreased progesterone receptor activity contributes to depression-like behavior in mice, consistent with the hypothesis that progesterone withdrawal may contribute to the symptoms of premenstrual syndrome or postpartum depression. PMID:21163582
Oldham, Mark A; Ciraulo, Domenic A
2014-04-01
Bright light therapy (BLT) is considered among the first-line treatments for seasonal affective disorder (SAD), yet a growing body of literature supports its use in other neuropsychiatric conditions including non-seasonal depression. Despite evidence of its antidepressant efficacy, clinical use of BLT remains highly variable internationally. In this article, we explore the autonomic effects of BLT and suggest that such effects may play a role in its antidepressant and chronotherapeutic properties. After providing a brief introduction on the clinical application of BLT, we review the chronobiological effects of BLT on depression and on the autonomic nervous system in depressed and non-depressed individuals with an emphasis on non-seasonal depression. Such a theory of autonomic modulation via BLT could serve to integrate aspects of recent work centered on alleviating allostatic load, the polyvagal theory, the neurovisceral integration model and emerging evidence on the roles of glutamate and gamma-hydroxybutyric acid (GABA).
ERIC Educational Resources Information Center
Gebhardt, Christine; Albrecht, Doris
2018-01-01
Capsaicin has been shown to modulate synaptic plasticity in various brain regions including the amygdala. Whereas in the lateral amygdala the modulatory effect of capsaicin on long-term potentiation (LA-LTP) is mediated by TRPV1 channels, we have recently shown that capsaicin-induced enhancement of long term depression (LA-LTD) is mediated by…
HYDROCARBON SPILL SCREENING MODEL (HSSM) VOLUME 1: USER'S GUIDE
This users guide describes the Hydrocarbon Spill Screening Model (HSSM). The model is intended for simulation of subsurface releases of light nonaqueous phase liquids (LNAPLs). The model consists of separate modules for LNAPL flow through the vadose zone, spreading in the capil...
Low Cost Anti-Jam Digital Data-Links Techniques Investigations. Volume II.
1979-05-01
to spectrum-spreading factors of the order of lO 3 to 104. It is also shown that the amount of gain is a function not only of the interference to...from a standard coherent product demodulation of the band-pass radio-frequency signal. A vector-Markov data generating model is hypothesized, as in...E/N( where S is total carrier power, K is number of samples per symbol, and L(AO) is a modulation loss factor of the modulation index, A . L(AO
González-Inchauspe, Carlota; Urbano, Francisco J; Di Guilmi, Mariano N; Uchitel, Osvaldo D
2017-03-08
Acid-sensing ion channels (ASICs) regulate synaptic activities and play important roles in neurodegenerative diseases. We found that these channels can be activated in neurons of the medial nucleus of the trapezoid body (MNTB) of the auditory system in the CNS. A drop in extracellular pH induces transient inward ASIC currents (I ASIC s) in postsynaptic MNTB neurons from wild-type mice. The inhibition of I ASIC s by psalmotoxin-1 (PcTx1) and the absence of these currents in knock-out mice for ASIC-1a subunit (ASIC1a -/- ) suggest that homomeric ASIC-1as are mediating these currents in MNTB neurons. Furthermore, we detect ASIC1a-dependent currents during synaptic transmission, suggesting an acidification of the synaptic cleft due to the corelease of neurotransmitter and H + from synaptic vesicles. These currents are capable of eliciting action potentials in the absence of glutamatergic currents. A significant characteristic of these homomeric ASIC-1as is their permeability to Ca 2+ Activation of ASIC-1a in MNTB neurons by exogenous H + induces an increase in intracellular Ca 2+ Furthermore, the activation of postsynaptic ASIC-1as during high-frequency stimulation (HFS) of the presynaptic nerve terminal leads to a PcTx1-sensitive increase in intracellular Ca 2+ in MNTB neurons, which is independent of glutamate receptors and is absent in neurons from ASIC1a -/- mice. During HFS, the lack of functional ASICs in synaptic transmission results in an enhanced short-term depression of glutamatergic EPSCs. These results strongly support the hypothesis of protons as neurotransmitters and demonstrate that presynaptic released protons modulate synaptic transmission by activating ASIC-1as at the calyx of Held-MNTB synapse. SIGNIFICANCE STATEMENT The manuscript demonstrates that postsynaptic neurons of the medial nucleus of the trapezoid body at the mouse calyx of Held synapse express functional homomeric Acid-sensing ion channel-1a (ASIC-1as) that can be activated by protons (coreleased with neurotransmitter from acidified synaptic vesicles). These ASIC-1as contribute to the generation of postsynaptic currents and, more relevant, to calcium influx, which could be involved in the modulation of presynaptic transmitter release. Inhibition or deletion of ASIC-1a leads to enhanced short-term depression, demonstrating that they are concerned with short-term plasticity of the synapse. ASICs represent a widespread communication system with unique properties. We expect that our experiments will have an impact in the neurobiology field and will spread in areas related to neuronal plasticity. Copyright © 2017 the authors 0270-6474/17/372589-11$15.00/0.
Methods and apparatuses using filter banks for multi-carrier spread spectrum signals
DOE Office of Scientific and Technical Information (OSTI.GOV)
Moradi, Hussein; Farhang, Behrouz; Kutsche, Carl A
2017-01-31
A transmitter includes a synthesis filter bank to spread a data symbol to a plurality of frequencies by encoding the data symbol on each frequency, apply a common pulse-shaping filter, and apply gains to the frequencies such that a power level of each frequency is less than a noise level of other communication signals within the spectrum. Each frequency is modulated onto a different evenly spaced subcarrier. A demodulator in a receiver converts a radio frequency input to a spread-spectrum signal in a baseband. A matched filter filters the spread-spectrum signal with a common filter having characteristics matched to themore » synthesis filter bank in the transmitter by filtering each frequency to generate a sequence of narrow pulses. A carrier recovery unit generates control signals responsive to the sequence of narrow pulses suitable for generating a phase-locked loop between the demodulator, the matched filter, and the carrier recovery unit.« less
Methods and apparatuses using filter banks for multi-carrier spread spectrum signals
DOE Office of Scientific and Technical Information (OSTI.GOV)
Moradi, Hussein; Farhang, Behrouz; Kutsche, Carl A.
2016-06-14
A transmitter includes a synthesis filter bank to spread a data symbol to a plurality of frequencies by encoding the data symbol on each frequency, apply a common pulse-shaping filter, and apply gains to the frequencies such that a power level of each frequency is less than a noise level of other communication signals within the spectrum. Each frequency is modulated onto a different evenly spaced subcarrier. A demodulator in a receiver converts a radio frequency input to a spread-spectrum signal in a baseband. A matched filter filters the spread-spectrum signal with a common filter having characteristics matched to themore » synthesis filter bank in the transmitter by filtering each frequency to generate a sequence of narrow pulses. A carrier recovery unit generates control signals responsive to the sequence of narrow pulses suitable for generating a phase-locked loop between the demodulator, the matched filter, and the carrier recovery unit.« less
Pulse Shaped 8-PSK Bandwidth Efficiency and Spectral Spike Elimination
NASA Technical Reports Server (NTRS)
Tao, Jian-Ping
1998-01-01
The most bandwidth-efficient communication methods are imperative to cope with the congested frequency bands. Pulse shaping methods have excellent effects on narrowing bandwidth and increasing band utilization. The position of the baseband filters for the pulse shaping is crucial. Post-modulation pulse shaping (a low pass filter is located after the modulator) can change signals from constant envelope to non-constant envelope, and non-constant envelope signals through non-linear device (a SSPA or TWT) can further spread the power spectra. Pre-modulation pulse shaping (a filter is located before the modulator) will have constant envelope. These two pulse shaping methods have different effects on narrowing the bandwidth and producing bit errors. This report studied the effect of various pre-modulation pulse shaping filters with respect to bandwidth, spectral spikes and bit error rate. A pre-modulation pulse shaped 8-ary Phase Shift Keying (8PSK) modulation was used throughout the simulations. In addition to traditional pulse shaping filters, such as Bessel, Butterworth and Square Root Raised Cosine (SRRC), other kinds of filters or pulse waveforms were also studied in the pre-modulation pulse shaping method. Simulations were conducted by using the Signal Processing Worksystem (SPW) software package on HP workstations which simulated the power spectral density of pulse shaped 8-PSK signals, end to end system performance and bit error rates (BERS) as a function of Eb/No using pulse shaping in an AWGN channel. These results are compared with the post-modulation pulse shaped 8-PSK results. The simulations indicate traditional pulse shaping filters used in pre-modulation pulse shaping may produce narrower bandwidth, but with worse BER than those in post-modulation pulse shaping. Theory and simulations show pre- modulation pulse shaping could also produce discrete line power spectra (spikes) at regular frequency intervals. These spikes may cause interference with adjacent channel and reduce power efficiency. Some particular pulses (filters), such as trapezoid and pulses with different transits (such as weighted raised cosine transit) were found to reduce bandwidth and not generate spectral spikes. Although a solid state power amplifier (SSPA) was simulated in the non-linear (saturation) region, output power spectra did not spread due to the constant envelope 8-PSK signals.
The role of neuroinflammation and neurovascular dysfunction in major depressive disorder.
Jeon, Sang Won; Kim, Yong-Ku
2018-01-01
Although depression has generally been explained with monoamine theory, it is far more multifactorial, and therapies that address the disease's pathway have not been developed. In this context, an understanding of neuroinflammation and neurovascular dysfunction would enable a more comprehensive approach to depression. Inflammation is in a sense a type of allostatic load involving the immune, endocrine, and nervous systems. Neuroinflammation is involved in the pathophysiology of depression by increasing proinflammatory cytokines, activating the hypothalamus-pituitary-adrenal axis, increasing glucocorticoid resistance, and affecting serotonin synthesis and metabolism, neuronal apoptosis and neurogenesis, and neuroplasticity. In future, identifying the subtypes of depression with increased vulnerability to inflammation and testing the effects of inflammatory modulating agents in these patient groups through clinical trials will lead to more concrete conclusions on the matter. The vascular depression hypothesis is supported by evidence for the association between vascular disease and late-onset depression and between ischemic brain lesions and distinctive depressive symptoms. Vascular depression may be the entity most suitable for studies of the mechanisms of depression. Pharmacotherapies used in the prevention and treatment of cerebrovascular disease may help prevent vascular depression. In future, developments in structural and functional imaging, electrophysiology, chronobiology, and genetics will reveal the association between depression and brain lesions. This article aims to give a general review of the existing issues examined in the literature pertaining to depression-related neuroinflammatory and vascular functions, related pathophysiology, applicability to depression treatment, and directions for future research.
The role of neuroinflammation and neurovascular dysfunction in major depressive disorder
Jeon, Sang Won; Kim, Yong-Ku
2018-01-01
Although depression has generally been explained with monoamine theory, it is far more multifactorial, and therapies that address the disease’s pathway have not been developed. In this context, an understanding of neuroinflammation and neurovascular dysfunction would enable a more comprehensive approach to depression. Inflammation is in a sense a type of allostatic load involving the immune, endocrine, and nervous systems. Neuroinflammation is involved in the pathophysiology of depression by increasing proinflammatory cytokines, activating the hypothalamus–pituitary–adrenal axis, increasing glucocorticoid resistance, and affecting serotonin synthesis and metabolism, neuronal apoptosis and neurogenesis, and neuroplasticity. In future, identifying the subtypes of depression with increased vulnerability to inflammation and testing the effects of inflammatory modulating agents in these patient groups through clinical trials will lead to more concrete conclusions on the matter. The vascular depression hypothesis is supported by evidence for the association between vascular disease and late-onset depression and between ischemic brain lesions and distinctive depressive symptoms. Vascular depression may be the entity most suitable for studies of the mechanisms of depression. Pharmacotherapies used in the prevention and treatment of cerebrovascular disease may help prevent vascular depression. In future, developments in structural and functional imaging, electrophysiology, chronobiology, and genetics will reveal the association between depression and brain lesions. This article aims to give a general review of the existing issues examined in the literature pertaining to depression-related neuroinflammatory and vascular functions, related pathophysiology, applicability to depression treatment, and directions for future research. PMID:29773951
[The genetics of depressive disorders].
Schulte-Körne, Gerd; Allgaier, Antje-Kathrin
2008-01-01
Among the most common severe psychiatric disorders worldwide, depressive disorders are a leading cause of morbidity, the onset usually occurring during childhood or adolescence. Symptomatology, prevalence, outcome and treatment differentiate depressive disorder nosologically as being either unipolar depression or bipolar disorder, which is characterized by one or more episodes of mania with or without episodes of depression. Genetic factors decisively influence the susceptibility to depressive disorders. Family studies and twin studies have been essential in defining the magnitude of familial risk and liability to heritability, particularly in the case of bipolar disorder. In recent years, linkage and association studies have made great strides towards identifying candidate genes. Particularly the s-allele of the serotonin transporter has been repeatedly confirmed to be a risk factor. Meta-analyses suggest, however, that the genetic contributions of the ascertained loci are relatively small. Along with genetic factors, environmental factors are heavily involved. Gene-environment action plays a pivotal role, particularly in unipolar depression. The genetic disposition seems to be modulated by a protective or pathogenic environment. Early-onset disorders must be further investigated in future as studies to date are somewhat limited.
Hong, Ji Sun; Kim, Sun Mi; Bae, Sujin; Han, Doug Hyun
2018-01-01
Problematic Internet game play is often accompanied by major depressive disorder (MDD). Depression seems to be closely related to altered functional connectivity (FC) within (and between) the default mode network (DMN) and salience network. In addition, serotonergic neurotransmission may regulate the symptoms of depression, including impulsivity, potentially by modulating the DMN. We hypothesized that altered connectivity between the DMN and salience network could mediate an association between the 5HTTLPR genotype and impulsivity in patients with depression. A total of 54 participants with problematic Internet game play and MDD completed the research protocol. We genotyped for 5HTTLPR and assessed the DMN FC using resting-state functional magnetic resonance imaging. The severity of Internet game play, depressive symptoms, anxiety, attention and impulsivity, and behavioral inhibition and activation were assessed using the Young Internet Addiction Scale (YIAS), Beck Depressive Inventory, Beck Anxiety Inventory (BAI), Korean Attention Deficit Hyperactivity Disorder scale, and the Behavioral Inhibition and Activation Scales (BIS-BAS), respectively. The SS allele was associated with increased FC within the DMN, including the middle prefrontal cortex (MPFC) to the posterior cingulate cortex, and within the salience network, including the right supramarginal gyrus (SMG) to the right rostral prefrontal cortex (RPFC), right anterior insular (AInsular) to right SMG, anterior cingulate cortex (ACC) to left RPFC, and left AInsular to right RPFC, and between the DMN and salience network, including the MPFC to the ACC. In addition, the FC from the MPFC to ACC positively correlated with the BIS and YIAS scores in the SS allele group. The SS allele of 5HTTLPR might modulate the FC within and between the DMN and salience network, which may ultimately be a risk factor for impulsive Internet game play in patients with MDD.
Su, J Y; Chang, Y I
1993-05-01
Ryanodine causes depression of the caffeine-induced tension transient (ryanodine depression) in skinned muscle fibers, because it blocks the sarcoplasmic reticulum (SR) Ca(2+)-release channels [Su, J. Y. (1988) Pflügers Arch 411:132-136, 371-377; (1992) Pflügers Arch 421:1-6]. This study was performed to examine the sensitivity of SR Ca(2+)-release channels to ryanodine in fetal compared to adult myocardium and to investigate the influence of Ca2+, caffeine, and Mg2+ on ryanodine depression in skinned fibers. Ryanodine (0.3 nM-1 microM) caused a dose-dependent depression in skinned myocardial fibers of the rat, and the fetal fibers (IC50 approximately 74 nM) were 26-fold less sensitive than those of the adult (IC50 approximately 2.9 nM). The depression induced by 0.1 microM or 1 microM ryanodine was a function of [caffeine], or [Ca2+] (pCa < 6.0), which was potentiated by caffeine, and an inverse function of [Mg2+]. At pCa > 8.0 plus 25 mM caffeine, a 20% ryanodine depression was observed in both the fetal and adult fibers, indicating independence from Ca2+. Ryanodine depression in skinned fibers of the fetus was less affected than that seen in the adult by pCai, [caffeine]i, or 25 mM caffeine plus pCai or plus pMgi (IC50 approximately pCa 4.5 versus 5.1; caffeine 12.7 mM versus 2 mM; pCa 6.7 versus 7.3; and pMg 3.9 versus 3.3 respectively). The results show that the SR Ca(2+)-release channel in both fetal and adult myocardium is modulated by Ca2+, caffeine, and Mg2+.(ABSTRACT TRUNCATED AT 250 WORDS)
Aguilera, Adrian; Garza, Monica J.; Muñoz, Ricardo F.
2014-01-01
The authors applied cognitive-behavioral therapy (CBT) for depression using the Healthy Management of Reality treatment manual. This 16-week group treatment comprised four 4-week modules: thoughts (cognitive restructuring), activities (behavioral activation), people (interpersonal skills training), and health (addresses physical health and depression). They illustrated the use of the culture-sensitive treatment manuals by way of the member characteristics and clinical process of a Spanish-language CBT group for depression. They highlighted the challenges and satisfactions of working with a Spanish-speaking population in the public sector, and focused on how culture and socioeconomic status influence patients, and how to adapt treatment to these factors. Last, they demonstrated how technological advances integrate with culture-sensitive, evidence-based treatments to better serve this population and reduce disparities. PMID:20549680
Aguilera, Adrian; Garza, Monica J; Muñoz, Ricardo F
2010-08-01
The authors applied cognitive-behavioral therapy (CBT) for depression using the Healthy Management of Reality treatment manual. This 16-week group treatment comprised four 4-week modules: thoughts (cognitive restructuring), activities (behavioral activation), people (interpersonal skills training), and health (addresses physical health and depression). They illustrated the use of the culture-sensitive treatment manuals by way of the member characteristics and clinical process of a Spanish-language CBT group for depression. They highlighted the challenges and satisfactions of working with a Spanish-speaking population in the public sector, and focused on how culture and socioeconomic status influence patients, and how to adapt treatment to these factors. Last, they demonstrated how technological advances integrate with culture-sensitive, evidence-based treatments to better serve this population and reduce disparities.
Juhas, Mario; Dimopoulou, Ioanna; Robinson, Esther; Elamin, Abdel; Harding, Rosalind; Hood, Derek; Crook, Derrick
2013-09-01
A significant part of horizontal gene transfer is facilitated by genomic islands. Haemophilus influenzae genomic island ICEHin1056 is an archetype of a genomic island that accounts for pandemic spread of antibiotics resistance. ICEHin1056 has modular structure and harbors modules involved in type IV secretion and integration. Previous studies have shown that ICEHin1056 encodes a functional type IV secretion system; however, other modules have not been characterized yet. Here we show that the module on the 5' extremity of ICEHin1056 consists of 15 genes that are well conserved in a number of related genomic islands. Furthermore by disrupting six genes of the investigated module of ICEHin1056 by site-specific mutagenesis we demonstrate that in addition to type IV secretion system module, the investigated module is also important for the successful conjugal transfer of ICEHin1056 from donor to recipient cells. Copyright © 2013 Elsevier Inc. All rights reserved.
Insights into Corona Formation through Statistical Analyses
NASA Technical Reports Server (NTRS)
Glaze, L. S.; Stofan, E. R.; Smrekar, S. E.; Baloga, S. M.
2002-01-01
Statistical analysis of an expanded database of coronae on Venus indicates that the populations of Type 1 (with fracture annuli) and 2 (without fracture annuli) corona diameters are statistically indistinguishable, and therefore we have no basis for assuming different formation mechanisms. Analysis of the topography and diameters of coronae shows that coronae that are depressions, rimmed depressions, and domes tend to be significantly smaller than those that are plateaus, rimmed plateaus, or domes with surrounding rims. This is consistent with the model of Smrekar and Stofan and inconsistent with predictions of the spreading drop model of Koch and Manga. The diameter range for domes, the initial stage of corona formation, provides a broad constraint on the buoyancy of corona-forming plumes. Coronae are only slightly more likely to be topographically raised than depressions, with Type 1 coronae most frequently occurring as rimmed depressions and Type 2 coronae most frequently occuring with flat interiors and raised rims. Most Type 1 coronae are located along chasmata systems or fracture belts, while Type 2 coronas are found predominantly as isolated features in the plains. Coronae at hotspot rises tend to be significantly larger than coronae in other settings, consistent with a hotter upper mantle at hotspot rises and their active state.
Depressive disorders: Processes leading to neurogeneration and potential novel treatments.
Brown, Gregory M; McIntyre, Roger S; Rosenblat, Joshua; Hardeland, Rüdiger
2018-01-03
Mood disorders are wide spread with estimates that one in seven of the population are affected at some time in their life (Kessler et al., 2012). Many of those affected with severe depressive disorders have cognitive deficits which may progress to frank neurodegeneration. There are several peripheral markers shown by patients who have cognitive deficits that could represent causative factors and could potentially serve as guides to the prevention or even treatment of neurodegeneration. Circadian rhythm misalignment, immune dysfunction and oxidative stress are key pathologic processes implicated in neurodegeneration and cognitive dysfunction in depressive disorders. Novel treatments targeting these pathways may therefore potentially improve patient outcomes whereby the primary mechanism of action is outside of the monoaminergic system. Moreover, targeting immune dysfunction, oxidative stress and circadian rhythm misalignment (rather than primarily the monoaminergic system) may hold promise for truly disease modifying treatments that may prevent neurodegeneration rather than simply alleviating symptoms with no curative intent. Further research is required to more comprehensively understand the contributions of these pathways to the pathophysiology of depressive disorders to allow for disease modifying treatments to be discovered. Copyright © 2017 Elsevier Inc. All rights reserved.
Advanced Optimal Extraction for the Spitzer/IRS
NASA Astrophysics Data System (ADS)
Lebouteiller, V.; Bernard-Salas, J.; Sloan, G. C.; Barry, D. J.
2010-02-01
We present new advances in the spectral extraction of pointlike sources adapted to the Infrared Spectrograph (IRS) on board the Spitzer Space Telescope. For the first time, we created a supersampled point-spread function of the low-resolution modules. We describe how to use the point-spread function to perform optimal extraction of a single source and of multiple sources within the slit. We also examine the case of the optimal extraction of one or several sources with a complex background. The new algorithms are gathered in a plug-in called AdOpt which is part of the SMART data analysis software.
NASA Technical Reports Server (NTRS)
1976-01-01
The results of the spread spectrum despreader project are reported and three principal products are designed and tested. The products are, (1) a spread spectrum despreader breadboard, (2) associated test equipment consisting of a spectrum spreader and bit reconstruction/error counter and (3) paper design of a Ku-band receiver which would incorporate the despreader as a principal subsystem. The despreader and test set are designed for maximum flexibility. A choice of unbalanced quadriphase or biphase shift keyed data modulation is available. Selectable integration time and threshold voltages on the despreader further lend true usefulness as laboratory test equipment to the delivered hardware.
Topographical distribution of fast and slow sleep spindles in medicated depressive patients.
Nishida, Masaki; Nakashima, Yusaku; Nishikawa, Toru
2014-10-01
To compare the properties of sleep spindles between healthy subjects and medicated patients with major depressive episode, including frequency range, spectra power, and spatial distribution of spindle power. Continuous 16-channel EEG was used to record nocturnal sleep in healthy control subjects and medicated depressive patients. Recordings were analyzed for changes in EEG power spectra and power topography. Additionally, we graphically demonstrated the pattern of spatial distribution of each type of sleep spindle, divided into fast (12.5-14 Hz) and slow spindles (11-12.5 Hz). Sleep EEG records of depressive subjects exhibited a significantly higher amplitude of slow spindles in the prefrontal region, compared with the healthy controls (P < 0.01). Fast spindles were dominant in the centroparietal region in both depressive patients and the control group. Enhanced slow spindles in the prefrontal region were observed in the medicated depressive patients and not in the healthy controls. The frequency of fast spindles in depressive patients was globally higher than that in healthy participants. The alteration in sleep spindles seen in medicated depressive subjects may reflect a pharmacological modulation of synaptic function involving the thalamic-reticular and thalamocortical mechanisms.
López-Cruz, Laura; Salamone, John D.; Correa, Mercè
2018-01-01
Major depressive disorder is one of the most common and debilitating psychiatric disorders. Some of the motivational symptoms of depression, such anergia (lack of self-reported energy) and fatigue are relatively resistant to traditional treatments such as serotonin uptake inhibitors. Thus, new pharmacological targets are being investigated. Epidemiological data suggest that caffeine consumption can have an impact on aspects of depressive symptomatology. Caffeine is a non-selective adenosine antagonist for A1/A2A receptors, and has been demonstrated to modulate behavior in classical animal models of depression. Moreover, selective adenosine receptor antagonists are being assessed for their antidepressant effects in animal studies. This review focuses on how caffeine and selective adenosine antagonists can improve different aspects of depression in humans, as well as in animal models. The effects on motivational symptoms of depression such as anergia, fatigue, and psychomotor slowing receive particular attention. Thus, the ability of adenosine receptor antagonists to reverse the anergia induced by dopamine antagonism or depletion is of special interest. In conclusion, although further studies are needed, it appears that caffeine and selective adenosine receptor antagonists could be therapeutic agents for the treatment of motivational dysfunction in depression. PMID:29910727
Xu, Weifeng; Wolff, Brian S.
2014-01-01
Low-intensity alternating electric fields applied to the scalp are capable of modulating cortical activity and brain functions, but the underlying mechanisms remain largely unknown. Here, we report two distinct components of voltage-sensitive dye signals induced by low-intensity, alternating electric fields in rodent cortical slices: a “passive component,” which corresponds to membrane potential changes directly induced by the electric field; and an “active component,” which is a widespread depolarization that is dependent on excitatory synaptic transmission. The passive component is stationary, with amplitude and phase accurately reflecting the cortical cytoarchitecture. In contrast, the active component is initiated from a local “hot spot” of activity and spreads to a large population as a propagating wave with rich local dynamics. The propagation of the active component may play a role in modulating large-scale cortical activity by spreading a low level of excitation from a small initiation point to a vast neuronal population. PMID:25122710
Brownstein, John S; Wolfe, Cecily J; Mandl, Kenneth D
2006-01-01
Background The influence of air travel on influenza spread has been the subject of numerous investigations using simulation, but very little empirical evidence has been provided. Understanding the role of airline travel in large-scale influenza spread is especially important given the mounting threat of an influenza pandemic. Several recent simulation studies have concluded that air travel restrictions may not have a significant impact on the course of a pandemic. Here, we assess, with empirical data, the role of airline volume on the yearly inter-regional spread of influenza in the United States. Methods and Findings We measured rate of inter-regional spread and timing of influenza in the United States for nine seasons, from 1996 to 2005 using weekly influenza and pneumonia mortality from the Centers for Disease Control and Prevention. Seasonality was characterized by band-pass filtering. We found that domestic airline travel volume in November (mostly surrounding the Thanksgiving holiday) predicts the rate of influenza spread (r 2 = 0.60; p = 0.014). We also found that international airline travel influences the timing of influenza mortality (r 2 = 0.59; p = 0.016). The flight ban in the US after the terrorist attack on September 11, 2001, and the subsequent depression of the air travel market, provided a natural experiment for the evaluation of flight restrictions; the decrease in air travel was associated with a delayed and prolonged influenza season. Conclusions We provide the first empirical evidence for the role of airline travel in long-range dissemination of influenza. Our results suggest an important influence of international air travel on the timing of influenza introduction, as well as an influence of domestic air travel on the rate of inter-regional influenza spread in the US. Pandemic preparedness strategies should account for a possible benefit of airline travel restrictions on influenza spread. PMID:16968115
Report of the Indo-US health care summit 2009 - Mental health section.
Pandurangi, Anand K; Desai, Nimesh G
2009-01-01
The 2nd Indo-US Health Care Summit held in January 2009 was a forum to discuss collaboration between physicians in the US and India on medical education, health care services and research. Six specialties were represented including Mental Health (MH). Using Depression as the paradigmatic disorder, the following objectives were developed. Objective I - Leadership and Public Education: Linkage with like-minded agencies and organizations. The core message should be simple. Major Depression is a brain disorder. Depression is treatable. Timely treatment prevents disability and suicide. Objective II - Medical Education: To improve psychiatric education, it was proposed that (1) relations between US/UK and Indian mid-level institutions be established, (2) teaching methods such as tele-psychiatry and online courses be pursued, (3) use models of teaching excellence to arouse student interest, and (4) develop core curricula for other branches of medicine, and CME. Objective III - Reduce Complications of Depression (Suicide, Alcoholism): Goals include (1) decriminalizing attempted suicide, (2) improving reporting systems, and including depression, psychosis, alcoholism, and suicide in the national registry, (3) pilot studies in vulnerable groups on risk and interventions, and (4) education of colleagues on alcoholism as a link between psychiatric and medical disorders. Objective IV - Integrating MH Treatment& Primary Health Care: The focus should be on training of general practitioners in psychiatry. Available training modules including long distance learning modules to be suitably modified for India. Collaborations and specific project designs are to be developed, implemented and monitored by each specialty group and reviewed in future summits.
Defining and Predicting Patterns of Early Response in a Web-Based Intervention for Depression
Arndt, Alice; Rubel, Julian; Berger, Thomas; Schröder, Johanna; Späth, Christina; Meyer, Björn; Greiner, Wolfgang; Gräfe, Viola; Hautzinger, Martin; Fuhr, Kristina; Rose, Matthias; Nolte, Sandra; Löwe, Bernd; Hohagen, Fritz; Klein, Jan Philipp; Moritz, Steffen
2017-01-01
Background Web-based interventions for individuals with depressive disorders have been a recent focus of research and may be an effective adjunct to face-to-face psychotherapy or pharmacological treatment. Objective The aim of our study was to examine the early change patterns in Web-based interventions to identify differential effects. Methods We applied piecewise growth mixture modeling (PGMM) to identify different latent classes of early change in individuals with mild-to-moderate depression (n=409) who underwent a CBT-based web intervention for depression. Results Overall, three latent classes were identified (N=409): Two early response classes (n=158, n=185) and one early deterioration class (n=66). Latent classes differed in terms of outcome (P<.001) and adherence (P=.03) in regard to the number of modules (number of modules with a duration of at least 10 minutes) and the number of assessments (P<.001), but not in regard to the overall amount of time using the system. Class membership significantly improved outcome prediction by 24.8% over patient intake characteristics (P<.001) and significantly added to the prediction of adherence (P=.04). Conclusions These findings suggest that in Web-based interventions outcome and adherence can be predicted by patterns of early change, which can inform treatment decisions and potentially help optimize the allocation of scarce clinical resources. PMID:28600278
Acute Stress-Induced Epigenetic Modulations and Their Potential Protective Role Toward Depression.
Rusconi, Francesco; Battaglioli, Elena
2018-01-01
Psychiatric disorders entail maladaptive processes impairing individuals' ability to appropriately interface with environment. Among them, depression is characterized by diverse debilitating symptoms including hopelessness and anhedonia, dramatically impacting the propensity to live a social and active life and seriously affecting working capability. Relevantly, besides genetic predisposition, foremost risk factors are stress-related, such as experiencing chronic psychosocial stress-including bullying, mobbing and abuse-, and undergoing economic crisis or chronic illnesses. In the last few years the field of epigenetics promised to understand core mechanisms of gene-environment crosstalk, contributing to get into pathogenic processes of many disorders highly influenced by stressful life conditions. However, still very little is known about mechanisms that tune gene expression to adapt to the external milieu. In this Perspective article, we discuss a set of protective, functionally convergent epigenetic processes induced by acute stress in the rodent hippocampus and devoted to the negative modulation of stress-induced immediate early genes (IEGs) transcription, hindering stress-driven morphostructural modifications of corticolimbic circuitry. We also suggest that chronic stress damaging protective epigenetic mechanisms, could bias the functional trajectory of stress-induced neuronal morphostructural modification from adaptive to maladaptive, contributing to the onset of depression in vulnerable individuals. A better understanding of the epigenetic response to stress will be pivotal to new avenues of therapeutic intervention to treat depression, especially in light of limited efficacy of available antidepressant drugs.
Chang, Shuo-Hsiu; Tseng, Shih-Chiao; McHenry, Colleen L.; Littmann, Andrew E.; Suneja, Manish; Shields, Richard K.
2012-01-01
Objective We investigated the effect of various doses of vertical oscillation (vibration) on soleus H-reflex amplitude and post-activation depression in individuals with and without SCI. We also explored the acute effect of short-term limb vibration on skeletal muscle mRNA expression of genes associated with spinal plasticity. Methods Six healthy adults and five chronic complete SCI subjects received vibratory stimulation of their tibia over three different gravitational accelerations (0.3g, 0.6g, and 1.2g) at a fixed frequency (30 Hz). Soleus H-reflexes were measured before, during, and after vibration. Two additional chronic complete SCI subjects had soleus muscle biopsies 3 h following a single bout of vibration. Results H-reflex amplitude was depressed over 83% in both groups during vibration. This vibratory-induced inhibition lasted over 2 min in the control group, but not in the SCI group. Post-activation depression was modulated during the long-lasting vibratory inhibition. A single bout of mechanical oscillation altered mRNA expression from selected genes associated with synaptic plasticity. Conclusions Vibration of the lower leg inhibits the H-reflex amplitude, influences post-activation depression, and alters skeletal muscle mRNA expression of genes associated with synaptic plasticity. Significance Limb segment vibration may offer a long term method to reduce spinal reflex excitability after SCI. PMID:21963319
Patron, Elisabetta; Messerotti Benvenuti, Simone; Favretto, Giuseppe; Valfrè, Carlo; Bonfà, Carlotta; Gasparotto, Renata; Palomba, Daniela
2013-03-01
The current study investigated whether biofeedback training aimed at increasing respiratory sinus arrhythmia (RSA), a measure of cardiac vagal modulation, can reduce depressive symptoms in patients after cardiac surgery. This randomized controlled study enrolled 26 patients after first-time cardiac surgery. The patients were randomly assigned to an RSA-biofeedback group (N = 13) or to a treatment as usual group (N = 13). The biofeedback training consisted of five 45 min sessions designed to increase RSA. The outcome was assessed as changes in RSA and in the Centre for Epidemiologic Studies of Depression (CES-D) values from pre- to post-training. Both groups were comparable for demographic and biomedical characteristics. RSA increased significantly in patients who underwent RSA-biofeedback compared to controls. Moreover, the CES-D scores were reduced significantly from pre- to post-training in the RSA-biofeedback group compared to the controls. Changes in RSA were inversely related to changes in CES-D scores from pre- to post-training. These findings extend the effectiveness of RSA-biofeedback for increasing vagal modulation as well as for reducing depressive symptoms in post-surgical patients. Overall, the current study also suggests that this biobehavioral intervention may add to the efficacy of postoperative risk reduction programs and rehabilitation protocols in cardiac surgery patients.
Acute Stress-Induced Epigenetic Modulations and Their Potential Protective Role Toward Depression
Rusconi, Francesco; Battaglioli, Elena
2018-01-01
Psychiatric disorders entail maladaptive processes impairing individuals’ ability to appropriately interface with environment. Among them, depression is characterized by diverse debilitating symptoms including hopelessness and anhedonia, dramatically impacting the propensity to live a social and active life and seriously affecting working capability. Relevantly, besides genetic predisposition, foremost risk factors are stress-related, such as experiencing chronic psychosocial stress—including bullying, mobbing and abuse—, and undergoing economic crisis or chronic illnesses. In the last few years the field of epigenetics promised to understand core mechanisms of gene-environment crosstalk, contributing to get into pathogenic processes of many disorders highly influenced by stressful life conditions. However, still very little is known about mechanisms that tune gene expression to adapt to the external milieu. In this Perspective article, we discuss a set of protective, functionally convergent epigenetic processes induced by acute stress in the rodent hippocampus and devoted to the negative modulation of stress-induced immediate early genes (IEGs) transcription, hindering stress-driven morphostructural modifications of corticolimbic circuitry. We also suggest that chronic stress damaging protective epigenetic mechanisms, could bias the functional trajectory of stress-induced neuronal morphostructural modification from adaptive to maladaptive, contributing to the onset of depression in vulnerable individuals. A better understanding of the epigenetic response to stress will be pivotal to new avenues of therapeutic intervention to treat depression, especially in light of limited efficacy of available antidepressant drugs. PMID:29904343
Development of cognitive-behavioral therapy intervention for patients with Dhat syndrome
Salam, K. P. Abdul; Sharma, Mahendra P.; Prakash, Om
2012-01-01
Dhat syndrome is a culture-bound syndrome prevalent in the natives of the Indian subcontinent characterized by excessive concern about harmful consequences of loss of semen (ICD-10). Treatment offered to the patients suffering from it continues to be esoteric, unstructured and without standardization. The present study aimed to develop and examine the feasibility of Cognitive – Behavior Therapy module for patients with Dhat syndrome. A draft module was developed based on existing theoretical knowledge and suggestions from five mental health professionals. This module was then applied on five patients with Dhat syndrome to assess and judge the suitability of the module. The pre and post-assessments were carried out using Sexual Knowledge and Attitude Questionnaire - II, Hamilton Depression Rating Scale, The Cognitive-Somatic Anxiety Scale, Screener for Somatoform Disorder, International Index for Erectile Function, Clinical Global Impressions, The World Health Organization Quality of Life Assessment - BREF. Experiences and insights gained from each patient were used to refine the module before applying on the next patient. The final module consisted of the following components was developed: Basic sex education, cognitive restructuring, relaxation training, imaginal desensitization, masturbatory training as homework and Kegel's exercises and ‘start-stop technique’ and ‘squeeze technique’ for sexual dysfunctions. Results of the study reveal that it is feasible to carry out the CBT module in clinical settings. Number of sessions ranged from 11 to 16 sessions. The duration of the session was 45 minutes on the average. Findings of the present study revealed improvement in sexual knowledge, anxiety, depressive and somatic symptoms. Implications and limitations of the study are highlighted and suggestions for future research offered. PMID:23372242
Adherence to a web-based intervention program for traumatized persons in mainland China.
Wang, Zhiyun
2014-01-01
This paper investigated adherence to a self-help web-based intervention for PTSD (Chinese My Trauma Recovery, CMTR) in mainland China and evaluated the association between adherence measures and potential predictors, for example, traumatic symptoms and self-efficacy. Data from 56 urban and 90 rural trauma survivors were reported who used at least one of the seven recovery modules of CMTR. The results showed that 80% urban users visited CMTR four or less days and 87% rural users visited CMTR for 5 or 6 days. On average, urban users visited 2.54 (SD=1.99) modules on the first visiting day and less from the second day; rural users visited 1.10 (SD=0.54) modules on the first visiting day, and it became stable in the following days. In both samples, depression scores at pre-test were significantly or trend significantly associated with the number of visited web pages in the relaxation and professional help modules (r=0.20-0.26, all p<0.14); traumatic symptom scores at pre-test significantly or trend significantly correlated to the number of visited web pages in the relaxation, professional help, and mastery tools modules (r=0.20-0.26, all p<0.10). Moreover, urban users' coping self-efficacy scores at pre-test significantly or trend significantly related to the number of visited web pages in the relaxation, professional help, social support, and mastery tool modules (r=0.20-0.33, all p<0.16). These findings suggest that individuals tend to focus on one or two recovery modules when they visit CMTR, and the number of web pages visited during the intervention period relates to users' traumatic and depressive symptoms and self-efficacy before intervention.
Tadayonnejad, Reza; Ajilore, Olusola; Mickey, Brian J.; Crane, Natania A.; Hsu, David T.; Kumar, Anand; Zubieta, Jon-Kar; Langenecker, Scott A.
2016-01-01
The pulvinar, the largest thalamus nucleus, has rich anatomical connections with several different cortical and subcortical regions suggesting its important involvement in high-level cognitive and emotional functions. Unfortunately, pulvinar dysfunction in psychiatric disorders particularly major depression disorder has not been thoroughly examined to date. In this study we explored the alterations in the baseline regional and network activities of the pulvinar in MDD by applying spectral analysis of resting-state oscillatory activity, functional connectivity and directed (effective) connectivity on resting-state fMRI data acquired from 20 healthy controls and 19 participants with MDD. Furthermore, we tested how pharmacological treatment with duloxetine can modulate the measured local and network variables in ten participants who completed treatment. Our results revealed a frequency-band dependent modulation of power spectrum characteristics of pulvinar regional oscillatory activity. At the network level, we found MDD is associated with aberrant causal interactions between pulvinar and several systems including default-mode and posterior insular networks. It was also shown that duloxetine treatment can correct or overcompensate the pathologic network behavior of the pulvinar. In conclusion, we suggest that pulvinar regional baseline oscillatory activity and its resting-state network dynamics are compromised in MDD and can be modulated therapeutically by pharmacological treatment. PMID:27148894
Duprat, Romain; Wu, Guo-Rong; De Raedt, Rudi; Baeken, Chris
2017-08-09
Accelerated intermittent theta-burst stimulation (aiTBS) anti-depressive working mechanisms are still unclear. Because aiTBS may work through modulating the reward system and the level of anhedonia may influence this modulation, we investigated the effect of aiTBS on reward responsiveness in high and low anhedonic MDD patients. In this registered RCT (NCT01832805), 50 MDD patients were randomised to a sham-controlled cross-over aiTBS treatment protocol over the left dorsolateral prefrontal cortex (DLPFC). Patients performed a probabilistic learning task in fMRI before and after each week of stimulation. Task performance analyses did not show any significant effects of aiTBS on reward responsiveness, nor differences between both groups of MDD patients. However, at baseline, low anhedonic patients displayed higher neural activity in the caudate and putamen. After the first week of aiTBS treatment, in low anhedonic patients we found a decreased neural activity within the reward system, in contrast to an increased activity observed in high anhedonic patients. No changes were observed in reward related neural regions after the first week of sham stimulation. Although both MDD groups showed no differences in task performance, our brain imaging findings suggest that left DLPFC aiTBS treatment modulates the reward system differently according to anhedonia severity.
Spreading Depressions as Secondary Insults after Traumatic Injury to the Human Brain
2012-09-01
earlier and larger craniotomies and better outcomes, despite being similar in initial injury characteristics compared to KCH patients. VCU patients also...enrolled patients with acute TBI who met the following inclusion criteria: clinical decision for craniotomy for lesion evacuation, de compression, or... craniotomies for evacuation of intracranial mass lesions or cerebral decompression, a median of 9·9 h (IQR 4·5–26·3) after trauma
Dissecting the Roles of Brain Injury and Combat-Related Stress in Post-Traumatic Headache
2015-10-01
were the major goals of the project? Post-traumatic headache (PTH) is an epidemic in our military personnel. It is a chronic, migraine -like...and affective processing that lead to PTH. Cortical spreading depression (CSD) is the physiological correlate of the migraine aura, but it also...paradigm. NTG infusion triggers migraine without aura in human migraineurs and reduced mechanical allodynia threshold in rodents. This enables 11
Depression, anxiety and somatization in primary care: syndrome overlap and functional impairment.
Löwe, Bernd; Spitzer, Robert L; Williams, Janet B W; Mussell, Monika; Schellberg, Dieter; Kroenke, Kurt
2008-01-01
To determine diagnostic overlap of depression, anxiety and somatization as well as their unique and overlapping contribution to functional impairment. Two thousand ninety-one consecutive primary care clinic patients participated in a multicenter cross-sectional survey in 15 primary care clinics in the United States (participation rate, 92%). Depression, anxiety, somatization and functional impairment were assessed using validated scales from the Patient Health Questionnaire (PHQ) (PHQ-8, eight-item depression module; GAD-7, seven-item Generalized Anxiety Disorder Scale; and PHQ-15, 15-item somatic symptom scale) and the Short-Form General Health Survey (SF-20). Multiple linear regression analyses were used to investigate unique and overlapping associations of depression, anxiety and somatization with functional impairment. In over 50% of cases, comorbidities existed between depression, anxiety and somatization. The contribution of the commonalities of depression, anxiety and somatization to functional impairment substantially exceeded the contribution of their independent parts. Nevertheless, depression, anxiety and somatization did have important and individual effects (i.e., separate from their overlap effect) on certain areas of functional impairment. Given the large syndrome overlap, a potential consideration for future diagnostic classification would be to describe basic diagnostic criteria for a single overarching disorder and to optionally code additional diagnostic features that allow a more detailed classification into specific depressive, anxiety and somatoform subtypes.
Lokman, Suzanne; Leone, Stephanie S; Sommers-Spijkerman, Marion; van der Poel, Agnes; Smit, Filip; Boon, Brigitte
2017-01-04
Prevention of depression is important due to the substantial burden of disease associated with it. To this end, we developed a novel, brief, and low-threshold Web-based self-help approach for depressive complaints called complaint-directed mini-interventions (CDMIs). These CDMIs focus on highly prevalent complaints that are demonstrably associated with depression and have a substantial economic impact: stress, sleep problems, and worry. The aim was to evaluate the effectiveness of the Web-based self-help CDMIs in a sample of adults with mild-to-moderate depressive symptoms compared to a wait-list control group. A two-armed randomized controlled trial was conducted. An open recruitment strategy was used. Participants were randomized to either the Web-based CDMIs or the no-intervention wait-list control group. The CDMIs are online, unguided, self-help interventions, largely based on cognitive behavioral techniques, which consist of 3 to 4 modules with up to 6 exercises per module. Participants are free to choose between the modules and exercises. Assessments, using self-report questionnaires, took place at baseline and at 3 and 6 months after baseline. The control group was given access to the intervention following the 3-month assessment. The primary goal of the CDMIs is to reduce depressive complaints. The primary outcome of the study was a reduction in depressive complaints as measured by the Inventory of Depressive Symptomatology Self-Report (IDS-SR). Secondary outcomes included reductions in stress, worry, sleep problems, and anxiety complaints, and improvements in well-being. Data were analyzed using linear mixed models. In total, 329 participants enrolled in the trial, of which 165 were randomized to the intervention group and 164 to the control group. Approximately three-quarters of the intervention group actually created an account. Of these participants, 91.3% (116/127) logged into their chosen CDMI at least once during the 3-month intervention period (median 3, range 0-166). After 3 months, there was a significant reduction in depressive symptomatology for participants in the intervention group compared to participants in the wait-list control group (reduction in depression: mean -4.47, 95% CI -6.54 to -2.40; Cohen d=-0.70). Furthermore, significant effects were observed for sleep problems, worry, anxiety, and well-being, with effect sizes ranging from -0.29 to -0.40. The intervention did not significantly reduce stress. At 6-month follow-up, the improvements in the intervention group were generally sustained. This study shows that the online self-help CDMIs have a positive impact on various mental health outcomes. Future research should focus on which specific strategies may boost adherence, and increase the reach of the CDMIs among people with low socioeconomic status. Netherlands Trial Register (NTR): NTR4612; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4612 (Archived by WebCite at http://www.webcitation.org/6n4PVYddM). ©Suzanne Lokman, Stephanie S Leone, Marion Sommers-Spijkerman, Agnes van der Poel, Filip Smit, Brigitte Boon. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 04.01.2017.
Fernández-Carrión, E; Ivorra, B; Martínez-López, B; Ramos, A M; Sánchez-Vizcaíno, J M
2016-04-01
Be-FAST is a computer program based on a time-spatial stochastic spread mathematical model for studying the transmission of infectious livestock diseases within and between farms. The present work describes a new module integrated into Be-FAST to model the economic consequences of the spreading of classical swine fever (CSF) and other infectious livestock diseases within and between farms. CSF is financially one of the most damaging diseases in the swine industry worldwide. Specifically in Spain, the economic costs in the two last CSF epidemics (1997 and 2001) reached jointly more than 108 million euros. The present analysis suggests that severe CSF epidemics are associated with significant economic costs, approximately 80% of which are related to animal culling. Direct costs associated with control measures are strongly associated with the number of infected farms, while indirect costs are more strongly associated with epidemic duration. The economic model has been validated with economic information around the last outbreaks in Spain. These results suggest that our economic module may be useful for analysing and predicting economic consequences of livestock disease epidemics. Copyright © 2016 Elsevier B.V. All rights reserved.
Santos, Edgar; Schöll, Michael; Kunzmann, Kevin; Stock, Christian; Silos, Humberto; Unterberg, Andreas W; Sakowitz, Oliver W
2016-01-01
Spreading depolarization (SD) generates significant alterations in cerebral haemodynamics, which can have detrimental consequences on brain function and integrity. Ketamine has shown an important capacity to modulate SD; however, its impact on SD haemodynamic response is incompletely understood. We investigated the effect of two therapeutic ketamine dosages, a low-dose of 2 mg/kg/h and a high-dose of 4 mg/kg/h, on the haemodynamic response to SD in the gyrencephalic swine brain. Cerebral blood volume, pial arterial diameter and cerebral blood flow were assessed through intrinsic optical signal imaging and laser-Doppler flowmetry. Our findings indicate that frequent SDs caused a persistent increase in the baseline pial arterial diameter, which can lead to a diminished capacity to further dilate. Ketamine infused at a low-dose reduced the hyperemic/vasodilative response to SD; however, it did not alter the subsequent oligemic/vasoconstrictive response. This low-dose did not prevent the baseline diameter increase and the diminished dilative capacity. Only infusion of ketamine at a high-dose suppressed SD and the coupled haemodynamic response. Therefore, the haemodynamic response to SD can be modulated by continuous infusion of ketamine. However, its use in pathological models needs to be explored to corroborate its possible clinical benefit. PMID:27126324
Sánchez-Porras, Renán; Santos, Edgar; Schöll, Michael; Kunzmann, Kevin; Stock, Christian; Silos, Humberto; Unterberg, Andreas W; Sakowitz, Oliver W
2017-05-01
Spreading depolarization (SD) generates significant alterations in cerebral haemodynamics, which can have detrimental consequences on brain function and integrity. Ketamine has shown an important capacity to modulate SD; however, its impact on SD haemodynamic response is incompletely understood. We investigated the effect of two therapeutic ketamine dosages, a low-dose of 2 mg/kg/h and a high-dose of 4 mg/kg/h, on the haemodynamic response to SD in the gyrencephalic swine brain. Cerebral blood volume, pial arterial diameter and cerebral blood flow were assessed through intrinsic optical signal imaging and laser-Doppler flowmetry. Our findings indicate that frequent SDs caused a persistent increase in the baseline pial arterial diameter, which can lead to a diminished capacity to further dilate. Ketamine infused at a low-dose reduced the hyperemic/vasodilative response to SD; however, it did not alter the subsequent oligemic/vasoconstrictive response. This low-dose did not prevent the baseline diameter increase and the diminished dilative capacity. Only infusion of ketamine at a high-dose suppressed SD and the coupled haemodynamic response. Therefore, the haemodynamic response to SD can be modulated by continuous infusion of ketamine. However, its use in pathological models needs to be explored to corroborate its possible clinical benefit.
USDA-ARS?s Scientific Manuscript database
Antibiotics can improve ruminant growth and efficiency by altering rumen fermentation via selective inhibition of microorganisms. However, antibiotic use is increasingly restricted due to concerns about the spread of antibiotic-resistance. Plant-based antimicrobials are alternatives to antibiotics ...
High gain photoconductive semiconductor switch having tailored doping profile zones
Baca, Albert G.; Loubriel, Guillermo M.; Mar, Alan; Zutavern, Fred J; Hjalmarson, Harold P.; Allerman, Andrew A.; Zipperian, Thomas E.; O'Malley, Martin W.; Helgeson, Wesley D.; Denison, Gary J.; Brown, Darwin J.; Sullivan, Charles T.; Hou, Hong Q.
2001-01-01
A photoconductive semiconductor switch with tailored doping profile zones beneath and extending laterally from the electrical contacts to the device. The zones are of sufficient depth and lateral extent to isolate the contacts from damage caused by the high current filaments that are created in the device when it is turned on. The zones may be formed by etching depressions into the substrate, then conducting epitaxial regrowth in the depressions with material of the desired doping profile. They may be formed by surface epitaxy. They may also be formed by deep diffusion processes. The zones act to reduce the energy density at the contacts by suppressing collective impact ionization and formation of filaments near the contact and by reducing current intensity at the contact through enhanced current spreading within the zones.
Music in depression: Neural correlates of emotional experience in remitted depression.
Aust, Sabine; Filip, Karin; Koelsch, Stefan; Grimm, Simone; Bajbouj, Malek
2013-06-22
To investigate neural and behavioral correlates of emotional experiences as potential vulnerability markers in remitted depression. Fourteen remitted participants with a history of major depression and fourteen closely matched healthy control participants took part in the study. We used two psychiatric interviews (Hamilton Depression Rating Scale, Montgomery-Asberg Depression Rating Scale) and one self-report scale (Beck Depression Inventory) to assess remission. Healthy control participants were interviewed by an experienced psychiatrist to exclude those who showed any current or lifetime psychiatric or neurological disorders. To explore psychosocial and cognitive-interpersonal underpinnings of potential vulnerability markers of depression, early life stress, coping styles and alexithymia were also assessed. We induced pleasant and unpleasant emotional states using congruent combinations of music and human emotional faces to investigate neural and behavioral correlates of emotional experiences; neutral stimuli were used as a control condition. Brain responses were recorded using functional magnetic resonance imaging. Behavioral responses of pleasantness, arousal, joy and fear were measured via button-press inside the resonance imaging scanner. The mean age of the sample was 54.9 (± 11.3) years. There were no differences between remitted depressed (RD) (n = 14; 9 females and 5 males) and healthy participants (n = 14; 8 females and 6 males) regarding age, current degree of depression, early life stress, coping styles and alexithymia. On a neural level, RD participants showed reduced activations in the pregenual anterior cingulate cortex (pgACC) in response to pleasant [parameter estimates: -0.78 vs 0.32; t(26) = -3.41, P < 0.05] and unpleasant [parameter estimates: -0.88 vs 0.56; t(26)= -4.02, P < 0.05] emotional stimuli. Linear regression analysis revealed that pgACC activity was modulated by early life stress [β = -0.48; R(2) = 0.23, F(1,27) = 7.83, P < 0.01] and task-oriented coping style [β = 0.63; R(2) = 0.37, F(1,27) = 16.91, P < 0.001]. Trait anxiety modulated hippocampal responses to unpleasant stimuli [β = 0.62; R(2) = 0.38, F(1,27) = 15.95, P < 0.001]. Interestingly, in their reported experiences of pleasantness, arousal, happiness and fear in response to pleasant, unpleasant and neutral stimuli, RD participants did not differ significantly from healthy control participants. Adding trait anxiety or alexithymia as a covariate did not change the results. The present study indicates that, in euthymic individuals, depression history alters neural correlates, but not the subjective dimension of pleasant and unpleasant emotional experiences.
Sander, L; Paganini, S; Lin, J; Schlicker, S; Ebert, D D; Buntrock, C; Baumeister, H
2017-01-21
Reducing the disease burden of major depressive disorder (MDD) is of major public health relevance. The prevention of depression is regarded as one possible approach to reach this goal. People with multiple risk factors for MDD such as chronic back pain and subthreshold depressive symptoms may benefit most from preventive measures. The Internet as intervention setting allows for scaling up preventive interventions on a public mental health level. This study is a multicenter pragmatic randomized controlled trial (RCT) of parallel design aiming to investigate the (cost-) effectiveness of an Internet- and mobile-based intervention (IMI) for the prevention of depression in chronic back pain patients (PROD-BP) with subthreshold depressive symptoms. eSano BackCare-DP is a guided, chronic back pain-specific depression prevention intervention based on cognitive behavioral therapy (CBT) principles comprising six weekly plus three optional modules and two booster sessions after completion of the intervention. Trained psychologists provide guidance by sending feedback messages after each module. A total of 406 patients with chronic back pain and without a depressive disorder at baseline will be recruited following orthopedic rehabilitation care and allocated to either intervention or treatment-as-usual (TAU). Primary patient-relevant endpoint of the trial is the time to onset of MDD measured by the telephone-administered Structured Clinical Interview for DSM (SCID) at baseline and 1-year post-randomization. Key secondary outcomes are health-related quality of life, depression severity, pain intensity, pain-related disability, ability to work, intervention satisfaction and adherence as well as side effects of the intervention. Online assessments take place at baseline and 9 weeks as well as 6 and 12 months post-randomization. Cox regression survival analysis will be conducted to estimate hazard ratio at 12-month follow-up. Moreover, an economic analysis will be conducted from a societal and public health perspective. This is the first study examining an IMI for depression prevention in a sample of chronic pain patients. If this implementation of a depression prevention IMI into orthopedic aftercare proves effective, the intervention could be integrated into routine care with minimal costs and extended for use with other chronic diseases. Results will have implications for researchers, health care providers and public health policy makers. The trial is registered at the WHO International Clinical Trials Registry Platform via the German Clinical Studies Trial Register (DRKS): DRKS00007960 . Registered 12 August 2015.
Crystalline lens MTF measurement during simulated accommodation
NASA Astrophysics Data System (ADS)
Borja, David; Takeuchi, Gaku; Ziebarth, Noel; Acosta, Ana C.; Manns, Fabrice; Parel, Jean-Marie
2005-04-01
Purpose: To design and test an optical system to measure the optical quality of post mortem lenses during simulated accommodation. Methods: An optical bench top system was designed to measure the point spread function and calculate the modulation transfer function (MTF) of monkey and human ex-vivo crystalline lenses. The system consists of a super luminescent diode emitting at 850nm, collimated into a 3mm beam which is focused by the ex-vivo lens under test. The intensity distribution at the focus (point spread function) is re-imaged and magnified onto a beam profiler CCD camera. The optical quality in terms of spatial frequency response (modulation transfer function) is calculated by Fourier transform of the point spread function. The system was used on ex-vivo lenses with attached zonules, ciliary body and sclera. The sclera was glued to 8 separate PMMA segments and stretched radial by 5mm on an accommodation simulating lens stretching device. The point spread function was measured for each lens in the relaxed and stretched state for 5 human (ages 38-86 years) and 5 cynomolgus monkey (ages 53 - 67 months) fresh post mortem crystalline lenses. Results: Stretching induced measurable changes in the MTF. The cutoff frequency increased from 54.4+/-13.6 lp/mm unstretched to 59.5+/-21.4 lp/mm stretched in the post-presbyopic human and from 51.9+/-24.7 lp/mm unstretched to 57.7+/-18.5 lp/mm stretched cynomolgus monkey lenses. Conclusion: The results demonstrate the feasibility of measuring the optical quality of ex-vivo human and cynomolgus monkey lenses during simulated accommodation. Additional experiments are underway to quantify changes in optical quality induced by stretching.
LSWS linked with the low-latitude Es and its implications for the growth of the R-T instability
NASA Astrophysics Data System (ADS)
Joshi, L. M.
2016-07-01
A comprehensive investigation of spread F irregularities over the Indian sector has been carried out using VHF radar and ionosonde observations. Two different categories of spread F observations, one where the onset of the range spread F (RSF) was concurrent with the peak h'F (category 1) and another where the RSF onset happened ~90 min after the peak h'F time (category 2), are presented. RSF in category 2 was preceded by the presence of oblique echoes in ionograms, indicating the irregularity genesis westward of Sriharikota. The average peak h'F in category 1 was ~30 km higher than that in category 2 indicating the presence of standing large-scale wave structure (LSWS). Occurrence of the blanketing Es during 19:30 to 20:30 Indian Standard Time in category 1 (category 2) was 0% (>50%). Model computation is also carried out to further substantiate the observational results. Model computation indicates that zonal variation of low-latitude Es can generate zonal modulation in the F layer height rise. It is found that the modulation of the F layer height, linked with the low-latitude Es, assists the equatorial spread F onset by modifying both the growth rate of the collisional Rayleigh-Taylor (R-T) instability and also its efficiency. A predominant presence of low-latitude Es has been observed, but the increase in the F layer height and the R-T instability growth in the evening hours will maximize with complete absence of low-latitude Es. A new mechanism for the generation of LSWS and its implications on R-T instability is discussed.
Sorcin modulation of Ca2+ sparks in rat vascular smooth muscle cells
Rueda, Angélica; Song, Ming; Toro, Ligia; Stefani, Enrico; Valdivia, Héctor H
2006-01-01
Spontaneous, local Ca2+ release events or Ca2+ sparks by ryanodine receptors (RyRs) are important determinants of vascular tone and arteriolar resistance, but the mechanisms that modulate their properties in smooth muscle are poorly understood. Sorcin, a Ca2+-binding protein that associates with cardiac RyRs and quickly stops Ca2+ release in the heart, provides a potential mechanism to modulate Ca2+ sparks in vascular smooth muscle, but little is known about the functional role of sorcin in this tissue. In this work, we characterized the expression and intracellular location of sorcin in aorta and cerebral artery and gained mechanistic insights into its functional role as a modulator of Ca2+ sparks. Sorcin is present in endothelial and smooth muscle cells, as assessed by immunocytochemical and Western blot analyses. Smooth muscle sorcin translocates from cytosolic to membranous compartments in a Ca2+-dependent manner and associates with RyRs, as shown by coimmunoprecipitation and immunostaining experiments. Ca2+ sparks recorded in saponin-permeabilized vascular myocytes have increased frequency, duration and spatial spread but reduced amplitude with respect to Ca2+ sparks in intact cells, suggesting that permeabilization disrupts the normal organization of RyRs and releases diffusible substances that control Ca2+ spark properties. Perfusion of 2 μm sorcin onto permeabilized myocytes reduced the amplitude, duration and spatial spread of Ca2+ sparks, demonstrating that sorcin effectively regulates Ca2+ signalling in vascular smooth muscle. Together with a dense distribution in the perimeter of the cell along a pool of RyRs, these properties make sorcin a viable candidate to modulate vascular tone in smooth muscle. PMID:16931553
Minh Tran, Tuan; MacIntyre, April; Khokhani, Devanshi; Hawes, Martha; Allen, Caitilyn
2016-11-01
Ralstonia solanacearum is a soil-borne vascular pathogen that colonizes plant xylem vessels, a flowing, low-nutrient habitat where biofilms could be adaptive. Ralstonia solanacearum forms biofilm in vitro, but it was not known if the pathogen benefits from biofilms during infection. Scanning electron microscopy revealed that during tomato infection, R. solanacearum forms biofilm-like masses in xylem vessels. These aggregates contain bacteria embedded in a matrix including chromatin-like fibres commonly observed in other bacterial biofilms. Chemical and enzymatic assays demonstrated that the bacterium releases extracellular DNA in culture and that DNA is an integral component of the biofilm matrix. An R. solanacearum mutant lacking the pathogen's two extracellular nucleases (exDNases) formed non-spreading colonies and abnormally thick biofilms in vitro. The biofilms formed by the exDNase mutant in planta contained more and thicker fibres. This mutant was also reduced in virulence on tomato plants and did not spread in tomato stems as well as the wild-type strain, suggesting that these exDNases facilitate biofilm maturation and bacterial dispersal. To our knowledge, this is the first demonstration that R. solanacearum forms biofilms in plant xylem vessels, and the first documentation that plant pathogens use DNases to modulate their biofilm structure for systemic spread and virulence. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.
Modulation of H-Reflex Depression with Paired-Pulse Stimulation in Healthy Active Humans.
Oza, Preeti D; Dudley-Javoroski, Shauna; Shields, Richard K
2017-01-01
Depression of the Hoffman reflex (H-reflex) is used to examine spinal control mechanisms during exercise, fatigue, and vibration and in response to training. H-reflex depression protocols frequently use trains of stimuli; this is time-consuming and prevents instantaneous assessment of motor neuronal excitability. The purpose of this study was to determine if paired-pulse H-reflex depression is reproducible and whether paired-pulse stimulation adequately estimates the depression induced by the more traditional ten-pulse train. H-reflexes were elicited via ten-pulse trains at 0.1, 0.2, 1, 2, and 5 Hz in ten neurologically intact individuals on two separate days. We measured the depression elicited by the second pulse (H2) and the mean depression elicited by pulses 2-10 (Hmean). H2 was consistent at all frequencies on both days ( r 2 = 0.97, p < 0.05, and ICC (3,1) = 0.81). H2 did not differ from Hmean ( p > 0.05). The results indicate that paired-pulse H-reflex depression has high between-day reliability and yields depression estimates that are comparable to those obtained via ten-pulse trains. Paired-pulse H-reflex depression may be especially useful for studies that require rapid assessment of motor neuronal excitability, such as during exercise, fatigue, and vibration, or to establish recovery curves following inhibition.
Park, Albert; Conway, Mike
2017-03-20
Major depression is a serious challenge at both the individual and population levels. Although online health communities have shown the potential to reduce the symptoms of depression, emotional contagion theory suggests that negative emotion can spread within a community, and prolonged interactions with other depressed individuals has potential to worsen the symptoms of depression. The goals of our study were to investigate longitudinal changes in psychological states that are manifested through linguistic changes in depression community members who are interacting with other depressed individuals. We examined emotion-related language usages using the Linguistic Inquiry and Word Count (LIWC) program for each member of a depression community from Reddit. To measure the changes, we applied linear least-squares regression to the LIWC scores against the interaction sequence for each member. We measured the differences in linguistic changes against three online health communities focusing on positive emotion, diabetes, and irritable bowel syndrome. On average, members of an online depression community showed improvement in 9 of 10 prespecified linguistic dimensions: "positive emotion," "negative emotion," "anxiety," "anger," "sadness," "first person singular," "negation," "swear words," and "death." Moreover, these members improved either significantly or at least as much as members of other online health communities. We provide new insights into the impact of prolonged participation in an online depression community and highlight the positive emotion change in members. The findings of this study should be interpreted with caution, because participating in an online depression community is not the sole factor for improvement or worsening of depressive symptoms. Still, the consistent statistical results including comparative analyses with different communities could indicate that the emotion-related language usage of depression community members are improving either significantly or at least as much as members of other online communities. On the basis of these findings, we contribute practical suggestions for designing online depression communities to enhance psychosocial benefit gains for members. We consider these results to be an important step toward a better understanding of the impact of prolonged participation in an online depression community, in addition to providing insights into the long-term psychosocial well-being of members. ©Albert Park, Mike Conway. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 20.03.2017.
Salting the landscapes in Transbaikalia: natural and technogenic factors
NASA Astrophysics Data System (ADS)
Peryazeva, E. G.; Plyusnin, A. M.; Chinavlev, A. M.
2010-05-01
Salting the soils, surface and subsurface waters is widespread in Transbaikalia. Hearths of salting occur within intermountain depressions of the Mesozoic and Cenozoic age both in the steppe arid and forest humid landscapes. Total water mineralization reaches 80 g/dm3 in lakes and 4-5 g/dm3 in subsurface waters. The waters belong to hydrocarbonate sodium and sulfate sodium types by chemical composition. The soda type of waters is widely spread through the whole area. Sulfate waters are found in several hearths of salting. Deposition of salts takes place in some lakes. Mirabilite and soda depositions are most commonly observed in muds of salt lakes. Deposition of salts occurs both as a result of evaporative concentrating and during freezing out the solvent. In the winter period, efflorescences of salts, where decawater soda is main mineral, are observed on ice surface. Solonchaks are spread in areas of shallow ground waters (1-2m). Soil salting is most intense in the lower parts of depressions, where surface of ground waters is at depth 0.5-1.0m. In soil cover of solonchaks, salt horizon is of various thicknesses, and it has various morphological forms of occurrence, i.e. as thick deposits of salts on soil surface and salting the surficial horizons. The soil has low alkaline reaction of medium and is characterized by high content of exchangeable bases with significant content of exchangeable sodium in the absorbing complex. Total amount of salts varies from 0.7 to 1.3%. Their maximal quantity (3.1%) is confined to the surficial layer. Sulfate-sodium type of salting is noted in the solonchak upper horizons and sulfate-magnesium-calcium one in the lower ones (Ubugunov et al, 2009). Formation of salting hearths is associated with natural and technogenic conditions. The Mesozoic depressions of Transbaikalia are characterized by intense volcanism. Covers of alkaline and moderately alkaline basalts that are enriched in potassium, sodium, carbon dioxide, fluorine, chlorine, sulphur, strontium, lithium, molybdenum, nickel, and vanadium are widely spread there. Geochemical habit of basalts largely determines chemical compositions of waters and mineral formations in hearths of salting. Unloading the fissure-vein waters that evacuate solute from the Jurassic-Cretaceous volcanogenic-sedimentary deposits greatly effects chemical composition in some hearths of salting. Irrigation systems in many intermountain depressions influence the salting hearth formation. The associated secondary salting occurs as spots in the areas, where ground water surface reaches foot of loams during irrigation. Salting the landscapes takes out big areas of fertile lands from agricultural use, threatens with breakdowns at enterprises of thermal energetic that consume water as heat carrier.
Schramm, N L; McDonald, M P; Limbird, L E
2001-07-01
The noradrenergic system is involved in the regulation of many physiological and psychological processes, including the modulation of mood. The alpha(2)-adrenergic receptors (alpha(2)-ARs) modulate norepinephrine release, as well as the release of serotonin and other neurotransmitters, and are therefore potential targets for antidepressant and anxiolytic drug development. The current studies were undertaken to examine the role of the alpha(2A) subtype of alpha(2)-AR in mouse behavioral models of depression and anxiety. We have observed that the genetic knock-out of the alpha(2A)-AR makes mice less active in a modified version of Porsolt's forced swim test and insensitive to the antidepressant effects of the tricyclic drug imipramine in this paradigm. Furthermore, alpha(2A)-AR knock-out mice appear more anxious than wild-type C57 Bl/6 mice in the rearing and light-dark models of anxiety after injection stress. These findings suggest that the alpha(2A)-AR may play a protective role in some forms of depression and anxiety and that the antidepressant effects of imipramine may be mediated by the alpha(2A)-AR.
Duric, Vanja
2014-01-01
Since the 1960s, when the first tricyclic and monoamine oxidase inhibitor antidepressant drugs were introduced, most of the ensuing agents were designed to target similar brain pathways that elevate serotonin and/or norepinephrine signaling. Fifty years later, the main goal of the current depression research is to develop faster-acting, more effective therapeutic agents with fewer side effects, as currently available antidepressants are plagued by delayed therapeutic onset and low response rates. Clinical and basic science research studies have made significant progress towards deciphering the pathophysiological events within the brain involved in development, maintenance, and treatment of major depressive disorder. Imaging and postmortem brain studies in depressed human subjects, in combination with animal behavioral models of depression, have identified a number of different cellular events, intracellular signaling pathways, proteins, and target genes that are modulated by stress and are potentially vital mediators of antidepressant action. In this review, we focus on several neural mechanisms, primarily within the hippocampus and prefrontal cortex, which have recently been implicated in depression and treatment response. PMID:22585060
Enduring financial crisis in Greece: prevalence and correlates of major depression and suicidality.
Economou, Marina; Angelopoulos, Elias; Peppou, Lily Evangelia; Souliotis, Kyriakos; Tzavara, Chara; Kontoangelos, Konstantinos; Madianos, Michael; Stefanis, Costas
2016-07-01
A series of repeated cross-sectional surveys conducted in 2008, 2009, 2011 and 2013 were conducted with the aim of estimating the prevalence of major depression and suicidality as well as of investigating its risk factors. The present report concentrates on the 2013 survey. A random and representative sample of 2.188 people was telephone interviewed with regard to various socio-economic indicators and the presence of major depression and suicidality, which were assessed with the germane module of the Structured Clinical Interview. Findings suggest a rise in 1-month prevalence of major depression (12.3 %) and a decline in prevalence of suicidality (2.8 %). Female gender, residence in rural area, low educational attainment, unemployment and economic hardship were found to increase the odds of suffering from major depression. The influence of economic hardship and unemployment on suicidality was also substantial and independent of major depression. Results stress the imperative need for the design and implementation of social policies and interventions that would offset the dire impact of the sustained recession in Greece.
Beckley, Ethan H; Scibelli, Angela C; Finn, Deborah A
2011-07-01
Progesterone withdrawal has been proposed as an underlying factor in premenstrual syndrome and postpartum depression. Progesterone withdrawal induces forced swim test (FST) immobility in mice, a depression-like behavior, but the contribution of specific receptors to this effect is unclear. The role of progesterone's GABA(A) receptor-modulating metabolite allopregnanolone in depression- and anxiety-related behaviors has been extensively documented, but little attention has been paid to the role of progesterone receptors. We administered the classic progesterone receptor antagonist mifepristone (RU-38486) and the specific progesterone receptor antagonist CDB-4124 to mice that had been primed with progesterone for five days, and found that both compounds induced FST immobility reliably, robustly, and in a dose-dependent fashion. Although CDB-4124 increased FST immobility, it did not suppress initial activity in a locomotor test. These findings suggest that decreased progesterone receptor activity contributes to depression-like behavior in mice, consistent with the hypothesis that progesterone withdrawal may contribute to the symptoms of premenstrual syndrome or postpartum depression. Copyright © 2010 Elsevier Ltd. All rights reserved.
Engel, Daiane Fátima; de Oliveira, Jade; Lopes, Jadna Bogado; Santos, Danúbia Bonfanti; Moreira, Eduardo Luiz Gasnhar; Farina, Marcelo; Rodrigues, Ana Lúcia S; de Souza Brocardo, Patricia; de Bem, Andreza Fabro
2016-09-15
Although epidemiological studies have reported an association between hypercholesterolemia and mood disorders, there is a lack of data regarding depressive-like behavior in animal models of hypercholesterolemia. To address these questions, we assessed depressive-like behavior and hippocampal and cortical monoaminergic metabolism in three-month-old, low-density lipoprotein receptor knockout (LDLr(-/-)) and C57BL/6 wild-type mice. The LDLr(-/-) mice exhibited depressive-like behavior in the sucrose preference test, splash test, and tail suspension test. Increased monoamine oxidase (MAO) A and B activity was evidenced in the hippocampus of LDLr(-/-) mice. Furthermore, to address whether or not cholesterol modulates MAO activity, we exposed SH-SY5Y human neuroblastoma cells to human isolated low-density lipoprotein (LDL). Notably, LDL increased the activity of MAO-A and stimulated the reactive species generation in vitro. These findings indicate that depressive-like behavior in hypercholesterolemic mice is accompanied by alterations in the monoaminergic metabolism, providing new evidence about the association between hypercholesterolemia and depression. Copyright © 2016. Published by Elsevier B.V.
Pulse transmission transceiver architecture for low power communications
Dress, Jr., William B.; Smith, Stephen F.
2003-08-05
Systems and methods for pulse-transmission low-power communication modes are disclosed. A method of pulse transmission communications includes: generating a modulated pulse signal waveform; transforming said modulated pulse signal waveform into at least one higher-order derivative waveform; and transmitting said at least one higher-order derivative waveform as an emitted pulse. The systems and methods significantly reduce lower-frequency emissions from pulse transmission spread-spectrum communication modes, which reduces potentially harmful interference to existing radio frequency services and users and also simultaneously permit transmission of multiple data bits by utilizing specific pulse shapes.
Wireless Headset Communication System
NASA Technical Reports Server (NTRS)
Lau, Wilfred K.; Swanson, Richard; Christensen, Kurt K.
1995-01-01
System combines features of pagers, walkie-talkies, and cordless telephones. Wireless headset communication system uses digital modulation on spread spectrum to avoid interference among units. Consists of base station, 4 radio/antenna modules, and as many as 16 remote units with headsets. Base station serves as network controller, audio-mixing network, and interface to such outside services as computers, telephone networks, and other base stations. Developed for use at Kennedy Space Center, system also useful in industrial maintenance, emergency operations, construction, and airport operations. Also, digital capabilities exploited; by adding bar-code readers for use in taking inventories.
NASA Technical Reports Server (NTRS)
Simon, M. K.; Polydoros, A.
1981-01-01
This paper examines the performance of coherent QPSK and QASK systems combined with FH or FH/PN spread spectrum techniques in the presence of partial-band multitone or noise jamming. The worst-case jammer and worst-case performance are determined as functions of the signal-to-background noise ratio (SNR) and signal-to-jammer power ratio (SJR). Asymptotic results for high SNR are shown to have a linear dependence between the jammer's optimal power allocation and the system error probability performance.
Urban area change detection procedures with remote sensing data
NASA Technical Reports Server (NTRS)
Maxwell, E. L. (Principal Investigator); Riordan, C. J.
1980-01-01
The underlying factors affecting the detection and identification of nonurban to urban land cover change using satellite data were studied. Computer programs were developed to create a digital scene and to simulate the effect of the sensor point spread function (PSF) on the transfer of modulation from the scene to an image of the scene. The theory behind the development of a digital filter representing the PSF is given as well as an example of its application. Atmospheric effects on modulation transfer are also discussed. A user's guide and program listings are given.
Early life stress paradigms in rodents: potential animal models of depression?
Schmidt, Mathias V; Wang, Xiao-Dong; Meijer, Onno C
2011-03-01
While human depressive illness is indeed uniquely human, many of its symptoms may be modeled in rodents. Based on human etiology, the assumption has been made that depression-like behavior in rats and mice can be modulated by some of the powerful early life programming effects that are known to occur after manipulations in the first weeks of life. Here we review the evidence that is available in literature for early life manipulation as risk factors for the development of depression-like symptoms such as anhedonia, passive coping strategies, and neuroendocrine changes. Early life paradigms that were evaluated include early handling, separation, and deprivation protocols, as well as enriched and impoverished environments. We have also included a small number of stress-related pharmacological models. We find that for most early life paradigms per se, the actual validity for depression is limited. A number of models have not been tested with respect to classical depression-like behaviors, while in many cases, the outcome of such experiments is variable and depends on strain and additional factors. Because programming effects confer vulnerability rather than disease, a number of paradigms hold promise for usefulness in depression research, in combination with the proper genetic background and adult life challenges.
Cognitive-behavioural theories of helplessness/hopelessness: valid models of depression?
Henkel, V; Bussfeld, P; Möller, H-J; Hegerl, U
2002-10-01
Helplessness and hopelessness are central aspects of cognitive-behavioural explanations for the development and persistence of depression. In this article a general overview concerning the evolution of those approaches to depression is provided. Included is a critical examination of the theories. The review of the literature suggests that those cognitive models describing helplessness/hopelessness as trait factors mediating depression do not really have a strong empirical base. The majority of those studies had been conducted in healthy or only mildly depressed subjects. Thus, there seems to be little justification for broad generalisations beyond the populations studied. It seems that some of the reported studies have not tested the underlying theories adequately (e. g. correlation had sometimes been interpreted as causation; adequate prospective longitudinal study designs had seldom been applied). Moreover, the theoretical models are not generally prepared to explain all depressive features (e. g. the possibility of a spontaneous shift in a manic episode). Despite those limitations, there is a relevant impact of the learned helplessness paradigm on preclinical research in neurobiological correlates of depressive states. Last but not least, the models are of high interest with respect to the theoretical background of important modules of cognitive-behavioural therapy and its acute and prophylactic effects.
[Modulating variables of work disability in depressive disorders].
Catalina Romero, C; Cabrera Sierra, M; Sainz Gutiérrez, J C; Barrenechea Albarrán, J L; Madrid Conesa, A; Calvo Bonacho, E
2011-01-01
To describe the duration of sickness absence in unipolar depression and to determine the relationship of demographic, job-related and clinical variables with length of temporary work disability in depressive disorders. Prospective observational study. A total of 1,292 subjects with depressive disorder diagnosis (ICD-9-CM) were selected claiming sick leave in an Occupational Diseases and Accident sat Work Insurance Scheme (sampling on successive occasions). Descriptive analyses of sickness absence duration, and bivariate (median test) and multivariate analysis (logistic regression) were performed to find relationships between demographic, job-related and clinical variables. Mean duration of sickness absence episodes due to a depressive disorder was 120 days. After multivariate analyses, female sex (p < 0.01), higher age (p < 0.01), lower educational level (p < 0.01), method of payment according to whether self-employed or unemployed workers (p < 0.01) and being referred to both psychiatrist and psychologist (p < 0.01) remained significantly associated with sick leave length. These findings confirm a strong association of depression with long periods of work disability and high absenteeism, and also suggest the need for improvements in functional ability assessment and promotion, treatment and referral of depressed patients. Copyright © 2010 SECA. Published by Elsevier Espana. All rights reserved.
Patron, Elisabetta; Messerotti Benvenuti, Simone; Favretto, Giuseppe; Valfrè, Carlo; Bonfà, Carlotta; Gasparotto, Renata; Palomba, Daniela
2012-07-01
Depression is a risk factor for cardiovascular diseases. Reduced heart rate variability (HRV), which reflects altered autonomic nervous system activity, has been suggested as one of the mechanisms linking depression to cardiovascular diseases. However, the relationship between depression and HRV has not yet been investigated in patients undergone cardiac surgery. Therefore, the main aim of this study was to examine whether postoperative depression could be related to reduced HRV. Eleven patients with depression and 22 patients without depression, who had undergone cardiac surgery, were enrolled postoperatively. In all patients, HRV was derived from a four-minute blood volume pulse recording at rest. Analyses of covariance and partial correlations, while controlling for anxiety, were used to examine the associations between postoperative depression and each HRV parameter. Compared to non-depressed patients, patients with depression showed significantly lower standard deviation of N-to-N intervals (SDNN) (p=.02), root mean square successive difference of N-to-N intervals (rMSSD) (p=.001), and high-frequency power (p=.002). Partial correlation analyses showed that depression was inversely related to SDNN (r=-.49, p=.005), rMSSD (r=-.58, p=.001), and high-frequency power (r=-.41, p=.02), whereas it was unrelated to other HRV parameters (p's>.09). The current findings extend the depression-reduced HRV relationship to the patients after cardiac surgery. Also, our study suggests that postoperative depression is more likely to be associated with reduced vagal modulation on the heart than with excessive sympathetic activity. Copyright © 2012 Elsevier Inc. All rights reserved.
Alamri, Sultan Hassan; Bari, Abdulaziz Ihsan; Ali, Abdulrahman Talal
2017-01-01
Depression in the elderly is a serious and often underdiagnosed psychiatric disorder that has been linked to adverse outcomes in the hospital setting. To determine the prevalence of depression and possible associated factors among hospitalized elderly. An analytical cross-sectional study. Medical and surgical wards of King Abdulaziz University Hospital, Jeddah, Saudi Arabia. The study included 200 consecutively hospitalized patients aged 60 years and older. Participants were evaluated within 48 hours of admission using an interviewer-administered question-naire to provide basic demographic and clinical information. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9) screening method and the Structured Clinical Interview for the Diagnostic and Statistical Manual, Fifth Edition (DSM-5) mood disorder module. According to PHQ-9, 17% and 10.5% of the hospitalized patients were diagnosed with a major depressive disorder and other depressive disorders, respectively. The DSM-5 criteria identified 12% of elderly with major depression. Overall, the number of comorbidities associated with depression was signifi-cantly higher in the major depressive disorder group than in the no depression group (post hoc P=.022). Depression was also associated with female gender, unmarried status, lower income, and polypharmacy. In addition, cardiovascular disease and cancer were the most prevalent medical illnesses associated with depression among hospitalized elderly. Major depressive disorder was prevalent among hospitalized elderly, especially among those with comorbid conditions. Hospital physicians must, therefore, maintain a high index of suspicion to identify early and manage depressive symptoms in these patients. The small size of certain subgroups limits the statistical power to examine for associations of depression with particular conditions.
Fischer, Susanne; Strawbridge, Rebecca; Vives, Andres Herane; Cleare, Anthony J
2017-02-01
Many patients with depressive disorders demonstrate resistance to psychological therapy. A frequent finding is hypothalamic-pituitary-adrenal (HPA) axis alterations. As cortisol is known to modulate cognitive processes, those patients may be less likely to profit from psychological therapy. To conduct a systematic review and meta-analysis on cortisol as a predictor of psychological therapy response. The Cochrane Library, EMBASE, MEDLINE and PsycINFO databases were searched. Records were included if they looked at patients with any depressive disorder engaging in psychological therapy, with a pre-treatment cortisol and a post-treatment symptom measure. Eight articles satisfied our selection criteria. The higher the cortisol levels before starting psychological therapy, the more symptoms patients with depression experienced at the end of treatment and/or the smaller their symptom change. Our findings suggest that patients with depression with elevated HPA functioning are less responsive to psychological therapy. © The Royal College of Psychiatrists 2017.
Roy, Bhaskar; Wang, Qingzhong; Dwivedi, Yogesh
2018-01-01
Abstract Background Recent emergence of long noncoding RNAs in regulating gene expression and thereby modulating physiological functions in brain has manifested their possible role in psychiatric disorders. In this study, the roles of long noncoding RNAs in susceptibility and resiliency to develop stress-induced depression and their response to antidepressant treatment were examined. Methods Microarray-based transcriptome-wide changes in long noncoding RNAs were determined in hippocampus of male Holtzman rats who showed susceptibility (learned helplessness) or resiliency (nonlearned helplessness) to develop depression. Changes in long noncoding RNA expression were also ascertained after subchronic administration of fluoxetine to learned helplessness rats. Bioinformatic and target prediction analyses (cis- and trans-acting) and qPCR-based assays were performed to decipher the functional role of altered long noncoding RNAs. Results Group-wise comparison showed an overrepresented class of long noncoding RNAs that were uniquely associated with nonlearned helplessness or learned helplessness behavior. Chromosomal mapping within the 5-kbp flank region of the top 20 dysregulated long noncoding RNAs in the learned helplessness group showed several target genes that were regulated through cis- or trans-actions, including Zbtb20 and Zfp385b from zinc finger binding protein family. Genomic context of differentially expressed long noncoding RNAs showed an overall blunted response in the learned helplessness group regardless of the long noncoding RNA classes analyzed. Gene ontology exhibited the functional clustering for anatomical structure development, cellular architecture modulation, protein metabolism, and cellular communications. Fluoxetine treatment reversed learned helplessness-induced changes in many long noncoding RNAs and target genes. Conclusions The involvement of specific classes of long noncoding RNAs with distinctive roles in modulating target gene expression could confer the role of long noncoding RNAs in resiliency or susceptibility to develop depression with a reciprocal response to antidepressant treatment. PMID:29390069
Pain intensity influences the relationship between anger management style and depression.
Estlander, Ann-Mari; Knaster, Peter; Karlsson, Hasse; Kaprio, Jaakko; Kalso, Eija
2008-11-30
There is an abundance of studies concerning depression and pain, while the mechanisms and the relationships of anger expression and pain are less well known. The validity of commonly used depression questionnaires as measures of depression in pain patients has been questioned, as they include items which can be related to the pain problem as well as to signs of depression. The aim of this study was to investigate the relationships between pain severity, various signs of depression, and anger management style. Subjects were 100 consecutive patients referred to the Helsinki University Pain Clinic. Demographic data and pain intensity (VAS) were collected by a questionnaire. Two subscales (negative view and physical function) from the Beck Depression Inventory, and the Anger Expression Scales (Anger-in and Anger-out) from the Spielberg State Trait Anger Expression Inventory 2 were used to assess depression and anger expression, respectively. The results showed that pain severity modulates the relationship between anger expression and physical signs of depression. In patients with more severe pain, the relationships between anger management style, specifically, inhibition of anger and depression were strong, while no such relationships were found in the group of patients with less severe pain. No correlations were found between pain intensity and depression as measured by the sum score of the BDI. However, analysing separately the two subscales of the BDI, negative view and physical function, significant positive relationships between pain intensity and both subscales appeared.
Impact of Food Insecurity on Depressive Symptoms Among HIV-HCV Co-infected People.
Aibibula, Wusiman; Cox, Joseph; Hamelin, Anne-Marie; Moodie, Erica E M; Naimi, Ashley I; McLinden, Taylor; Klein, Marina B; Brassard, Paul
2017-12-01
Food insecurity (FI) is associated with depressive symptoms among HIV mono-infected people. Our objective was to examine to what extent this association holds among HIV-hepatitis C virus (HCV) co-infected people. We used data from a prospective cohort study of HIV-HCV co-infected people in Canada. FI was measured using the ten-item adult scale of Health Canada's Household Food Security Survey Module and was classified into three categories: food secure, moderate FI, and severe FI. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale (CES-D-10) and was classified into absence or presence of depressive symptoms. FI, depressive symptoms, and other covariates were updated every 6 months. The association between FI and depressive symptoms was assessed using a stabilized inverse probability weighted marginal structural model. The study sample included 725 HIV-HCV co-infected people with 1973 person-visits over 3 years of follow up. At baseline, 23% of participants experienced moderate food insecurity, 34% experienced severe food insecurity and 52% had depressive symptoms. People experiencing moderate FI had 1.63 times (95% CI 1.44-1.86) the risk of having depressive symptoms and people experiencing severe FI had 2.01 times (95% CI 1.79-2.25) the risk of having depressive symptoms compared to people who were food secure. FI is a risk factor for developing depressive symptoms among HIV-HCV co-infected people. Food supplementation, psychosocial support and counseling may improve patient health outcomes.
2006-11-01
sustained penetrating brain injury (PBI). Emergency craniotomies are performed to treat these severe injuries in theater, sometimes on a daily...after craniotomy surgery. ECoG recordings were made subsequently for 1-10 days. CSD was identified by rapidly developing depression of ECoG amplitude...treat patients with moderate-to-severe TBI provides the opportunity to monitor for CSD by ECoG recordings. In these cases, craniotomy is performed as
Non-invasive monitoring of spreading depression.
Bastany, Zoya J R; Askari, Shahbaz; Dumont, Guy A; Speckmann, Erwin-Josef; Gorji, Ali
2016-10-01
Spreading depression (SD), a slow propagating depolarization wave, plays an important role in pathophysiology of different neurological disorders. Yet, research into SD-related disorders has been hampered by the lack of non-invasive recording techniques of SD. Here we compared the manifestations of SD in continuous non-invasive electroencephalogram (EEG) recordings to invasive electrocorticographic (ECoG) recordings in order to obtain further insights into generator structures and electrogenic mechanisms of surface recording of SD. SD was induced by KCl application and simultaneous SD recordings were performed by scalp EEG as well as ECoG electrodes of somatosensory neocortex of rats using a novel homemade EEG amplifier, AgCl recording electrodes, and high chloride conductive gel. Different methods were used to analyze the data; including the spectrogram, bi-spectrogram, pattern distribution, relative spectrum power, and multivariable Gaussian fit analysis. The negative direct current (DC) shifts recorded by scalp electrodes exhibited a high homogeneity to those recorded by ECoG electrodes. Furthermore, this novel method of recording and analysis was able to separate SD recorded by scalp electrodes from non-neuronal DC shifts induced by other potential generators, such as the skin, muscles, arteries, dura, etc. These data suggest a novel application for continuous non-invasive monitoring of DC potential changes, such as SD. Non-invasive monitoring of SD would allow early intervention and improve outcome in SD-related neurological disorders. Copyright © 2016 IBRO. All rights reserved.
NASA Astrophysics Data System (ADS)
Carreira, Ricardo J.; Shyti, Reinald; Balluff, Benjamin; Abdelmoula, Walid M.; van Heiningen, Sandra H.; van Zeijl, Rene J.; Dijkstra, Jouke; Ferrari, Michel D.; Tolner, Else A.; McDonnell, Liam A.; van den Maagdenberg, Arn M. J. M.
2015-06-01
Cortical spreading depression (CSD) is the electrophysiological correlate of migraine aura. Transgenic mice carrying the R192Q missense mutation in the Cacna1a gene, which in patients causes familial hemiplegic migraine type 1 (FHM1), exhibit increased propensity to CSD. Herein, mass spectrometry imaging (MSI) was applied for the first time to an animal cohort of transgenic and wild type mice to study the biomolecular changes following CSD in the brain. Ninety-six coronal brain sections from 32 mice were analyzed by MALDI-MSI. All MSI datasets were registered to the Allen Brain Atlas reference atlas of the mouse brain so that the molecular signatures of distinct brain regions could be compared. A number of metabolites and peptides showed substantial changes in the brain associated with CSD. Among those, different mass spectral features showed significant ( t-test, P < 0.05) changes in the cortex, 146 and 377 Da, and in the thalamus, 1820 and 1834 Da, of the CSD-affected hemisphere of FHM1 R192Q mice. Our findings reveal CSD- and genotype-specific molecular changes in the brain of FHM1 transgenic mice that may further our understanding about the role of CSD in migraine pathophysiology. The results also demonstrate the utility of aligning MSI datasets to a common reference atlas for large-scale MSI investigations.
Maia, Luciana Maria Silva de Seixas; Amancio-Dos-Santos, Angela; Germano, Paula Catirina Pereira da Silva; Falcão, Anna Carolina Santos Marinho; Duda-de-Oliveira, Desirré; Guedes, Rubem Carlos Araújo
2017-05-22
In the rat, we previously demonstrated that serotonin-enhancing drugs impair cortical spreading depression (CSD) and that l-arginine (arginine) treatment enhances CSD. Here, we investigated the interaction between topical application of the serotonin uptake enhancer tianeptine and systemic arginine administration on CSD. From postnatal day 7-28, female Wistar rats (n=40) received by gavage 300mg/Kg/day arginine (n=20) or water (n=20). Half of the arginine- or water-treated rats underwent CSD recording at 30-40days of age (young), while the other half was recorded at 90-120days (adult). Following baseline recording (four episodes of CSD), we applied tianeptine solution (10mg/ml) to a rectangular portion of the intact dura mater for 10-min and then elicited CSD. This procedure was repeated three times. Compared to baseline values, CSD velocities and amplitudes following tianeptine application increased, and CSD duration decreased significantly (p<0.05) in both young and adult rats, regardless of treatment group. CSD acceleration caused by systemic treatment with arginine is in agreement with previous findings. Topical cortical application of tianeptine replicated the effect of systemic application, suggesting a cortically based mechanism for tianeptine's action. However, the absence of interaction between arginine and tianeptine treatments suggests that they probably act through separate mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.
Makarova, Julia; Ibarz, José M; Canals, Santiago; Herreras, Oscar
2007-06-15
Spreading depression (SD) is a pathological wave of transient neuronal inactivation. We recently reported that the characteristic sustained complete depolarization is restricted to specific cell domains where the input resistance (R(in)) first becomes negligible before achieving partial recovery, whereas in adjacent, more polarized membranes it drops by much less. The experimental study of the participating membrane channels is hindered by their mixed contribution and heterogeneous distribution. Therefore, we derived a biophysical model to analyze the conductances that replicate the subcellular profile of R(in) during SD. Systematic variation of conductance densities far beyond the ranges reported failed to fit the experimental values. Besides standard potassium, sodium, and Glu-mediated conductances, the initial opening and gradual closing of an as yet undetermined large conductance is required to account for the evolution of R(in). Potassium conductances follow in the relative contribution and their closing during the late phase is also predicted. Large intracellular potential gradients from zero to rest are readily sustained between shunted and adjacent SD-spared membranes, which remain electroregenerative. The gradients are achieved by a combination of high-conductance subcellular domains and transmembrane ion redistribution in extended but discrete dendritic domains. We conclude that the heterogeneous subcellular behavior is due to local membrane properties, some of which may be specifically activated under extreme SD conditions.
NASA Astrophysics Data System (ADS)
Dahlem, Markus A.
2013-12-01
Migraine is a common disabling headache disorder characterized by recurrent episodes sometimes preceded or accompanied by focal neurological symptoms called aura. The relation between two subtypes, migraine without aura (MWoA) and migraine with aura (MWA), is explored with the aim to identify targets for neuromodulation techniques. To this end, a dynamically regulated control system is schematically reduced to a network of the trigeminal nerve, which innervates the cranial circulation, an associated descending modulatory network of brainstem nuclei, and parasympathetic vasomotor efferents. This extends the idea of a migraine generator region in the brainstem to a larger network and is still simple and explicit enough to open up possibilities for mathematical modeling in the future. In this study, it is suggested that the migraine generator network (MGN) is driven and may therefore respond differently to different spatio-temporal noxious input in the migraine subtypes MWA and MWoA. The noxious input is caused by a cortical perturbation of homeostasis, known as spreading depression (SD). The MGN might even trigger SD in the first place by a failure in vasomotor control. As a consequence, migraine is considered as an inherently dynamical disease to which a linear course from upstream to downstream events would not do justice. Minimally invasive and noninvasive neuromodulation techniques are briefly reviewed and their rational is discussed in the context of the proposed mechanism.
Lee, Yi-Hui; Salman, Ali; Fitzpatrick, Joyce J
2009-05-01
High incidence rates of HIV/AIDS infections among youth draw attention to the need for emphasizing the reduction of risky sexual behavior, a major contributor to the spread of HIV/AIDS. Few researchers have examined the relationship between self-efficacy for HIV/AIDS preventions, depressive symptoms, and adolescent risky sexual behavior. This insufficient understanding limits nurses' ability to provide effective programs for reducing adolescents' risky sexual behaviors. This study was conducted to investigate the relationships among HIV/AIDS preventive self-efficacy, depressive symptoms, and risky sexual behavior in Taiwanese adolescents. A cross-sectional, correlational study. Seven vocational high schools located in a metropolitan area in southern Taiwan. A convenience sample of 16-18-year-old vocational high school Taiwanese adolescents (n=734) participated in this study. Several self-administrated questionnaires, including HIV/AIDS Preventive Self-efficacy scale, the Center for Epidemiological Studies-Depression scale, Safe Sex Behavior Questionnaire, and a form for demographic data, were used to collect data. Taiwanese adolescents who had higher HIV/AIDS preventive self-efficacy scores had less overall risky sexual behavior. Adolescents who had less depressive symptoms had higher HIV/AIDS preventive self-efficacy. More depressive symptoms were correlated to more risky sexual behavior. Improving Taiwanese adolescents' HIV/AIDS preventive self-efficacy could be useful to reduce risky sexual behaviors in this population. Results of this study may assist nurses in understanding factors related to adolescents HIV/AIDS related risky sexual behavior and its' preventions. However, future longitudinal studies are needed to clarify whether depressive symptoms is a major influential factor that might interfere with the effectiveness of HIV/AIDS prevention programs.
Beam Conditioning and Harmonic Generation in Free ElectronLasers
DOE Office of Scientific and Technical Information (OSTI.GOV)
Charman, A.E.; Penn, G.; Wolski, A.
2004-07-05
The next generation of large-scale free-electron lasers (FELs) such as Euro-XFEL and LCLS are to be devices which produce coherent X-rays using Self-Amplified Spontaneous Emission (SASE). The performance of these devices is limited by the spread in longitudinal velocities of the beam. In the case where this spread arises primarily from large transverse oscillation amplitudes, beam conditioning can significantly enhance FEL performance. Future X-ray sources may also exploit harmonic generation starting from laser-seeded modulation. Preliminary analysis of such devices is discussed, based on a novel trial-function/variational-principle approach, which shows good agreement with more lengthy numerical simulations.
Nabavi, Seyed Fazel; Habtemariam, Solomon; Di Lorenzo, Arianna; Sureda, Antoni; Khanjani, Sedigheh; Nabavi, Seyed Mohammad; Daglia, Maria
2016-04-28
Gallic acid (3,4,5-trihydroxybenzoic acid, GA) is a plant secondary metabolite, which shows antioxidant activity and is commonly found in many plant-based foods and beverages. Recent evidence suggests that oxidative stress contributes to the development of many human chronic diseases, including cardiovascular and neurodegenerative pathologies, metabolic syndrome, type 2 diabetes and cancer. GA and its derivative, methyl-3-O-methyl gallate (M3OMG), possess physiological and pharmacological activities closely related to their antioxidant properties. This paper describes the antidepressive-like effects of intraperitoneal administration of GA and two synthetic analogues, M3OMG and P3OMG (propyl-3-O-methylgallate), in balb/c mice with post-stroke depression, a secondary form of depression that could be due to oxidative stress occurring during cerebral ischemia and the following reperfusion. Moreover, this study determined the in vivo antioxidant activity of these compounds through the evaluation of superoxide dismutase (SOD) and catalase (Cat) activity, thiobarbituric acid-reactive substances (TBARS) and reduced glutathione (GSH) levels in mouse brain. GA and its synthetic analogues were found to be active (at doses of 25 and 50 mg/kg) in the modulation of depressive symptoms and the reduction of oxidative stress, restoring normal behavior and, at least in part, antioxidant endogenous defenses, with M3OMG being the most active of these compounds. SOD, TBARS, and GSH all showed strong correlation with behavioral parameters, suggesting that oxidative stress is tightly linked to the pathological processes involved in stroke and PSD. As a whole, the obtained results show that the administration of GA, M3OMG and P3OMG induce a reduction in depressive symptoms and oxidative stress.
Nabavi, Seyed Fazel; Habtemariam, Solomon; Di Lorenzo, Arianna; Sureda, Antoni; Khanjani, Sedigheh; Nabavi, Seyed Mohammad; Daglia, Maria
2016-01-01
Gallic acid (3,4,5-trihydroxybenzoic acid, GA) is a plant secondary metabolite, which shows antioxidant activity and is commonly found in many plant-based foods and beverages. Recent evidence suggests that oxidative stress contributes to the development of many human chronic diseases, including cardiovascular and neurodegenerative pathologies, metabolic syndrome, type 2 diabetes and cancer. GA and its derivative, methyl-3-O-methyl gallate (M3OMG), possess physiological and pharmacological activities closely related to their antioxidant properties. This paper describes the antidepressive-like effects of intraperitoneal administration of GA and two synthetic analogues, M3OMG and P3OMG (propyl-3-O-methylgallate), in balb/c mice with post-stroke depression, a secondary form of depression that could be due to oxidative stress occurring during cerebral ischemia and the following reperfusion. Moreover, this study determined the in vivo antioxidant activity of these compounds through the evaluation of superoxide dismutase (SOD) and catalase (Cat) activity, thiobarbituric acid-reactive substances (TBARS) and reduced glutathione (GSH) levels in mouse brain. GA and its synthetic analogues were found to be active (at doses of 25 and 50 mg/kg) in the modulation of depressive symptoms and the reduction of oxidative stress, restoring normal behavior and, at least in part, antioxidant endogenous defenses, with M3OMG being the most active of these compounds. SOD, TBARS, and GSH all showed strong correlation with behavioral parameters, suggesting that oxidative stress is tightly linked to the pathological processes involved in stroke and PSD. As a whole, the obtained results show that the administration of GA, M3OMG and P3OMG induce a reduction in depressive symptoms and oxidative stress. PMID:27136579
Hunter, Jessica Ezzell; Leslie, Mary; Novak, Gloria; Hamilton, Debra; Shubeck, Lisa; Charen, Krista; Abramowitz, Ann; Epstein, Michael P; Lori, Adriana; Binder, Elisabeth; Cubells, Joseph F; Sherman, Stephanie L
2012-07-01
The fragile X mental retardation gene, FMR1, contains a polymorphic CGG repeat in the 5'-untranslated region of exon 1. Once unstable, this repeat is capable of expansion across generations. Women who carry a premutation allele (55-199 repeats) are at risk of passing on a full mutation allele (>200 repeats) to their offspring. A full mutation leads to the most common form of inherited intellectual disability, fragile X syndrome (FXS). Mounting evidence suggests that premutation carriers may be vulnerable to symptoms of anxiety and depression. The goal of this study was to test the hypothesis that among women who carry a premutation, the stress of raising a child with FXS would be moderated by genetic factors influencing endogenous cortisol responses, which could in turn modulate anxiety and depression symptoms. To this end, we genotyped single nucleotide polymorphisms (SNPs) at the corticotrophin releasing hormone receptor 1 locus (CRHR1) in 460 women. Participants completed self-report questionnaires assessing symptoms of depression [Centers for Epidemiological Studies Depression Scale (CESD)], anxiety [State-Trait Anxiety Inventory (STAI) and Social Phobia and Anxiety Inventory (SPAI)], and mood [Positive and Negative Affect Schedule (PANAS)]. Results indicate a statistically significant interaction between CRHR1 genotype and the status of raising a child with FXS to predict social anxiety symptoms reported on the SPAI (rs7209436, P = 0.0001). Our data suggest that genetic variants in CRHR1 that associate with differential cortisol activation may also modulate levels of anxiety related to the stress of raising a child with FXS among women who carry an FMR1 premutation. Copyright © 2012 Wiley Periodicals, Inc.
Gilbert, Jessica R; Yarrington, Julia S; Wills, Kathleen E; Nugent, Allison C; Zarate, Carlos A
2018-04-13
The glutamatergic modulator ketamine has rapid antidepressant effects in individuals with major depressive disorder (MDD) and bipolar depression. Thus, modulating glutamatergic transmission may be critical to effectively treating depression, though the mechanisms by which this occurs are not fully understood. This double-blind, crossover, placebo-controlled study analyzed data from 18 drug-free MDD subjects and 18 heathy controls who received a single intravenous infusion of ketamine hydrochloride (0.5 mg/kg) as well as an intravenous saline placebo. Magnetoencephalographic (MEG) recordings were collected prior to the first infusion and six to nine hours after both ketamine and placebo infusions. During scanning, participants passively received tactile stimulation to the right index finger. Antidepressant response was assessed across timepoints using the Montgomery-Asberg Depression Rating Scale (MADRS). Dynamic causal modeling (DCM) was used to measure changes in -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)- and N-methyl-D-aspartate (NMDA)-mediated connectivity estimates in MDD subjects and controls using a simple model of somatosensory evoked responses. Both MDD and healthy subjects showed ketamine-mediated NMDA-blockade sensitization, with MDD subjects showing enhanced NMDA connectivity estimates in backward connections, and controls showing enhanced NMDA connectivity estimates in forward connections in our model. Within our MDD subject group, ketamine efficacy-as measured by improved mood ratings-correlated with reduced NMDA and AMPA connectivity estimates in discrete extrinsic connections within the somatosensory cortical network. These findings suggest that AMPA- and NMDA-mediated glutamatergic signaling play a key role in antidepressant response to ketamine and, further, that DCM is a powerful tool for modeling AMPA- and NMDA-mediated connectivity in vivo. NCT#00088699.
Grosen, Kasper; Vase, Lene; Pilegaard, Hans K.; Pfeiffer-Jensen, Mogens; Drewes, Asbjørn M.
2014-01-01
Background Variability in patients' postoperative pain experience and response to treatment challenges effective pain management. Variability in pain reflects individual differences in inhibitory pain modulation and psychological sensitivity, which in turn may be clinically relevant for the disposition to acquire pain. The aim of this study was to investigate the effects of conditioned pain modulation and situational pain catastrophizing on postoperative pain and pain persistency. Methods Preoperatively, 42 healthy males undergoing funnel chest surgery completed the Spielberger's State-Trait Anxiety Inventory and Beck's Depression Inventory before undergoing a sequential conditioned pain modulation paradigm. Subsequently, the Pain Catastrophizing Scale was introduced and patients were instructed to reference the conditioning pain while answering. Ratings of movement-evoked pain and consumption of morphine equivalents were obtained during postoperative days 2–5. Pain was reevaluated at six months postoperatively. Results Patients reporting persistent pain at six months follow-up (n = 15) were not significantly different from pain-free patients (n = 16) concerning preoperative conditioned pain modulation response (Z = 1.0, P = 0.3) or level of catastrophizing (Z = 0.4, P = 1.0). In the acute postoperative phase, situational pain catastrophizing predicted movement-evoked pain, independently of anxiety and depression (β = 1.0, P = 0.007) whereas conditioned pain modulation predicted morphine consumption (β = −0.005, P = 0.001). Conclusions Preoperative conditioned pain modulation and situational pain catastrophizing were not associated with the development of persistent postoperative pain following funnel chest repair. Secondary outcome analyses indicated that conditioned pain modulation predicted morphine consumption and situational pain catastrophizing predicted movement-evoked pain intensity in the acute postoperative phase. These findings may have important implications for developing strategies to treat or prevent acute postoperative pain in selected patients. Pain may be predicted and the malfunctioning pain inhibition mechanism as tested with CPM may be treated with suitable drugs augmenting descending inhibition. PMID:24587268
NASA Astrophysics Data System (ADS)
Dahlem, Markus A.; Graf, Rudolf; Strong, Anthony J.; Dreier, Jens P.; Dahlem, Yuliya A.; Sieber, Michaela; Hanke, Wolfgang; Podoll, Klaus; Schöll, Eckehard
2010-06-01
We present spatio-temporal characteristics of spreading depolarizations (SD) in two experimental systems: retracting SD wave segments observed with intrinsic optical signals in chicken retina, and spontaneously occurring re-entrant SD waves that repeatedly spread across gyrencephalic feline cortex observed by laser speckle flowmetry. A mathematical framework of reaction-diffusion systems with augmented transmission capabilities is developed to explain the emergence and transitions between these patterns. Our prediction is that the observed patterns are reaction-diffusion patterns controlled and modulated by weak nonlocal coupling such as long-range, time-delayed, and global coupling. The described spatio-temporal characteristics of SD are of important clinical relevance under conditions of migraine and stroke. In stroke, the emergence of re-entrant SD waves is believed to worsen outcome. In migraine, retracting SD wave segments cause neurological symptoms and transitions to stationary SD wave patterns may cause persistent symptoms without evidence from noninvasive imaging of infarction.
Yuan, Han; Young, Kymberly D; Phillips, Raquel; Zotev, Vadim; Misaki, Masaya; Bodurka, Jerzy
2014-11-01
Amygdala hemodynamic responses to positive stimuli are attenuated in major depressive disorder (MDD) and normalize with remission. Real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) training with the goal of upregulating amygdala activity during recall of happy autobiographical memories (AMs) has been suggested, and recently explored, as a novel therapeutic approach that resulted in improvement in self-reported mood in depressed subjects. In this study, we assessed the possibility of sustained brain changes as well as the neuromodulatory effects of rtfMRI-nf training of the amygdala during recall of positive AMs in MDD and matched healthy subjects. MDD and healthy subjects went through one visit of rtfMRI-nf training. Subjects were assigned to receive active neurofeedback from the left amygdale (LA) or from a control region putatively not modulated by AM recall or emotion regulation, that is, the left horizontal segment of the intraparietal sulcus. To assess lasting effects of neurofeedback in MDD, the resting-state functional connectivity before and after rtfMRI-nf in 27 depressed subjects, as well as in 27 matched healthy subjects before rtfMRI-nf was measured. Results show that abnormal hypo-connectivity with LA in MDD is reversed after rtfMRI-nf training by recalling positive AMs. Although such neuromodulatory changes are observed in both MDD groups receiving feedback from respective active and control brain regions, only in the active group are larger decreases of depression severity associated with larger increases of amygdala connectivity and a significant, positive correlation is found between the connectivity changes and the days after neurofeedback. In addition, active neurofeedback training of the amygdala enhances connectivity with temporal cortical regions, including the hippocampus. These results demonstrate lasting brain changes induced by amygdala rtfMRI-nf training and suggest the importance of reinforcement learning in rehabilitating emotion regulation in depression.
2013-01-01
Background Major depressive disorder (MDD) is a prevalent and severe disorder. Although effective treatments for MDD are available, many patients remain untreated, mainly because of insufficient treatment capacities in the health care system. Resulting waiting periods are often associated with prolonged suffering and impairment as well as a higher risk of chronification. Web-based interventions may help to alleviate these problems. Numerous studies provided evidence for the efficacy of web-based interventions for depression. The aim of this study is to evaluate a new web-based guided self-help intervention (GET.ON-Mood Enhancer-WL) specifically developed for patients waiting to commence inpatient therapy for MDD. Methods In a two-armed randomised controlled trial (n = 200), the web-based guided intervention GET.ON-Mood Enhancer-WL in addition to treatment as usual (TAU) will be compared with TAU alone. The intervention contains six modules (psycho education, behavioural activation I & II, problem solving I & II, and preparation for subsequent inpatient depression therapy). The participants will be supported by an e-coach, who will provide written feedback after each module. Inclusion criteria include a diagnosis of MDD assessed with a structured clinical interview [SCID] and a waiting period of at least three weeks before start of inpatient treatment. The primary outcome is observer-rated depressive symptom severity (HRSD24). Further (explorative) questions include whether remission will be achieved earlier and by more patients during inpatient therapy because of the web-based preparatory intervention. Discussion If GET.ON-Mood Enhancer-WL is proven to be effective, patients may start inpatient therapy with reduced depressive symptom severity, ideally leading to higher remission rates, shortened inpatient therapy, reduced costs, and decreased waiting times. Trial registration German Clinical Trial Registration (DRKS): DRKS00004708. PMID:24279841
Young, Kymberly D.; Phillips, Raquel; Zotev, Vadim; Misaki, Masaya
2014-01-01
Abstract Amygdala hemodynamic responses to positive stimuli are attenuated in major depressive disorder (MDD) and normalize with remission. Real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) training with the goal of upregulating amygdala activity during recall of happy autobiographical memories (AMs) has been suggested, and recently explored, as a novel therapeutic approach that resulted in improvement in self-reported mood in depressed subjects. In this study, we assessed the possibility of sustained brain changes as well as the neuromodulatory effects of rtfMRI-nf training of the amygdala during recall of positive AMs in MDD and matched healthy subjects. MDD and healthy subjects went through one visit of rtfMRI-nf training. Subjects were assigned to receive active neurofeedback from the left amygdale (LA) or from a control region putatively not modulated by AM recall or emotion regulation, that is, the left horizontal segment of the intraparietal sulcus. To assess lasting effects of neurofeedback in MDD, the resting-state functional connectivity before and after rtfMRI-nf in 27 depressed subjects, as well as in 27 matched healthy subjects before rtfMRI-nf was measured. Results show that abnormal hypo-connectivity with LA in MDD is reversed after rtfMRI-nf training by recalling positive AMs. Although such neuromodulatory changes are observed in both MDD groups receiving feedback from respective active and control brain regions, only in the active group are larger decreases of depression severity associated with larger increases of amygdala connectivity and a significant, positive correlation is found between the connectivity changes and the days after neurofeedback. In addition, active neurofeedback training of the amygdala enhances connectivity with temporal cortical regions, including the hippocampus. These results demonstrate lasting brain changes induced by amygdala rtfMRI-nf training and suggest the importance of reinforcement learning in rehabilitating emotion regulation in depression. PMID:25329241
Moses-Kolko, Eydie L; Forbes, Erika E; Stepp, Stephanie; Fraser, David; Keenan, Kate E; Guyer, Amanda E; Chase, Henry W; Phillips, Mary L; Zevallos, Carlos R; Guo, Chaohui; Hipwell, Alison E
2016-04-01
Given the association between maternal caregiving behavior and heightened neural reward activity in experimental animal studies, the present study examined whether motherhood in humans positively modulates reward-processing neural circuits, even among mothers exposed to various life stressors and depression. Subjects were 77 first-time mothers and 126 nulliparous young women from the Pittsburgh Girls Study, a longitudinal study beginning in childhood. Subjects underwent a monetary reward task during functional magnetic resonance imaging in addition to assessment of current depressive symptoms. Life stress was measured by averaging data collected between ages 8-15 years. Using a region-of-interest approach, we conducted hierarchical regression to examine the relationship of psychosocial factors (life stress and current depression) and motherhood with extracted ventral striatal (VST) response to reward anticipation. Whole-brain regression analyses were performed post-hoc to explore non-striatal regions associated with reward anticipation in mothers vs nulliparous women. Anticipation of monetary reward was associated with increased neural activity in expected regions including caudate, orbitofrontal, occipital, superior and middle frontal cortices. There was no main effect of motherhood nor motherhood-by-psychosocial factor interaction effect on VST response during reward anticipation. Depressive symptoms were associated with increased VST activity across the entire sample. In exploratory whole brain analysis, motherhood was associated with increased somatosensory cortex activity to reward (FWE cluster forming threshold p<0.001). These findings indicate that motherhood is not associated with reward anticipation-related VST activity nor does motherhood modulate the impact of depression or life stress on VST activity. Future studies are needed to evaluate whether earlier postpartum assessment of reward function, inclusion of mothers with more severe depressive symptoms, and use of reward tasks specific for social reward might reveal an impact of motherhood on reward system activity. Copyright © 2016 Elsevier Ltd. All rights reserved.
Yeh, Yi-Wei; Ho, Pei-Shen; Chen, Chun-Yen; Kuo, Shin-Chang; Liang, Chih-Sung; Yen, Che-Hung; Huang, Chang-Chih; Shiue, Chyng-Yann; Huang, Wen-Sheng; Ma, Kuo-Hsing; Lu, Ru-Band; Huang, San-Yuan
2015-10-01
Suicide is an important issue in the military service, since it can influence military morale and create dangerous situations for other personnel. The serotonin transporter (SERT) has been suggested to be involved in the pathophysiology of depression and suicidal behaviours. The aims of this study were to examine whether the brain SERT availability differs between military conscripts with depression and control subjects, and whether suicidal ideation is correlated with SERT availability. We used N,N-dimethyl-2-(2-amino-4-[(18)F]-fluorophenylthio)benzylamine (4-[(18)F]-ADAM) as a radioligand for positron emission tomography (PET) imaging. All participants completed the Hamilton Depression Rating Scale and Beck Scale for Suicide Ideation (BSS) prior to PET imaging. The effect of major depression and BSS scores had an interaction on SERT availability. After adjusting for the BSS score, subjects with depression had lower SERT availability than control subjects (F1,17 = 23.85, P < 0.001). A positive correlation between SERT availability and BSS scores was observed in the depression group (F1,8 = 30.67, P = 0.001). The status of depression and intensity of suicidal ideation exert opposite effects on SERT availability. The extent of suicidal ideation may moderate the reduction effect in SERT binding observed in major depression in male military conscripts.
Household food insecurity is associated with depressive symptoms among low-income pregnant Latinas
Hromi-Fiedler, Amber; Bermúdez-Millán, Angela; Segura-Pérez, Sofia; Pérez-Escamilla, Rafael
2010-01-01
Latinas experience high rates of poverty, household food insecurity, and prenatal depression. To date, only one U.S. study has examined the relationship between household food insecurity and prenatal depression, yet it focused primarily on non-Latina white and non-Latina Black populations. Therefore, this study examined the independent association of household food insecurity with depressive symptoms among low-income pregnant Latinas. This cross-sectional study included 135 low income pregnant Latinas living in Hartford, Connecticut. Women were assessed at enrollment for household food security during pregnancy using an adapted and validated version of the U.S. Household Food Security Survey Module. Prenatal depressive symptoms were assessed using the Center for Epidemiological Studies Depression Scale (CES-D). A cutoff of ≥ 21 was used to indicate elevated levels of prenatal depressive symptoms (EPDS). Multivariate backwards stepwise logistic regression was used to identify risk factors for EPDS. Almost one third of participants had EPDS. Women who were food insecure were more likely to experience EPDS compared to food secure women (OR=2.59; 95% CI=1.03–6.52). Being primiparous, experiencing heartburn and reporting poor/fair health during pregnancy, as well as having a history of depression were also independent risk factors for experiencing EPDS. Findings from this study suggest the importance of assessing household food insecurity when evaluating depression risk among pregnant Latinas. PMID:20735732
Philip, Noah S; Barredo, Jennifer; Aiken, Emily; Carpenter, Linda L
2018-03-01
Research into therapeutic transcranial magnetic stimulation (TMS) for major depression has dramatically increased in the last decade. Understanding the mechanism of action of TMS is crucial to improve efficacy and develop the next generation of therapeutic stimulation. Early imaging research provided initial data supportive of widely held assumptions about hypothesized inhibitory or excitatory consequences of stimulation. Early work also indicated that while TMS modulated brain activity under the stimulation site, effects at deeper regions, in particular, the subgenual anterior cingulate cortex, were associated with clinical improvement. Concordant with earlier findings, functional connectivity studies also demonstrated that clinical improvements were related to changes distal, rather than proximal, to the site of stimulation. Moreover, recent work suggests that TMS modulates and potentially normalizes functional relationships between neural networks. An important observation that emerged from this review is that similar patterns of connectivity changes are observed across studies regardless of TMS parameters. Though promising, we stress that these imaging findings must be evaluated cautiously given the widespread reliance on modest sample sizes and little implementation of statistical validation. Additional limitations included use of imaging before and after a course of TMS, which provided little insight into changes that might occur during the weeks of stimulation. Furthermore, as studies to date have focused on depression, it is unclear whether our observations were related to mechanisms of action of TMS for depression or represented broader patterns of functional brain changes associated with clinical improvement. Published by Elsevier Inc.
Chikezie, U E; Otakpor, A N; Kuteyi, O B; James, B O
2013-01-01
Depression is a common co-morbidity among persons living with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) (PLWHAs). It is associated with poor treatment adherence and higher mortality rates. Few reports have, however, emanated from developing countries where socioeconomic factors may confound this association. We conducted a cross-sectional comparative study of PLWHAs and apparently healthy staff of three LGA's. The depression module of the Schedule for the Clinical Assessment in Neuropsychiatry (SCAN) and the Beck Depression Inventory (BDI) was used to diagnose depression and depression symptom severity, respectively. Depression was commonly co-morbid among individuals with HIV/AIDS. It was five times more common in PLWHAs than in apparently healthy populations (29.3% vs. 7.3%, OR: 5.25, 95% CI: 2.50-11.76). A similar trend was observed for depression symptom severity. Among PLWHAs, depression was significantly more likely among females (OR: 7.91, 95% CI: 1.83-71.00, P < 0.01), those unemployed (OR: 2.94, 95% CI: 0.18-1.82, P < 0.04), and with an illness duration >3 years (OR: 7.90, P < 0.0001). Having at least one child (OR: 2.79, 95% CI: 1.25-6.16, P < 0.001) and living with others (OR: 4.71, 95% CI: 1.51-15.52, P < 0.003) significantly reduced depression risk. Depression was commonly co-morbid among PLWHAs studied. Clinicians should be aware of risk factors for depression among PLWHAs in order to improve treatment outcomes.
Harms, Jonathan E.; Benveniste, Morris; Maclean, John K. F.; Partin, Kathryn M.; Jamieson, Craig
2012-01-01
Positive allosteric modulators of α-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) receptors facilitate synaptic plasticity and can improve various forms of learning and memory. These modulators show promise as therapeutic agents for the treatment of neurological disorders such as schizophrenia, ADHD, and mental depression. Three classes of positive modulator, the benzamides, the thiadiazides, and the biarylsulfonamides differentially occupy a solvent accessible binding pocket at the interface between the two subunits that form the AMPA receptor ligand-binding pocket. Here, we describe the electrophysiological properties of a new chemotype derived from a structure-based drug design strategy (SBDD), which makes similar receptor interactions compared to previously reported classes of modulator. This pyrazole amide derivative, JAMI1001A, with a promising developability profile, efficaciously modulates AMPA receptor deactivation and desensitization of both flip and flop receptor isoforms. PMID:22735771
NASA Astrophysics Data System (ADS)
Ciszak, Marzena; Bellesi, Michele
2011-12-01
The transitions between waking and sleep states are characterized by considerable changes in neuronal firing. During waking, neurons fire tonically at irregular intervals and a desynchronized activity is observed at the electroencephalogram. This activity becomes synchronized with slow wave sleep onset when neurons start to oscillate between periods of firing (up-states) and periods of silence (down-states). Recently, it has been proposed that the connections between neurons undergo potentiation during waking, whereas they weaken during slow wave sleep. Here, we propose a dynamical model to describe basic features of the autonomous transitions between such states. We consider a network of coupled neurons in which the strength of the interactions is modulated by synaptic long term potentiation and depression, according to the spike time-dependent plasticity rule (STDP). The model shows that the enhancement of synaptic strength between neurons occurring in waking increases the propensity of the network to synchronize and, conversely, desynchronization appears when the strength of the connections become weaker. Both transitions appear spontaneously, but the transition from sleep to waking required a slight modification of the STDP rule with the introduction of a mechanism which becomes active during sleep and changes the proportion between potentiation and depression in accordance with biological data. At the neuron level, transitions from desynchronization to synchronization and vice versa can be described as a bifurcation between two different states, whose dynamical regime is modulated by synaptic strengths, thus suggesting that transition from a state to an another can be determined by quantitative differences between potentiation and depression.
NASA Astrophysics Data System (ADS)
Baisya, Himadri; Pattnaik, Sandeep; Rajesh, P. V.
2017-03-01
A series of numerical experiments are carried out to investigate the sensitivity of a landfalling monsoon depression to land surface conditions using the Weather Research and Forecasting (WRF) model. Results suggest that precipitation is largely modulated by moisture influx and precipitation efficiency. Three cloud microphysical schemes (WSM6, WDM6, and Morrison) are examined, and Morrison is chosen for assessing the land surface-precipitation feedback analysis, owing to better precipitation forecast skills. It is found that increased soil moisture facilitates Moisture Flux Convergence (MFC) with reduced moisture influx, whereas a reduced soil moisture condition facilitates moisture influx but not MFC. A higher Moist Static Energy (MSE) is noted due to increased evapotranspiration in an elevated moisture scenario which enhances moist convection. As opposed to moist surface, sensible heat dominates in a reduced moisture scenario, ensued by an overall reduction in MSE throughout the Planetary Boundary Layer (PBL). Stability analysis shows that Convective Available Potential Energy (CAPE) is comparable in magnitude for both increased and decreased moisture scenarios, whereas Convective Inhibition (CIN) shows increased values for the reduced moisture scenario as a consequence of drier atmosphere leading to suppression of convection. Simulations carried out with various fixed soil moisture levels indicate that the overall precipitation features of the storm are characterized by initial soil moisture condition, but precipitation intensity at any instant is modulated by soil moisture availability. Overall results based on this case study suggest that antecedent soil moisture plays a crucial role in modulating precipitation distribution and intensity of a monsoon depression.
Castiglione, Alessandro; Benatti, Alice; Velardita, Carmelita; Favaro, Diego; Padoan, Elisa; Severi, Daniele; Pagliaro, Michela; Bovo, Roberto; Vallesi, Antonino; Gabelli, Carlo; Martini, Alessandro
2016-01-01
A growing interest in cognitive effects associated with speech and hearing processes is spreading throughout the scientific community essentially guided by evidence that central and peripheral hearing loss is associated with cognitive decline. For the present research, 125 participants older than 65 years of age (105 with hearing impairment and 20 with normal hearing) were enrolled, divided into 6 groups according to their degree of hearing loss and assessed to determine the effects of the treatment applied. Patients in our research program routinely undergo an extensive audiological and cognitive evaluation protocol providing results from the Digit Span test, Stroop color-word test, Montreal Cognitive Assessment and Geriatric Depression Scale, before and after rehabilitation. Data analysis was performed for a cross-sectional and longitudinal study of the outcomes for the different treatment groups. Each group demonstrated improvement after auditory rehabilitation or training on short- and long-term memory tasks, level of depression and cognitive status scores. Auditory rehabilitation by cochlear implants or hearing aids is effective also among older adults (median age of 74 years) with different degrees of hearing loss, and enables positive improvements in terms of social isolation, depression and cognitive performance. © 2016 The Author(s) Published by S. Karger AG, Basel.
Oldenburg, Catherine E; Biello, Katie B; Colby, Donn; Closson, Elizabeth F; Mai, Thi; Nguyen, Thi; Nguyen, Ngoc A; Mimiaga, Matthew J
2014-10-01
Male sex workers (MSW) in Vietnam face high levels of stigma related to sex work, which may be associated with depression and increased vulnerability to HIV. In 2010, 300 MSW completed a behavioral and psychosocial survey. Multivariable models assessed factors associated with sex work-related stigma and the association between stigma and depression. Factors associated with increased stigma included having disclosed sexual orientation to healthcare workers (b 1.75, 95 % CI 0.69-2.80), meeting clients in the street/park (b 1.42, 95 % CI 0.32-2.52), and having been forced to have sex without a condom (b 2.36, 95 % CI 1.27-3.45). Factors associated with decreased stigma included meeting clients via the telephone or internet (b -1.26, 95 % CI -2.39 to -0.12) and receiving financial support from family or friends (b -1.31, 95 % CI -2.46 to -0.17). Stigma was significantly associated with increased odds of depression (AOR 1.07, 95 % CI 1.01-1.15). Addressing stigma and depression in HIV prevention interventions is crucial for tailoring these programs to MSWs' needs, and may result in decreased HIV spread.
Duprat, Romain; Desmyter, Stefanie; Rudi, De Raedt; van Heeringen, Kees; Van den Abbeele, Dirk; Tandt, Hannelore; Bakic, Jasmina; Pourtois, Gilles; Dedoncker, Josefien; Vervaet, Myriam; Van Autreve, Sara; Lemmens, Gilbert M D; Baeken, Chris
2016-08-01
Although accelerated repetitive Transcranial Magnetic Stimulation (rTMS) paradigms and intermittent Theta-burst Stimulation (iTBS) may have the potency to result in superior clinical outcomes in Treatment Resistant Depression (TRD), accelerated iTBS treatment has not yet been studied. In this registered randomized double-blind sham-controlled crossover study, spread over four successive days, 50 TRD patients received 20 iTBS sessions applied to the left dorsolateral prefrontal cortex (DLPFC). The accelerated iTBS treatment procedure was found to be safe and resulted in immediate statistically significant decreases in depressive symptoms regardless of order/type of stimulation (real/sham). While only 28% of the patients showed a 50% reduction of their initial Hamilton Depression Rating Scale score at the end of the two-week procedure, this response rate increased to 38% when assessed two weeks after the end of the sham-controlled iTBS protocol, indicating delayed clinical effects. Importantly, 30% of the responders were considered in clinical remission. We found no demographic predictors for response. Our findings indicate that only four days of accelerated iTBS treatment applied to the left DLPFC in TRD may lead to meaningful clinical responses within two weeks post stimulation. Copyright © 2016 Elsevier B.V. All rights reserved.
Busquet, Perrine; Nguyen, Ngoc Khoi; Schmid, Eduard; Tanimoto, Naoyuki; Seeliger, Mathias W; Ben-Yosef, Tamar; Mizuno, Fengxia; Akopian, Abram; Striessnig, Jörg; Singewald, Nicolas
2010-05-01
Mounting evidence suggests that voltage-gated L-type Ca2+ channels can modulate affective behaviour. We therefore explored the role of CaV1.3 L-type Ca2+ channels in depression- and anxiety-like behaviours using CaV1.3-deficient mice (CaV1.3-/-). We showed that CaV1.3-/- mice displayed less immobility in the forced swim test as well as in the tail suspension test, indicating an antidepressant-like phenotype. Locomotor activity in the home cage or a novel open-field test was not influenced. In the elevated plus maze (EPM), CaV1.3-/- mice entered the open arms more frequently and spent more time there indicating an anxiolytic-like phenotype which was, however, not supported in the stress-induced hyperthermia test. By performing parallel experiments in Claudin 14 knockout mice (Cldn14-/-), which like CaV1.3-/- mice are congenitally deaf, an influence of deafness on the antidepressant-like phenotype could be ruled out. On the other hand, a similar EPM behaviour indicative of an anxiolytic phenotype was also found in the Cldn14-/- animals. Using electroretinography and visual behavioural tasks we demonstrated that at least in mice, CaV1.3 channels do not significantly contribute to visual function. However, marked morphological changes were revealed in synaptic ribbons in the outer plexiform layer of CaV1.3-/- retinas by immunohistochemistry suggesting a possible role of this channel type in structural plasticity at the ribbon synapse. Taken together, our findings indicate that CaV1.3 L-type Ca2+ channels modulate depression-like behaviour but are not essential for visual function. The findings raise the possibility that selective modulation of CaV1.3 channels could be a promising new therapeutic concept for the treatment of mood disorders.
2004-08-01
established MTCIL tumor rolls retain this unique biologic feature. -ll suspeniionsw from sth moat vsital porn MTP ntutur arnd injected we inoutlated...rather than linear or continuous process. This biologic growth pattern is not unique nor unprecedented. Growth studies in children using serial height
The Spread of ICT Innovation in Accounting Education
ERIC Educational Resources Information Center
Jebeile, Sam; Abeysekera, Indra
2010-01-01
This paper conveys the findings of a study conducted to evaluate the initiation of an interactive online computer-assisted learning module, called WEBLEARN, in an undergraduate introductory accounting course at an Australian university. The purpose was to aid students in the preparation of cash flow statements, a topic that from the student…
Current directions in non-invasive low intensity electric brain stimulation for depressive disorder.
Schutter, Dennis J L G; Sack, Alexander T
2014-01-01
Non-invasive stimulation of the human brain to improve depressive symptoms is increasingly finding its way in clinical settings as a viable form of somatic treatment. Following successful modulation of neural excitability with subsequent antidepressant effects, neural polarization by administrating weak direct currents to the scalp has gained renewed interest. A new wave of basic and clinical studies seems to underscore the potential therapeutic value of direct current stimulation in the treatment of depression. Issues concerning the lack of mechanistic insights into the workings of modifying brain function through neural polarization and how this process translates to its antidepressant properties calls for additional research. The range of its clinical applicability has yet to be established.
Experimental research of adaptive OFDM and OCT precoding with a high SE for VLLC system
NASA Astrophysics Data System (ADS)
Liu, Shuang-ao; He, Jing; Chen, Qinghui; Deng, Rui; Zhou, Zhihua; Chen, Shenghai; Chen, Lin
2017-09-01
In this paper, an adaptive orthogonal frequency division multiplexing (OFDM) modulation scheme with 128/64/32/16-quadrature amplitude modulation (QAM) and orthogonal circulant matrix transform (OCT) precoding is proposed and experimentally demonstrated for a visible laser light communication (VLLC) system with a cost-effective 450-nm blue-light laser diode (LD). The performance of OCT precoding is compared with conventional the adaptive Discrete Fourier Transform-spread (DFT-spread) OFDM scheme, 32 QAM OCT precoding OFDM scheme, 64 QAM OCT precoding OFDM scheme and adaptive OCT precoding OFDM scheme. The experimental results show that OCT precoding can achieve a relatively flat signal-to-noise ratio (SNR) curve, and it can provide performance improvement in bit error rate (BER). Furthermore, the BER of the proposed OFDM signal with a raw bit rate 5.04 Gb/s after 5-m free space transmission is less than 20% of soft-decision forward error correlation (SD-FEC) threshold of 2.4 × 10-2, and the spectral efficiency (SE) of 4.2 bit/s/Hz can be successfully achieved.
Structure of kinetic Alfvén waves with small transverse scale length
NASA Astrophysics Data System (ADS)
Morales, G. J.; Maggs, J. E.
1997-11-01
This analytical study illustrates the spatial pattern of kinetic Alfvén waves excited by a current-modulating disk whose dimension a, transverse to the confining magnetic field, is comparable to the ion sound gyroradius cs/Ωi, where cs is the sound speed and Ωi the ion cyclotron frequency. The radial structure of the wave azimuthal magnetic field is found to consist of four regions: a Bessel function behavior for r
Impact of Stratospheric Sudden Warming on the Occurrence of the Equatorial Spread-F
NASA Astrophysics Data System (ADS)
Jose, Lijo; Vineeth, C.; Pant, T. K.
2017-12-01
This study presents the influence of stratospheric sudden warming (SSW) events in modulating the start time of the equatorial spread-F (ESF) through enhanced planetary wave (PW) activity during the winter months of the SSW years. The analysis based on the data from a digital ionosonde and proton precession magnetometer over Trivandrum (8.5°N, 77°E, 0.5°N dip lat.) revealed that the PWs of quasi-16 day periodicity influence the start time of the ESF to a significant extent during the SSW years. On the other hand, during a normal year such effect is not very evidently present. It has been observed that the quasi-16 day wave propagates to ionospheric dynamo region from the atmosphere below and modifies the electrodynamical processes like the equatorial electrojet and prereversal enhancement, which is more pronounced during both the SSW periods. Such a modification in the electrodynamics can modulate the equatorial plasma fountain and influence the F region neutral dynamics, which in turn can affect the occurrence of ESF by modifying the seeding conditions.
Dhar, R S; Ban, D
2013-07-01
The distribution of charge carriers inside the active region of a terahertz (THz) quantum cascade laser (QCL) has been measured with scanning spreading resistance microscopy (SSRM) and scanning capacitance microscopy (SCM). Individual quantum well-barrier modules with a 35.7-nm single module thickness in the active region of the device have been resolved for the first time using high-resolution SSRM and SCM techniques at room temperature. SSRM and SCM measurements on the quantum well-barrier structure were calibrated utilizing known GaAs dopant staircase samples. Doping concentrations derived from SSRM and SCM measurements were found to be in quantitative agreement with the designed average doping values of the n-type active region in the terahertz quantum cascade laser. The secondary ion mass spectroscopy provides a partial picture of internal device parameters, and we have demonstrated with our results the efficacy of uniting calibrated SSRM and SCM to delineate quantitatively the transverse cross-sectional structure of complex two-dimensional terahertz quantum cascade laser devices. © 2013 The Authors Journal of Microscopy © 2013 Royal Microscopical Society.
2003-05-01
As AIDS spreads rapidly in the South, a new picture is emerging, which shows the epidemic is becoming increasingly rural, female, African-American, and poor. Two new studies are helping identifying why so many rural Southerners avoid the health care systems and don't trust their doctors about HIV infection. Clinicians need to address high rates of depression and post-traumatic stress syndrome in HIV-infected patients living in the rural South.
Toniolo, Ricardo Alexandre; Silva, Michelle; Fernandes, Francy de Brito Ferreira; Amaral, José Antonio de Mello Siqueira; Dias, Rodrigo da Silva; Lafer, Beny
2018-02-01
Depressive episodes are a major cause of morbidity and dysfunction in individuals suffering from bipolar disorder. Currently available treatments for this condition have limited efficacy and new therapeutic options are needed. Extensive research in the pathophysiology of bipolar disorder points to the existence of mitochondrial and bioenergetic dysfunction. We hypothesized that creatine monohydrate, a nutraceutical that works as a mitochondrial modulator, would be effective as an adjunctive therapy for bipolar depression. We conducted a double-blind trial in which 35 patients with bipolar disorder type I or II in a depressive episode by DSM-IV criteria and in use of regular medication for the treatment of this phase of the disease were randomly allocated into two adjunctive treatment groups for 6 weeks: creatine monohydrate 6 g daily (N = 17) or placebo (N = 18). Primary efficacy was assessed by the change in the Montgomery-Åsberg Depression Rating Scale (MADRS). We did not find a statistically significant difference in the comparison between groups for the change in score on the MADRS after 6 weeks in an intention-to-treat (ITT) analysis (p = 0.560; Cohen's d = 0.231). However, we found significant superiority of creatine add-on vs. placebo when we considered the remission criterion of a MADRS score ≤ 12 at week 6 analyzing the outcome of the 35 randomized patients on ITT (52.9% remission in the creatine group vs. 11.1% remission in the placebo group) and of the 23 completers (66.7% remission in the creatine group vs. 18.2% remission in the placebo group) (p = 0.012; OR = 9.0 and p = 0.036; OR = 9.0, respectively). Two patients who received creatine switched to hypomania/mania early in the trial. No clinically relevant physical side-effects were reported or observed. This proof-of-concept study, aiming to restore brain bioenergetics using an adjunctive mitochondrial modulator, is not conclusive on the efficacy of creatine add-on for bipolar depression, but suggests that this compound may have a role in the adjunctive treatment of this phase of the illness. Further investigation through randomized controlled trials with larger samples should be conducted to verify the efficacy of creatine supplementation for bipolar depression and also for subsyndromal depressive symptoms.
Hardaway, Cecily R.; Larkby, Cynthia A.; Cornelius, Marie D.
2014-01-01
Objective This study examines whether exposure to community violence is indirectly related to academic performance through anxious/depressed symptoms and delinquent behaviors. Methods Three hundred eighteen mothers and adolescents who participated in a longitudinal investigation were interviewed when adolescents were age 10, 14, and 16. Results Community violence exposure at age 14 was significantly related to anxious/depressed symptoms and delinquent behaviors. Delinquent behaviors (but not anxious/depressed symptoms) were significantly associated with academic performance at age 16. Exposure to community violence was indirectly related to academic performance through delinquent behaviors. There was no significant indirect effect of exposure to community violence on academic performance through anxious/depressed symptoms. Covariates included sociodemographics and exposure to child abuse. Age 10 anxious/depressed symptoms, age 10 delinquent behaviors, and age 14 academic performance were also included in the model to control for preexisting differences in socioemotional adjustment and academic performance. Conclusions Results suggest that exposure to community violence may initiate a cascade of problems that spread from behavior problems to declines in academic performance. Our results highlight the need for schools to consider exposure to community violence as one form of trauma and to transform in ways that make them more trauma-sensitive. The use of trauma-sensitive practices that address the effects of violence exposure on youth may help limit the progression of adverse effects from delinquent behavior to other domains of functioning. PMID:25485167
Hardaway, Cecily R; Larkby, Cynthia A; Cornelius, Marie D
2014-07-01
This study examines whether exposure to community violence is indirectly related to academic performance through anxious/depressed symptoms and delinquent behaviors. Three hundred eighteen mothers and adolescents who participated in a longitudinal investigation were interviewed when adolescents were age 10, 14, and 16. Community violence exposure at age 14 was significantly related to anxious/depressed symptoms and delinquent behaviors. Delinquent behaviors (but not anxious/depressed symptoms) were significantly associated with academic performance at age 16. Exposure to community violence was indirectly related to academic performance through delinquent behaviors. There was no significant indirect effect of exposure to community violence on academic performance through anxious/depressed symptoms. Covariates included sociodemographics and exposure to child abuse. Age 10 anxious/depressed symptoms, age 10 delinquent behaviors, and age 14 academic performance were also included in the model to control for preexisting differences in socioemotional adjustment and academic performance. Results suggest that exposure to community violence may initiate a cascade of problems that spread from behavior problems to declines in academic performance. Our results highlight the need for schools to consider exposure to community violence as one form of trauma and to transform in ways that make them more trauma-sensitive. The use of trauma-sensitive practices that address the effects of violence exposure on youth may help limit the progression of adverse effects from delinquent behavior to other domains of functioning.
Galiano-Castillo, Noelia; Ariza-García, Angelica; Cantarero-Villanueva, Irene; Fernández-Lao, Carolina; Díaz-Rodríguez, Lourdes; Arroyo-Morales, Manuel
2014-04-01
One out of five cancer survivors suffer from depression after oncology treatment. The aim of this study was to examine the relationship between depression and quality of life (QoL), cancer-related symptoms, physical activity level, health-related fitness, and salivary flow rate in breast cancer survivors. 108 breast cancer survivors in the year after the conclusion of treatment were included in this cross-sectional study. Demographic and clinically relevant information, cancer-related fatigue (Piper Fatigue Scale), QoL (QLQ-Br23 module), pain intensity VAS scale, salivary flow rate, physical activity level (Minnesota Leisure Time Physical Activity Questionnaire), and health-related fitness were assessed in all participants. Depressed mood was measured with the Profile of Mood States (POMS) Depression subscale. Significant positive correlations between depressed mood and fatigue, systemic side effects, perceived shoulder pain, and breast-arms symptoms (r ranged between .57 and .28, P < .01) were found. In addition, significant negative correlations between depressed mood and body image, future perspective, force handgrip, and physical activity level (r ranged between -.41 and -.19; p < .05) were found. Regression analyses revealed that cancer-related fatigue, physical activity level, systemic side effects, and body image were significant predictors of depressed mood, and when combined, they explained 39.6% of the variance in depressed mood. Cancer-related fatigue, physical activity level, and QoL partially explain the variability of depressed mood in breast cancer survivors. This paper facilitates a better understanding of the relationship between depressed mood and possible factors associated with it. Copyright © 2013 Elsevier Ltd. All rights reserved.
Depression and Its Correlates Among Older Adults Accessing Aging Services
Richardson, Thomas M.; Friedman, Bruce; Podgorski, Carol; Knox, Kerry; Fisher, Susan; He, Hua; Conwell, Yeates
2011-01-01
Objectives To define the prevalence and correlates of depression among older adults receiving assessments by nonmedical community-based care managers at the point of entry to care and thus prior to provision of aging services. Our long-term goal is to inform development of collaborative care models for late life depression that incorporate Aging Services Providers. Methods Aging Services Provider Network (ASPN) clients receiving in-home assessments were administered the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition module for affective disorders and measures of depression symptom severity, alcohol use, physical health, functional status, social support, stressful life events, and religiosity. Engagement in mental healthcare was documented. Results Subjects (N = 378) were primarily white (84%) and women (69%) with household incomes under $1,750/month (62%). Half lived alone (48%). Their mean age was 77 years. Thirty-one percent had clinically significant depressive symptoms and 27% met criteria for a current major depressive episode, of which 61% were being treated with medication and 25% by a mental health provider. Nearly half (47%) had experienced one or more episodes of major depression during their lives. Disability, number of medical conditions, number and severity of recent stressful life events, low social support, and low religiosity were independently associated with current major depression. Conclusion Depressive illness was common among this sample of ASPN clients. Because ASPN care managers have expertise in managing many of the problems correlated with depression, they may play a significant role in identifying, preventing, and collaborating in the treatment of depressive illnesses among community-dwelling older adults. PMID:22434017
Suri, Rita; Altshuler, Lori; Hellemann, Gerhard; Burt, Vivien K; Aquino, Ana; Mintz, Jim
2007-08-01
The authors evaluated the effects of prenatal antidepressant exposure and maternal depression on infant gestational age at birth and risk of preterm birth. Ninety women were followed in a prospective, naturalistic design through pregnancy with monthly assessments of symptoms of depression and anxiety using the Structured Clinical Interview for DSM-IV mood module for depression, the Hamilton Depression Rating Scale, the Beck Depression Inventory, and the Perceived Stress Scale. Participants included 49 women with major depressive disorder who were treated with antidepressants during pregnancy (group 1), 22 women with major depressive disorder who were either not treated with antidepressants or had limited exposure to them during pregnancy (group 2), and 19 healthy comparison subjects (group 3). The primary outcome variables were the infants' gestational age at birth, birth weight, 1- and 5-minute Apgar scores, and admission to the special care nursery. Groups 1, 2, and 3 differed significantly in gestational age at birth (38.5 weeks, 39.4 weeks, 39.7 weeks, respectively), rates of preterm birth (14.3%, 0%, 5.3%, respectively), and rates of admission to the special care nursery (21%, 9%, 0%, respectively). Birth weight and Apgar scores did not differ significantly between groups. Mild to moderate depression during pregnancy did not affect outcome measures. Prenatal antidepressant use was associated with lower gestational age at birth and an increased risk of preterm birth. Presence of depressive symptoms was not associated with this risk. These results suggest that medication status, rather than depression, is a predictor of gestational age at birth.
Work Performance of Employees With Depression: The Impact of Work Stressors
Lerner, Debra; Adler, David A.; Rogers, William H.; Chang, Hong; Lapitsky, Leueen; McLaughlin, Thomas; Reed, John
2014-01-01
Purpose Depressed employees are vulnerable to adverse work outcomes. We hypothesized that work performance is impaired by depression and is worsened by exposure to psychosocial work stressors. Design Longitudinal cohort study with surveys administered at baseline, 6, 12, and 18 months. Setting Recruitment in primary care offices. Subjects A total of 14,268 were screened; 286 depressed, employed adults (18–62 years) and 193 controls were enrolled. Measures At-work limitations (presenteeism) and absenteeism were measured with the Work Limitations Questionnaire (WLQ) and WLQ Work Absence Module, respectively. Work stressors were assessed using a modified version of the Job Content Questionnaire. Analysis Univariate and multivariate tests assessed the degree to which at-work limitations were related to depression and/or stressful work. Results Presenteeism and absenteeism were significantly worse for the depression group at each time point (p ≤ .001). In cross-sectional models, presenteeism was associated with more severe depression symptoms, poorer general physical health, psychologically demanding work, the interaction of psychologically demanding work with depression, and less job control (r2 range = .33–.54). Absences were explained by depression symptom severity and poorer general physical health but not work stressors (r2 = .19). Because of minimal change in the work stressors, their longitudinal effects on outcomes were mostly nonsignificant. Conclusion This study found that depression symptoms are related to work absences and impaired work performance, and results partly confirmed that work stressors add to this impact. Results suggest that workers with depression may benefit from care involving medical and vocational interventions. PMID:20073388
Song, Jiho; Shawky, Joseph H; Kim, YongTae; Hazar, Melis; LeDuc, Philip R; Sitti, Metin; Davidson, Lance A
2015-07-01
Cells in tissues encounter a range of physical cues as they migrate. Probing single cell and collective migratory responses to physically defined three-dimensional (3D) microenvironments and the factors that modulate those responses are critical to understanding how tissue migration is regulated during development, regeneration, and cancer. One key physical factor that regulates cell migration is topography. Most studies on surface topography and cell mechanics have been carried out with single migratory cells, yet little is known about the spreading and motility response of 3D complex multi-cellular tissues to topographical cues. Here, we examine the response to complex topographical cues of microsurgically isolated tissue explants composed of epithelial and mesenchymal cell layers from naturally 3D organized embryos of the aquatic frog Xenopus laevis. We control topography using fabricated micropost arrays (MPAs) and investigate the collective 3D migration of these multi-cellular systems in these MPAs. We find that the topography regulates both collective and individual cell migration and that dense MPAs reduce but do not eliminate tissue spreading. By modulating cell size through the cell cycle inhibitor Mitomycin C or the spacing of the MPAs we uncover how 3D topographical cues disrupt collective cell migration. We find surface topography can direct both single cell motility and tissue spreading, altering tissue-scale processes that enable efficient conversion of single cell motility into collective movement. Copyright © 2015 Elsevier Ltd. All rights reserved.
2010-04-01
help outside their chain of command. 41 Your family member may also: • feel depressed • begin to abuse alcohol or drugs • have problems with...P.O. Box 5715 Helena, MT 59604 P.O. Box 95083 301 Centennial Mall South, 6th Floor Lincoln, NE 68509 5460 Reno Corporation Dr. Reno, NV 89511 275...main.htm or call the toll-free line at 1-800-444-5445. DoD Mental Health Self Assessment Program Anonymous self-assessments are available for depression
Patel, Sangram Kishor; Ganju, Deepika; Prabhakar, Parimi; Adhikary, Rajatashuvra
2016-01-01
Background The relationship between mobility, violence and mental health has largely been unexplored in developing countries. This study screens for signs of major depression, and assesses its association with mobility and violence among female sex workers (FSWs) in southern India. Methods Data (N=2400) for this study were used from a cross-sectional Behavioral Tracking Survey (BTS-2014) conducted among FSWs from a southern state of India as part of the Avahan programme. Major depression of FSWs was assessed using the Patient Health Questionnaire-2 depression scale. Descriptive statistics, frequency, bivariate, interaction effect and multivariate logistic regression techniques were used for the analysis. Results More than one-fourth of FSWs (29%) screened positive for major depression. The likelihood of screening positive for major depression was 6 times higher among FSWs who were both mobile for sex work outside their district of residence and had experienced any violence (combined association) during the past 1 year (62% vs 19%, adjusted OR 6.1, 95% CI 4.4 to 8.6) compared with those who reported neither. The individual association results show that FSWs who reported being mobile outside the district, and FSWs who were beaten or raped in the past 1 year, were 3 times more likely to screen positive for major depression. Conclusions The findings indicate that violence and mobility are independently associated with major depression among FSWs. The combined association of mobility and violence poses a greater risk to the mental health of FSWs than their independent association. These results point to the need for creating an enabling environment for FSWs to enhance existing efforts to reduce the spread of HIV and mental health problems. The study highlights that HIV prevention efforts among FSWs in India require evidence-based research and integrated programme approaches to address mental health issues. PMID:27612536
Antidepressive effects of targeting ELK-1 signal transduction.
Apazoglou, Kallia; Farley, Séverine; Gorgievski, Victor; Belzeaux, Raoul; Lopez, Juan Pablo; Grenier, Julien; Ibrahim, El Chérif; El Khoury, Marie-Anne; Tse, Yiu C; Mongredien, Raphaele; Barbé, Alexandre; de Macedo, Carlos E A; Jaworski, Wojciech; Bochereau, Ariane; Orrico, Alejandro; Isingrini, Elsa; Guinaudie, Chloé; Mikasova, Lenka; Louis, Franck; Gautron, Sophie; Groc, Laurent; Massaad, Charbel; Yildirim, Ferah; Vialou, Vincent; Dumas, Sylvie; Marti, Fabio; Mechawar, Naguib; Morice, Elise; Wong, Tak P; Caboche, Jocelyne; Turecki, Gustavo; Giros, Bruno; Tzavara, Eleni T
2018-05-07
Depression, a devastating psychiatric disorder, is a leading cause of disability worldwide. Current antidepressants address specific symptoms of the disease, but there is vast room for improvement 1 . In this respect, new compounds that act beyond classical antidepressants to target signal transduction pathways governing synaptic plasticity and cellular resilience are highly warranted 2-4 . The extracellular signal-regulated kinase (ERK) pathway is implicated in mood regulation 5-7 , but its pleiotropic functions and lack of target specificity prohibit optimal drug development. Here, we identified the transcription factor ELK-1, an ERK downstream partner 8 , as a specific signaling module in the pathophysiology and treatment of depression that can be targeted independently of ERK. ELK1 mRNA was upregulated in postmortem hippocampal tissues from depressed suicides; in blood samples from depressed individuals, failure to reduce ELK1 expression was associated with resistance to treatment. In mice, hippocampal ELK-1 overexpression per se produced depressive behaviors; conversely, the selective inhibition of ELK-1 activation prevented depression-like molecular, plasticity and behavioral states induced by stress. Our work stresses the importance of target selectivity for a successful approach for signal-transduction-based antidepressants, singles out ELK-1 as a depression-relevant transducer downstream of ERK and brings proof-of-concept evidence for the druggability of ELK-1.
[Coffee consumption in depressive disorders: it's not one size fits all].
Rusconi, Anna Carlotta; Valeriani, Giuseppe; Carluccio, Giuseppe Mattia; Majorana, Michele; Carlone, Cristiano; Raimondo, Pasquale; Ripà, Stefano; Marino, Pietropaolo; Coccanari de Fornari, Maria Antonietta; Biondi, Massimo
2014-01-01
Caffeine is considered the world's most popular psychoactive substance. Its actions on the central nervous system, mainly mediated by antagonism of adenosine receptors and subsequent modulation of dopaminergic activity, would be particularly sought by depressed patients, as an attempt of self-medication. However, published data suggested that coffee consumption may worsen psychopathological conditions in mood disorders. Thus, we reviewed available evidence in the literature that investigated the effects of coffee consumption on clinical development of underlying psychopathology. Literature research was done by typing on Medline/PubMed and PsychINFO the key words "coffee AND major depression", "coffee AND dysthymia". The research was limited to English language publications and to studies conducted exclusively on humans. Although literature data are conflicting, extensive follow-up studies indicate a significant caffeine effect on risk reduction of developing clinical depression symptoms. Clinical worsening was observed mainly in cases of postpartum depression and comorbid panic disorder. Taking in account the study limitations, we observed a biphasic profile in caffeine psychostimulant effect: low to moderate doses may correlate with a reduction in depressive risk in healthy subjects and an improvement of many clinical symptoms (attention, arousal, psychomotor performance) in depressed patients, whereas the assumption of high doses may result in thymic dysregulation, favor mixed affective states and worsen circadian profiles and anxiety symptoms.
Di Lorenzo, Arianna; Nabavi, Seyed Fazel; Sureda, Antoni; Moghaddam, Akbar Hajizadeh; Khanjani, Sedigheh; Arcidiaco, Patrizia; Nabavi, Seyed Mohammad; Daglia, Maria
2016-03-01
Growing evidence suggests that oxidative stress plays a role in the development of chronic diseases such as cardiovascular disease and some psychiatric disorders. Tea consumption exerts beneficial effects against damage induced by cerebral ischemia-reperfusion in ischemic stroke and depressive symptoms in depression. The aim of this study was to evaluate, in vivo, the protective activity of green tea (GT) and GABA green tea (GGT) against post-stroke depression (PSD), a common consequence of stroke. The antidepressive-like effects of GT and GGT were determined by behavioral tests in a mouse model of post-stroke depression. The antioxidant activity was evaluated by GSH, SOD, and TBARS measurements on mouse brain. The chemical composition of tea extracts was characterized through chromatographic methods. GGT and GT resulted active in the modulation of depressive symptoms and the reduction of oxidative stress, restoring normal behavior, and at least in part, antioxidant endogenous defenses. The higher polyphenol, theanine, glutamine, and caffeine content may justify the higher activity found in GGT. This work represents the first attempt to demonstrate the positive effect of tea, and especially GGT, on post-stroke depression and to correlate this effect with the antioxidant activity and phytochemical composition of tea. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Figueira, Cláudio Pereira; Carvalhal, Djalma Gomes Ferrão; Almeida, Rafaela Andrade; Hermida, Micely d' El-Rei; Touchard, Dominique; Robert, Phillipe; Pierres, Anne; Bongrand, Pierre; dos-Santos, Washington L C
2015-08-07
Contact with Leishmania leads to a decreases in mononuclear phagocyte adherence to connective tissue. In this work, we studied the early stages of bond formation between VLA4 and fibronectin, measured the kinetics of membrane alignment and the monocyte cytoplasm spreading area over a fibronectin-coated surface, and studied the expression of high affinity integrin epitope in uninfected and Leishmania-infected human monocytes. Our results show that the initial VLA4-mediated interaction of Leishmania-infected monocyte with a fibronectin-coated surface is preserved, however, the later stage, leukocyte spreading over the substrate is abrogated in Leishmania-infected cells. The median of spreading area was 72 [55-89] μm(2) for uninfected and 41 [34-51] μm(2) for Leishmania-infected monocyte. This cytoplasm spread was inhibited using an anti-VLA4 blocking antibody. After the initial contact with the fibronectrin-coated surface, uninfected monocyte quickly spread the cytoplasm at a 15 μm(2) s(-1) ratio whilst Leishmania-infected monocytes only made small contacts at a 5.5 μm(2) s(-1) ratio. The expression of high affinity epitope by VLA4 (from 39 ± 21% to 14 ± 3%); and LFA1 (from 37 ± 32% to 18 ± 16%) molecules was reduced in Leishmania-infected monocytes. These changes in phagocyte function may be important for parasite dissemination and distribution of lesions in leishmaniasis.
STS-55 German payload specialist Schlegel and MS3 Harris work in SL-D2 module
NASA Technical Reports Server (NTRS)
1993-01-01
STS-55 German Payload Specialist 2 Ulrich Walter, wearing special head gear, finds plenty of room to 'spread out' (head to the floor, feet at the ceiling) while conducting Tissue Thickness and Compliance Along Body Axis salt-water balance experiment in the Spacelab Deutsche 2 (SL-D2) science module aboard the Earth-orbiting Columbia, Orbiter Vehicle (OV) 102. Schlegel represents the German Aerospace Research Establishment (DLR). In the background, Mission Specialist 3 (MS3) Bernard A. Harris, Jr monitors an experiment in Rack 11, an experiment rack.
Impact of foliage on LoRa 433MHz propagation in tropical environment
NASA Astrophysics Data System (ADS)
Ahmad, Khairol Amali; Salleh, Mohd Sharil; Segaran, Jivitraa Devi; Hashim, Fakroul Ridzuan
2018-02-01
LoRa is being considered as one of the promising system for Low-Power-Wide-Area-Network (LPWAN) to support the growth of Internet of Things (IoT) applications. Designed to operate in the industrial, scientific and medical (ISM) bands, LoRa had been tested and evaluated mainly in Europe and US in the 868 MHz and 915 MHz modulation bands. Using chirp spread spectrum technology, LoRa is expected to be robust against degredation. This paper provides some early results in the performance of LoRa signal propagation of 433 MHz modulation in tropical foliage environments.
Postquench prethermalization in a disordered quantum fluid of light
NASA Astrophysics Data System (ADS)
Larré, Pierre-Élie; Delande, Dominique; Cherroret, Nicolas
2018-04-01
We study the coherence of a disordered and interacting quantum light field after propagation along a nonlinear optical fiber. Disorder is generated by a cross-phase modulation with a randomized auxiliary classical light field, while interactions are induced by self-phase modulation. When penetrating the fiber from free space, the incoming quantum light undergoes a disorder and interaction quench. By calculating the coherence function of the transmitted quantum light, we show that the decoherence induced by the quench spreads in a light-cone fashion in the nonequilibrium many-body quantum system, leaving the latter prethermalize with peculiar features originating from disorder.
Synaptic potentiation onto habenula neurons in the learned helplessness model of depression
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, B.; Schulz, D.; Li, B
The cellular basis of depressive disorders is poorly understood. Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected positive reward or receives a stimulus that predicts aversive conditions (that is, disappointment or anticipation of a negative outcome). LHb neurons project to, and modulate, dopamine-rich regions, such as the ventral tegmental area (VTA), that control reward-seeking behaviour and participate in depressive disorders. Here we show that in two learned helplessness models of depression, excitatory synapses ontomore » LHb neurons projecting to the VTA are potentiated. Synaptic potentiation correlates with an animal's helplessness behaviour and is due to an enhanced presynaptic release probability. Depleting transmitter release by repeated electrical stimulation of LHb afferents, using a protocol that can be effective for patients who are depressed, markedly suppresses synaptic drive onto VTA-projecting LHb neurons in brain slices and can significantly reduce learned helplessness behaviour in rats. Our results indicate that increased presynaptic action onto LHb neurons contributes to the rodent learned helplessness model of depression.« less
Kaye, Erica C; Brinkman, Tara M; Baker, Justin N
2017-06-01
As therapeutic and supportive care interventions become increasingly effective, growing numbers of childhood and adolescent cancer survivors face a myriad of physical and psychological sequelae secondary to their disease and treatment. Mental health issues, in particular, present a significant problem in this unique patient population, with depression affecting a sizable number of childhood and adolescent cancer survivors. Multiple key determinants impact a survivor's risk of developing depression, with variables traversing across biologic, individual, family, community, and global levels, as well as spanning throughout the life course of human development from the preconception and prenatal periods to adulthood. A multi-level life course conceptual model offers a valuable framework to identify and organize the diverse variables that modulate the risk of developing depression in survivors of childhood and adolescent cancer. This review describes the first multi-level life course perspective applied to development of depression in childhood and adolescent cancer survivors. This conceptual framework may be used to guide the investigation of mental health interventions for SCACs to ensure that key determinants of depression occurrence are adequately addressed across various levels and throughout the life trajectory.
Chourbaji, Sabine; Brandwein, Christiane; Gass, Peter
2011-01-01
According to the "neurotrophin hypothesis", brain-derived neurotrophic factor (BDNF) is an important candidate gene in depression. Moreover, environmental stress is known to represent a risk factor in the pathophysiology and treatment of this disease. To elucidate, whether changes of BDNF availability signify cause or consequence of depressive-like alterations, it is essential to look for endophenotypes under distinct genetic conditions (e.g. altered BDNF expression). Furthermore it is crucial to examine environment-driven BDNF regulation and its effect on depressive-linked features. Consequently, gene × environment studies investigating prospective genetic mouse models of depression in different environmental contexts become increasingly important. The present review summarizes recent findings in BDNF-mutant mice, which have been controversially discussed as models of depression and anxiety. It furthermore illustrates the potential of environment to serve as naturalistic stressor with the potential to modulate the phenotype in wildtype and mutant mice. Moreover, environment may exert protective effects by regulating BDNF levels as attributed to "environmental enrichment". The effect of this beneficial condition will also be discussed with regard to probable "curative/therapeutic" approaches. Copyright © 2010 Elsevier Ltd. All rights reserved.
Synaptic potentiation onto habenula neurons in learned helplessness model of depression
Li, Bo; Piriz, Joaquin; Mirrione, Martine; Chung, ChiHye; Proulx, Christophe D.; Schulz, Daniela; Henn, Fritz; Malinow, Roberto
2010-01-01
The cellular basis of depressive disorders is poorly understood1. Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected positive reward or receives a stimulus that predicts aversive conditions (i.e. disappointment or anticipation of a negative outcome)2, 3, 4. LHb neurons project to and modulate dopamine-rich regions such as the ventral-tegmental area (VTA)2, 5 that control reward-seeking behavior6 and participate in depressive disorders7. Here we show in two learned helplessness models of depression that excitatory synapses onto LHb neurons projecting to the VTA are potentiated. Synaptic potentiation correlates with an animal’s helplessness behavior and is due to an enhanced presynaptic release probability. Depleting transmitter release by repeated electrical stimulation of LHb afferents, using a protocol that can be effective on depressed patients8, 9, dramatically suppresses synaptic drive onto VTA-projecting LHb neurons in brain slices and can significantly reduce learned helplessness behavior in rats. Our results indicate that increased presynaptic action onto LHb neurons contributes to the rodent learned helplessness model of depression. PMID:21350486
Synaptic potentiation onto habenula neurons in the learned helplessness model of depression.
Li, Bo; Piriz, Joaquin; Mirrione, Martine; Chung, ChiHye; Proulx, Christophe D; Schulz, Daniela; Henn, Fritz; Malinow, Roberto
2011-02-24
The cellular basis of depressive disorders is poorly understood. Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected positive reward or receives a stimulus that predicts aversive conditions (that is, disappointment or anticipation of a negative outcome). LHb neurons project to, and modulate, dopamine-rich regions, such as the ventral tegmental area (VTA), that control reward-seeking behaviour and participate in depressive disorders. Here we show that in two learned helplessness models of depression, excitatory synapses onto LHb neurons projecting to the VTA are potentiated. Synaptic potentiation correlates with an animal's helplessness behaviour and is due to an enhanced presynaptic release probability. Depleting transmitter release by repeated electrical stimulation of LHb afferents, using a protocol that can be effective for patients who are depressed, markedly suppresses synaptic drive onto VTA-projecting LHb neurons in brain slices and can significantly reduce learned helplessness behaviour in rats. Our results indicate that increased presynaptic action onto LHb neurons contributes to the rodent learned helplessness model of depression.
Prevalence of depressive and anxiety disorders in Chinese gastroenterological outpatients
Li, Xiao-Jing; He, Yan-Ling; Ma, Hong; Liu, Zhe-Ning; Jia, Fu-Jun; Zhang, Ling; Zhang, Lan
2012-01-01
AIM: To investigate the prevalence and physicians’ detection rate of depressive and anxiety disorders in gastrointestinal (GI) outpatients across China. METHODS: A hospital-based cross-sectional survey was conducted in the GI outpatient departments of 13 general hospitals. A total of 1995 GI outpatients were recruited and screened with the Hospital Anxiety and Depression Scale (HADS). The physicians of the GI departments performed routine clinical diagnosis and management without knowing the HADS score results. Subjects with HADS scores ≥ 8 were subsequently interviewed by psychiatrists using the Mini International Neuropsychiatric Interview (MINI) to make further diagnoses. RESULTS: There were 1059 patients with HADS score ≥ 8 and 674 (63.64%) of them undertook the MINI interview by psychiatrists. Based on the criteria of Diagnostic and Statistical Manual of Mental Disorders (4th edition), the adjusted current prevalence for depressive disorders, anxiety disorders, and comorbidity of both disorders in the GI outpatients was 14.39%, 9.42% and 4.66%, respectively. Prevalence of depressive disorders with suicidal problems [suicide attempt or suicide-related ideation prior or current; module C (suicide) of MINI score ≥ 1] was 5.84% in women and 1.64% in men. The GI physicians’ detection rate of depressive and anxiety disorders accounted for 4.14%. CONCLUSION: While the prevalence of depressive and anxiety disorders is high in Chinese GI outpatients, the detection rate of depressive and anxiety disorders by physicians is low. PMID:22654455
NASA Astrophysics Data System (ADS)
Sleeper, Jonathan D.
This dissertation examines magmatic and tectonic processes in backarc basins, and how they are modulated by plate- and mantle-driven mechanisms. Backarc basins initiate by tectonic rifting near the arc volcanic front and transition to magmatic seafloor spreading. As at mid-ocean ridges (MORs), spreading can be focused in narrow plate boundary zones, but we also describe a diffuse spreading mode particular to backarc basins. At typical MORs away from hot spots and other melting anomalies, spreading rate is the primary control on the rate of mantle upwelling and decompression melting. At backarc spreading centers, water derived from the subducting slab creates an additional mantle-driven source of melt and buoyant upwelling. Furthermore, because basins open primarily in response to trench rollback, which is inherently a non-rigid process, backarc extensional systems often have to respond to a constantly evolving stress regime, generating complex tectonics and unusual plate boundaries not typically found at MORs. The interplay between these plate- and mantle-driven processes gives rise to the variety of tectonic and volcanic morphologies peculiar to backarc basins. Chapter 2 is focused on the Fonualei Rift and Spreading Center in the Lau Basin. The southern portion of the axis is spreading at ultraslow (<20 mm/yr) opening rates in close proximity to the arc volcanic front and axial morphology abruptly changes from a volcanic ridge to spaced volcanic cones resembling arc volcanoes. Spreading rate and arc proximity appear to control transitions between two-dimensional and three-dimensional mantle upwelling and volcanism. In the second study (Chapter 3), I develop a new model for the rollback-driven kinematic and tectonic evolution of the Lau Basin, where microplate tectonics creates rapidly changing plate boundary configurations. The third study (Chapter 4) focuses on the southern Mariana Trough and the transitions between arc rifting, seafloor spreading, and a new mode of "diffuse spreading," where new crust is accreted in broad zones rather than along a narrow spreading axis, apparently controlled by a balance between slab water addition and its extraction due to melting and crustal accretion.
Rice, Simon M; Fallon, Barry J; Aucote, Helen M; Möller-Leimkühler, AnneMaria; Treeby, Matt S; Amminger, G Paul
2015-05-01
Clinical reports indicate that men tend to engage in a range of externalising behaviours in response to negative emotional states. Such externalising behaviours have been theorised to reflect a male sub-type of depression that is inconsistent with current diagnostic criteria, resulting in impeded detection and treatment rates of depressed men. In addressing previous study design limitations, this article presents self-report longitudinal data for the multidimensional Male Depression Risk Scale (MDRS-22) against ratings of diagnostic criteria for major depressive disorder as assessed by the Patient Health Questionnaire-Depression Module (PHQ-9). Longitudinal psychometric properties of the MDRS-22 are reported and symptom trajectories described. A sample of 233 adults (males = 125; 54%) completed measures of externalising and prototypic depression symptoms at Time 1, and again at Time 2 (15 weeks later). Psychometric properties were examined and within-subjects analyses undertaken. The MDRS-22 demonstrated stable internal consistency and test-retest correlations equivalent to those observed for the PHQ-9. Both prototypic and externalising depression symptoms increased with experiences of recent negative life events. Marked gender differences were observed. Males experiencing ≥ 2 stressful negative life events reported significantly higher MDRS-22 scores at both Time 1 and Time 2 relative to comparable females. Findings contribute to the validity of the MDRS-22 as a measure of externalising depression symptoms. Results suggest that while both males and females experience externalising depression symptoms, these symptoms may be particularly elevated for men following experiences of negative life events. Findings suggest that externalising symptoms may be a special feature of depression for men. Given the problematic nature of such externalising symptoms (e.g. excessive substance use, aggression, risk-taking), their clinical assessment appears warranted. © The Author(s) 2014.
Time Reversal Acoustic Communication Using Filtered Multitone Modulation
Sun, Lin; Chen, Baowei; Li, Haisen; Zhou, Tian; Li, Ruo
2015-01-01
The multipath spread in underwater acoustic channels is severe and, therefore, when the symbol rate of the time reversal (TR) acoustic communication using single-carrier (SC) modulation is high, the large intersymbol interference (ISI) span caused by multipath reduces the performance of the TR process and needs to be removed using the long adaptive equalizer as the post-processor. In this paper, a TR acoustic communication method using filtered multitone (FMT) modulation is proposed in order to reduce the residual ISI in the processed signal using TR. In the proposed method, FMT modulation is exploited to modulate information symbols onto separate subcarriers with high spectral containment and TR technique, as well as adaptive equalization is adopted at the receiver to suppress ISI and noise. The performance of the proposed method is assessed through simulation and real data from a trial in an experimental pool. The proposed method was compared with the TR acoustic communication using SC modulation with the same spectral efficiency. Results demonstrate that the proposed method can improve the performance of the TR process and reduce the computational complexity of adaptive equalization for post-process. PMID:26393586
Time Reversal Acoustic Communication Using Filtered Multitone Modulation.
Sun, Lin; Chen, Baowei; Li, Haisen; Zhou, Tian; Li, Ruo
2015-09-17
The multipath spread in underwater acoustic channels is severe and, therefore, when the symbol rate of the time reversal (TR) acoustic communication using single-carrier (SC) modulation is high, the large intersymbol interference (ISI) span caused by multipath reduces the performance of the TR process and needs to be removed using the long adaptive equalizer as the post-processor. In this paper, a TR acoustic communication method using filtered multitone (FMT) modulation is proposed in order to reduce the residual ISI in the processed signal using TR. In the proposed method, FMT modulation is exploited to modulate information symbols onto separate subcarriers with high spectral containment and TR technique, as well as adaptive equalization is adopted at the receiver to suppress ISI and noise. The performance of the proposed method is assessed through simulation and real data from a trial in an experimental pool. The proposed method was compared with the TR acoustic communication using SC modulation with the same spectral efficiency. Results demonstrate that the proposed method can improve the performance of the TR process and reduce the computational complexity of adaptive equalization for post-process.
The Bidirectional Relationship between Diabetes and Depression: A Literature Review.
Alzoubi, Abdallah; Abunaser, Rnad; Khassawneh, Adi; Alfaqih, Mahmoud; Khasawneh, Aws; Abdo, Nour
2018-05-01
Diabetes is a major public health problem worldwide. Depression is a serious mental condition that decreases mental and physical functioning and reduces the quality of life. Several lines of evidence suggest a bidirectional relationship between diabetes and depression: diabetes patients are twice as likely to experience depression than nondiabetic individuals. In contrast, depression increases the risk of diabetes and interferes with its daily self-management. Diabetes patients with depression have poor glycemic control, reduced quality of life, and an increased risk of diabetes complications, consequently having an increased mortality rate. Conflicting evidence exists on the potential role of factors that may account for or modulate the relationship between diabetes and depression. Therefore, this review aims to highlight the most notable body of literature that dissects the various facets of the bidirectional relationship between diabetes and depression. A focused discussion of the proposed mechanisms underlying this relationship is also provided. We systematically reviewed the relevant literature in the PubMed database, using the keywords "Diabetes AND Depression". After exclusion of duplicate and irrelevant material, literature eligible for inclusion in this review was based on meta-analysis studies, clinical trials with large sample sizes (n≥1,000), randomized clinical trials, and comprehensive national and cross-country clinical studies. The evidence we present in this review supports the pressing need for long, outcome-oriented, randomized clinical trials to determine whether the identification and treatment of patients with these comorbid conditions will improve their medical outcomes and quality of life.
Olaya, Beatriz; Moneta, Maria Victoria; Koyanagi, Ai; Lara, Elvira; Miret, Marta; Ayuso-Mateos, José Luis; Chatterji, Somnath; Leonardi, Matilde; Koskinen, Seppo; Tobiasz-Adamczyk, Beata; Lobo, Antonio; Haro, Josep Maria
2016-04-01
To explore the joint association of depression and cognitive function with severe disability in nationally-representative samples of community-dwelling adults aged 50 years and older from Finland, Poland and Spain. Cross-sectional. Community-based. Population-based sample of 7987 non-institutionalized adults aged 50 and older. The outcome was severe disability, defined as ≥ 90th percentile of the 12-item version of the World Health Organization Disability Assessment Schedule (WHODAS 2.0). Past 12-month DSM-IV major depressive disorder was assessed with the depression module of the WHO Composite International Diagnostic Interview (CIDI). A global cognitive function score was obtained through neuropsychological tests. Product terms between depression and cognition were introduced in multivariable logistic regression models to test for interaction. Lower cognitive function and depression were both significantly associated with severe disability in all countries. A significant interaction was only found in Finland where the ORs (95% CIs) of depression for severe disability at the 25th (worse), 50th, and 75th (better) percentiles of cognitive function were 7.26 (4.28-12.32), 11.1 (6.7-18.38), and 17.56 (9.29-33.2), respectively. People with depression and cognitive decline are likely to benefit from the usual evidence-based treatments to reduce the burden of disability. However, in Finland, those with better cognitive function may benefit from more aggressive depression treatment. Future research is warranted to assess whether our results may be replicated.
Silton, Rebecca Levin; Heller, Wendy; Engels, Anna S; Towers, David N; Spielberg, Jeffrey M; Edgar, J Christopher; Sass, Sarah M; Stewart, Jennifer L; Sutton, Bradley P; Banich, Marie T; Miller, Gregory A
2011-05-01
A network consisting of left dorsolateral prefrontal cortex (LDLPFC) and dorsal anterior cingulate cortex (dACC) has been implicated in top-down attentional control. Few studies have systematically investigated how this network is altered in psychopathology, despite evidence that depression and anxiety are associated with attentional control impairments. Functional MRI and dense-array event-related brain potential (ERP) data were collected in separate sessions from 100 participants during a color-word Stroop task. Functional MRI results guided ERP source modeling to characterize the time course of activity in LDLPFC (300-440 ms) and dACC (520-680 ms). At low levels of depression, LDLPFC activity was indirectly related to Stroop interference and only via dACC activity. In contrast, at high levels of depression, dACC did not play an intervening role, and increased LDLPFC activity was directly related to decreased Stroop interference. Specific to high levels of anxious apprehension, higher dACC activity was related to more Stroop interference. Results indicate that depression and anxious apprehension modulate temporally and functionally distinct aspects of the frontocingulate network involved in top-down attention control.
Why Don't You Try Harder? An Investigation of Effort Production in Major Depression
Cléry-Melin, Marie-Laure; Schmidt, Liane; Lafargue, Gilles; Baup, Nicolas; Fossati, Philippe; Pessiglione, Mathias
2011-01-01
Depression is mainly characterized as an emotional disorder, associated with reduced approach behavior. It remains unclear whether the difficulty in energising behavior relates to abnormal emotional states or to a flattened response to potential rewards, as suggested by several neuroimaging studies. Here, we aimed to demonstrate a specific incentive motivation deficit in major depression, independent of patients' emotional state. We employed a behavioral paradigm designed to measure physical effort in response to both emotional modulation and incentive motivation. Patients did exert more effort following emotionally arousing pictures (whether positive or negative) but not for higher monetary incentives, contrary to healthy controls. These results show that emotional and motivational sources of effort production are dissociable in pathological conditions. In addition, patients' ratings of perceived effort increased for high incentives, whereas controls' ratings were decreased. Thus, depressed patients objectively behave as if they do not want to gain larger rewards, but subjectively feel that they try harder. We suggest that incentive motivation impairment is a core deficit of major depression, which may render everyday tasks abnormally effortful for patients. PMID:21853083
Lopresti, Adrian L; Hood, Sean D; Drummond, Peter D
2012-12-01
Curcumin is the principal curcuminoid of the popular Indian spice turmeric and has attracted increasing attention for the treatment of a range of conditions. Research into its potential as a treatment for depression is still in its infancy, although several potential antidepressant mechanisms of action have been identified. Research completed to date on the multiple effects of curcumin is reviewed in this paper, with a specific emphasis on the biological systems that are compromised in depression. The antidepressant effects of curcumin in animal models of depression are summarised, and its influence on neurotransmitters such as serotonin and dopamine is detailed. The effects of curcumin in moderating hypothalamus-pituitary-adrenal disturbances, lowering inflammation and protecting against oxidative stress, mitochondrial damage, neuroprogression and intestinal hyperpermeability, all of which are compromised in major depressive disorder, are also summarised. With increasing interest in natural treatments for depression, and efforts to enhance current treatment outcomes, curcumin is presented as a promising novel, adjunctive or stand-alone natural antidepressant.
NASA Astrophysics Data System (ADS)
Medynski, S.; Pik, R.; Burnard, P.; Vye-Brown, C.; France, L.; Schimmelpfennig, I.; Whaler, K.; Johnson, N.; Benedetti, L.; Ayelew, D.; Yirgu, G.
2015-01-01
Unravelling the volcanic history of the Dabbahu/Manda Hararo rift segment in the Afar depression (Ethiopia) using a combination of cosmogenic (36Cl and 3He) surface exposure dating of basaltic lava-flows, field observations, geological mapping and geochemistry, we show in this paper that magmatic activity in this rift segment alternates between two distinct magma chambers. Recent activity in the Dabbahu rift (notably the 2005-2010 dyking crises) has been fed by a seismically well-identified magma reservoir within the rift axis, and we show here that this magma body has been active over the last 30 kyr. However, in addition to this axial magma reservoir, we highlight in this paper the importance of a second, distinct magma reservoir, located 15 km west of the current axis, which has been the principal focus of magma accumulation from 15 ka to the subrecent. Magma supply to the axial reservoir substantially decreased between 20 ka and the present day, while the flank reservoir appears to have been regularly supplied with magma since 15 ka ago, resulting in less variably differentiated lavas. The trace element characteristics of magmas from both reservoirs were generated by variable degrees of partial melting of a single homogeneous mantle source, but their respective magmas evolved separately in distinct crustal plumbing systems. Magmatism in the Dabbahu/Manda Hararo rift segment is not focussed within the current axial depression but instead is spread out over at least 15 km on the western flank. This is consistent with magneto-telluric observations which show that two magma bodies are present below the segment, with the main accumulation of magma currently located below the western flank, precisely where the most voluminous recent (<15 ka) flank volcanism is observed at the surface. Applying these observations to slow spreading mid-ocean ridges indicates that magma bodies likely have a lifetime of a least 20 ka, and that the continuity of magmatic activity is maintained by a system of separate relaying reservoirs, which could in return control the location of spreading. This long term (>105 yr) alternation between distinct crustal reservoirs located broadly at the same location relative to the segment appears to be a key feature for organizing and maintaining active spreading centres over stable soft points in the mantle.
Maske, Ulrike E; Buttery, Amanda K; Beesdo-Baum, Katja; Riedel-Heller, Steffi; Hapke, Ulfert; Busch, Markus A
2016-01-15
While standardized diagnostic interviews using established criteria are the gold standard for assessing depression, less time consuming measures of depression and depressive symptoms are commonly used in large population health surveys. We examine the prevalence and health-related correlates of three depression measures among adults aged 18-79 years in Germany. Using cross-sectional data from the national German Health Interview and Examination Survey for Adults (DEGS1) (n=7987) and its mental health module (DEGS1-MH) (n=4483), we analysed prevalence and socio-demographic and health-related correlates of (a) major depressive disorder (MDD) established by Composite International Diagnostic Interview (CIDI) using DSM-IV-TR criteria (CIDI-MDD) in the last 12 months, (b) self-reported physician or psychotherapist diagnosed depression in the last 12 months, and (c) current depressive symptoms in the last two weeks (PHQ-9, score ≥10). Prevalence of 12-month CIDI-MDD was 4.2% in men and 9.9% in women. Prevalence of 12-month self-reported health professional-diagnosed depression was 3.8% and 8.1% and of current depressive symptoms 6.1% and 10.2% in men and women, respectively. Case-overlap between measures was only moderate (32-45%). In adjusted multivariable analyses, depression according to all three measures was associated with lower self-rated health, lower physical and social functioning, higher somatic comorbidity (except for women with 12-month CIDI-MDD), more sick leave and higher health service utilization. Persons with severe depression may be underrepresented. Associations between CIDI-MDD and correlates and overlap with other measures may be underestimated due to time lag between DEGS1 and DEGS1-MH. Prevalence and identified cases varied between these three depression measures, but all measures were consistently associated with a wide range of adverse health outcomes. Copyright © 2015 Elsevier B.V. All rights reserved.
Ohura, Shunsuke
2018-01-01
Axonal spike is an important upstream process of transmitter release, which directly impacts on release probability from the presynaptic terminals. Despite the functional significance, possible activity-dependent modulation of axonal spikes has not been studied extensively, partly due to inaccessibility of the small structures of axons for electrophysiological recordings. In this study, we tested the possibility of use-dependent changes in axonal spikes at the hippocampal mossy fibers, where direct recordings from the axon terminals are readily feasible. Hippocampal slices were made from mice of either sex, and loose-patch clamp recordings were obtained from the visually identified giant mossy fiber boutons located in the stratum lucidum of the CA3 region. Stimulation of the granule cell layer of the dentate gyrus elicited axonal spikes at the single bouton which occurred in all or none fashion. Unexpected from the digital nature of spike signaling, the peak amplitude of the second spikes in response to paired stimuli at a 50-ms interval was slightly but reproducibly smaller than the first spikes. Repetitive stimuli at 20 or 100 Hz also caused progressive use-dependent depression during the train. Notably, veratridine, an inhibitor of inactivation of sodium channels, significantly accelerated the depression with minimal effect on the initial spikes. These results suggest that sodium channels contribute to use-dependent depression of axonal spikes at the hippocampal mossy fibers, possibly by shaping the afterdepolarization (ADP) following axonal spikes. Prolonged depolarization during ADP may inactivate a fraction of sodium channels and thereby suppresses the subsequent spikes at the hippocampal mossy fibers. PMID:29468192
Modulation of hepatic reticuloendothelial system phagocytosis by pancreatic hormones.
Cornell, R P; McClellan, C C
1982-12-01
Experiments were conducted to determine the influence of the pancreatic hormones insulin, glucagon, and somatostatin on reticuloendothelial system (RES) phagocytosis both in vivo and in the isolated perfused livers of rats. Chronic pancreatic hormonal treatment consisted of twice daily injections SC of NPH insulin with doses ranging from 0.75 U on day 1 to 9.0 U on day 13 and unchanged doses of glucagon (200 micrograms) and somatostatin (50 micrograms). Chronic treatment with insulin significantly depressed by 48% intravascular phagocytosis of colloidal carbon administered IV at a dose of 8 mg/100 g, while glucagon and somatostatin stimulated macrophage endocytic function by 32% and 26%, respectively, compared to the control value. Acute treatment with the three pancreatic hormones at 30 min prior to carbon administration similarly produced insulin depression as well as glucagon and somatostatin stimulation of RES phagocytosis. Addition of the three hormones at near physiologic concentrations (20 ng/ml for insulin, 10 ng/ml for glucagon, and 5 ng/ml for somatostatin) to the recirculating perfusate of isolated perfused rat livers simultaneous with 24 mg of colloidal carbon likewise resulted in phagocytic reduction after insulin and enhancement after glucagon and somatostatin. Experiments involving insulin in vitro with isolated perfused livers as well as glucose replacement therapy concomitant with insulin in vivo demonstrated that hypoglycemia is not necessary for phagocytic depression by insulin while severe hypoglycemia in the perfusion medium is sufficient to depress carbon uptake by isolated perfused livers independent of insulin. Both pancreatic hormones and the level of glycemia seem to be important in modulating hepatic reticuloendothelial system phagocytosis.
Vai, Benedetta; Bulgarelli, Chiara; Godlewska, Beata R; Cowen, Philip J; Benedetti, Francesco; Harmer, Catherine J
2016-12-01
The timely selection of the optimal treatment for depressed patients is critical to improve remission rates. The detection of pre-treatment variables able to predict differential treatment response may provide novel approaches for treatment selection. Selective serotonin reuptake inhibitors (SSRIs) modulate the fronto-limbic functional response and connectivity, an effect preceding the overt clinical antidepressant effects. Here we investigated whether the cortico-limbic connectivity associated with emotional bias measured before SSRI administration predicts the efficacy of antidepressant treatment in MDD patients. fMRI and Dynamic Causal Modeling (DCM) were combined to study if effective connectivity might differentiate healthy controls (HC) and patients affected by major depression who later responded (RMDD, n=21), or failed to respond (nRMDD, n=12), to 6 weeks of escitalopram administration. Sixteen DCMs exploring connectivity between anterior cingulate cortex (ACC), ventrolateral prefrontal cortex (VLPFC), Amygdala (Amy), and fusiform gyrus (FG) were constructed. Analyses revealed that nRMDD had reduced endogenous connectivity from Amy to VLPFC and to ACC, with an increased connectivity and modulation of the ACC to Amy connectivity when processing of fearful emotional stimuli compared to HC. RMDD and HC did not significantly differ among themselves. Pre-treatment effective connectivity in fronto-limbic circuitry could be an important factor affecting antidepressant response, and highlight the mechanisms which may be involved in recovery from depression. These results suggest that fronto-limbic connectivity might provide a neural biomarker to predict the clinical outcome to SSRIs administration in major depression. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.
Seo, Jeho; Cho, Hojin; Kim, Gun Tae; Kim, Chul Hoon; Kim, Dong Goo
2017-10-01
Episodic experiences of stress have been identified as the leading cause of major depressive disorder (MDD). The occurrence of MDD is profoundly influenced by the individual's coping strategy, rather than the severity of the stress itself. Resting brain activity has been shown to alter in several mental disorders. However, the functional relationship between resting brain activity and coping strategies has not yet been studied. In the present study, we observed different patterns of resting brain activity in rats that had determined either positive (resilient to stress) or negative (vulnerable to stress) coping strategies, and examined whether modulation of the preset resting brain activity could influence the behavioral phenotype associated with negative coping strategy (i.e., depressive-like behaviors). We used a learned helplessness paradigm-a well-established model of MDD-to detect coping strategies. Differences in resting state brain activity between animals with positive and negative coping strategies were assessed using 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET). Glutamatergic stimulation was used to modulate resting brain activity. After exposure to repeated uncontrollable stress, seven of 23 rats exhibited positive coping strategies, while eight of 23 rats exhibited negative coping strategies. Increased resting brain activity was observed only in the left ventral dentate gyrus of the positive coping rats using FDG-PET. Furthermore, glutamatergic stimulation of the left dentate gyrus abolished depressive-like behaviors in rats with negative coping strategies. Increased resting brain activity in the left ventral dentate gyrus helps animals to select positive coping strategies in response to future stress. Copyright © 2016 Elsevier Inc. All rights reserved.
Serotonin Modulation of Cerebral Glucose Metabolism in Depressed Older Adults
Smith, Gwenn S.; Kramer, Elisse; Hermann, Carol.; Ma, Yilong; Dhawan, Vijay; Chaly, Thomas; Eidelberg, David
2009-01-01
Background Monoamine dysfunction, particularly of the serotonin system, has been the dominant hypothesis guiding research and treatment development in affective disorders. The majority of research has been performed in mid-life depressed adults. The importance of understanding the neurobiology of depression in older adults is underscored by increased rates of mortality and completed suicide and an increased risk of Alzheimer's dementia. To evaluate the dynamic response of the serotonin system, the acute effects of citalopram infusion on cerebral glucose metabolism was measured in depressed older adults and control subjects. The hypothesis was tested that smaller decreases in metabolism would be observed in cortical and limbic regions in depressed older adults relative to controls. Methods Sixteen depressed older adults and thirteen controls underwent two resting Positron Emission Tomography (PET) studies with the radiotracer [18F]-2-deoxy-2-fluoro-D-glucose after placebo and citalopram infusions. Results In controls compared to depressed older adults, greater citalopram induced decreases in cerebral metabolism were observed in the right anterior cingulate, middle temporal (bilaterally), left precuneus, and left parahippocampal gyri. Greater decreases in the depressed older adults than controls was observed in left superior and left middle frontal gyri and increases in left inferior parietal lobule, left cuneus, left thalamus and right putamen. Conclusion In depressed older adults relative to controls, the cerebral metabolic response to citalopram is blunted in cortico-cortico and cortico-limbic pathways and increased in the left hemisphere (greater decrease interiorly and increases posterior). These findings suggest both blunted and compensatory cerebral metabolic responses to citalopram in depressed older adults. PMID:19368900
Optimal Methods for Classification of Digitally Modulated Signals
2013-03-01
of using a ratio of likelihood functions, the proposed approach uses the Kullback - Leibler (KL) divergence. KL...58 List of Acronyms ALRT Average LRT BPSK Binary Shift Keying BPSK-SS BPSK Spread Spectrum or CDMA DKL Kullback - Leibler Information Divergence...blind demodulation for develop classification algorithms for wider set of signals types. Two methodologies were used : Likelihood Ratio Test
Experimental Packet Radio System Design Plan
1974-03-13
specific design parameters (packet format, data rates, modulation type, spread factor, etc.) for the initial system configuration. c. Prototype...are described along with size, weight and power estimates, and projections of per- formance parameters . d. Measurement and Test. The plan...are presented covering the communications link, system parameters , and various levels of network operation and performance. This plan is a snapshot
Sañudo, Borja; Carrasco, Luis; de Hoyo, Moisés; Figueroa, Arturo; Saxton, John M
2015-01-01
To examine the effects of a supervised aerobic exercise programme on heart rate variability (HRV) parameters and symptom severity in women with fibromyalgia (FM). Thirty-two women with FM were randomly allocated to one of two groups: aerobic exercise (AE) or usual care control for 24 weeks. Women allocated to AE performed two aerobic exercise sessions per week of 45-60 min duration including 15-20 min of steady-state aerobic exercise at 60-65% of predicted maximum heart rate (HRmax) and 15 min of interval training at 75-80% HRmax (six repetitions of 1.5 min, with 1 min interpolated rest intervals). Cardiac autonomic modulation was assessed using power spectral analysis of HRV. Symptom severity was assessed by a 10 cm visual analogue scale (VAS) for pain, sleep disturbances, stiffness, anxiety and depression. After 24 weeks, the women in the exercise group showed an increase (4.8 ± 0.2 to 5.2 ± 0.2) in total power (LnTP, p<0.001), low frequency power (LnLF, p<0.01), high frequency power (LnHF, p<0.001), and the root-mean-square of successive R-R intervals (rMSSD, p<0.001). In addition, significant group-by-time interaction effects were observed for LnHF (p=0.036) and LnLF/HF (p=0.014). Improvements in anxiety and depression were also observed in AE versus control patients. These results show that a programme of aerobic exercise training induced changes in cardiac autonomic nervous system modulation in FM and that these changes in HRV parameters were accompanied by changes in anxiety and depression.
Yu, Q; Teixeira, C M; Mahadevia, D; Huang, Y; Balsam, D; Mann, J J; Gingrich, J A; Ansorge, M S
2014-06-01
Pharmacologic blockade of monoamine oxidase A (MAOA) or serotonin transporter (5-HTT) has antidepressant and anxiolytic efficacy in adulthood. Yet, genetically conferred MAOA or 5-HTT hypoactivity is associated with altered aggression and increased anxiety/depression. Here we test the hypothesis that increased monoamine signaling during development causes these paradoxical aggressive and affective phenotypes. We find that pharmacologic MAOA blockade during early postnatal development (P2-P21) but not during peri-adolescence (P22-41) increases anxiety- and depression-like behavior in adult (>P90) mice, mimicking the effect of P2-21 5-HTT inhibition. Moreover, MAOA blockade during peri-adolescence, but not P2-21 or P182-201, increases adult aggressive behavior, and 5-HTT blockade from P22-P41 reduced adult aggression. Blockade of the dopamine transporter, but not the norepinephrine transporter, during P22-41 also increases adult aggressive behavior. Thus, P2-21 is a sensitive period during which 5-HT modulates adult anxiety/depression-like behavior, and P22-41 is a sensitive period during which DA and 5-HT bi-directionally modulate adult aggression. Permanently altered DAergic function as a consequence of increased P22-P41 monoamine signaling might underlie altered aggression. In support of this hypothesis, we find altered aggression correlating positively with locomotor response to amphetamine challenge in adulthood. Proving that altered DA function and aggression are causally linked, we demonstrate that optogenetic activation of VTA DAergic neurons increases aggression. It therefore appears that genetic and pharmacologic factors impacting dopamine and serotonin signaling during sensitive developmental periods can modulate adult monoaminergic function and thereby alter risk for aggressive and emotional dysfunction.
Kato, Taro; Takata, Makoto; Kitaichi, Maiko; Kassai, Momoe; Inoue, Mitsuhiro; Ishikawa, Chihiro; Hirose, Wataru; Yoshida, Kozo; Shimizu, Isao
2015-06-15
Modulation of monoaminergic systems has been the main stream of treatment for patients with mood disorders. However, recent evidence suggests that the glutamatergic system plays an important role in the pathophysiology of these disorders. This study pharmacologically characterized a structurally novel metabotropic glutamate 5 (mGlu5) receptor negative allosteric modulator, DSR-98776, and evaluated its effect on rodent models of depression and mania. First, DSR-98776 in vitro profile was assessed using intracellular calcium and radioligand binding assays. This compound showed dose-dependent inhibitory activity for mGlu5 receptors by binding to the same allosteric site as 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a known mGlu5 inhibitor. The in vivo therapeutic benefits of DSR-98776 were evaluated in common rodent models of depression and mania. In the rat forced swimming test, DSR-98776 (1-3mg/kg) significantly reduced rats immobility time after treatment for 7 consecutive days, while paroxetine (3 and 10mg/kg) required administration for 2 consecutive weeks to reduce rats immobility time. In the mouse forced swimming test, acute administration of DSR-98776 (10-30 mg/kg) significantly reduced immobility time. This effect was not influenced by 4-chloro-DL-phenylalanine methyl ester hydrochloride-induced 5-HT depletion. Finally, DSR-98776 (30 mg/kg) significantly decreased methamphetamine/chlordiazepoxide-induced hyperactivity in mice, which reflects this compound antimanic-like effect. These results indicate that DSR-98776 acts as an orally potent antidepressant and antimanic in rodent models and can be a promising therapeutic option for the treatment of a broad range of mood disorders with depressive and manic states. Copyright © 2015 Elsevier B.V. All rights reserved.
Evolution of Spin and Superorbital Modulation in 4U 0114+650
NASA Astrophysics Data System (ADS)
Hu, Chin-Ping; Ng, Chi-Yung; Chou, Yi
2016-09-01
We report on a systematic analysis of the spin and superorbital modulations of the high-mass X-ray binary 4U 0114+650, which consists of the slowest spinning neutron star known. Utilizing dynamic power spectra, we found that the spin period varied dramatically during the RXTE ASM and Swift BAT observations. This variation consists of a long-term spin-up trend, and two ~1,000 day and one ~600 day random walk epochs previously, MJD 51,000, ~MJD 51,400-52,000, and ~MJD 55,100-56,100. We further found that the events appear together with depressions of superorbital modulation amplitude. This provides evidence of the existence of an accretion disk, although the physical mechanism of superorbital modulation remains unclear. Furthermore, the decrease of the superorbital modulation amplitude may be associated with the decrease of mass accretion rate from the disk, and may distribute the accretion torque of the neutron star randomly in time.
Knapp, Levente; Szita, Bence; Kocsis, Kitti; Vécsei, László; Toldi, József
2017-01-01
The complex pathophysiology of migraine is not yet clearly understood; therefore, experimental models are essential for the investigation of the processes related to migraine headache, which include cortical spreading depression (CSD) and NO donor-induced neurovascular changes. Data on the assessment of drug efficacy in these models are often limited, which prompted us to investigate a novel combined migraine model in which an effective pharmacon could be more easily identified. In vivo electrophysiological experiments were performed to investigate the effect of nitroglycerin (NTG) on CSD induced by KCl application. In addition, sumatriptan and newly synthesized neuroactive substances (analogues of the neuromodulator kynurenic acid [KYNA]) were also tested. The basic parameters of CSDs were unchanged following NTG administration; however, propagation failure was decreased compared to the controls. Sumatriptan decreased the number of CSDs, whereas propagation failure was as minimal as in the NTG group. On the other hand, both of the KYNA analogues restored the ratio of propagation to the control level. The ratio of propagation appeared to be the indicator of the effect of NTG. This is the first study providing direct evidence that NTG influences CSD; furthermore, we observed different effects of sumatriptan and KYNA analogues. Sumatriptan changed the generation of CSDs, whereas the analogues acted on the propagation of the waves. Our experimental design overlaps with a large spectrum of processes present in migraine pathophysiology, and it can be a useful experimental model for drug screening.
Knapp, Levente; Szita, Bence; Kocsis, Kitti; Vécsei, László; Toldi, József
2017-01-01
Background The complex pathophysiology of migraine is not yet clearly understood; therefore, experimental models are essential for the investigation of the processes related to migraine headache, which include cortical spreading depression (CSD) and NO donor-induced neurovascular changes. Data on the assessment of drug efficacy in these models are often limited, which prompted us to investigate a novel combined migraine model in which an effective pharmacon could be more easily identified. Materials and methods In vivo electrophysiological experiments were performed to investigate the effect of nitroglycerin (NTG) on CSD induced by KCl application. In addition, sumatriptan and newly synthesized neuroactive substances (analogues of the neuromodulator kynurenic acid [KYNA]) were also tested. Results The basic parameters of CSDs were unchanged following NTG administration; however, propagation failure was decreased compared to the controls. Sumatriptan decreased the number of CSDs, whereas propagation failure was as minimal as in the NTG group. On the other hand, both of the KYNA analogues restored the ratio of propagation to the control level. Discussion The ratio of propagation appeared to be the indicator of the effect of NTG. This is the first study providing direct evidence that NTG influences CSD; furthermore, we observed different effects of sumatriptan and KYNA analogues. Sumatriptan changed the generation of CSDs, whereas the analogues acted on the propagation of the waves. Our experimental design overlaps with a large spectrum of processes present in migraine pathophysiology, and it can be a useful experimental model for drug screening. PMID:28053504
17-β-Estradiol induces spreading depression and pain behavior in alert female rats
Sandweiss, Alexander J.; Cottier, Karissa E.; McIntosh, Mary I.; Dussor, Gregory; Davis, Thomas P.; Vanderah, Todd W.; Largent-Milnes, Tally M.
2017-01-01
Aims Test the putative contribution of 17-β-estradiol in the development of spreading depression (SD) events and head pain in awake, non-restrained rats. Main Methods Female, Sprague-Dawley rats were intact or underwent ovariectomy followed one week later by surgery to place electrodes onto the dura to detect epidural electroencephalographic activity (dEEG). dEEG activity was recorded two days later for 12 hours after systemic administration of 17-β-estradiol (180 μg/kg, i.p.). A separate set of rats were observed for changes in exploratory, ambulatory, fine, and rearing behaviors; periorbital allodynia was also assessed. Key Findings A bolus of 17-β-estradiol significantly elevated serum estrogen levels, increased SD episodes over a 12-hour recording period and decreased rearing behaviors in ovariectomized rats. Pre-administration of ICI 182,780, an estrogen receptor antagonist, blocked 17-β-estradiol-evoked SD events and pain behaviors; similar results were observed when the antimigraine therapeutic sumatriptan was used. Significance These data indicate that an estrogen receptor-mediated mechanism contributes to SD events in ovariectomized rats and pain behaviors in both ovariectomized -and intact- rats. This suggests that estrogen plays a different role in each phenomenon of migraine where intense fluctuations in concentration may influence SD susceptibility. This is the first study to relate estrogen peaks to SD development and pain behaviors in awake, freely moving female rats, establishing a framework for future preclinical migraine studies. PMID:29371973
Reaction-diffusion waves in neuronal tissue and the window of cortical excitability
NASA Astrophysics Data System (ADS)
Dahlem, M. A.; Müller, S. C.
2004-07-01
Spreading depression (SD) is a dynamic wave phenomenon occurring in all gray matter regions of the central nervous systems (CNS). It is characterized by a sudden breakdown of neuronal activity and accompanied by a massive influx and efflux of ions across the membrane of neurons. The retina is a constituent of the CNS in which one can easily observe the dynamic behavior of the SD wave fronts, because SD changes the optical properties of the tissue. There is ample evidence that SD belongs to the self-organization processes due to the coupling of reaction with diffusion in excitable medium. It is assumed that the occurrence of SD is associated with some neurological symptoms of migraine with aura. A frequently reported aura symptom is a traveling visual blind region (scotoma) with a preceding figure of scintillating line segments. The characteristic form and development of the scotoma suggests that the underlying phenomenon is a wave propagating through the primary visual cortex, most likely the cortical spreading depression. In this article we discuss similarities between SD waves and the migraine aura on the basis of properties of reaction-diffusion waves known from other excitable media. In particular, the propagation velocities, the shape and the dynamics of the waves are compared with each other. We find that the assumption of the neuronal tissue to be in a state of only weak excitability explains some properties of the migraine aura, such as the confined appearance and its propagation with a stable velocity.
Decreased subcortical cholinergic arousal in focal seizures
Motelow, Joshua E.; Li, Wei; Zhan, Qiong; Mishra, Asht M.; Sachdev, Robert N. S.; Liu, Geoffrey; Gummadavelli, Abhijeet; Zayyad, Zaina; Lee, Hyun Seung; Chu, Victoria; Andrews, John P.; Englot, Dario J.; Herman, Peter; Sanganahalli, Basavaraju G.; Hyder, Fahmeed; Blumenfeld, Hal
2015-01-01
SUMMARY Impaired consciousness in temporal lobe seizures has a major negative impact on quality of life. The prevailing view holds that this disorder impairs consciousness by seizure spread to the bilateral temporal lobes. We propose instead that seizures invade subcortical regions and depress arousal, causing impairment through decreases rather than through increases in activity. Using functional magnetic resonance imaging in a rodent model, we found increased activity in regions known to depress cortical function including lateral septum and anterior hypothalamus. Importantly, we found suppression of intralaminar thalamic and brainstem arousal systems and suppression of the cortex. At a cellular level, we found reduced firing of identified cholinergic neurons in the brainstem pedunculopontine tegmental nucleus and basal forebrain. Finally, we used enzyme-based amperometry to demonstrate reduced cholinergic neurotransmission in both cortex and thalamus. Decreased subcortical arousal is a novel mechanism for loss of consciousness in focal temporal lobe seizures. PMID:25654258
Liquid Crystal Spatial Light Modulators for Simulating Zonal Multifocal Lenses.
Li, Yiyu; Bradley, Arthur; Xu, Renfeng; Kollbaum, Pete S
2017-09-01
To maximize efficiency of the normally lengthy and costly multizone lens design and testing process, it is advantageous to evaluate the potential efficacy of a design as thoroughly as possible prior to lens fabrication and on-eye testing. The current work describes an ex vivo approach of optical design testing. The aim of this study was to describe a system capable of examining the optical characteristics of multizone bifocal and multifocal optics by subaperture stitching using liquid crystal technologies. A liquid crystal spatial light modulator (SLM) was incorporated in each of two channels to generate complementary subapertures by amplitude modulation. Additional trial lenses and phase plates were placed in pupil conjugate planes of either channel to integrate the desired bifocal and multifocal optics once the two optical paths were recombined. A high-resolution Shack-Hartmann aberrometer was integrated to measure the optics of the dual-channel system. Power and wavefront error maps as well as point spread functions were measured and computed for each of three multizone multifocal designs. High transmission modulation was achieved by introducing half-wavelength optical path differences to create two- and five-zone bifocal apertures. Dual-channel stitching revealed classic annular rings in the point spread functions generated from two-zone designs when the outer annular optic was defocused. However, low efficiency of the SLM prevented us from simultaneously measuring the eye + simulator aberrations, and the higher-order diffraction patterns generated by the cellular structure of the liquid crystal arrays limited the visual field to ±0.45 degrees. The system successfully simulated bifocal and multifocal simultaneous lenses allowing for future evaluation of both objective and subjective evaluation of complex optical designs. However, low efficiency and diffraction phenomena of the SLM limit the utility of this technology for simulating multizone and multifocal optics.
NASA Astrophysics Data System (ADS)
Hwang, Ui-Jung; Shin, Dongho; Lee, Se Byeong; Lim, Young Kyung; Jeong, Jong Hwi; Kim, Hak Soo; Kim, Ki Hwan
2018-05-01
To apply a scintillating fiber dosimetry system to measure the range of a proton therapy beam, a new method was proposed to correct for the quenching effect on measuring an spread out Bragg peak (SOBP) proton beam whose range is modulated by a range modulator wheel. The scintillating fiber dosimetry system was composed of a plastic scintillating fiber (BCF-12), optical fiber (SH 2001), photo multiplier tube (H7546), and data acquisition system (PXI6221 and SCC68). The proton beam was generated by a cyclotron (Proteus-235) in the National Cancer Center in Korea. It operated in the double-scattering mode and the spread out of the Bragg peak was achieved by a spinning range modulation wheel. Bragg peak beams and SOBP beams of various ranges were measured, corrected, and compared to the ion chamber data. For the Bragg peak beam, quenching equation was used to correct the quenching effect. On the proposed process of correcting SOBP beams, the measured data using a scintillating fiber were separated by the Bragg peaks that the SOBP beam contained, and then recomposed again to reconstruct an SOBP after correcting for each Bragg peak. The measured depth-dose curve for the single Bragg peak beam was well corrected by using a simple quenching equation. Correction for SOBP beam was conducted with a newly proposed method. The corrected SOBP signal was in accordance with the results measured with an ion chamber. We propose a new method to correct for the SOBP beam from the quenching effect in a scintillating fiber dosimetry system. This method can be applied to other scintillator dosimetry for radiation beams in which the quenching effect is shown in the scintillator.
Feingold, Daniel; Brill, Silviu; Goor-Aryeh, Itay; Delayahu, Yael; Lev-Ran, Shaul
2017-08-15
High rates of depression and anxiety have been consistently reported among patients suffering from chronic pain. Prescription opioids are one of the most common modalities for pharmacological treatment of pain, however in recent years medical marijuana(MM) has been increasingly used for pain control in the US and in several countries worldwide. The aim of this study was to compare levels of depression and anxiety among pain patients receiving prescription opioids and MM. Participants were patients suffering from chronic pain treated with prescription opioids (OP,N=474), MM (N=329) or both (OPMM,N=77). Depression and anxiety were assessed using the depression module of the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder scale (GAD-7). Prevalence of depression among patients in the OP, MM and OPMM groups was 57.1%, 22.3% and 51.4%, respectively and rates of anxiety were 48.4%, 21.5% and 38.7%, respectively. After controlling for confounders, patients in the OP group were significantly more likely to screen positive for depression (Adjusted Odds Ratio(AOR)=6.18;95%CI=4.12-9.338) and anxiety(AOR=4.12;CI=3.84-5.71)) compared to those in the MM group. Individuals in the OPMM group were more prone for depression (AOR for depression=3.34;CI=1.52-7.34)) compared to those in the MM group. Cross-sectional study, restricting inference of causality. Levels of depression and anxiety are higher among chronic pain patients receiving prescription opioids compared to those receiving MM. Findings should be taken into consideration when deciding on the most appropriate treatment modality for chronic pain, particularly among those at risk for depression and anxiety. Copyright © 2017 Elsevier B.V. All rights reserved.
Blozik, Eva; Scherer, Martin; Lacruz, Maria E; Ladwig, Karl-Heinz
2013-12-23
Screening for depressive disorders in the general adult population is recommended, however, it is unclear which instruments combine user friendliness and diagnostic utility. We evaluated the test performance of a yes/no single item screener for depressive disorders ("Have you felt depressed or sad much of the time in the past year?") in comparison to the depressive disorder module of the Patient Health Questionnaire (PHQ-9). Data from 3184 participants of the population-based KORA F3 survey in Augsburg/ Germany were used to analyse sensitivity, specificity, ROC area, positive likelihood ratio (LR+), negative likelihood ratio (LR-), positive predictive value (PPV), and negative predictive value (NPV) of the single item screener in comparison with "depressive mood" and "major depressive disorder" defined according to PHQ-9 (both interviewer-administered versions). In comparison to PHQ-9 "depressive mood", sensitivity was low (46%) with an excellent specificity (94%), (PPV 76%; NPV 82%; LR + 8.04; LR- .572, ROC area .702). When using the more conservative definition for "major depressive disorder", sensitivity increased to 83% with a specificity of 88%. The PPV under the conservative definition was low (32%), but NPV was 99% (LR + 6.65; LR- .196; ROC area .852). Results varied across age groups and between males and females. The single item screener is able to moderately decrease post-test probability of major depressive disorders and to identify populations that should undergo additional, more detailed evaluation for depression. It may have limited utility in combination with additional screening tests or for selection of at-risk populations, but cannot be recommended for routine use as a screening tool in clinical practice.
Wang, Mei-Yeh; Chiu, Chen-Huan; Lee, Hsin-Chien; Su, Chien-Tien; Tsai, Pei-Shan
2016-03-01
Depression increases the risk of adverse cardiac events. Cardiovascular reactivity is defined as the pattern of cardiovascular responses to mental stress. An altered pattern of cardiovascular reactivity is an indicator of subsequent cardiovascular disease. Because depression and adverse cardiac events may have a dose-dependent association, this study examined the differences in cardiovascular reactivity to mental stress between patients with major depressive disorder (MDD) with high depression levels and those with low depression levels. Moreover, autonomic nervous system regulation is a highly plausible biological mechanism for the pattern of cardiovascular reactivity to mental stress. The association between cardiovascular reactivity and parameters of heart rate variability (HRV), an index for quantifying autonomic nervous system activity modulation, was thus examined. This study included 88 patients with MDD. HRV was measured before stress induction. The Stroop Color and Word Test and mirror star-tracing task were used to induce mental stress. We observed no significant association between depressive symptom level and any of the cardiovascular reactivity parameters. Cardiovascular reactivity to mental stress was comparable between patients with MDD with high-level depressive symptoms and those with low-level depressive symptoms. After adjusting for confounding variables, the high-frequency domain of HRV was found to be an independent predictor of the magnitude of heart rate reactivity (β = -.33, p = .002). In conclusion, the magnitude of cardiovascular reactivity may be independent of depression severity in patients with MDD. The autonomic regulation of cardiovascular responses to mental stress primarily influences heart rate reactivity in patients with MDD. © The Author(s) 2015.
2013-01-01
Background Screening for depressive disorders in the general adult population is recommended, however, it is unclear which instruments combine user friendliness and diagnostic utility. We evaluated the test performance of a yes/no single item screener for depressive disorders (“Have you felt depressed or sad much of the time in the past year?”) in comparison to the depressive disorder module of the Patient Health Questionnaire (PHQ-9). Methods Data from 3184 participants of the population-based KORA F3 survey in Augsburg/ Germany were used to analyse sensitivity, specificity, ROC area, positive likelihood ratio (LR+), negative likelihood ratio (LR-), positive predictive value (PPV), and negative predictive value (NPV) of the single item screener in comparison with “depressive mood” and “major depressive disorder” defined according to PHQ-9 (both interviewer-administered versions). Results In comparison to PHQ-9 “depressive mood”, sensitivity was low (46%) with an excellent specificity (94%), (PPV 76%; NPV 82%; LR + 8.04; LR- .572, ROC area .702). When using the more conservative definition for “major depressive disorder”, sensitivity increased to 83% with a specificity of 88%. The PPV under the conservative definition was low (32%), but NPV was 99% (LR + 6.65; LR- .196; ROC area .852). Results varied across age groups and between males and females. Conclusions The single item screener is able to moderately decrease post-test probability of major depressive disorders and to identify populations that should undergo additional, more detailed evaluation for depression. It may have limited utility in combination with additional screening tests or for selection of at-risk populations, but cannot be recommended for routine use as a screening tool in clinical practice. PMID:24359193
Best Practices in Working with Students with Emotion Dysregulation
ERIC Educational Resources Information Center
Cunningham, Jennifer; Mendez, Linda M. Raffaele; Sundman-Wheat, Ashley N.
2011-01-01
Students with emotion dysregulation have significant difficulty modulating emotional reactions, particularly in response to frustration or challenge. These children can present with a variety of DSM diagnoses in schools, including attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), major depressive disorder (MDD),…
Hypothyroidism Affects D2 Receptor-mediated Breathing without altering D2 Receptor Expression
Schlenker, Evelyn H.; Rio, Rodrigo Del; Schultz, Harold D.
2015-01-01
Bromocriptine depressed ventilation in air and D2 receptor expression in the nucleus tractus solitaries (NTS) in male hypothyroid hamsters. Here we postulated that in age- matched hypothyroid female hamsters, the pattern of D2 receptor modulation of breathing and D2 receptor expression would differ from those reported in hypothyroid males. In females hypothyroidism did not affect D2 receptor protein levels in the NTS, carotid bodies or striatum. Bromocriptine, but not carmoxirole (a peripheral D2 receptor agonist), increased oxygen consumption and body temperature in awake air-exposed hypothyroid female hamsters and stimulated their ventilation before and following exposure to hypoxia. Carmoxirole depressed frequency of breathing in euthyroid hamsters prior to, during and following hypoxia exposures and stimulated it in the hypothyroid hamsters following hypoxia. Although hypothyroidism did not affect expression of D2 receptors, it influenced central D2 modulation of breathing in a disparate manner relative to euthyroid hamsters. PMID:24434437
Hypothyroidism affects D2 receptor-mediated breathing without altering D2 receptor expression.
Schlenker, Evelyn H; Del Rio, Rodrigo; Schultz, Harold D
2014-03-01
Bromocriptine depressed ventilation in air and D2 receptor expression in the nucleus tractus solitaries (NTS) in male hypothyroid hamsters. Here we postulated that in age-matched hypothyroid female hamsters, the pattern of D2 receptor modulation of breathing and D2 receptor expression would differ from those reported in hypothyroid males. In females hypothyroidism did not affect D2 receptor protein levels in the NTS, carotid bodies or striatum. Bromocriptine, but not carmoxirole (a peripheral D2 receptor agonist), increased oxygen consumption and body temperature in awake air-exposed hypothyroid female hamsters and stimulated their ventilation before and following exposure to hypoxia. Carmoxirole depressed frequency of breathing in euthyroid hamsters prior to, during and following hypoxia exposures and stimulated it in the hypothyroid hamsters following hypoxia. Although hypothyroidism did not affect expression of D2 receptors, it influenced central D2 modulation of breathing in a disparate manner relative to euthyroid hamsters. Copyright © 2014 Elsevier B.V. All rights reserved.
Cortical spreading depression occurs during elective neurosurgical procedures.
Carlson, Andrew P; William Shuttleworth, C; Mead, Brittany; Burlbaw, Brittany; Krasberg, Mark; Yonas, Howard
2017-01-01
OBJECTIVE Cortical spreading depression (CSD) has been observed with relatively high frequency in the period following human brain injury, including traumatic brain injury and ischemic/hemorrhagic stroke. These events are characterized by loss of ionic gradients through massive cellular depolarization, neuronal dysfunction (depression of electrocorticographic [ECoG] activity) and slow spread (2-5 mm/min) across the cortical surface. Previous data obtained in animals have suggested that even in the absence of underlying injury, neurosurgical manipulation can induce CSD and could potentially be a modifiable factor in neurosurgical injury. The authors report their initial experience with direct intraoperative ECoG monitoring for CSD. METHODS The authors prospectively enrolled patients undergoing elective craniotomy for supratentorial lesions in cases in which the surgical procedure was expected to last > 2 hours. These patients were monitored for CSD from the time of dural opening through the time of dural closure, using a standard 1 × 6 platinum electrode coupled with an AC or full-spectrum DC amplifier. The data were processed using standard techniques to evaluate for slow potential changes coupled with suppression of high-frequency ECoG propagating across the electrodes. Data were compared with CSD validated in previous intensive care unit (ICU) studies, to evaluate recording conditions most likely to permit CSD detection, and identify likely events during the course of neurosurgical procedures using standard criteria. RESULTS Eleven patients underwent ECoG monitoring during elective neurosurgical procedures. During the periods of monitoring, 2 definite CSDs were observed to occur in 1 patient and 8 suspicious events were detected in 4 patients. In other patients, either no events were observed or artifact limited interpretation of the data. The DC-coupled amplifier system represented an improvement in stability of data compared with AC-coupled systems. Compared with more widely used postoperative ICU monitoring, there were additional challenges with artifact from saturation during bipolar cautery as well as additional noise peaks detected. CONCLUSIONS CSD can occur during elective neurosurgical procedures even in brain regions distant from the immediate operative site. ECoG monitoring with a DC-coupled full-spectrum amplifier seemed to provide the most stable signal despite significant challenges to the operating room environment. CSD may be responsible for some cases of secondary surgical injury. Though further studies on outcome related to the occurrence of these events is needed, efforts to decrease the occurrence of CSD by modification of anesthetic regimen may represent a novel target for study to increase the safety of neurosurgical procedures.
Understanding the influence of all nodes in a network
Lawyer, Glenn
2015-01-01
Centrality measures such as the degree, k-shell, or eigenvalue centrality can identify a network's most influential nodes, but are rarely usefully accurate in quantifying the spreading power of the vast majority of nodes which are not highly influential. The spreading power of all network nodes is better explained by considering, from a continuous-time epidemiological perspective, the distribution of the force of infection each node generates. The resulting metric, the expected force, accurately quantifies node spreading power under all primary epidemiological models across a wide range of archetypical human contact networks. When node power is low, influence is a function of neighbor degree. As power increases, a node's own degree becomes more important. The strength of this relationship is modulated by network structure, being more pronounced in narrow, dense networks typical of social networking and weakening in broader, looser association networks such as the Internet. The expected force can be computed independently for individual nodes, making it applicable for networks whose adjacency matrix is dynamic, not well specified, or overwhelmingly large. PMID:25727453
NASA Astrophysics Data System (ADS)
HéBert, HéLèNe; Deplus, Christine; Huchon, Philippe; Khanbari, Khaled; Audin, Laurence
2001-11-01
The Aden spreading ridge (Somalia/Arabia plate boundary) does not connect directly to the Red Sea spreading ridge. It propagates toward the East African Rift through the Afar depression, where the presence of a hot spot has been postulated from seismological and geochemical evidence. The spreading direction (N37°E) is highly oblique to the overall trend (N90°E) of the ridge. We present and interpret new geophysical data gathered during the Tadjouraden cruise (R/V L'Atalante, 1995) in the Gulf of Aden west of 46°E. These data allow us to study the propagation of the ridge toward the Afar and to discuss the processes of the seafloor spreading initiation. We determine the lithospheric structure of the ridge using gravity data gathered during the cruise with the constraint of available refraction data. A striking Bouguer anomaly gradient together with the identification of magnetic anomalies defines the geographical extent of oceanic crust. The inversion of the Bouguer anomaly is performed in terms of variations of crustal thickness only and then discussed with respect to the expected thermal structure of the mantle lithosphere, which should depend not only on the seafloor spreading but also on the hot spot beneath East Africa. Our results allow us to define three distinct lithospheric domains in the western Gulf of Aden. East of 44°45'E the lithosphere displays an oceanic character (thermal subsidence recorded for the last 10 Ma and constant crustal thickness). Between 43°30'E and 44°10'E the lithosphere is of continental type but locally thinned beneath the axial valley. The central domain defined between 44°10'E and 44°45'E is characterized by a transitional lithosphere which can be seen as a stretched continental crust where thick blocks are mixed with thinned crust; it displays en echelon basins that are better interpreted as extension cells rather than accretion cells.
Detailed study of the Cobb offset of the Juan de Fuca ridge: evolution of a propagating rift
DOE Office of Scientific and Technical Information (OSTI.GOV)
Johnson, H.P.; Karsten, J.L.; Delaney, J.R.
The Cobb Offset on the northern portion of the Juan de Fuca Ridge has been identified as the tip of a northward propagating rift (Hey and Wilson, 1982). Map compilations of magnetic and seismic data from four new cruises define the present locus of spreading and volcanism on the two ridge segments abutting the Offset and permit detailed modeling of the recent evolution within this transform zone. The axis of recent spreading on the southern ridge segment bends from the normal rdige trend (N20/sup 0/E) to a N-S trend, north of 47/sup 0/15'N. The spreading axis on the northern ridgemore » segment generally defines a N20/sup 0/E trend, except at the southern terminus, where the spreading center is offset slightly to the east. The two spreading centers overlap by about 33 km in the Offset vicinity, and there is evidence of recent volcanism on both segments. Present ridge axis morphology exhibits a transitional sequence from a symmetrical, axial high along the more 'normal' portions of each ridge segment to a grabenlike depression as the tip is approached. The magnetic anomaly patterns observed in the Cobb Offset vicinity are not consistent with the patterns predicted by models of continuous, northward propagation. The magnetic anomaly patterns of the Brunhes Epoch require an event of rapid northward propagation about 0.7 m.y. B.P., followed by a more gradual southward propagation in the middle Brunhes Epoch; most recently, the spreading center on the southern ridge has extended northward to its present configuration. Prior to the Brunhes Epoch, modeling of the magnetic anomaly patterns does not indicate a unique solution; however, net propagation has been northward. We present alternative models for the period beginning 1.7 m.y. B.P.« less
2010-01-01
The downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, binds specifically to DNA and several nucleoproteins regulating gene expression and with proteins outside the nucleus to regulate membrane excitability or calcium homeostasis. DREAM is highly expressed in the central nervous system including the hippocampus and cortex; however, the roles of DREAM in hippocampal synaptic transmission and plasticity have not been investigated. Taking advantage of transgenic mice overexpressing a Ca2+-insensitive DREAM mutant (TgDREAM), we used integrative methods including electrophysiology, biochemistry, immunostaining, and behavior tests to study the function of DREAM in synaptic transmission, long-term plasticity and fear memory in hippocampal CA1 region. We found that NMDA receptor but not AMPA receptor-mediated current was decreased in TgDREAM mice. Moreover, synaptic plasticity, such as long-term depression (LTD) but not long-term potentiation (LTP), was impaired in TgDREAM mice. Biochemical experiments found that DREAM interacts with PSD-95 and may inhibit NMDA receptor function through this interaction. Contextual fear memory was significantly impaired in TgDREAM mice. By contrast, sensory responses to noxious stimuli were not affected. Our results demonstrate that DREAM plays a novel role in postsynaptic modulation of the NMDA receptor, and contributes to synaptic plasticity and behavioral memory. PMID:20205763
Herbal Medicine for Anxiety, Depression and Insomnia
Liu, Lei; Liu, Changhong; Wang, Yicun; Wang, Pu; Li, Yuxin; Li, Bingjin
2015-01-01
The prevalence and comorbidity of psychiatric disorders such as depression, anxiety and insomnia are very common. These well-known forms of psychiatric disorders have been affecting many people from all around the world. Herb alone, as well as herbal formula, is commonly prescribed for the therapies of mental illnesses. Since various adverse events of western medication exist, the number of people who use herbs to benefit their health is increasing. Over the past decades, the exploration in the area of herbal psychopharmacology has received much attention. Literatures showed a variety of herbal mechanisms of action used for the therapy of depression, anxiety and insomnia, involving re-uptake of monoamines, affecting neuroreceptor binding and channel transporter activity, modulating neuronal communication or hypothalamic-pituitary adrenal axis (HPA) etc. Nonetheless, a systematic review on herbal pharmacology in depression, anxiety and insomnia is still lacking. This review has been performed to further identify modes of action of different herbal medicine, and thus provides useful information for the application of herbal medicine. PMID:26412068
Chen, Wei-Guan; Zheng, Jia-Xuan; Xu, Xi; Hu, Yu-Ming; Ma, Yu-Min
2018-06-01
As a well-known bile acid receptor, the role of Farnesoid X receptor (FXR) in the digestive system and cardiovascular system has been widely explored. However, there are very few studies involving FXR in the central nervous system. In this study, we explored the role of FXR in the pathogenesis of depression, a serious and worldwide neuropsychiatric disease. It was found that chronic unpredictable mild stress (CUMS) fully enhanced the protein and mRNA expressions of FXR in hippocampus, but not medial prefrontal cortex (mPFC). Overexpression of hippocampal FXR induced notable depressive-like behaviors and decreased expression of brain-derived neurotrophic factor (BDNF) in naïve rats, while knockdown of hippocampal FXR fully prevented the effects of CUMS on rat behaviors and hippocampal BDNF expression. Taken together, our research extends the knowledge of FXR's role in the central nervous system, and may provide a potential and novel therapeutic target for treating depression. Copyright © 2018 Elsevier B.V. All rights reserved.
Arloth, Janine; Bogdan, Ryan; Weber, Peter; Frishman, Goar; Menke, Andreas; Wagner, Klaus V.; Balsevich, Georgia; Schmidt, Mathias V.; Karbalai, Nazanin; Czamara, Darina; Altmann, Andre; Trümbach, Dietrich; Wurst, Wolfgang; Mehta, Divya; Uhr, Manfred; Klengel, Torsten; Erhardt, Angelika; Carey, Caitlin E.; Conley, Emily Drabant; Ripke, Stephan; Wray, Naomi R.; Lewis, Cathryn M.; Hamilton, Steven P.; Weissman, Myrna M.; Breen, Gerome; Byrne, Enda M.; Blackwood, Douglas H.R.; Boomsma, Dorret I.; Cichon, Sven; Heath, Andrew C.; Holsboer, Florian; Lucae, Susanne; Madden, Pamela A.F.; Martin, Nicholas G.; McGuffin, Peter; Muglia, Pierandrea; Noethen, Markus M.; Penninx, Brenda P.; Pergadia, Michele L.; Potash, James B.; Rietschel, Marcella; Lin, Danyu; Müller-Myhsok, Bertram; Shi, Jianxin; Steinberg, Stacy; Grabe, Hans J.; Lichtenstein, Paul; Magnusson, Patrik; Perlis, Roy H.; Preisig, Martin; Smoller, Jordan W.; Stefansson, Kari; Uher, Rudolf; Kutalik, Zoltan; Tansey, Katherine E.; Teumer, Alexander; Viktorin, Alexander; Barnes, Michael R.; Bettecken, Thomas; Binder, Elisabeth B.; Breuer, René; Castro, Victor M.; Churchill, Susanne E.; Coryell, William H.; Craddock, Nick; Craig, Ian W.; Czamara, Darina; De Geus, Eco J.; Degenhardt, Franziska; Farmer, Anne E.; Fava, Maurizio; Frank, Josef; Gainer, Vivian S.; Gallagher, Patience J.; Gordon, Scott D.; Goryachev, Sergey; Gross, Magdalena; Guipponi, Michel; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hoefels, Susanne; Hoogendijk, Witte; Hottenga, Jouke Jan; Iosifescu, Dan V.; Ising, Marcus; Jones, Ian; Jones, Lisa; Jung-Ying, Tzeng; Knowles, James A.; Kohane, Isaac S.; Kohli, Martin A.; Korszun, Ania; Landen, Mikael; Lawson, William B.; Lewis, Glyn; MacIntyre, Donald; Maier, Wolfgang; Mattheisen, Manuel; McGrath, Patrick J.; McIntosh, Andrew; McLean, Alan; Middeldorp, Christel M.; Middleton, Lefkos; Montgomery, Grant M.; Murphy, Shawn N.; Nauck, Matthias; Nolen, Willem A.; Nyholt, Dale R.; O’Donovan, Michael; Oskarsson, Högni; Pedersen, Nancy; Scheftner, William A.; Schulz, Andrea; Schulze, Thomas G.; Shyn, Stanley I.; Sigurdsson, Engilbert; Slager, Susan L.; Smit, Johannes H.; Stefansson, Hreinn; Steffens, Michael; Thorgeirsson, Thorgeir; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, Edwin J.C.G.; Van Grootheest, Gerard; Völzke, Henry; Weilburg, Jeffrey B.; Willemsen, Gonneke; Zitman, Frans G.; Neale, Benjamin; Daly, Mark; Levinson, Douglas F.; Sullivan, Patrick F.; Ruepp, Andreas; Müller-Myhsok, Bertram; Hariri, Ahmad R.; Binder, Elisabeth B.
2015-01-01
Summary Depression risk is exacerbated by genetic factors and stress exposure; however, the biological mechanisms through which these factors interact to confer depression risk are poorly understood. One putative biological mechanism implicates variability in the ability of cortisol, released in response to stress, to trigger a cascade of adaptive genomic and non-genomic processes through glucocorticoid receptor (GR) activation. Here, we demonstrate that common genetic variants in long-range enhancer elements modulate the immediate transcriptional response to GR activation in human blood cells. These functional genetic variants increase risk for depression and co-heritable psychiatric disorders. Moreover, these risk variants are associated with inappropriate amygdala reactivity, a transdiagnostic psychiatric endophenotype and an important stress hormone response trigger. Network modeling and animal experiments suggest that these genetic differences in GR-induced transcriptional activation may mediate the risk for depression and other psychiatric disorders by altering a network of functionally related stress-sensitive genes in blood and brain. Video Abstract PMID:26050039
NASA Astrophysics Data System (ADS)
Corti, Giacomo
2009-09-01
The Main Ethiopian Rift is a key sector of the East African Rift System that connects the Afar depression, at Red Sea-Gulf of Aden junction, with the Turkana depression and Kenya Rift to the South. It is a magmatic rift that records all the different stages of rift evolution from rift initiation to break-up and incipient oceanic spreading: it is thus an ideal place to analyse the evolution of continental extension, the rupture of lithospheric plates and the dynamics by which distributed continental deformation is progressively focused at oceanic spreading centres. The first tectono-magmatic event related to the Tertiary rifting was the eruption of voluminous flood basalts that apparently occurred in a rather short time interval at around 30 Ma; strong plateau uplift, which resulted in the development of the Ethiopian and Somalian plateaus now surrounding the rift valley, has been suggested to have initiated contemporaneously or shortly after the extensive flood-basalt volcanism, although its exact timing remains controversial. Voluminous volcanism and uplift started prior to the main rifting phases, suggesting a mantle plume influence on the Tertiary deformation in East Africa. Different plume hypothesis have been suggested, with recent models indicating the existence of deep superplume originating at the core-mantle boundary beneath southern Africa, rising in a north-northeastward direction toward eastern Africa, and feeding multiple plume stems in the upper mantle. However, the existence of this whole-mantle feature and its possible connection with Tertiary rifting are highly debated. The main rifting phases started diachronously along the MER in the Mio-Pliocene; rift propagation was not a smooth process but rather a process with punctuated episodes of extension and relative quiescence. Rift location was most probably controlled by the reactivation of a lithospheric-scale pre-Cambrian weakness; the orientation of this weakness (roughly NE-SW) and the Late Pliocene (post 3.2 Ma)-recent extensional stress field generated by relative motion between Nubia and Somalia plates (roughly ESE-WNW) suggest that oblique rifting conditions have controlled rift evolution. However, it is still unclear if these kinematical boundary conditions have remained steady since the initial stages of rifting or the kinematics has changed during the Late Pliocene or at the Pliocene-Pleistocene boundary. Analysis of geological-geophysical data suggests that continental rifting in the MER evolved in two different phases. An early (Mio-Pliocene) continental rifting stage was characterised by displacement along large boundary faults, subsidence of rift depression with local development of deep (up to 5 km) asymmetric basins and diffuse magmatic activity. In this initial phase, magmatism encompassed the whole rift, with volcanic activity affecting the rift depression, the major boundary faults and limited portions of the rift shoulders (off-axis volcanism). Progressive extension led to the second (Pleistocene) rifting stage, characterised by a riftward narrowing of the volcano-tectonic activity. In this phase, the main boundary faults were deactivated and extensional deformation was accommodated by dense swarms of faults (Wonji segments) in the thinned rift depression. The progressive thinning of the continental lithosphere under constant, prolonged oblique rifting conditions controlled this migration of deformation, possibly in tandem with the weakening related to magmatic processes and/or a change in rift kinematics. Owing to the oblique rifting conditions, the fault swarms obliquely cut the rift floor and were characterised by a typical right-stepping arrangement. Ascending magmas were focused by the Wonji segments, with eruption of magmas at surface preferentially occurring along the oblique faults. As soon as the volcano-tectonic activity was localised within Wonji segments, a strong feedback between deformation and magmatism developed: the thinned lithosphere was strongly modified by the extensive magma intrusion and extension was facilitated and accommodated by a combination of magmatic intrusion, dyking and faulting. In these conditions, focused melt intrusion allows the rupture of the thick continental lithosphere and the magmatic segments act as incipient slow-spreading mid-ocean spreading centres sandwiched by continental lithosphere. Overall the above-described evolution of the MER (at least in its northernmost sector) documents a transition from fault-dominated rift morphology in the early stages of extension toward magma-assisted rifting during the final stages of continental break-up. A strong increase in coupling between deformation and magmatism with extension is documented, with magma intrusion and dyking playing a larger role than faulting in strain accommodation as rifting progresses to seafloor spreading.
Van Den Houte, Maaike; Van Oudenhove, Lukas; Van Diest, Ilse; Bogaerts, Katleen; Persoons, Philippe; De Bie, Jozef; Van den Bergh, Omer
2018-01-01
Background: Several studies have shown that patients with functional somatic syndromes (FSS) have, on average, deficient endogenous pain modulation (EPM), as well as elevated levels of negative affectivity (NA) and high comorbidity with depression and reduced resting heart rate variability (HRV) compared to healthy controls (HC). The goals of this study were (1) to replicate these findings and (2) to investigate the moderating role of NA, depression, and resting HRV in EPM efficiency within a patient group with fibromyalgia and/or chronic fatigue syndrome (CFS). Resting HRV was quantified as the root mean square of successive differences between inter-beat intervals (RMSSD) in rest, a vagally mediated time domain measure of HRV. Methods: Seventy-eight patients with fibromyalgia and/or CFS and 33 HC completed a counter-irritation paradigm as a measure of EPM efficiency. Participants rated the painfulness of electrocutaneous stimuli (of individually calibrated intensity) on the ankle before (baseline phase), during (counter-irritation phase) and after (recovery phase) the application of a cold pain stimulus on the forearm. A larger reduction in pain in the counter-irritation phase compared to the baseline phase reflects a more efficient EPM. Results: In contrast to our expectations, there was no difference between pain ratings in the baseline compared to counter-irritation phase for both patients and HC. Therefore, reliable conclusions on the moderating effect of NA, depression, and RMSSD could not be made. Surprisingly, patients reported more pain in the recovery compared to the counter-irritation and baseline phase, while HC did not. This latter effect was more pronounced in patients with comorbid depression, patients who rated the painfulness of the counter-irritation stimulus as high and patients who rated the painfulness of the electrocutaneous stimuli as low. We did not manage to successfully replicate the counter-irritation effect in HC or FSS patients. Therefore, no valid conclusions on the association between RMSSD, depression, NA and EPM efficiency can be drawn from this study. Possible reasons for the lack of the counter-irritation effect are discussed.
Kent, Justine M; Daly, Ella; Kezic, Iva; Lane, Rosanne; Lim, Pilar; De Smedt, Heidi; De Boer, Peter; Van Nueten, Luc; Drevets, Wayne C; Ceusters, Marc
2016-06-03
This phase 2a, randomized, multicenter, double-blind, proof-of-concept study was designed to evaluate, efficacy, safety and tolerability of JNJ-40411813/ADX71149, a novel metabotropic glutamate 2 receptor positive allosteric modulator as an adjunctive treatment for major depressive disorder (MDD) with significant anxiety symptoms. Eligible patients (18-64 years) had a DSM-IV diagnosis of MDD, Hamilton Depression Rating Scale-17 (HDRS17) score of ≥ 18, HDRS17 anxiety/somatization factor score of ≥ 7, and an insufficient response to current treatment with a selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor. The doubly-randomized, 8-week double-blind treatment phase was comprised of two 4-week periods, from which a combined test statistic was generated, with pre-determined weights assigned to each of the 2 treatment periods. Period 1: patients (n=121) were randomly assigned (1:1) to JNJ-40411813 (n=62; 50mg to 150 mg b.i.d, flexibly dosed) or placebo (n=59); Period 2: placebo-treated patients (n=22) who continued to meet entry severity criteria were re-randomized (1:1) to JNJ-40411813 or placebo, while other patients underwent sham re-randomization and continued on their same treatment. Of 121 randomized patients, 100 patients (82.6%) were completers. No efficacy signal was detected on the primary endpoint, the 6-item Hamilton Anxiety Subscale (HAM-A6, p=0.51). Efficacy signals (based on prespecified 1-sided p<0.20) were evident on several secondary outcome measures of both depression (HDRS17 total score, 6-item subscale of HDRS17 assessing core depressive symptoms [HAM-D6], and Inventory of Depressive Symptomatology [IDS-C30]) and anxiety (HDRS17 anxiety/somatization factor, IDS-C30 anxiety subscale). Although well-tolerated, the results do not suggest efficacy for JNJ-40411813 as an adjunctive treatment for patients with MDD with significant anxious symptoms in the dose range studied. Copyright © 2016 Elsevier Inc. All rights reserved.
Ketamine and other glutamate receptor modulators for depression in adults.
Caddy, Caroline; Amit, Ben H; McCloud, Tayla L; Rendell, Jennifer M; Furukawa, Toshi A; McShane, Rupert; Hawton, Keith; Cipriani, Andrea
2015-09-23
Considering the ample evidence of involvement of the glutamate system in the pathophysiology of depression, pre-clinical and clinical studies have been conducted to assess the antidepressant efficacy of glutamate inhibition, and glutamate receptor modulators in particular. This review focuses on the use of glutamate receptor modulators in unipolar depression. To assess the effects - and review the acceptability - of ketamine and other glutamate receptor modulators in comparison to placebo (or saline placebo), other pharmacologically active agents, or electroconvulsive therapy (ECT) in alleviating the acute symptoms of depression in people with unipolar major depressive disorder. We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR, to 9 January 2015). This register includes relevant randomised controlled trials (RCTs) from: the Cochrane Library (all years), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). We did not apply any restrictions to date, language or publication status. Double- or single-blind RCTs comparing ketamine, memantine, or other glutamate receptor modulators with placebo (or saline placebo), other active psychotropic drugs, or electroconvulsive therapy (ECT) in adults with unipolar major depression. Three review authors independently identified studies, assessed trial quality and extracted data. The primary outcomes for this review were response rate and adverse events. We included 25 studies (1242 participants) on ketamine (9 trials), memantine (3), AZD6765 (3), D-cycloserine (2), Org26576 (2), atomoxetine (1), CP-101,606 (1), MK-0657 (1), N-acetylcysteine (1), riluzole (1) and sarcosine (1). Twenty-one studies were placebo-controlled and the majority were two-arm studies (23 out of 25). Twenty-two studies defined an inclusion criteria specifying the severity of depression; 11 specified at least moderate depression; eight, severe depression; and the remaining three, mild-moderate depression. Nine studies recruited only treatment-resistant patients.We rated the risk of bias as low or unclear for most domains, though lack of detail regarding masking of treatment in the studies reduced our certainty in the effect for all outcomes. We rated three studies as having high risk for selective outcome reporting. Many trials did not provide information on all the prespecified outcomes and we found no data, or very limited data, on very important issues like suicidality, cognition, quality of life, costs to healthcare services and dropouts due to lack of efficacy.Among all glutamate receptor modulators, only ketamine (administered intravenously) proved to be more efficacious than placebo, though the quality of evidence was limited by risk of bias and small sample sizes. There was low quality evidence that treatment with ketamine increased the likelihood of response after 24 hours (odds ratio (OR) 10.77, 95% confidence interval (CI) 2.00 to 58.00; 3 RCTs, 56 participants), 72 hours (OR 12.59, 95% CI 2.38 to 66.73; 3 RCTs, 56 participants), and one week (OR 2.58, 95% CI 1.08 to 6.16; 4 RCTs, 131 participants). The effect of ketamine was even less certain at two weeks, as data were available from only one trial (OR 0.93, 95% CI 0.31 to 2.83; 51 participants, low quality evidence). This was consistent across all efficacy outcomes. Ketamine caused more confusion and emotional blunting compared to placebo. There was insufficient evidence to determine if this increased the likelihood of leaving the study early (OR 1.90, 95% CI 0.43 to 8.47; 5 RCTs, 139 participants, low quality evidence).One RCT with 72 participants reported higher numbers of responders on ketamine than midazolam at 24 hours (OR 0.36, 95% CI 0.14 to 0.58), 72 hours (OR 0.37, 95% CI 0.16 to 0.59), and one week (OR 0.29, 95% CI 0.08 to 0.49). However, midazolam was better tolerated than ketamine in terms of blurred vision, dizziness, general malaise and nausea/vomiting at 24 hours post-infusion. The evidence contributing to these outcomes was of low quality.We found better efficacy of sarcosine over citalopram at four weeks (OR 6.93, 95% CI 1.53 to 31.38; 1 study, 40 participants), but not at two weeks (OR: 8.14, 95% CI 0.88 to 75.48); fewer participants in the sarcosine group experienced adverse events (OR 0.04, 95% CI 0.00 to 0.68; P = 0.03, 1 study, 40 participants). This was based on low quality evidence. No significant results were found for the remaining glutamate receptor modulators.In one study with 18 participants, ketamine was more effective than ECT at 24 hours (OR 28.00, 95% CI 2.07 to 379.25) and 72 hours (OR 12.25, 95% CI 1.33 to 113.06), but not at one week (OR 3.35, 95% CI 0.12 to 93.83), or two weeks (OR 3.35, 95% CI 0.12 to 93.83). No differences in terms of adverse events were found between ketamine and ECT, however the only adverse events reported were blood pressure and heart rate. This study was rated as very low quality. We found limited evidence for ketamine's efficacy over placebo at time points up to one week in terms of the primary outcome, response rate. The effects were less certain at two weeks post-treatment. No significant results were found for the remaining ten glutamate receptor modulators, except for sarcosine being more effective than citalopram at four weeks. In terms of adverse events, the only significant differences in favour of placebo over ketamine were in regards to confusion and emotional blunting. Despite the promising nature of these preliminary results, our confidence in the evidence was limited by risk of bias and the small number of participants. Many trials did not provide information on all the prespecified outcomes and we found no data, or very limited data, on very important issues like suicidality, cognition, quality of life, costs to healthcare services and dropouts due to lack of efficacy.All included studies administered ketamine intravenously, which can pose practical problems in clinical practice. Very few trials were included in the meta-analyses for each comparison; the majority of comparisons contained only one study. Further RCTs (with adequate blinding) are needed to explore different modes of administration of ketamine with longer follow-up, which test the comparative efficacy of ketamine and the efficacy of repeated administrations.
Kinematics of the southern Red Sea-Afar Triple Junction and implications for plate dynamics
NASA Astrophysics Data System (ADS)
McClusky, Simon; Reilinger, Robert; Ogubazghi, Ghebrebrhan; Amleson, Aman; Healeb, Biniam; Vernant, Philippe; Sholan, Jamal; Fisseha, Shimelles; Asfaw, Laike; Bendick, Rebecca; Kogan, Lewis
2010-03-01
GPS measurements adjacent to the southern Red Sea and Afar Triple Junction, indicate that the Red Sea Rift bifurcates south of 17° N latitude with one branch following a continuation of the main Red Sea Rift (˜150° Az.) and the other oriented more N-S, traversing the Danakil Depression. These two rift branches account for the full Arabia-Nubia relative motion. The partitioning of extension between rift branches varies approximately linearly along strike; north of ˜16°N latitude, extension (˜15 mm/yr) is all on the main Red Sea Rift while at ˜13°N, extension (˜20 mm/yr) has transferred completely to the Danakil Depression. The Danakil Block separates the two rifts and rotates in a counterclockwise sense with respect to Nubia at a present-day rate of 1.9 ± 0.1°/Myr around a pole located at 17.0 ± 0.2°N, 39.7 ± 0.2°E, accommodating extension along the rifts and developing the roughly triangular geometry of the Danakil Depression. Rotating the Danakil Block back in time to close the Danakil Depression, and assuming that the rotation rate with respect to Nubia has been roughly constant, the present width of the Danakil Depression is consistent with initiation of block rotation at 9.3 ± 4 Ma, approximately coincident with the initiation of ocean spreading in the Gulf of Aden, and a concomitant ˜70% increase in the rate of Nubia-Arabia relative motion.
Ramasubbu, Rajamannar; Anderson, Susan; Haffenden, Angela; Chavda, Swati; Kiss, Zelma H T
2013-09-01
Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) is reported to be a safe and effective new treatment for treatment-resistant depression (TRD). However, the optimal electrical stimulation parameters are unknown and generally selected by trial and error. This pilot study investigated the relationship between stimulus parameters and clinical effects in SCC-DBS treatment for TRD. Four patients with TRD underwent SCC-DBS surgery. In a double-blind stimulus optimization phase, frequency and pulse widths were randomly altered weekly, and corresponding changes in mood and depression were evaluated using a visual analogue scale (VAS) and the 17-item Hamilton Rating Scale for Depression (HAM-D-17). In the open-label postoptimization phase, depressive symptoms were evaluated biweekly for 6 months to determine long-term clinical outcomes. Longer pulse widths (270-450 μs) were associated with reductions in HAM-D-17 scores in 3 patients and maximal happy mood VAS responses in all 4 patients. Only 1 patient showed acute clinical or mood effects from changing the stimulation frequency. After 6 months of open-label therapy, 2 patients responded and 1 patient partially responded. Limitations include small sample size, weekly changes in stimulus parameters, and fixed-order and carry-forward effects. Longer pulse width stimulation may have a role in stimulus optimization for SCC-DBS in TRD. Longer pulse durations produce larger apparent current spread, suggesting that we do not yet know the optimal target or stimulus parameters for this therapy. Investigations using different stimulus parameters are required before embarking on large-scale randomized sham-controlled trials.
Hippocampal structure and function are maintained despite severe innate peripheral inflammation.
Süß, Patrick; Kalinichenko, Liubov; Baum, Wolfgang; Reichel, Martin; Kornhuber, Johannes; Loskarn, Sandra; Ettle, Benjamin; Distler, Jörg H W; Schett, Georg; Winkler, Jürgen; Müller, Christian P; Schlachetzki, Johannes C M
2015-10-01
Chronic peripheral inflammation mediated by cytokines such as TNFα, IL-1β, and IL-6 is associated with psychiatric disorders like depression and anxiety. However, it remains elusive which distinct type of peripheral inflammation triggers neuroinflammation and affects hippocampal plasticity resulting in depressive-like behavior. We hypothesized that chronic peripheral inflammation in the human TNF-α transgenic (TNFtg) mouse model of rheumatoid arthritis spreads into the central nervous system and induces depressive state manifested in specific behavioral pattern and impaired adult hippocampal neurogenesis. TNFtg mice showed severe erosive arthritis with increased IL-1β and IL-6 expression in tarsal joints with highly elevated human TNF-α levels in the serum. Intriguingly, IL-1β and IL-6 mRNA levels were not altered in the hippocampus of TNFtg mice. In contrast to the pronounced monocytosis in joints and spleen of TNFtg mice, signs of hippocampal microgliosis or astrocytosis were lacking. Furthermore, locomotion was impaired, but there was no locomotion-independent depressive behavior in TNFtg mice. Proliferation and maturation of hippocampal neural precursor cells as well as survival of newly generated neurons were preserved in the dentate gyrus of TNFtg mice despite reduced motor activity and peripheral inflammatory signature. We conclude that peripheral inflammation in TNFtg mice is mediated by chronic activation of the innate immune system. However, severe peripheral inflammation, though impairing locomotor activity, does not elicit depressive-like behavior. These structural and functional findings indicate the maintenance of hippocampal immunity, cellular plasticity, and behavior despite peripheral innate inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.
Anxiety, depression and suicidal ideation in Lebanese patients undergoing hemodialysis.
Macaron, Gabrielle; Fahed, Mario; Matar, Dany; Bou-Khalil, Rami; Kazour, Francois; Nehme-Chlela, Dania; Richa, Sami
2014-02-01
Anxiety, depression and suicidal thoughts are highly prevalent comorbidities of end-stage-renal-disease (ESRD). There are no studies in Lebanon on the prevalence of these symptoms in Lebanese end-stage-renal-disease patients. Moreover, the association between ESRD on one hand, and anxiety, depression and suicidal ideation on the other has never been established in Lebanon. Groups of patients at a high-risk of development of these symptoms are not determined. The Hospital Anxiety and Depression Score and M.I.N.I (module C) were used to measure the prevalence of anxiety, depression and suicidal ideation in 51 patients from the dialysis center of Hotel-Dieu de France Hospital in Lebanon. In our sample, 45% of included patients suffered from symptoms of anxiety and 50% presented symptoms of depression.The prevalence of suicidal ideation as detected by the M.I.N.I. is at 37%. No patients presented with a high risk of suicide. There was a statistically significant correlation between the existence of organic comorbidities and the presence of symptoms of depression and suicidal ideation. As for anxiety, the association was marginally significant. The results obtained by our study are consistent with those found in studies performed in other societies. The profile of depression- and suicidal ideation-prone patients has been determined. It consists of patients with at least one medical comorbidity to the ESRD. This, in turn, should lead to increased awareness and better treatment of these psychiatric ailments, considering their impact on morbidity and mortality in ESRD.
Maternal response to child affect: Role of maternal depression and relationship quality.
Morgan, Judith K; Ambrosia, Marigrace; Forbes, Erika E; Cyranowski, Jill M; Amole, Marlissa C; Silk, Jennifer S; Elliott, Rosalind D; Swartz, Holly A
2015-11-15
Maternal depression is associated with negative outcomes for offspring, including increased incidence of child psychopathology. Quality of mother-child relationships can be compromised among affectively ill dyads, such as those characterized by maternal depression and child psychopathology, and negatively impact outcomes bidirectionally. Little is known about the neural mechanisms that may modulate depressed mothers' responses to their psychiatrically ill children during middle childhood and adolescence, partially because of a need for ecologically valid personally relevant fMRI tasks that might most effectively elicit these neural mechanisms. The current project evaluated maternal response to child positive and negative affective video clips in 19 depressed mothers with psychiatrically ill offspring using a novel fMRI task. The task elicited activation in the ventral striatum when mothers viewed positive clips and insula when mothers viewed negative clips of their own (versus unfamiliar) children. Both types of clips elicited activation in regions associated with affect regulation and self-related and social processing. Greater lifetime number of depressive episodes, comorbid anxiety, and poor mother-child relationship quality all emerged as predictors of maternal response to child affect. Findings may be specific to dyads with psychiatrically ill children. Altered neural response to child affect may be an important characteristic of chronic maternal depression and may impact mother-child relationships negatively. Existing interventions for depression may be improved by helping mothers respond to their children's affect more adaptively. Copyright © 2015 Elsevier B.V. All rights reserved.
Genome-wide DNA methylation in 1-year-old infants of mothers with major depressive disorder.
Cicchetti, Dante; Hetzel, Susan; Rogosch, Fred A; Handley, Elizabeth D; Toth, Sheree L
2016-11-01
A genome-wide methylation study was conducted among a sample of 114 infants (M age = 13.2 months, SD = 1.08) of low-income urban women with (n = 73) and without (n = 41) major depressive disorder. The Illumina HumanMethylation450 BeadChip array with a GenomeStudio Methylation Module and Illumina Custom model were used to conduct differential methylation analyses. Using the 5.0 × 10-7 p value, 2,119 loci were found to be significantly different between infants of depressed and nondepressed mothers. Infants of depressed mothers had greater methylation at low methylation sites (0%-29%) compared to infants of nondepressed mothers. At high levels of methylation (70%-100%), the infants of depressed mothers were predominantly hypomethylated. The mean difference in methylation between the infants of depressed and infants of nondepressed mothers was 5.23%. Disease by biomarker analyses were also conducted using GeneGo MetaCore Software. The results indicated significant cancer-related differences in biomarker networks such as prostatic neoplasms, ovarian and breast neoplasms, and colonic neoplasms. The results of a process networks analysis indicated significant differences in process networks associated with neuronal development and central nervous system functioning, as well as cardiac development between infants of depressed and nondepressed mothers. These findings indicate that early in development, infants of mothers with major depressive disorder evince epigenetic differences relative to infants of well mothers that suggest risk for later adverse health outcomes.
Guo, M; Lu, Y; Garza, J C; Li, Y; Chua, S C; Zhang, W; Lu, B; Lu, X-Y
2012-01-01
The glutamatergic system has been implicated in the pathophysiology of depression and the mechanism of action of antidepressants. Leptin, an adipocyte-derived hormone, has antidepressant-like properties. However, the functional role of leptin receptor (Lepr) signaling in glutamatergic neurons remains to be elucidated. In this study, we generated conditional knockout mice in which the long form of Lepr was ablated selectively in glutamatergic neurons located in the forebrain structures, including the hippocampus and prefrontal cortex (Lepr cKO). Lepr cKO mice exhibit normal growth and body weight. Behavioral characterization of Lepr cKO mice reveals depression-like behavioral deficits, including anhedonia, behavioral despair, enhanced learned helplessness and social withdrawal, with no evident signs of anxiety. In addition, loss of Lepr in forebrain glutamatergic neurons facilitates N-methyl--aspartate (NMDA)-induced hippocampal long-term synaptic depression (LTD), whereas conventional LTD or long-term potentiation (LTP) was not affected. The facilitated LTD induction requires activation of the NMDA receptor GluN2B (NR2B) subunit as it was completely blocked by a selective GluN2B antagonist. Moreover, Lepr cKO mice are highly sensitive to the antidepressant-like behavioral effects of the GluN2B antagonist but resistant to leptin. These results support important roles for Lepr signaling in glutamatergic neurons in regulating depression-related behaviors and modulating excitatory synaptic strength, suggesting a possible association between synaptic depression and behavioral manifestation of behavioral depression. PMID:22408745
[Sensory and psychoemotional productivity in the type I diabetes mellitus].
Korkeliia, M T; Tsibadze, A D; Naneishvili, G B
2005-10-01
Depressive psychosis with anxiety or without it is the most spread disorder among the patients with diabetes mellitus. According to our investigations the depression was found in 36.6% of cases of patients with the I type diabetes mellitus which affects negatively their mental working ability. Based on the mentioned above we aimed to study a sensory and psychoemotional productivity of patients with the type I diabetes mellitus for their further purposeful treatment. Thirty patients with the type I diabetes mellitus were observed and divided into two groups -- 19 -- without and 11 with a depression. Sensor and motor reaction was studied by means of Landolt's rings in computerized mode. A deterioration of the patients' mental working ability while resolving the simple sensor and motor task is expressed as the increased quantity of missed reactions on the light stimulus and chaotic character of the reaction time histograms that is stipulated by the diminished ability to concentrate attention be carrying out a monotonous work. Psychoemotional test has proved our conclusion drawn by means of sensor-motor task, but the analysis of the reaction time histograms allows suggesting that given contingent of patients fulfill the task of the various conditions of resolving easier then the monotonous one.
Bilateral Epidural Prefrontal Cortical Stimulation for Treatment-Resistant Depression
Nahas, Ziad; Anderson, Berry S.; Borckardt, Jeff; Arana, Ashley B.; George, Mark S.; Reeves, Scott T.; Takacs, Istvan
2010-01-01
Background Treatment-resistant depression presents a serious challenge to both patients and clinicians. The anterior and midlateral prefrontal cortices play complementary roles in integrating emotional and cognitive experiences and in modulating subcortical regions. Both regions offer a distinct opportunity for targeted antidepressant treatments. We chose to pilot the safety and therapeutic benefits of chronic and intermittent epidural prefrontal cortical stimulation (EpCS) in patients with treatment-resistant depression. Methods We enrolled five adults with an average of 5.8 failed antidepressant treatments in their current depressive episode. All subjects underwent comprehensive clinical assessments, detailed neuropsychological testing, and presurgical magnetic resonance imaging. Four cortical stimulation paddle leads were stereotactically placed bilaterally over the anterior frontal poles and midlateral prefrontal cortex. We also acquired a postsurgical computed tomography scan and repeatedly assessed clinical outcomes over time of EpCS as an adjunctive treatment to constant medications. Results All patients tolerated the therapy. At 7-month follow-up, the average improvement from preimplant baseline on the Hamilton Rating Scale for Depression and the Inventory of Depressive Symptoms—Self-Report were 54.9% (± 37.7) and 60.1% (± 34.1), respectively. Three implanted subjects reached remission. One patient's left hemisphere leads were explanted 12 weeks postsurgery because of a scalp infection. Conclusions Bilateral EpCS over anterior and midlateral frontal cortex is a promising new technology for treatment-resistant depression. Future double-blind studies are warranted. PMID:19819427
Inflammation and neuronal plasticity: a link between childhood trauma and depression pathogenesis.
Cattaneo, Annamaria; Macchi, Flavia; Plazzotta, Giona; Veronica, Begni; Bocchio-Chiavetto, Luisella; Riva, Marco Andrea; Pariante, Carmine Maria
2015-01-01
During the past two decades, there has been increasing interest in understanding and characterizing the role of inflammation in major depressive disorder (MDD). Indeed, several are the evidences linking alterations in the inflammatory system to Major Depression, including the presence of elevated levels of pro-inflammatory cytokines, together with other mediators of inflammation. However, it is still not clear whether inflammation represents a cause or whether other factors related to depression result in these immunological effects. Regardless, exposure to early life stressful events, which represent a vulnerability factor for the development of psychiatric disorders, act through the modulation of inflammatory responses, but also of neuroplastic mechanisms over the entire life span. Indeed, early life stressful events can cause, possibly through epigenetic changes that persist over time, up to adulthood. Such alterations may concur to increase the vulnerability to develop psychopathologies. In this review we will discuss the role of inflammation and neuronal plasticity as relevant processes underlying depression development. Moreover, we will discuss the role of epigenetics in inducing alterations in inflammation-immune systems as well as dysfunction in neuronal plasticity, thus contributing to the long-lasting negative effects of stressful life events early in life and the consequent enhanced risk for depression. Finally we will provide an overview on the potential role of inflammatory system to aid diagnosis, predict treatment response, enhance treatment matching, and prevent the onset or relapse of Major Depression.
Understanding adolescent response to a technology-based depression prevention program.
Gladstone, Tracy; Marko-Holguin, Monika; Henry, Jordan; Fogel, Joshua; Diehl, Anne; Van Voorhees, Benjamin W
2014-01-01
Guided by the Behavioral Vaccine Theory of prevention, this study uses a no-control group design to examine intervention variables that predict favorable changes in depressive symptoms at 6- to 8-week follow-up in at-risk adolescents who participated in a primary care, Internet-based prevention program. Participants included 83 adolescents from primary care settings ages 14 to 21 (M = 17.5, SD = 2.04), 56.2% female, with 41% non-White. Participants completed self-report measures, met with a physician, and then completed a 14-module Internet intervention targeting the prevention of depression. Linear regression models indicated that several intervention factors (duration on website in days, the strength of the relationship with the physician, perceptions of ease of use, and the perceived relevance of the material presented) were significantly associated with greater reductions in depressive symptoms from baseline to follow-up. Automatic negative thoughts significantly mediated the relation between change in depressive symptoms scores and both duration of use and physician relationship. Several intervention variables predicted favorable changes in depressive symptom scores among adolescents who participated in an Internet-based prevention program, and the strength of two of these variables was mediated by automatic negative thoughts. These findings support the importance of cognitive factors in preventing adolescent depression and suggest that modifiable aspects of technology-based intervention experience and relationships should be considered in optimizing intervention design.
Impaired social decision making in patients with major depressive disorder.
Zhang, Hui-Jun; Sun, Delin; Lee, Tatia M C
2012-07-01
Research on how depression influences social decision making has been scarce. This study investigated how people with depression make decisions in an interpersonal trust-reciprocity game. Fifty female patients diagnosed with major depressive disorders (MDDs) and 49 healthy women participated in this study. The experiment was conducted on a one-to-one basis. Participants were asked to play the role of a trustee responsible for investing money given to them by an anonymous female investor playing on another computer station. In each trial, the investor would send to a participant (the trustee) a request for a certain percentage of the appreciated investment (repayment proportion). Since only the participant knew the exact amount of the appreciated investment, she could decide to pay more (altruistic act), the same, or less (deceptive act) than the requested amount. The participant's money acquired in the trial would be confiscated if her deceptive act was caught. The frequency of deceptive or altruistic decisions and relative monetary gain in each decision choice were examined. People with depression made fewer deceptive and fewer altruistic responses than healthy controls in all conditions. Moreover, the specific behavioral pattern presented by people with depression was modulated by the task factors, including the risk of deception detection and others' intentions (benevolence vs. malevolence). Findings of this study contribute to furthering our understanding of the specific pattern of social behavioral changes associated with depression.
Figueira, Cláudio Pereira; Carvalhal, Djalma Gomes Ferrão; Almeida, Rafaela Andrade; Hermida, Micely d’ El-Rei; Touchard, Dominique; Robert, Phillipe; Pierres, Anne; Bongrand, Pierre; dos-Santos, Washington LC
2015-01-01
Contact with Leishmania leads to a decreases in mononuclear phagocyte adherence to connective tissue. In this work, we studied the early stages of bond formation between VLA4 and fibronectin, measured the kinetics of membrane alignment and the monocyte cytoplasm spreading area over a fibronectin-coated surface, and studied the expression of high affinity integrin epitope in uninfected and Leishmania-infected human monocytes. Our results show that the initial VLA4-mediated interaction of Leishmania-infected monocyte with a fibronectin-coated surface is preserved, however, the later stage, leukocyte spreading over the substrate is abrogated in Leishmania-infected cells. The median of spreading area was 72 [55–89] μm2 for uninfected and 41 [34–51] μm2 for Leishmania-infected monocyte. This cytoplasm spread was inhibited using an anti-VLA4 blocking antibody. After the initial contact with the fibronectrin-coated surface, uninfected monocyte quickly spread the cytoplasm at a 15 μm2 s−1 ratio whilst Leishmania-infected monocytes only made small contacts at a 5.5 μm2 s−1 ratio. The expression of high affinity epitope by VLA4 (from 39 ± 21% to 14 ± 3%); and LFA1 (from 37 ± 32% to 18 ± 16%) molecules was reduced in Leishmania-infected monocytes. These changes in phagocyte function may be important for parasite dissemination and distribution of lesions in leishmaniasis. PMID:26249106
The w-effect in interferometric imaging: from a fast sparse measurement operator to superresolution
NASA Astrophysics Data System (ADS)
Dabbech, A.; Wolz, L.; Pratley, L.; McEwen, J. D.; Wiaux, Y.
2017-11-01
Modern radio telescopes, such as the Square Kilometre Array, will probe the radio sky over large fields of view, which results in large w-modulations of the sky image. This effect complicates the relationship between the measured visibilities and the image under scrutiny. In algorithmic terms, it gives rise to massive memory and computational time requirements. Yet, it can be a blessing in terms of reconstruction quality of the sky image. In recent years, several works have shown that large w-modulations promote the spread spectrum effect. Within the compressive sensing framework, this effect increases the incoherence between the sensing basis and the sparsity basis of the signal to be recovered, leading to better estimation of the sky image. In this article, we revisit the w-projection approach using convex optimization in realistic settings, where the measurement operator couples the w-terms in Fourier and the de-gridding kernels. We provide sparse, thus fast, models of the Fourier part of the measurement operator through adaptive sparsification procedures. Consequently, memory requirements and computational cost are significantly alleviated at the expense of introducing errors on the radio interferometric data model. We present a first investigation of the impact of the sparse variants of the measurement operator on the image reconstruction quality. We finally analyse the interesting superresolution potential associated with the spread spectrum effect of the w-modulation, and showcase it through simulations. Our c++ code is available online on GitHub.
Web Intervention for Adolescents Affected by Disaster: Population-Based Randomized Controlled Trial
Ruggiero, Kenneth J.; Price, Matthew; Adams, Zachary; Stauffacher, Kirstin; McCauley, Jenna; Danielson, Carla Kmett; Knapp, Rebecca; Hanson, Rochelle F.; Davidson, Tatiana M.; Amstadter, Ananda B.; Carpenter, Matthew J.; Saunders, Benjamin E.; Kilpatrick, Dean G.; Resnick, Heidi S.
2015-01-01
Objective To assess the efficacy of Bounce Back Now (BBN), a modular, web-based intervention for disaster-affected adolescents and their parents. Method A population-based randomized controlled trial used address-based sampling to enroll 2,000 adolescents and parents from communities affected by tornadoes in Joplin, MO, and Alabama. Data collection via baseline and follow-up semi-structured telephone interviews was completed between September 2011 and August 2013. All families were invited to access the BBN study web portal irrespective of mental health status at baseline. Families who accessed the web portal were assigned randomly to 3 groups: (1) BBN, which featured modules for adolescents and parents targeting adolescents’ mental health symptoms; (2) BBN plus additional modules targeting parents’ mental health symptoms; or (3) assessment only. The primary outcomes were adolescent symptoms of posttraumatic stress disorder (PTSD) and depression. Results Nearly 50% of families accessed the web portal. Intent-to-treat analyses revealed time × condition interactions for PTSD symptoms (B=−0.24, SE=0.08, p<.01) and depressive symptoms (B=−0.23, SE=0.09, p<.01). Post-hoc comparisons revealed fewer PTSD and depressive symptoms for adolescents in the experimental vs. control conditions at 12-month follow-up (PTSD: B=−0.36, SE=0.19, p=.06; depressive symptoms: B=−0.42, SE=0.19, p=0.03). A time × condition interaction also was found favoring the BBN vs. BBN + parent self-help condition for PTSD symptoms (B=0.30, SE=0.12, p=.02), but not depressive symptoms (B=0.12, SE=0.12, p=.33). Conclusion Results supported the feasibility and initial efficacy of BBN as a scalable disaster mental health intervention for adolescents. Technology-based solutions have tremendous potential value if found to reduce the mental health burden of disasters. PMID:26299292
Web Intervention for Adolescents Affected by Disaster: Population-Based Randomized Controlled Trial.
Ruggiero, Kenneth J; Price, Matthew; Adams, Zachary; Stauffacher, Kirstin; McCauley, Jenna; Danielson, Carla Kmett; Knapp, Rebecca; Hanson, Rochelle F; Davidson, Tatiana M; Amstadter, Ananda B; Carpenter, Matthew J; Saunders, Benjamin E; Kilpatrick, Dean G; Resnick, Heidi S
2015-09-01
To assess the efficacy of Bounce Back Now (BBN), a modular, Web-based intervention for disaster-affected adolescents and their parents. A population-based randomized controlled trial used address-based sampling to enroll 2,000 adolescents and parents from communities affected by tornadoes in Joplin, MO, and several areas in Alabama. Data collection via baseline and follow-up semi-structured telephone interviews was completed between September 2011 and August 2013. All families were invited to access the BBN study Web portal irrespective of mental health status at baseline. Families who accessed the Web portal were assigned randomly to 1 of 3 groups: BBN, which featured modules for adolescents and parents targeting adolescents' mental health symptoms; BBN plus additional modules targeting parents' mental health symptoms; or assessment only. The primary outcomes were adolescent symptoms of posttraumatic stress disorder (PTSD) and depression. Nearly 50% of families accessed the Web portal. Intent-to-treat analyses revealed time × condition interactions for PTSD symptoms (B = -0.24, SE = 0.08, p < .01) and depressive symptoms (B = -0.23, SE = 0.09, p < .01). Post hoc comparisons revealed fewer PTSD and depressive symptoms for adolescents in the experimental versus control conditions at 12-month follow-up (PTSD: B = -0.36, SE = 0.19, p = .06; depressive symptoms: B = -0.42, SE = 0.19, p = 0.03). A time × condition interaction also was found that favored the BBN versus BBN + parent self-help condition for PTSD symptoms (B = 0.30, SE = 0.12, p = .02) but not depressive symptoms (B = 0.12, SE = 0.12, p = .33). Results supported the feasibility and initial efficacy of BBN as a scalable disaster mental health intervention for adolescents. Technology-based solutions have tremendous potential value if found to reduce the mental health burden of disasters. Web-based Intervention for Disaster-Affected Youth and Families; http://clinicaltrials.gov; NCT01606514. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. All rights reserved.
Modulating Hippocampal Plasticity with In Vivo Brain Stimulation
2016-11-17
Boggio et al., 2009), depression (Fregni et al., 2006; Loo et al., 2012; Brunoni et al., 2014), schizophrenia (Goder et al., 2013) and post-traumatic...Effects of transcranial direct current stimulation during sleep on memory performance in patients with schizophrenia . Schizophr Res 144:153-154. Gruart
[Diagnostics and multimodal treatment of depression in old age : New developments].
Eschweiler, Gerhard W
2017-02-01
Depressive disorders in elderly persons are frequent and can either first be manifested at a younger age and show a recurrent pattern during later life (ICD 10, F33.*) or have an onset beyond 60 years, which is termed late onset depression (LOD). This LOD has a higher tendency to chronification and implies an increased risk of progression, especially to vascular dementia. The multifactorial genesis of depression in old age includes psychosocial, vascular and metabolic factors and requires multimodal therapy modules at the biological and psychosocial level, which is now increasingly being empirically proven. Depressive disorders with executive and cognitive deficits have to be considered a defined entity with respect to prognosis and treatment. As a first step of treatment watchful waiting is appropriate, especially in depressive adjustment disorders triggered by acute psychosocial stressors (e.g. loss of relatives and conflicts). After 2-4 weeks pharmacological antidepressant therapy should be initiated, at least in a moderate depressive episode. Furthermore, the revised national guidelines for depressive disorders also explicitly recommend psychotherapy as an alternative or supplement to pharmacotherapy in the elderly. Several forms of psychotherapy are emphasized: cognitive behavioral therapy, interpersonal therapy and in particular problem solving, as this is a form of treatment that can also be carried out by other professional groups, thus alleviating the treatment gap caused by the lack of psychotherapists. In summary, a depressive disorder in old age should not induce therapeutic nihilism: after stepped diagnostic assessments, multimodal therapies are individually adapted to the physical, cognitive and social resources of the patients.
Symptom-specific self-referential cognitive processes in bipolar disorder: a longitudinal analysis.
Pavlickova, H; Varese, F; Turnbull, O; Scott, J; Morriss, R; Kinderman, P; Paykel, E; Bentall, R P
2013-09-01
Although depression and mania are often assumed to be polar opposites, studies have shown that, in patients with bipolar disorder, they are weakly positively correlated and vary somewhat independently over time. Thus, when investigating relationships between specific psychological processes and specific symptoms (mania and depression), co-morbidity between the symptoms and changes over time must be taken into account. Method A total of 253 bipolar disorder patients were assessed every 24 weeks for 18 months using the Hamilton Rating Scale for Depression (HAMD), the Bech-Rafaelsen Mania Assessment Scale (MAS), the Rosenberg Self-Esteem Questionnaire (RSEQ), the Dysfunctional Attitudes Scale (DAS), the Internal, Personal and Situational Attributions Questionnaire (IPSAQ) and the Personal Qualities Questionnaire (PQQ). We calculated multilevel models using the xtreg module of Stata 9.1, with psychological and clinical measures nested within each participant. Mania and depression were weakly, yet significantly, associated; each was related to distinct psychological processes. Cross-sectionally, self-esteem showed the most robust associations with depression and mania: depression was associated with low positive and high negative self-esteem, and mania with high positive self-esteem. Depression was significantly associated with most of the other self-referential measures, whereas mania was weakly associated only with the externalizing bias of the IPSAQ and the achievement scale of the DAS. Prospectively, low self-esteem predicted future depression. The associations between different self-referential thinking processes and different phases of bipolar disorder, and the presence of the negative self-concept in both depression and mania, have implications for therapeutic management, and also for future directions of research.
Altered Intrinsic Functional Brain Architecture in Children at Familial Risk of Major Depression
Chai, Xiaoqian J.; Hirshfeld-Becker, Dina; Biederman, Joseph; Uchida, Mai; Doehrmann, Oliver; Leonard, Julia; Salvatore, John; Kenworthy, Tara; Brown, Ariel; Kagan, Elana; de los Angeles, Carlo; Gabrieli, John D.E.; Whitfield-Gabrieli, Susan
2015-01-01
Background Neuroimaging studies of patients with major depression have revealed abnormal intrinsic functional connectivity measured during the resting state in multiple, distributed networks. However, it is unclear whether these findings reflect the state of major depression or reflect trait neurobiological underpinnings of risk for major depression. Methods We compared resting-state functional connectivity, measured with functional magnetic resonance imaging (fMRI), between unaffected children of parents who had documented histories of major depression (at-risk, n = 27; 8–14 years of age) and age-matched children of parents with no lifetime history of depression (controls, n = 16). Results At-risk children exhibited hyperconnectivity between the default mode network (DMN) and subgenual anterior cingulate cortex (sgACC) / orbital frontal cortex (OFC), and the magnitude of connectivity positively correlated with individual symptom scores. At-risk children also exhibited (1) hypoconnectivity within the cognitive control network, which also lacked the typical anticorrelation with the DMN; (2) hypoconnectivity between left dorsolateral prefrontal cortex (DLPFC) and sgACC; and (3) hyperconnectivity between the right amygdala and right inferior frontal gyrus, a key region for top-down modulation of emotion. Classification between at-risk children and controls based on resting-state connectivity yielded high accuracy with high sensitivity and specificity that was superior to clinical rating scales. Conclusions Children at familial risk for depression exhibited atypical functional connectivity in the default-mode, cognitive-control, and affective networks. Such task-independent functional brain measures of risk for depression in children could be used to promote early intervention to reduce the likelihood of developing depression. PMID:26826874