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Sample records for homotopic long-term depression

  1. Long-term potentiation and long-term depression: a clinical perspective

    PubMed Central

    Bliss, Timothy V.P.; Cooke, Sam F

    2011-01-01

    Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke. PMID:21779718

  2. Long-term prognosis of depression in primary care.

    PubMed Central

    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

  3. Stochastic Induction of Long-Term Potentiation and Long-Term Depression.

    PubMed

    Antunes, G; Roque, A C; Simoes-de-Souza, F M

    2016-01-01

    Long-term depression (LTD) and long-term potentiation (LTP) of granule-Purkinje cell synapses are persistent synaptic alterations induced by high and low rises of the intracellular calcium ion concentration ([Ca(2+)]), respectively. The occurrence of LTD involves the activation of a positive feedback loop formed by protein kinase C, phospholipase A2, and the extracellular signal-regulated protein kinase pathway, and its expression comprises the reduction of the population of synaptic AMPA receptors. Recently, a stochastic computational model of these signalling processes demonstrated that, in single synapses, LTD is probabilistic and bistable. Here, we expanded this model to simulate LTP, which requires protein phosphatases and the increase in the population of synaptic AMPA receptors. Our results indicated that, in single synapses, while LTD is bistable, LTP is gradual. Ca(2+) induced both processes stochastically. The magnitudes of the Ca(2+) signals and the states of the signalling network regulated the likelihood of LTP and LTD and defined dynamic macroscopic Ca(2+) thresholds for the synaptic modifications in populations of synapses according to an inverse Bienenstock, Cooper and Munro (BCM) rule or a sigmoidal function. In conclusion, our model presents a unifying mechanism that explains the macroscopic properties of LTP and LTD from their dynamics in single synapses. PMID:27485552

  4. Stochastic Induction of Long-Term Potentiation and Long-Term Depression

    PubMed Central

    Antunes, G.; Roque, A. C.; Simoes-de-Souza, F. M.

    2016-01-01

    Long-term depression (LTD) and long-term potentiation (LTP) of granule-Purkinje cell synapses are persistent synaptic alterations induced by high and low rises of the intracellular calcium ion concentration ([Ca2+]), respectively. The occurrence of LTD involves the activation of a positive feedback loop formed by protein kinase C, phospholipase A2, and the extracellular signal-regulated protein kinase pathway, and its expression comprises the reduction of the population of synaptic AMPA receptors. Recently, a stochastic computational model of these signalling processes demonstrated that, in single synapses, LTD is probabilistic and bistable. Here, we expanded this model to simulate LTP, which requires protein phosphatases and the increase in the population of synaptic AMPA receptors. Our results indicated that, in single synapses, while LTD is bistable, LTP is gradual. Ca2+ induced both processes stochastically. The magnitudes of the Ca2+ signals and the states of the signalling network regulated the likelihood of LTP and LTD and defined dynamic macroscopic Ca2+ thresholds for the synaptic modifications in populations of synapses according to an inverse Bienenstock, Cooper and Munro (BCM) rule or a sigmoidal function. In conclusion, our model presents a unifying mechanism that explains the macroscopic properties of LTP and LTD from their dynamics in single synapses. PMID:27485552

  5. Future imperfect: the long-term outcome of depression.

    PubMed

    Surtees, P G; Barkley, C

    1994-03-01

    During 1976, 80 patients with a primary depressive illness were selected from a consecutive series of referrals to the Royal Edinburgh Hospital for a short-term follow-up study. This paper concerns the 12-year longitudinal assessment of the survivors. During the follow-up, mortality risk for the sample was almost doubled. Of the series, 35% had experienced a recurrence within 2 years of the initial interview, and just over 60% within the entire study time of 12 years. The risk of recurrence was enhanced for those aged over 45 years at index, for those with a history of depressive disorder and for those who had not engaged in parasuicidal behaviour during the index episode. The observed effect of previous episodes was largely accounted for by age. The chance of recurrence was not affected by whether the treatment of the index episode included ECT, or by whether diagnosis was 'endogenous' or 'neurotic'. Application of the Lee-Murray outcome criteria showed that about one-third of the Edinburgh series experienced a very poor outcome. Results are presented concerning the prediction of long-term outcome as represented by the Depression Outcome Scale (DOS), a measure specially constructed for this study. PMID:8199786

  6. Propofol effects on cerebellar long-term depression.

    PubMed

    Lee, Kwan Young; Kim, Young Im; Kim, Se Hoon; Park, Hyung Seo; Park, Youn Joon; Ha, Myung Sook; Jin, Yunju; Kim, Dong Kwan

    2015-11-16

    Propofol is an intravenously administered anesthetic that induces γ-aminobutyric acid-mediated inhibition in the central nervous system. It has been implicated in prolonged movement disorders. Since the cerebellum is important for motor coordination and learning, we investigated the potential effects of propofol on cerebellar circuitry. Using the whole-cell patch-clamp technique in Wister rat cerebellar slices, we demonstrated that propofol administration impaired long-term depression from the parallel fiber (PF) to Purkinje cell (PC) synapses (PF-LTD). Also, propofol reduced metabotropic glutamate receptor 1 (mGluR1)-mediated and group I mGluR agonist-induced slow currents in PCs. These results suggest that the propofol-induced PF-LTD impairment may be related to an alteration in mGluR1 signaling, which is essential to motor learning. PMID:26455962

  7. Postsynaptic density-95 mimics and occludes hippocampal long-term potentiation and enhances long-term depression.

    PubMed

    Stein, Valentin; House, David R C; Bredt, David S; Nicoll, Roger A

    2003-07-01

    Previous studies have shown that overexpression of the protein PSD-95 (postsynaptic density-95) selectively enhances AMPA receptor-mediated synaptic responses in hippocampal pyramidal cells. To determine whether this effect is related to synaptic plasticity at these synapses, we examined whether PSD-95 expression mimics long-term potentiation (LTP), and also whether it influences LTP and long-term depression (LTD) in hippocampal slice cultures. Using simultaneous recording from transfected or infected cells and control pyramidal cells, we found that PSD-95, similar to LTP, increases the amplitude and frequency of miniature EPSCs. It also converts silent synapses to functional synapses, as does LTP. In addition, LTP is completely occluded in cells expressing PSD-95, whereas LTD is greatly enhanced. These results suggest that common mechanisms are involved in controlling synaptic AMPA receptors by PSD-95 and synaptic plasticity. PMID:12843250

  8. Induction of long-term potentiation and long-term depression is cell-type specific in the spinal cord.

    PubMed

    Kim, Hee Young; Jun, Jaebeom; Wang, Jigong; Bittar, Alice; Chung, Kyungsoon; Chung, Jin Mo

    2015-04-01

    The underlying mechanism of chronic pain is believed to be changes in excitability in spinal dorsal horn (DH) neurons that respond abnormally to peripheral input. Increased excitability in pain transmission neurons, and depression of inhibitory neurons, are widely recognized in the spinal cord of animal models of chronic pain. The possible occurrence of 2 parallel but opposing forms of synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD) was tested in 2 types of identified DH neurons using whole-cell patch-clamp recordings in mouse spinal cord slices. The test stimulus was applied to the sensory fibers to evoke excitatory postsynaptic currents in identified spinothalamic tract neurons (STTn) and GABAergic neurons (GABAn). Afferent conditioning stimulation (ACS) applied to primary afferent fibers with various stimulation parameters induced LTP in STTn but LTD in GABAn, regardless of stimulation parameters. These opposite responses were further confirmed by simultaneous dual patch-clamp recordings of STTn and GABAn from a single spinal cord slice. Both the LTP in STTn and the LTD in GABAn were blocked by an NMDA receptor antagonist, AP5, or an intracellular Ca chelator, BAPTA. Both the pattern and magnitude of intracellular Ca after ACS were almost identical between STTn and GABAn based on live-cell calcium imaging. The results suggest that the intense sensory input induces an NMDA receptor-dependent intracellular Ca increase in both STTn and GABAn, but produces opposing synaptic plasticity. This study shows that there is cell type-specific synaptic plasticity in the spinal DH. PMID:25785524

  9. No requirement of TRPV1 in long-term potentiation or long-term depression in the anterior cingulate cortex

    PubMed Central

    2014-01-01

    One major interest in the study of transient receptor potential vanilloid type 1 (TRPV1) in sensory system is that it may serve as a drug target for treating chronic pain. While the roles of TRPV1 in peripheral nociception and sensitization have been well documented, less is known about its contribution to pain-related cortical plasticity. Here, we used 64 multi-electrode array recording to examine the potential role of TRPV1 in two major forms of synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD), in the anterior cingulate cortex (ACC). We found that pharmacological blockade of TRPV1 with either [(E)-3-(4-t-Butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide] (AMG9810, 10 μM) or N-(3-methoxyphenyl)-4-chlorocinnamide (SB366791, 20 μM) failed to affect LTP induced by strong theta burst stimulation in the ACC of adult mice. Similarly, neither AMG9810 nor SB366791 blocked the cingulate LTD induced by low-frequency stimulation. Analysis of the results from different layers of the ACC obtained the same conclusions. Spatial distribution of LTP or LTD-showing channels among the ACC network was also unaltered by the TRPV1 antagonists. Since cortical LTP and LTD in the ACC play critical roles in chronic pain triggered by inflammation or nerve injury, our findings suggest that TRPV1 may not be a viable target for treating chronic pain, especially at the cortical level. PMID:24708859

  10. Prefrontal asymmetry in depression? The long-term effect of unilateral brain lesions

    PubMed Central

    Koenigs, Michael; Grafman, Jordan

    2009-01-01

    The proposal that a functional asymmetry in prefrontal cortex (PFC) may play a role in the pathophysiology of depression has sparked vigorous debate and investigation. One particularly contentious issue of clinical and theoretical importance is whether left PFC lesions are associated with the development of depression, and whether any such lesion-depression association is stable over time. To address this issue, we assessed the long-term depressive symptomotology of Vietnam veterans who had acquired left PFC lesions (n=21), right PFC lesions (n=18), non-PFC lesions (n=38), or no brain lesions (n=31) during the Vietnam War. Depressive symptoms were assessed at two different timepoints, approximately 15 and 35 years after lesion onset, respectively. There was no significant effect of PFC lesion laterality on overall depression severity at either timepoint. These data converge with previous stroke studies to suggest that PFC lesion laterality has no long-term systematic effect on vulnerability to depression. PMID:19422881

  11. Breast reconstruction after mastectomy: does it decrease depression at the long-term?

    PubMed Central

    Derks, Eveline Anne-Jet; Torensma, Bart; Honig, Adriaan; Vrouenraets, Bartholomeus Cornelius

    2016-01-01

    Background Depression is associated with breast cancer survivors in 22%. Although breast reconstruction (BR) is intended to provide psychological improvements such as reducing depression, literature is inconclusive and without long-term follow-up. The objective is to evaluate the impact of BR after breast cancer related mastectomy on the long-term depression risk and assess predictive factors for depression. Methods Women who underwent a curative mastectomy between 1999 and 2009 were included. After a mean follow-up of more than 6 years after operation, the Beck Depression Inventory-13 (BDI-13) evaluated depressive symptoms. Multivariable regression analysis provided predictors for depression. Results A total of 139 patients, 34 (24.5%) with and 105 (75.5%) without BR, were analyzed. Seventy-seven patients (48.2%) were at high risk for mild (n=58), moderate (n=5) or severe (n=4) depression. There was a trend for slightly better BDI-13 outcomes for women who underwent BR (2 vs. 4; P=0.06). Living alone [odds ratio (OR): 2.16; P=0.04], low educational level (OR: 3.70; P<0.01) and adjuvant hormonal/endocrine-therapy (OR: 2.36; P=0.02) were associated with an increased depression risk. Conclusions BR has no clear influence on depressive symptoms on the long-term. Predictive factors should alert clinicians to assess depressive symptoms in specific breast cancer patients during follow-up. PMID:27563558

  12. Notation of Depression in Case Records of Older Adults in Community Long-Term Care

    ERIC Educational Resources Information Center

    Proctor, Enola K.

    2008-01-01

    Although significant numbers of social service clients experience mental health problems, virtually no research has examined the responsiveness of social service agencies to mental disorder. This article examines the extent to which client depression is reflected in records of a public social service agency, community long-term care (CLTC).…

  13. Long-Term Effects of a Home-Visiting Intervention for Depressed Mothers and Their Infants

    ERIC Educational Resources Information Center

    Kersten-Alvarez, Laura E.; Hosman, Clemens M. H.; Riksen-Walraven, J. Marianne; Van Doesum, Karin T. M.; Hoefnagels, Cees

    2010-01-01

    Background: Whereas preventive interventions for depressed mothers and their infants have yielded positive short-term outcomes, few studies have examined their long-term effectiveness. The present follow-up of a randomised controlled trial (RCT) is one of the first to examine the longer-term effects of an intervention for mothers with postpartum…

  14. 24-hour-restraint stress induces long-term depressive-like phenotypes in mice.

    PubMed

    Chu, Xixia; Zhou, Ying; Hu, Zhiqiang; Lou, Jingyu; Song, Wei; Li, Jing; Liang, Xiao; Chen, Chen; Wang, Shuai; Yang, Beimeng; Chen, Lei; Zhang, Xu; Song, Jinjing; Dong, Yujie; Chen, Shiqing; He, Lin; Xie, Qingguo; Chen, Xiaoping; Li, Weidong

    2016-01-01

    There is an increasing risk of mental disorders, such as acute stress disorder (ASD), post-traumatic stress disorder (PTSD) and depression among survivors who were trapped in rubble during earthquake. Such long-term impaction of a single acute restraint stress has not been extensively explored. In this study, we subjected mice to 24-hour-restraint to simulate the trapping episode, and investigated the acute (2 days after the restraint) and long-term (35 days after the restraint) impacts. Surprisingly, we found that the mice displayed depression-like behaviors, decreased glucose uptake in brain and reduced adult hippocampal neurogenesis 35 days after the restraint. Differential expression profiling based on microarrays suggested that genes and pathways related to depression and other mental disorders were differentially expressed in both PFC and hippocampus. Furthermore, the depression-like phenotypes induced by 24-hour-restraint could be reversed by fluoxetine, a type of antidepressant drug. These findings demonstrated that a single severe stressful event could produce long-term depressive-like phenotypes. Moreover, the 24-hour-restraint stress mice could also be used for further studies on mood disorders. PMID:27609090

  15. 24-hour-restraint stress induces long-term depressive-like phenotypes in mice

    PubMed Central

    Zhou, Ying; Hu, Zhiqiang; Lou, Jingyu; Song, Wei; Li, Jing; Liang, Xiao; Chen, Chen; Wang, Shuai; Yang, Beimeng; Chen, Lei; Zhang, Xu; Song, Jinjing; Dong, Yujie; Chen, Shiqing; He, Lin; Xie, Qingguo; Chen, Xiaoping; Li, Weidong

    2016-01-01

    There is an increasing risk of mental disorders, such as acute stress disorder (ASD), post-traumatic stress disorder (PTSD) and depression among survivors who were trapped in rubble during earthquake. Such long-term impaction of a single acute restraint stress has not been extensively explored. In this study, we subjected mice to 24-hour-restraint to simulate the trapping episode, and investigated the acute (2 days after the restraint) and long-term (35 days after the restraint) impacts. Surprisingly, we found that the mice displayed depression-like behaviors, decreased glucose uptake in brain and reduced adult hippocampal neurogenesis 35 days after the restraint. Differential expression profiling based on microarrays suggested that genes and pathways related to depression and other mental disorders were differentially expressed in both PFC and hippocampus. Furthermore, the depression-like phenotypes induced by 24-hour-restraint could be reversed by fluoxetine, a type of antidepressant drug. These findings demonstrated that a single severe stressful event could produce long-term depressive-like phenotypes. Moreover, the 24-hour-restraint stress mice could also be used for further studies on mood disorders. PMID:27609090

  16. Long-term Effects of Fathers’ Depressed Mood on Youth Internalizing Symptoms in Early Adulthood

    PubMed Central

    Reeb, Ben T.; Wu, Ed Y.; Martin, Monica J.; Gelardi, Kristina L.; Shirley Chan, Sut Yee; Conger, Katherine J.

    2014-01-01

    While an accumulating body of research has documented increased risk for psychopathology among children of depressed fathers, most studies have used cross-sectional design and little is known about offspring outcomes beyond childhood. Using prospective data from a community sample (N = 395), we found that paternal depressive symptoms when children were in early adolescence (age 13) predicted offspring depressive and anxiety symptoms at age 21, controlling for baseline youth symptoms, maternal depressive symptoms, and other known correlates of internalizing problems in early adulthood. Associations were not moderated by maternal depressive symptoms or child gender. These results suggest that the unique and long-term effects of paternal depression on children's risk for mood disorders may persist into adulthood. PMID:25750495

  17. Adapting Collaborative Depression Care for Public Community Long-Term Care: Using Research-Practice Partnerships

    PubMed Central

    Lenze, Shannon; Brown, Teresa; Lawrence, Lisa; Nickel, Mike; Morrow-Howell, Nancy; Proctor, Enola K.

    2014-01-01

    Description This manuscript details potential benefits for using a research-practice partnership to adapt collaborative depression care for public community long-term care agencies serving older adults. We used sequential, multi-phase, and mixed methods approaches for documenting the process of adaptation within a case study. Systematic adaptation strategies are described, such as leveraging long-term research-practice collaborations, consulting with multiple stakeholders across all levels and disciplines, and balancing demands to monitor treatment fidelity, clinical outcomes, and implementation results. These examples demonstrate that researchers interested in implementation science need skills to negotiate the competing demands that arise from both the research and practice settings. PMID:24072560

  18. Increased NR2A:NR2B ratio compresses long-term depression range and constrains long-term memory.

    PubMed

    Cui, Zhenzhong; Feng, Ruiben; Jacobs, Stephanie; Duan, Yanhong; Wang, Huimin; Cao, Xiaohua; Tsien, Joe Z

    2013-01-01

    The NR2A:NR2B subunit ratio of the NMDA receptors is widely known to increase in the brain from postnatal development to sexual maturity and to aging, yet its impact on memory function remains speculative. We have generated forebrain-specific NR2A overexpression transgenic mice and show that these mice had normal basic behaviors and short-term memory, but exhibited broad long-term memory deficits as revealed by several behavioral paradigms. Surprisingly, increased NR2A expression did not affect 1-Hz-induced long-term depression (LTD) or 100 Hz-induced long-term potentiation (LTP) in the CA1 region of the hippocampus, but selectively abolished LTD responses in the 3-5 Hz frequency range. Our results demonstrate that the increased NR2A:NR2B ratio is a critical genetic factor in constraining long-term memory in the adult brain. We postulate that LTD-like process underlies post-learning information sculpting, a novel and essential consolidation step in transforming new information into long-term memory. PMID:23301157

  19. Ubiquitin-Proteasome System Inhibition Promotes Long-Term Depression and Synaptic Tagging/Capture.

    PubMed

    Li, Qin; Korte, Martin; Sajikumar, Sreedharan

    2016-06-01

    A balance of protein synthesis and degradation is critical for the dynamic regulation and implementation of long-term memory storage. The role of the ubiquitin-proteasome system (UPS) in regulating the plasticity at potentiated synapses is well studied, but its roles in depressed synaptic populations remain elusive. In this study, we probed the possibility of regulating the UPS by inhibiting the proteasome function during the induction of protein synthesis-independent form of hippocampal long-term depression (early-LTD), an important component of synaptic plasticity. Here, we show that protein degradation is involved in early-LTD induction and interfering with this process facilitates early-LTD to late-LTD. We provide evidence here that under the circumstances of proteasome inhibition brain-derived neurotrophic factor is accumulated as plasticity-related protein and it drives the weakly depressed or potentiated synapses to associativity. Thus, UPS inhibition promotes LTD and establishes associativity between weakly depressed or potentiated synapses through the mechanisms of synaptic tagging/capture or cross-capture. PMID:25924950

  20. Depression, anxiety and quality of life in caregivers of long-term home care patients.

    PubMed

    Yıkılkan, Hülya; Aypak, Cenk; Görpelioğlu, Süleyman

    2014-06-01

    Family caregivers of patient in long-term care facilities often have high rates of stress, burden and psychological illness. A descriptive study was carried out with 63 caregivers. Caregivers were asked to complete a demographic questionnaire, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Short form 36 (SF-36), which measures health related quality of life (QoL). The majority of caregivers were female (79.4%), and most often the daughter of the patient in long-term care (47.6%). The mean BDI score of the sample was 18.8, and the mean BAI score was 20.0. Almost all the mean scores referring to the QoL were decreased (lower than 50), with the exception of mental health. On the SF-36 questionnaire, the lowest scores were observed on the role-emotional, role-physical, social functioning and vitality scales of the SF-36. PMID:24856272

  1. Negative symptoms and their association with depressive symptoms in the long-term course of schizophrenia.

    PubMed

    An der Heiden, Wolfram; Leber, Anne; Häfner, Heinz

    2016-08-01

    Depressive symptoms abound in schizophrenia and even in subclinical states of the disorder. We studied the frequency of these symptoms and their relationship to negative symptoms from the first psychotic episode on over a long-term course of 134 months on data for 107 patients in our ABC Schizophrenia Study. Prevalence rates of 90 % for presenting at least one negative symptom and of 60 % for presenting at least one depressive symptom in the first psychotic episode illustrate the frequency of these syndromes. After the remission of psychosis the rates fell to 50 % (negative symptoms) and 40 % (depressive symptoms) over a period of 5 years, remaining stable thereafter. After we broke the negative syndrome down into (SANS) subsyndromes, a positive association emerged between anhedonia and depressive symptoms and remained stable over the entire period studied. In contrast, the association between abulia and depression grew increasingly pronounced over the illness course. However, a more detailed look revealed this to be the case in female patients only, whereas male patients showed no such association of these symptom dimensions. We have no explanation at hand for this sex difference yet. PMID:27107764

  2. Nitric oxide-dependent long-term depression but not endocannabinoid-mediated long-term potentiation is crucial for visual recognition memory

    PubMed Central

    Tamagnini, Francesco; Barker, Gareth; Warburton, E Clea; Burattini, Costanza; Aicardi, Giorgio; Bashir, Zafar I

    2013-01-01

    Synaptic plasticity in perirhinal cortex is essential for recognition memory. Nitric oxide and endocannabinoids (eCBs), which are produced in the postsynaptic cell and act on the presynaptic terminal, are implicated in mechanisms of long-term potentiation (LTP) and long-term depression (LTD) in other brain regions. In this study, we examine these two retrograde signalling cascades in perirhinal cortex synaptic plasticity and in visual recognition memory in the rat. We show that inhibition of NO-dependent signalling prevented both carbachol- and activity (5 Hz)-dependent LTD but not activity (100 Hz theta burst)-dependent LTP in the rat perirhinal cortex in vitro. In contrast, inhibition of the eCB-dependent signalling prevented LTP but not the two forms of LTD in vitro. Local administration into perirhinal cortex of the nitric oxide synthase inhibitor NPA (2 μm) disrupted acquisition of long-term visual recognition memory. In contrast, AM251 (10 μm), a cannabinoid receptor 1 antagonist, did not impair visual recognition memory. The results of this study demonstrate dissociation between putative retrograde signalling mechanisms in LTD and LTP in perirhinal cortex. Thus, LTP relies on cannabinoid but not NO signalling, whilst LTD relies on NO- but not eCB-dependent signalling. Critically, these results also establish, for the first time, that NO- but not eCB-dependent signalling is important in perirhinal cortex-dependent visual recognition memory. PMID:23671159

  3. Modelling bidirectional modulations in synaptic plasticity: A biochemical pathway model to understand the emergence of long term potentiation (LTP) and long term depression (LTD).

    PubMed

    He, Yao; Kulasiri, Don; Samarasinghe, Sandhya

    2016-08-21

    Synaptic plasticity induces bidirectional modulations of the postsynaptic response following a synaptic transmission. The long term forms of synaptic plasticity, named long term potentiation (LTP) and long term depression (LTD), are critical for the antithetic functions of the memory system, memory formation and removal, respectively. A common Ca(2+) signalling upstream triggers both LTP and LTD, and the critical proteins and factors coordinating the LTP/LTD inductions are not well understood. We develop an integrated model based on the sub-models of the indispensable synaptic proteins in the emergence of synaptic plasticity to validate and understand their potential roles in the expression of synaptic plasticity. The model explains Ca(2+)/calmodulin (CaM) complex dependent coordination of LTP/LTD expressions by the interactions among the indispensable proteins using the experimentally estimated kinetic parameters. Analysis of the integrated model provides us with insights into the effective timescales of the key proteins and we conclude that the CaM pool size is critical for the coordination between LTP/LTD expressions. PMID:27185535

  4. Synaptic Function of Rab11Fip5: Selective Requirement for Hippocampal Long-Term Depression.

    PubMed

    Bacaj, Taulant; Ahmad, Mohiuddin; Jurado, Sandra; Malenka, Robert C; Südhof, Thomas C

    2015-05-13

    Postsynaptic AMPA-type glutamate receptors (AMPARs) are among the major determinants of synaptic strength and can be trafficked into and out of synapses. Neuronal activity regulates AMPAR trafficking during synaptic plasticity to induce long-term changes in synaptic strength, including long-term potentiation (LTP) and long-term depression (LTD). Rab family GTPases regulate most membrane trafficking in eukaryotic cells; particularly, Rab11 and its effectors are implicated in mediating postsynaptic AMPAR insertion during LTP. To explore the synaptic function of Rab11Fip5, a neuronal Rab11 effector and a candidate autism-spectrum disorder gene, we performed shRNA-mediated knock-down and genetic knock-out (KO) studies. Surprisingly, we observed robust shRNA-induced synaptic phenotypes that were rescued by a Rab11Fip5 cDNA but that were nevertheless not observed in conditional KO neurons. Both in cultured neurons and acute slices, KO of Rab11Fip5 had no significant effect on basic parameters of synaptic transmission, indicating that Rab11Fip5 is not required for fundamental synaptic operations, such as neurotransmitter release or postsynaptic AMPAR insertion. KO of Rab11Fip5 did, however, abolish hippocampal LTD as measured both in acute slices or using a chemical LTD protocol in cultured neurons but did not affect hippocampal LTP. The Rab11Fip5 KO mice performed normally in several behavioral tasks, including fear conditioning, but showed enhanced contextual fear extinction. These are the first findings to suggest a requirement for Rab11Fip5, and presumably Rab11, during LTD. PMID:25972173

  5. Enhanced AMPA receptor function promotes cerebellar long-term depression rather than potentiation

    PubMed Central

    van Beugen, Boeke J.; Qiao, Xin; Simmons, Dana H.; De Zeeuw, Chris I.

    2014-01-01

    Ampakines are allosteric modulators of AMPA receptors that facilitate hippocampal long-term potentiation (LTP) and learning, and have been considered for the treatment of cognition and memory deficits. Here, we show that the ampakine CX546 raises the amplitude and slows the decay time of excitatory postsynaptic currents (EPSCs) at cerebellar parallel fiber (PF) to Purkinje cell synapses, thus resembling CX546 effects described at hippocampal synapses. Using the fluorescent calcium indicator dye Oregon Green BAPTA-2 and an ultra-high-speed CCD camera, we also monitored calcium transients in Purkinje cell dendrites. In the presence of CX546 in the bath, PF-evoked calcium transients were enhanced and prolonged, suggesting that CX546 not only enhances synaptic transmission, but also boosts dendritic calcium signaling at cerebellar synapses. In contrast to previous observations in the hippocampus, however, CX546 applied during cerebellar recordings facilitates long-term depression (LTD) rather than LTP at PF synapses. These findings show that ampakines selectively modify the LTP–LTD balance depending on the brain area and type of synapse, and may provide tools for the targeted regulation of synaptic memories. PMID:25403454

  6. Spatial olfactory learning facilitates long-term depression in the hippocampus.

    PubMed

    André, Marion Agnès Emma; Manahan-Vaughan, Denise

    2013-10-01

    Recently, it has emerged that visual spatial exploration facilitates synaptic plasticity at different synapses within the trisynaptic network. Particularly striking is the finding that visuospatial contexts facilitate hippocampal long-term depression (LTD), raising the possibility that this form of plasticity may be important for memory formation. It is not known whether other sensory modalities elicit similar permissive effects on LTD. Here, we explored if spatial olfactory learning facilitates LTD in the hippocampus region of freely behaving rats. Patterned afferent stimulation of the Schaffer collaterals elicited short-term depression (STD) (<1 h) of evoked responses in the Stratum radiatum of the CA1 region. Coupling of this protocol with novel exploration of a spatial constellation of olfactory cues facilitated short-term depression into LTD that lasted for over 24 h. Facilitation of LTD did not occur when animals were re-exposed 1 week later to the same odors in the same spatial constellation. Evaluation of learning behavior revealed that 1 week after the 1st odor exposure, the animals remembered the odors and their relative positions. These data support that the hippocampus can use nonvisuospatial resources, and specifically can use spatial olfactory information, to facilitate LTD and to generate spatial representations. The data also support that a tight relationship exists between the processing of spatial contextual information and the expression of LTD in the hippocampus. PMID:23804412

  7. Presynaptic long-term depression mediated by Gi/o-coupled receptors

    PubMed Central

    Atwood, Brady K.; Lovinger, David M.; Mathur, Brian N.

    2014-01-01

    Long-term depression (LTD) of the efficacy of synaptic transmission is now recognized as an important mechanism for regulation of information storage and control of actions, as well as synapse, neuron, and circuit development. Studies of LTD mechanisms have focused mainly on postsynaptic AMPA receptor trafficking. However, the focus has now expanded to include presynaptically expressed plasticity; the predominant form being initiated by presynaptically expressed Gi/o-coupled metabotropic receptor (Gi/o-GPCR) activation. Several forms of LTD involving activation of different presynaptic Gi/o-GPCRs as a “common pathway” are described. Here, we review the literature on presynaptic Gi/o-GPCR-mediated LTD, discuss known mechanisms, gaps in our knowledge, and evaluate if all Gi/o-GPCR are capable of inducing presynaptic LTD. PMID:25160683

  8. Long-term depression and other synaptic plasticity in the cerebellum

    PubMed Central

    HIRANO, Tomoo

    2013-01-01

    Cerebellar long-term depression (LTD) is a type of synaptic plasticity and has been considered as a critical cellular mechanism for motor learning. LTD occurs at excitatory synapses between parallel fibers and a Purkinje cell in the cerebellar cortex, and is expressed as reduced responsiveness to transmitter glutamate. Molecular induction mechanism of LTD has been intensively studied using culture and slice preparations, which has revealed critical roles of Ca2+, protein kinase C and endocytosis of AMPA-type glutamate receptors. Involvement of a large number of additional molecules has also been demonstrated, and their interactions relevant to LTD mechanisms have been studied. In vivo experiments including those on mutant mice, have reported good correlation of LTD and motor learning. However, motor learning could occur with impaired LTD. A possibility that cerebellar synaptic plasticity other than LTD compensates for the defective LTD has been proposed. PMID:23666089

  9. Long-Term Use of Selective Serotonin Reuptake Inhibitors and Risk of Glaucoma in Depression Patients

    PubMed Central

    Chen, Hsin-Yi; Lin, Cheng-Li; Kao, Chia-Hung

    2015-01-01

    Abstract This study investigated whether the long-term use of selective serotonin reuptake inhibitors (SSRIs) influences the risk of primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) in the Chinese ethnic population in Taiwan. The authors retrieved the data under analysis from the National Health Insurance Research Database in Taiwan and identified 26,186 newly diagnosed depression patients without preexisting glaucoma. The study cohort included 13,093 patients with over 1 year of SSRI use, and a comparison cohort of 13,093 patients who had never used SSRIs. The main outcome was a diagnosis of POAG or PACG during follow-up. The authors used univariable and multivariable Cox proportional hazards regression models to assess the effects of SSRIs on the risk of POAG and PACG. The cumulative incidences of POAG and PACG between the SSRI and comparison cohorts exhibited nonsignificant differences (log-rank test P = .52 for POAG, P = .32 for PACG). The overall incidence of POAG in the SSRI cohort was nonsignificantly higher than that in the comparison cohort (1.51 versus 1.39 per 1000 person-years), with an adjusted hazard ratio of 1.07 (95% confidence interval = 0.82–1.40). The overall incidence of PACG in the SSRI cohort was nonsignificantly lower than that in the comparison cohort (0.95 versus 1.11 per 1000 person-years), with an adjusted hazard ratio of 0.85 (95% confidence interval = 0.62–1.18). The long-term use of SSRIs does not influence the risk of POAG or PACG in depression patients. PMID:26559311

  10. Development of a Curriculum for Long-Term Care Nurses to Improve Recognition of Depression in Dementia

    ERIC Educational Resources Information Center

    Williams, Christine L.; Molinari, Victor; Bond, Jennifer; Smith, Michael; Hyer, Kathryn; Malphurs, Julie

    2006-01-01

    There is increasing recognition of the severe consequences of depression in long-term care residents with dementia. Most health care providers are unprepared to recognize and to manage the complexity of depression in dementia. Targeted educational initiatives in nursing homes are needed to address this growing problem. This paper describes the…

  11. GLP-1 receptor agonist liraglutide reverses long-term atypical antipsychotic treatment associated behavioral depression and metabolic abnormalities in rats.

    PubMed

    Sharma, Ajaykumar N; Ligade, Sagar S; Sharma, Jay N; Shukla, Praveen; Elased, Khalid M; Lucot, James B

    2015-04-01

    Mood disorder patients that are on long-term atypical antipsychotics treatment frequently experience metabolic dysfunctions. In addition to this, accumulating evidences points to increased risk of structural abnormalities, brain volume changes, altered neuroplasticity and behavioral depression with long-term antipsychotics use. However, there is paucity of preclinical evidences for long-term antipsychotic associated depression-like behavior. The objectives of the present study were: (1) to evaluate influence of long-term antipsychotic (olanzapine) treatment on rat behavior in forced swim test (FST) as a model for depression and; (2) to examine impact of glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide - an antidiabetic medication for type II diabetes, on long-term olanzapine associated metabolic and behavioral changes in rats. Daily olanzapine treatment (0.5 mg/kg; p.o.) for 8-9 weeks significantly increased body weights, food and water intake, plasma cholesterol and triglycerides and immobility time in FST with parallel reduction in plasma HDL cholesterol levels. These results points to development of metabolic abnormalities and depression-like behavior with long-term olanzapine treatment. Acute liraglutide (50 μg/kg; i.p.) and imipramine (10 mg/kg, i. p.) treatment per se significantly decreased duration of immobility in FST compared to vehicle treated rats. Additionally, 3-week liraglutide treatment (50 μg/kg; i.p., daily) partially reversed metabolic abnormalities and depression-like behavior with long-term olanzapine-treatment in rats. None of these treatment regimens affected locomotor behavior of rats. In summary, add-on GLP-1 receptor agonists promise novel alternatives to counteract long-term antipsychotics associated behavioral and metabolic complications. PMID:25023888

  12. Long-Term Outcome of Adolescent Depression Initially Resistant to SSRI Treatment

    PubMed Central

    Vitiello, Benedetto; Emslie, Graham; Clarke, Gregory; Wagner, Karen D.; Asarnow, Joan R.; Keller, Martin; Birmaher, Boris; Ryan, Neal; Kennard, Betsy; Mayes, Taryn; DeBar, Lynn; Lynch, Frances; Dickerson, John; Strober, Michael; Suddath, Robert; McCracken, James T.; Spirito, Anthony; Onorato, Matthew; Zelazny, Jamie; Porta, Giovanna; Iyengar, Satish; Brent, David

    2011-01-01

    Objective We examined the long-term outcome of participants in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study, a randomized trial of 334 adolescents (aged 12-18 years) with DSM-IV-defined major depression disorder initially resistant to selective serotonin reuptake inhibitor (SSRI) treatment who were and subsequently treated for 12 weeks with another SSRI, venlafaxine, another SSRI + cognitive behavioral therapy (CBT), or venlafaxine + CBT. Responders then continued with the same treatment through week 24, while non-responders were given open treatment. Method For the current study, patients were reassessed 48 (N=116) and 72 (N=130) weeks from intake. Data were gathered from February 2011 to February 2007. Standardized diagnostic interviews and measures of depression, suicidal ideation, related psychopathology and level of functioning were periodically administered. Remission was defined as ≥ 3 weeks with ≤ 1 clinically significant symptom and no associated functional impairment (score of 1 on the adolescent version of the Longitudinal Interval Follow-Up Evaluation [A-LIFE], and relapse as ≥ 2 weeks with probable or definite depressive disorder (score of 3 or 4 on the A-LIFE). Mixed effects regression models were applied to estimate remission, relapse, and functional recovery. Results By 72 weeks, an estimated 61.1% of the randomized youths had reached remission. Randomly assigned treatment (first 12 weeks) did not influence remission rate or time to remission, but the group assigned to SSRI's had a more rapid decline in self-reported depressive symptoms and suicidal ideation than those assigned to venlafaxine (p<.05). Participants with more severe depression, greater dysfunction, and alcohol/drug use at baseline were less likely to remit. The depressive symptom trajectory of the remitters diverged from that of non-remitters by the first 6 weeks of treatment (p<.001). Of the 130 participants in remission at week 24, 25.4% relapsed in

  13. Long-term depression of mGluR1 signaling

    PubMed Central

    Kim, Sang Jeong; Jin, Yunju; Kim, Jun; Worley, Paul F.; Linden, David J.

    2007-01-01

    Summary Glutamate produces both fast excitation through activation of ionotropic receptors and slower actions through metabotropic receptors (mGluRs). To date, ionotropic but not metabotropic neurotransmission has been shown to undergo long-term synaptic potentiation and depression. Burst stimulation of parallel fibers releases glutamate which activates perisynaptic mGluR1 in the dendritic spines of cerebellar Purkinje cells. Here we show that the mGluR1-dependent slow EPSC and its coincident Ca transient were selectively and persistently depressed by repeated climbing fiber-evoked depolarization of Purkinje cells in brain slices. LTD(mGluR1) was also observed when slow synaptic current was evoked by exogenous application of a group I mGluR agonist, implying a postsynaptic expression mechanism. Ca imaging further revealed that LTD(mGluR1) was expressed as coincident attenuation of both limbs of mGluR1 signaling: the slow EPSC and PLC/IP3-mediated dendritic Ca mobilization. Thus, different patterns of neural activity can evoke LTD of either fast ionotropic or slow mGluR1-mediated synaptic signaling. PMID:17640528

  14. The 5-HT7 receptor triggers cerebellar long-term synaptic depression via PKC-MAPK.

    PubMed

    Lippiello, Pellegrino; Hoxha, Eriola; Speranza, Luisa; Volpicelli, Floriana; Ferraro, Angela; Leopoldo, Marcello; Lacivita, Enza; Perrone-Capano, Carla; Tempia, Filippo; Miniaci, Maria Concetta

    2016-02-01

    The 5-HT7 receptor (5-HT7R) mediates important physiological effects of serotonin, such as memory and emotion, and is emerging as a therapeutic target for the treatment of cognitive disorders and depression. Although previous studies have revealed an expression of 5-HT7R in cerebellum, particularly at Purkinje cells, its functional role and signaling mechanisms have never been described. Using patch-clamp recordings in cerebellar slices of adult mice, we investigated the effects of a selective 5-HT7R agonist, LP-211, on the main plastic site of the cerebellar cortex, the parallel fiber-Purkinje cell synapse. Here we show that 5-HT7R activation induces long-term depression of parallel fiber-Purkinje cell synapse via a postsynaptic mechanism that involves the PKC-MAPK signaling pathway. Moreover, a 5-HT7R antagonist abolished the expression of PF-LTD, produced by pairing parallel fiber stimulation with Purkinje cell depolarization; whereas, application of a 5-HT7R agonist impaired LTP induced by 1 Hz parallel fiber stimulation. Our results indicate for the first time that 5-HT7R exerts a fine regulation of cerebellar bidirectional synaptic plasticity that might be involved in cognitive processes and neuropsychiatric disorders involving the cerebellum. PMID:26482421

  15. Coincident Activity of Converging Pathways Enables Simultaneous Long-Term Potentiation and Long-Term Depression in Hippocampal CA1 Network In Vivo

    PubMed Central

    Cao, Jun; Zhang, Xia; Xu, Lin

    2008-01-01

    Memory is believed to depend on activity-dependent changes in the strength of synapses, e.g. long-term potentiation (LTP) and long-term depression (LTD), which can be determined by the sequence of coincident pre- and postsynaptic activity, respectively. It remains unclear, however, whether and how coincident activity of converging efferent pathways can enable LTP and LTD in the pathways simultaneously. Here, we report that, in pentobarbital-anesthetized rats, stimulation (600 pulses, 5 Hz) to Schaffer preceding to commissural pathway within a 40-ms timing window induced similar magnitudes of LTP in both pathways onto synapses of CA1 neurons, with varied LTP magnitudes after reversal of the stimulation sequence. In contrast, in urethane-anesthetized or freely-moving rats, the stimulation to Schaffer preceding to commissural pathway induced Schaffer LTP and commissural LTD simultaneously within a 40-ms timing window, without affecting synaptic efficacy in the reversed stimulation sequence. Coincident activity of Schaffer pathways confirmed the above findings under pentobarbital and urethane anesthesia. Thus, coincident activity of converging afferent pathways tends to switch the pathways to be LTP only or LTP/LTD depending on the activity states of the hippocampus. This network rule strengthens the view that activity-dependent synaptic plasticity may well contribute to memory process of the hippocampal network with flexibility or stability from one state to another. PMID:18682723

  16. Wip1 phosphatase modulates both long-term potentiation and long-term depression through the dephosphorylation of CaMKII.

    PubMed

    He, Zhi-Yong; Hu, Wei-Yan; Zhang, Ming; Yang, Zara Zhuyun; Zhu, Hong-Mei; Xing, Da; Ma, Quan-Hong; Xiao, Zhi-Cheng

    2016-05-01

    Synaptic plasticity is an important mechanism that underlies learning and cognition. Protein phosphorylation by kinases and dephosphorylation by phosphatases play critical roles in the activity-dependent alteration of synaptic plasticity. In this study, we report that Wip1, a protein phosphatase, is essential for long-term potentiation (LTP) and long-term depression (LTD) processes. Wip1-deletion suppresses LTP and enhances LTD in the hippocampus CA1 area. Wip1 deficiency-induced aberrant elevation of CaMKII T286/287 and T305 phosphorylation underlies these dysfunctions. Moreover, we showed that Wip1 modulates CaMKII dephosphorylation. Wip1(-/-) mice exhibit abnormal GluR1 membrane expression, which could be reversed by the application of a CaMKII inhibitor, indicating that Wip1/CaMKII signaling is crucial for synaptic plasticity. Together, our results demonstrate that Wip1 phosphatase plays a vital role in regulating hippocampal synaptic plasticity by modulating the phosphorylation of CaMKII. PMID:27158969

  17. Dopaminergic neurotransmission dysfunction induced by amyloid-β transforms cortical long-term potentiation into long-term depression and produces memory impairment.

    PubMed

    Moreno-Castilla, Perla; Rodriguez-Duran, Luis F; Guzman-Ramos, Kioko; Barcenas-Femat, Alejandro; Escobar, Martha L; Bermudez-Rattoni, Federico

    2016-05-01

    Alzheimer's disease (AD) is a neurodegenerative condition manifested by synaptic dysfunction and memory loss, but the mechanisms underlying synaptic failure are not entirely understood. Although dopamine is a key modulator of synaptic plasticity, dopaminergic neurotransmission dysfunction in AD has mostly been associated to noncognitive symptoms. Thus, we aimed to study the relationship between dopaminergic neurotransmission and synaptic plasticity in AD models. We used a transgenic model of AD (triple-transgenic mouse model of AD) and the administration of exogenous amyloid-β (Aβ) oligomers into wild type mice. We found that Aβ decreased cortical dopamine levels and converted in vivo long-term potentiation (LTP) into long-term depression (LTD) after high-frequency stimulation delivered at basolateral amygdaloid nucleus-insular cortex projection, which led to impaired recognition memory. Remarkably, increasing cortical dopamine and norepinephrine levels rescued both high-frequency stimulation -induced LTP and memory, whereas depletion of catecholaminergic levels mimicked the Aβ-induced shift from LTP to LTD. Our results suggest that Aβ-induced dopamine depletion is a core mechanism underlying the early synaptopathy and memory alterations observed in AD models and acts by modifying the threshold for the induction of cortical LTP and/or LTD. PMID:27103531

  18. Postsynaptic Signal Transduction Models for Long-Term Potentiation and Depression

    PubMed Central

    Manninen, Tiina; Hituri, Katri; Kotaleski, Jeanette Hellgren; Blackwell, Kim T.; Linne, Marja-Leena

    2010-01-01

    More than a hundred biochemical species, activated by neurotransmitters binding to transmembrane receptors, are important in long-term potentiation (LTP) and long-term depression (LTD). To investigate which species and interactions are critical for synaptic plasticity, many computational postsynaptic signal transduction models have been developed. The models range from simple models with a single reversible reaction to detailed models with several hundred kinetic reactions. In this study, more than a hundred models are reviewed, and their features are compared and contrasted so that similarities and differences are more readily apparent. The models are classified according to the type of synaptic plasticity that is modeled (LTP or LTD) and whether they include diffusion or electrophysiological phenomena. Other characteristics that discriminate the models include the phase of synaptic plasticity modeled (induction, expression, or maintenance) and the simulation method used (deterministic or stochastic). We find that models are becoming increasingly sophisticated, by including stochastic properties, integrating with electrophysiological properties of entire neurons, or incorporating diffusion of signaling molecules. Simpler models continue to be developed because they are computationally efficient and allow theoretical analysis. The more complex models permit investigation of mechanisms underlying specific properties and experimental verification of model predictions. Nonetheless, it is difficult to fully comprehend the evolution of these models because (1) several models are not described in detail in the publications, (2) only a few models are provided in existing model databases, and (3) comparison to previous models is lacking. We conclude that the value of these models for understanding molecular mechanisms of synaptic plasticity is increasing and will be enhanced further with more complete descriptions and sharing of the published models. PMID:21188161

  19. Long-term depression is differentially expressed in distinct lamina of hippocampal CA1 dendrites.

    PubMed

    Ramachandran, Binu; Ahmed, Saheeb; Dean, Camin

    2015-01-01

    Information storage in CA1 hippocampal pyramidal neurons is compartmentalized in proximal vs. distal apical dendrites, cell bodies, and basal dendrites. This compartmentalization is thought to be essential for synaptic integration. Differences in the expression of long-term potentiation (LTP) in each of these compartments have been described, but less is known regarding potential differences in long-term depression (LTD). Here, to directly compare LTD expression in each compartment and to bypass possible differences in input-specificity and stimulation of presynaptic inputs, we used global application of NMDA to induce LTD. We then examined LTD expression in each dendritic sub-region-proximal and distal apical, and basal dendrites-and in cell bodies. Interestingly, we found that distal apical dendrites exhibited the greatest magnitude of LTD of all areas tested and this LTD was maintained, whereas LTD in proximal apical dendrites was not maintained. In basal dendrites, LTD was also maintained, but the magnitude of LTD was less than in distal apical dendrites. Blockade of inhibition blocked LTD maintenance in both distal apical and basal dendrites. Population spikes recorded from the cell body layer correlated with apical dendrite field EPSP (fEPSP), where LTD was maintained in distal dendrites and decayed in proximal dendrites. On the other hand, LTD of basal dendrite fEPSPs was maintained but population spike responses were not. Thus E-S coupling was distinct in basal and apical dendrites. Our data demonstrate cell autonomous differential information processing in somas and dendritic sub-regions of CA1 pyramidal neurons in the hippocampus, where LTD expression is intrinsic to distinct dendritic regions, and does not depend on the nature of stimulation and input specificity. PMID:25767434

  20. Early Impairment of Long-Term Depression in the Perirhinal Cortex of a Mouse Model of Alzheimer's Disease

    PubMed Central

    Tamagnini, Francesco; Burattini, Costanza; Casoli, Tiziana; Balietti, Marta; Fattoretti, Patrizia

    2012-01-01

    Abstract Visual recognition memory is early impaired in Alzheimer's disease. Long-term depression of synaptic transmission in the perirhinal cortex is critically involved in this form of memory. We found that synaptic transmission was impaired in perirhinal cortex slices obtained from 3-month-old Tg2576 mice, and that 3,000 pulses at 5 Hz induced long-term depression in perirhinal cortex slices from age-matched control mice, but not in those from Tg2576 mice. To our knowledge, these data provide the first evidence of synaptic transmission and long-term depression impairment in the perirhinal cortex in an animal model of Alzheimer's disease, and the earliest synaptic deficit in Tg2576 mice. PMID:22533438

  1. Presynaptic Spike Timing-Dependent Long-Term Depression in the Mouse Hippocampus.

    PubMed

    Andrade-Talavera, Yuniesky; Duque-Feria, Paloma; Paulsen, Ole; Rodríguez-Moreno, Antonio

    2016-08-01

    Spike timing-dependent plasticity (STDP) is a Hebbian learning rule important for synaptic refinement during development and for learning and memory in the adult. Given the importance of the hippocampus in memory, surprisingly little is known about the mechanisms and functions of hippocampal STDP. In the present work, we investigated the requirements for induction of hippocampal spike timing-dependent long-term potentiation (t-LTP) and spike timing-dependent long-term depression (t-LTD) and the mechanisms of these 2 forms of plasticity at CA3-CA1 synapses in young (P12-P18) mouse hippocampus. We found that both t-LTP and t-LTD can be induced at hippocampal CA3-CA1 synapses by pairing presynaptic activity with single postsynaptic action potentials at low stimulation frequency (0.2 Hz). Both t-LTP and t-LTD require NMDA-type glutamate receptors for their induction, but the location and properties of these receptors are different: While t-LTP requires postsynaptic ionotropic NMDA receptor function, t-LTD does not, and whereas t-LTP is blocked by antagonists at GluN2A and GluN2B subunit-containing NMDA receptors, t-LTD is blocked by GluN2C or GluN2D subunit-preferring NMDA receptor antagonists. Both t-LTP and t-LTD require postsynaptic Ca(2+) for their induction. Induction of t-LTD also requires metabotropic glutamate receptor activation, phospholipase C activation, postsynaptic IP3 receptor-mediated Ca(2+) release from internal stores, postsynaptic endocannabinoid (eCB) synthesis, activation of CB1 receptors and astrocytic signaling, possibly via release of the gliotransmitter d-serine. We furthermore found that presynaptic calcineurin is required for t-LTD induction. t-LTD is expressed presynaptically as indicated by fluctuation analysis, paired-pulse ratio, and rate of use-dependent depression of postsynaptic NMDA receptor currents by MK801. The results show that CA3-CA1 synapses display both NMDA receptor-dependent t-LTP and t-LTD during development and identify a

  2. Presynaptic Spike Timing-Dependent Long-Term Depression in the Mouse Hippocampus

    PubMed Central

    Andrade-Talavera, Yuniesky; Duque-Feria, Paloma; Paulsen, Ole; Rodríguez-Moreno, Antonio

    2016-01-01

    Spike timing-dependent plasticity (STDP) is a Hebbian learning rule important for synaptic refinement during development and for learning and memory in the adult. Given the importance of the hippocampus in memory, surprisingly little is known about the mechanisms and functions of hippocampal STDP. In the present work, we investigated the requirements for induction of hippocampal spike timing-dependent long-term potentiation (t-LTP) and spike timing-dependent long-term depression (t-LTD) and the mechanisms of these 2 forms of plasticity at CA3-CA1 synapses in young (P12–P18) mouse hippocampus. We found that both t-LTP and t-LTD can be induced at hippocampal CA3-CA1 synapses by pairing presynaptic activity with single postsynaptic action potentials at low stimulation frequency (0.2 Hz). Both t-LTP and t-LTD require NMDA-type glutamate receptors for their induction, but the location and properties of these receptors are different: While t-LTP requires postsynaptic ionotropic NMDA receptor function, t-LTD does not, and whereas t-LTP is blocked by antagonists at GluN2A and GluN2B subunit-containing NMDA receptors, t-LTD is blocked by GluN2C or GluN2D subunit-preferring NMDA receptor antagonists. Both t-LTP and t-LTD require postsynaptic Ca2+ for their induction. Induction of t-LTD also requires metabotropic glutamate receptor activation, phospholipase C activation, postsynaptic IP3 receptor-mediated Ca2+ release from internal stores, postsynaptic endocannabinoid (eCB) synthesis, activation of CB1 receptors and astrocytic signaling, possibly via release of the gliotransmitter d-serine. We furthermore found that presynaptic calcineurin is required for t-LTD induction. t-LTD is expressed presynaptically as indicated by fluctuation analysis, paired-pulse ratio, and rate of use-dependent depression of postsynaptic NMDA receptor currents by MK801. The results show that CA3-CA1 synapses display both NMDA receptor-dependent t-LTP and t-LTD during development and identify a

  3. Talking about depression: a qualitative study of barriers to managing depression in people with long term conditions in primary care

    PubMed Central

    2011-01-01

    Background The risk of depression is increased in people with long term conditions (LTCs) and is associated with poorer patient outcomes for both the depressive illness and the LTC, but often remains undetected and poorly managed. The aim of this study was to identify and explore barriers to detecting and managing depression in primary care in people with two exemplar LTCs: diabetes and coronary heart disease (CHD). Methods Qualitative in-depth interviews were conducted with 19 healthcare professionals drawn predominately from primary care, along with 7 service users and 3 carers (n = 29). One focus group was then held with a set of 6 healthcare professionals and a set of 7 service users and 1 carer (n = 14). Interviews and the focus group were digitally recorded, transcribed verbatim, and analysed independently. The two data sets were then inspected for commonalities using a constant comparative method, leading to a final thematic framework used in this paper. Results Barriers to detecting and managing depression in people with LTCs in primary care exist: i) when practitioners in partnership with patients conceptualise depression as a common and understandable response to the losses associated with LTCs - depression in the presence of LTCs is normalised, militating against its recognition and treatment; ii) where highly performanced managed consultations under the terms of the Quality and Outcomes Framework encourage reductionist approaches to case-finding in people with CHD and diabetes, and iii) where there is uncertainty among practitioners about how to negotiate labels for depression in people with LTCs in ways that might facilitate shared understanding and future management. Conclusion Depression was often normalised in the presence of LTCs, obviating rather than facilitating further assessment and management. Furthermore, structural constraints imposed by the QOF encouraged reductionist approaches to case-finding for depression in consultations for CHD and

  4. Both NR2A and NR2B Subunits of the NMDA Receptor Are Critical for Long-Term Potentiation and Long-Term Depression in the Lateral Amygdala of Horizontal Slices of Adult Mice

    ERIC Educational Resources Information Center

    Muller, Tobias; Albrecht, Doris; Gebhardt, Christine

    2009-01-01

    The lateral nucleus of the amygdala (LA) is implicated in emotional and social behaviors. We recently showed that in horizontal brain slices, activation of NMDA receptors (NMDARs) is a requirement for persistent synaptic alterations in the LA, such as long-term potentiation (LTP) and long-term depression (LTD). In the LA, NR2A- and NR2B-type NMDRs…

  5. Stargazin regulates AMPA receptor trafficking through adaptor protein complexes during long-term depression

    NASA Astrophysics Data System (ADS)

    Matsuda, Shinji; Kakegawa, Wataru; Budisantoso, Timotheus; Nomura, Toshihiro; Kohda, Kazuhisa; Yuzaki, Michisuke

    2013-11-01

    Long-term depression (LTD) underlies learning and memory in various brain regions. Although postsynaptic AMPA receptor trafficking mediates LTD, its underlying molecular mechanisms remain largely unclear. Here we show that stargazin, a transmembrane AMPA receptor regulatory protein, forms a ternary complex with adaptor proteins AP-2 and AP-3A in hippocampal neurons, depending on its phosphorylation state. Inhibiting the stargazin-AP-2 interaction disrupts NMDA-induced AMPA receptor endocytosis, and inhibiting that of stargazin-AP-3A abrogates the late endosomal/lysosomal trafficking of AMPA receptors, thereby upregulating receptor recycling to the cell surface. Similarly, stargazin’s interaction with AP-2 or AP-3A is necessary for low-frequency stimulus-evoked LTD in CA1 hippocampal neurons. Thus, stargazin has a crucial role in NMDA-dependent LTD by regulating two trafficking pathways of AMPA receptors—transport from the cell surface to early endosomes and from early endosomes to late endosomes/lysosomes—through its sequential binding to AP-2 and AP-3A.

  6. AMPA receptor signaling through BRAG2 and Arf6 critical for long-term synaptic depression.

    PubMed

    Scholz, Ralf; Berberich, Sven; Rathgeber, Louisa; Kolleker, Alexander; Köhr, Georg; Kornau, Hans-Christian

    2010-06-10

    Central nervous system synapses undergo activity-dependent alterations to support learning and memory. Long-term depression (LTD) reflects a sustained reduction of the synaptic AMPA receptor content based on targeted clathrin-mediated endocytosis. Here we report a current-independent form of AMPA receptor signaling, fundamental for LTD. We found that AMPA receptors directly interact via the GluA2 subunit with the synaptic protein BRAG2, which functions as a guanine-nucleotide exchange factor (GEF) for the coat-recruitment GTPase Arf6. BRAG2-mediated catalysis, controlled by ligand-binding and tyrosine phosphorylation of GluA2, activates Arf6 to internalize synaptic AMPA receptors upon LTD induction. Furthermore, acute blockade of the GluA2-BRAG2 interaction and targeted deletion of BRAG2 in mature hippocampal CA1 pyramidal neurons prevents LTD in CA3-to-CA1 cell synapses, irrespective of the induction pathway. We conclude that BRAG2-mediated Arf6 activation triggered by AMPA receptors is the convergent step of different forms of LTD, thus providing an essential mechanism for the control of vesicle formation by endocytic cargo. PMID:20547133

  7. A Computational Model for the AMPA Receptor Phosphorylation Master Switch Regulating Cerebellar Long-Term Depression

    PubMed Central

    Gallimore, Andrew R.; Aricescu, A. Radu; Yuzaki, Michisuke; Calinescu, Radu

    2016-01-01

    The expression of long-term depression (LTD) in cerebellar Purkinje cells results from the internalisation of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) from the postsynaptic membrane. This process is regulated by a complex signalling pathway involving sustained protein kinase C (PKC) activation, inhibition of serine/threonine phosphatase, and an active protein tyrosine phosphatase, PTPMEG. In addition, two AMPAR-interacting proteins–glutamate receptor-interacting protein (GRIP) and protein interacting with C kinase 1 (PICK1)–regulate the availability of AMPARs for trafficking between the postsynaptic membrane and the endosome. Here we present a new computational model of these overlapping signalling pathways. The model reveals how PTPMEG cooperates with PKC to drive LTD expression by facilitating the effect of PKC on the dissociation of AMPARs from GRIP and thus their availability for trafficking. Model simulations show that LTD expression is increased by serine/threonine phosphatase inhibition, and negatively regulated by Src-family tyrosine kinase activity, which restricts the dissociation of AMPARs from GRIP under basal conditions. We use the model to expose the dynamic balance between AMPAR internalisation and reinsertion, and the phosphorylation switch responsible for the perturbation of this balance and for the rapid plasticity initiation and regulation. Our model advances the understanding of PF-PC LTD regulation and induction, and provides a validated extensible platform for more detailed studies of this fundamental synaptic process. PMID:26807999

  8. A Computational Model for the AMPA Receptor Phosphorylation Master Switch Regulating Cerebellar Long-Term Depression.

    PubMed

    Gallimore, Andrew R; Aricescu, A Radu; Yuzaki, Michisuke; Calinescu, Radu

    2016-01-01

    The expression of long-term depression (LTD) in cerebellar Purkinje cells results from the internalisation of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) from the postsynaptic membrane. This process is regulated by a complex signalling pathway involving sustained protein kinase C (PKC) activation, inhibition of serine/threonine phosphatase, and an active protein tyrosine phosphatase, PTPMEG. In addition, two AMPAR-interacting proteins-glutamate receptor-interacting protein (GRIP) and protein interacting with C kinase 1 (PICK1)-regulate the availability of AMPARs for trafficking between the postsynaptic membrane and the endosome. Here we present a new computational model of these overlapping signalling pathways. The model reveals how PTPMEG cooperates with PKC to drive LTD expression by facilitating the effect of PKC on the dissociation of AMPARs from GRIP and thus their availability for trafficking. Model simulations show that LTD expression is increased by serine/threonine phosphatase inhibition, and negatively regulated by Src-family tyrosine kinase activity, which restricts the dissociation of AMPARs from GRIP under basal conditions. We use the model to expose the dynamic balance between AMPAR internalisation and reinsertion, and the phosphorylation switch responsible for the perturbation of this balance and for the rapid plasticity initiation and regulation. Our model advances the understanding of PF-PC LTD regulation and induction, and provides a validated extensible platform for more detailed studies of this fundamental synaptic process. PMID:26807999

  9. Developmental switch in the contribution of presynaptic and postsynaptic NMDA receptors to long-term depression.

    PubMed

    Corlew, Rebekah; Wang, Yun; Ghermazien, Haben; Erisir, Alev; Philpot, Benjamin D

    2007-09-12

    NMDA receptor (NMDAR) activation is required for many forms of learning and memory as well as sensory system receptive field plasticity, yet the relative contribution of presynaptic and postsynaptic NMDARs over cortical development remains unknown. Here we demonstrate a rapid developmental loss of functional presynaptic NMDARs in the neocortex. Presynaptic NMDARs enhance neurotransmitter release at synapses onto visual cortex pyramidal cells in young mice [before postnatal day 20 (P20)], but they have no apparent effect after the onset of the critical period for receptive field plasticity (>P23). Immunoelectron microscopy revealed that the loss of presynaptic NMDAR function is likely attributable in part to a 50% reduction in the prevalence of presynaptic NMDARs. Coincident with the observed loss of presynaptic NMDAR function, there is an abrupt change in the mechanisms of timing-dependent long-term depression (tLTD). Induction of tLTD before the onset of the critical period requires activation of presynaptic but not postsynaptic NMDARs, whereas the induction of tLTD in older mice requires activation of postsynaptic NMDARs. By demonstrating that both presynaptic and postsynaptic NMDARs contribute to the induction of synaptic plasticity and that their relative roles shift over development, our findings define a novel, and perhaps general, property of synaptic plasticity in emerging cortical circuits. PMID:17855598

  10. Factors Associated with Depression Assessed by the Patient Health Questionnaire-2 in Long-Term Cancer Survivors

    PubMed Central

    Goo, Ae-Jin; Shin, Jinyoung; Ko, Hyeonyoung

    2016-01-01

    Background This cross-sectional study aimed to evaluate the prevalence of depressive disorders and factors associated in long-term cancer survivors. Methods A total of 702 long-term cancer survivors over 5-years in remission were recruited in a university-affiliated tertiary hospital in Korea. Self-report using the Patient Health Questionnaire-2 and the Fatigue Severity Scale assessed depression and fatigue, respectively. Demographic characteristics, cancer-related clinical characteristics, comorbidity, health behaviors, and physical symptoms were assessed through the review of medical records or a structured self-administered questionnaire. Results We identified 26.1% of patients who had a depressed mood or displayed a loss of interest. The most prevalent primary site of cancer was the stomach (65.2%), followed by lung, breast, colorectal, and thyroid cancer. We also found that 5.7% of subjects experienced double or triple primary cancers. Larger proportion among depressive group (89.1%) complained at least one physical problem than among non-depressive group (53.2%). Physical symptoms including sleep problems, dry mouth, indigestion, pain, decreased appetite, and febrile sense were more frequent in the depressive group than in the non-depressive group. The Fatigue Severity Scale scores were higher in the depressive group than in the non-depressive group (P<0.001). Multiple logistic regression analysis showed that the highest tertile level of fatigue (odds ratio, 7.31; 95% confidence interval, 3.81–14.02) was associated with the increased risk of depression. Conclusion These findings suggest that careful concern about depression is necessary in long-term cancer survivors. Fatigue may be a surrogate sign for depression, and warrants further evaluation. PMID:27468341

  11. Long-Term Effectiveness of Collaborative Depression Care in Older Primary Care Patients with and without PTSD Symptoms

    PubMed Central

    Chan, Domin; Fan, Ming-Yu; Unützer, Jürgen

    2012-01-01

    Objective Depressed patients with comorbid posttraumatic stress disorder (PTSD) are more functionally impaired and may take longer to respond to depression treatment than patients without PTSD. This study examined the long-term effects of PTSD on depression severity, treatment response, and health care costs among older adults. Methods Patients were recruited from 18 primary care clinics in 5 states. A total of 1801 patients aged 60 years or older with major depression or dysthymia were randomized to IMPACT collaborative care or usual care. The study included 191 (10.6%) subjects who screened positive for PTSD. Depression severity, assessed by the Hopkins Depression Symptom Checklist, was used to estimate depression-free days (DFDs) over 24 months. Total health care costs included inpatient, outpatient, and pharmacy costs. Results Depressed patients with PTSD had higher depression severity than patients without PTSD symptoms at baseline. Over two years, intervention patients with PTSD symptoms had relatively the same benefits from collaborative care (99 more DFDs than usual care patients) as patients without PTSD (108 more DFDs than usual care) (p=0.85). Total health care costs did not differ significantly for depressed patients with and without PTSD symptoms. Conclusion Depressed older adults with PTSD symptoms were more depressed at baseline, but collaborative care (compared to usual care) produced similar improvements in depression severity in both groups. This reduction of depression symptoms was observed for up to 12 months after the intervention ended, suggesting that long-term improvements in depression are possible with collaborative care in patients with and without PTSD symptoms. PMID:21495079

  12. A Videotape-Based Training Method for Improving the Detection of Depression in Residents of Long-Term Care Facilities

    ERIC Educational Resources Information Center

    Wood, Stacey; Cummings, Jeffrey L.; Schnelle, Betha; Stephens, Mary

    2002-01-01

    Purpose: This article reviews the effectiveness of a new training program for improving nursing staffs' detection of depression within long-term care facilities. The course was designed to increase recognition of the Minimal Data Set (MDS) Mood Trigger items, to be brief, and to rely on images rather than didactics. Design and Methods: This study…

  13. Acceptance and Commitment Therapy for Depression: A Preliminary Randomized Clinical Trial for Unemployed on Long-Term Sick Leave

    ERIC Educational Resources Information Center

    Folke, Fredrik; Parling, Thomas; Melin, Lennart

    2012-01-01

    This preliminary study investigated the feasibility of a brief Acceptance and Commitment Therapy (ACT) in a Swedish sample of unemployed individuals on long-term sick leave due to depression. Participants were randomized to a nonstandardized control condition (N = 16) or to the ACT condition (N = 18) consisting of 1 individual and 5 group…

  14. Long-Term Effects of Child Corporal Punishment on Depressive Symptoms in Young Adults: Potential Moderators and Mediators

    ERIC Educational Resources Information Center

    Turner, Heather A.; Muller, Paul A.

    2004-01-01

    Based on a sample of 649 students from 3 New England colleges, this study examined the long-term effects of childhood corporal punishment on symptoms of depression and considered factors that may moderate or mediate the association. Similar to national studies, approximately 40% of the sample reported experiencing some level of corporal punishment…

  15. Antidepressant short-term and long-term brain effects during self-referential processing in major depression.

    PubMed

    Delaveau, Pauline; Jabourian, Maritza; Lemogne, Cédric; Allaïli, Najib; Choucha, Walid; Girault, Nathalie; Lehericy, Stéphane; Laredo, Judith; Fossati, Philippe

    2016-01-30

    Acute depression is associated with impaired self-referential processing. Antidepressant effects on the neural bases of self-referential processing in depression are unknown. This study aimed to assess short- and long-term effects of agomelatine on these neural bases in depressed patients and the association between pre-treatment brain activation and remission of depression 6 months later. We conducted a randomized double-blind, placebo-controlled, functional magnetic resonance imaging (fMRI) study during an emotional self-referential task, including three scanning sessions (baseline, after 1 week, and after 7 weeks). Twenty-five depressed outpatients were included, all treated with agomelatine or placebo for 1 week. Then, all patients received agomelatine for 24 weeks. Fourteen matched healthy volunteers (HV) who received placebo for 1 week were also included. After 7 days, only depressed patients receiving agomelatine significantly deactivated the ventrolateral prefrontal cortex during self-referential processing, as observed in HV at baseline. After 7 weeks, depressed patients significantly increased the activation of the ventral anterior cingulate cortex. Finally dorsomedial prefrontal cortex and precuneus activations at baseline significantly separated remitters from non-remitters at 24 weeks. In depressed patients, agomelatine had short- and long-term effects on brain structures involved in anhedonia and emotional regulation during self-referential processing. Activation of the dorsomedial prefrontal cortex and precuneus could be informative in the development of biomarker-based treatment of major depression. PMID:26655583

  16. Nitric Oxide Regulates Input Specificity of Long-Term Depression and Context Dependence of Cerebellar Learning

    PubMed Central

    Ogasawara, Hideaki; Doi, Tomokazu; Doya, Kenji; Kawato, Mitsuo

    2007-01-01

    Recent studies have shown that multiple internal models are acquired in the cerebellum and that these can be switched under a given context of behavior. It has been proposed that long-term depression (LTD) of parallel fiber (PF)–Purkinje cell (PC) synapses forms the cellular basis of cerebellar learning, and that the presynaptically synthesized messenger nitric oxide (NO) is a crucial “gatekeeper” for LTD. Because NO diffuses freely to neighboring synapses, this volume learning is not input-specific and brings into question the biological significance of LTD as the basic mechanism for efficient supervised learning. To better characterize the role of NO in cerebellar learning, we simulated the sequence of electrophysiological and biochemical events in PF–PC LTD by combining established simulation models of the electrophysiology, calcium dynamics, and signaling pathways of the PC. The results demonstrate that the local NO concentration is critical for induction of LTD and for its input specificity. Pre- and postsynaptic coincident firing is not sufficient for a PF–PC synapse to undergo LTD, and LTD is induced only when a sufficient amount of NO is provided by activation of the surrounding PFs. On the other hand, above-adequate levels of activity in nearby PFs cause accumulation of NO, which also allows LTD in neighboring synapses that were not directly stimulated, ruining input specificity. These findings lead us to propose the hypothesis that NO represents the relevance of a given context and enables context-dependent selection of internal models to be updated. We also predict sparse PF activity in vivo because, otherwise, input specificity would be lost. PMID:17222054

  17. Long-term depression-like plasticity of the blink reflex for the treatment of blepharospasm.

    PubMed

    Kranz, Gottfried; Shamim, Ejaz A; Lin, Peter T; Kranz, George S; Hallett, Mark

    2013-04-01

    Our previous work showed a beneficial therapeutic effect on blepharospasm using slow repetitive transcranial magnetic stimulation, which produces a long-term depression (LTD)-like effect. High-frequency supraorbital electrical stimulation, asynchronous with the R2 component of the blink reflex, can also induce LTD-like effects on the blink reflex circuit in healthy subjects. Patients with blepharospasm have reduced inhibition of their blink recovery curves; therefore, a LTD-like intervention might normalize the blink reflex recovery (BRR) and have a favorable therapeutic effect. This is a randomized, sham-controlled, observer-blinded prospective study. In 14 blepharospasm patients, we evaluated the effects of high-frequency supraorbital stimulation on three separate treatment days. We applied 28 trains of nine stimuli, 400 Hz, either before or after the R2 or used sham stimulation. The primary outcome was the blink rate, number of spasms rated by a blinded physician and patient rating before, immediately after and 1 hour after stimulation while resting, reading, and talking; secondary outcome was the BRR. Stimulation "before" and "after" the R2 both showed a similar improvement as sham stimulation in physician rating, but patients felt significantly better with the before condition. Improvement in recovery of the blink reflex was noted only in the before condition. Clinical symptoms differed in the three baseline conditions (resting, reading, and talking). Stimulation before R2 increased inhibition in trigeminal blink reflex circuits in blepharospasm toward normal values and produced subjective, but not objective, improvement. Inhibition of the blink reflex pathway by itself appeared to be insufficient for a useful therapeutic effect. PMID:23401198

  18. Effect of long-term supplementation with folic acid and B vitamins on risk of depression in older women

    PubMed Central

    Okereke, Olivia I.; Cook, Nancy R.; Albert, Christine M.; Van Denburgh, Martin; Buring, Julie E.; Manson, JoAnn E.

    2015-01-01

    Background Homocysteine-lowering nutrients may have preventive/ameliorative roles in depression. Aims To test whether long-term B-vitamin/folate supplementation reduces depression risk. Method Participants were 4331 women (mean age 63.6 years), without prior depression, from the Women’s Antioxidant and Folic Acid Cardiovascular Study – a randomised controlled trial of cardiovascular disease prevention among 5442 women. Participants were randomly assigned to receive a combination of folic acid (2.5 mg/d), vitamin B6 (50 mg/d) and vitamin B12 (1 mg/d) or a matching placebo. Average treatment duration was 7 years. The outcome was incident depression, defined as self-reported physician/clinician-diagnosed depression or clinically significant depressive symptoms. Results There were 524 incident cases. There was no difference between active v. placebo groups in depression risk (adjusted relative risk 1.02, 95% CI 0.86–1.21, P = 0.81), despite significant homocysteine level reduction. Conclusions Long-term, high-dose, daily supplementation with folic acid and vitamins B6 and B12 did not reduce overall depression risk in mid-life and older women. PMID:25573400

  19. Long-term effects of early-life environmental manipulations in rodents and primates: Potential animal models in depression research.

    PubMed

    Pryce, Christopher R; Rüedi-Bettschen, Daniela; Dettling, Andrea C; Weston, Anna; Russig, Holger; Ferger, Boris; Feldon, Joram

    2005-01-01

    Depression is one of the most common human illnesses and is of immense clinical and economic significance. Knowledge of the neuro-psychology, -biology and -pharmacology of depression is limited, as is the efficacy of antidepressant treatment. In terms of depression aetiology, whilst the evidence for causal mechanisms is sparse, some genomic and environmental factors associated with increased vulnerability have been identified. With regards to the latter, the environments in which human infants and children develop are fundamental to how they develop, and parental loss, emotional and physical neglect, and abuse have been shown to be associated with: traits of depression, traits of predisposition to depression triggered by subsequent life events, and associated physiological abnormalities, across the life span. Studies of postnatal environmental manipulations in rodents and primates can potentially yield evidence that abnormal early-life experience leading to dysfunction of the neurobiology, physiology and behaviour of emotion is a general mammalian characteristic, and therefore, that this approach can be used to develop animal models for depression research, with aetiological, face, construct and predictive validity. The establishment of models with such validity, if at all achievable, will require a sophisticated combination of (1) appropriate postnatal manipulations that induce acute stress responses in the infant brain which in turn lead to long-term neurobiological consequences, and (2) appropriate behavioural and physiological assays to identify and quantify any depression-like phenotypes resulting from these long-term neurobiological phenotypes. Here, we review some of the evidence-positive and negative-that neglect-like environments in rat pups and monkey infants lead to long-term, depression-like behavioural traits of reduced motivation for reward and impaired coping with adversity, and to altered activity in relevant physiological homeostatic systems. PMID

  20. Low-frequency stimulation induces long-term depression and slow onset long-term potentiation at perforant path-dentate gyrus synapses in vivo.

    PubMed

    Gonzalez, Jossina; Morales, Isaiah S; Villarreal, Desiree M; Derrick, Brian E

    2014-03-01

    The expression of homosynaptic long-term depression (LTD) is thought to mediate a crucial role in sustaining memory function. Our in vivo investigations of LTD expression at lateral (LPP) and medial perforant path (MPP) synapses in the dentate gyrus (DG) corroborate prior demonstrations that PP-DG LTD is difficult to induce in intact animals. In freely moving animals, LTD expression occurred inconsistently among LPP-DG and MPP-DG responses. Interestingly, following acute electrode implantation in anesthetized rats, low-frequency stimulation (LFS; 900 pulses, 1 Hz) promotes slow-onset LTP at both MPP-DG and LPP-DG synapses that utilize distinct induction mechanisms. Systemic administration of the N-methyl-d-aspartate (NMDA) receptor antagonist (+/-)-cyclopiperidine-6-piperiperenzine (CPP; 10 mg/kg) 90 min before LFS selectively blocked MPP-DG but not LPP-DG slow onset LTP, suggesting MPP-DG synapses express a NMDA receptor-dependent slow onset LTP whereas LPP-DG slow onset LTP induction is NMDA receptor independent. In experiments where paired-pulse LFS (900 paired pulses, 200-ms paired-pulse interval) was used to induce LTD, paired-pulse LFS of the LPP resulted in rapid onset LTP of DG responses, whereas paired-pulse LFS of the MPP induced slow onset LTP of DG responses. Although LTD observations were very rare following acute electrode implantation in anesthetized rats, LPP-DG LTD was demonstrated in some anesthetized rats with previously implanted electrodes. Together, our data indicate in vivo PP-DG LTD expression is an inconsistent phenomenon that is primarily observed in recovered animals, suggesting perturbation of the dentate through surgery-related tissue trauma influences both LTD incidence and LTP induction at PP-DG synapses in vivo. PMID:24335215

  1. Preliminary long-term follow-up of Mindfulness-based cognitive therapy-induced remission of depression.

    PubMed

    Munshi, Krishna; Eisendrath, Stuart; Delucchi, Kevin

    2013-12-01

    Major depressive disorder (MDD) is often chronic and characterized by relapse and recurrence despite successful treatments to induce remission. Mindfulness-based cognitive therapy (MBCT) was developed as a means of preventing relapse for individuals in remission using cognitive interventions. In addition, MBCT has preliminarily been found to be useful in treating active depression. This current investigation is unique in evaluating the long-term outcome of individuals with active depression who achieved remission with MBCT. 18 participants who achieved remission after an 8-week MBCT group were seen for evaluation at a mean follow-up interval of 48.7 months (SD=10.2) after completing treatment. The current study shows that in these participants, the gains achieved after the initial treatment including remission of depression, decreased rumination, decreased anxiety, and increased mindfulness continued for up to 58.9 months of follow-up. The data suggests that all levels of depression from less recurrent and mild to more recurrent and severe were responsive to MBCT. The average number of minutes per week of continued practice in our cohort was 210, but the number of minutes of practice did not correlate with depression outcomes. MBCT's effects may be more related to regularity of practice than specific quantity. This study provides a preliminary exploration of MBCT's long-term effects, which can aid in future research with a typically chronic illness. PMID:24443660

  2. Enhanced AMPA Receptor Function Promotes Cerebellar Long-Term Depression Rather than Potentiation

    ERIC Educational Resources Information Center

    van Beugen, Boeke J.; Qiao, Xin; Simmons, Dana H.; De Zeeuw, Chris I.; Hansel, Christian

    2014-01-01

    Ampakines are allosteric modulators of AMPA receptors that facilitate hippocampal long-term potentiation (LTP) and learning, and have been considered for the treatment of cognition and memory deficits. Here, we show that the ampakine CX546 raises the amplitude and slows the decay time of excitatory postsynaptic currents (EPSCs) at cerebellar…

  3. Long-term ovariectomy enhances anxiety and depressive-like behaviors in mice submitted to chronic unpredictable stress.

    PubMed

    Lagunas, Natalia; Calmarza-Font, Isabel; Diz-Chaves, Yolanda; Garcia-Segura, Luis M

    2010-11-01

    Ovarian hormones exert anti-depressive and anxiolytic actions. In this study we have analyzed the effects of ovariectomy on the development of anxiety and depression-like behaviors and on cell proliferation in the hippocampus of mice submitted to chronic unpredictable stress. Animals submitted to stress 4 months after ovariectomy showed a significant increase in immobility behavior in the forced swimming test compared to animals submitted to stress 2 weeks after ovariectomy. In addition, long-term ovariectomy resulted in a significant decrease on the time spent in the open arms in the elevated plus-maze test compared to control animals. Stress did not significantly affect cell proliferation in the hilus of the dentate gyrus. However, ovariectomy resulted in a significant decrease in cell proliferation. These results indicate that long-term deprivation of ovarian hormones enhances the effect of chronic unpredictable stress on depressive- and anxiety-like behaviors in mice. Therefore, a prolonged deprivation of ovarian hormones may represent a risk factor for the development of depressive and anxiety symptoms after the exposure to stressful experiences. PMID:20691693

  4. Are female children more vulnerable to the long-term effects of maternal depression during pregnancy?

    PubMed Central

    Quarini, Catherine; Pearson, Rebecca M.; Stein, Alan; Ramchandani, Paul G.; Lewis, Glyn; Evans, Jonathan

    2016-01-01

    Background Female fetuses are more vulnerable to high levels of maternal glucocorticoids. We examined whether exposure to prenatal maternal depression, a condition associated with high glucocorticoids, carries greater risk for depression at 12 and 18 years in girls. Methods Our sample comprised 7959 mothers and children from the Avon Longitudinal Study of Parents and Children following imputation for missing data. Maternal depression was assessed pre-and post-natally, and offspring depression at ages 12 and 18. We used logistic regression models to examine the relationship between exposure to prenatal and postnatal depression and offspring depression at 18 and 12 and interactions with gender. Results There was an interaction between prenatal depression and gender (P=0.027) and between postnatal depression and gender (P=0.027) for offspring depression at 18. Following adjustment in pre-natally depressed mothers, the odds ratio for offspring depression at 18 was 1.55 (95% c.i. 1.03–2.34) for girls and 0.54 (0.23–1.26) for boys. In post-natally depressed mothers, the odds ratio for offspring depression at 18 was 1.15 (0.70–1.89) in girls and 3.13 (1.52–6.45) in boys. However there was no evidence for interaction between prenatal or postnatal depression and gender (P=0.559 and 0.780 respectively) for offspring depression at 12. Limitations As expected with this large cohort spanning over 18 years, there was loss-to-follow-up. Conclusions This is the first evidence in humans that increased vulnerability of female fetuses to maternal stress responses during pregnancy persists into adolescence. One explanation for gender differences emerging later is more depressive symptomatology is attributed to heritable risk at 12, whereas biological processes involved in brain development at 18 may be influenced by foetal programming. If replicated, this study has potential to help understand intergenerational transmission of depression, a leading cause of morbidity worldwide

  5. Depressive symptoms among older adults: long-term reduction after a physical activity intervention.

    PubMed

    Motl, Robert W; Konopack, James F; McAuley, Edward; Elavsky, Steriani; Jerome, Gerald J; Marquez, David X

    2005-08-01

    We examined the effects of two physical activity modes on depressive symptoms over a 5-year period among older adults and change in physical self-esteem as a mediator of changes in depressive symptoms. Formerly sedentary, older adults (N = 174) were randomly assigned into 6-month conditions of either walking or low-intensity resistance/flexibility training. Depressive symptoms and physical self-esteem were measured before and after the 6-month intervention, and 12 and 60 months after intervention initiation. Depressive symptoms scores were decreased immediately after the intervention, followed by a sustained reduction for 12 and 60 months after intervention initiation; there was no differential pattern of change between the physical activity modes. Change in physical self-esteem predicted change in depressive symptoms. This study supports the effectiveness of an exercise intervention for the sustained reduction of depressive symptoms among sedentary older adults and physical self-esteem as a potential mediator of this effect. PMID:16049630

  6. Effects of Long Term Sertraline Treatment and Depression on Coronary Artery Atherosclerosis in Premenopausal Female Primates

    PubMed Central

    Shively, Carol A.; Register, Thomas C.; Appt, Susan E.; Clarkson, Thomas B.

    2015-01-01

    Objectives Major depressive disorder and coronary heart disease (CHD) often co-occur in the same individuals. Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for depression and other disorders, but their effects on CHD risk remain unclear. We determined the effects of a SSRI on coronary artery atherosclerosis (CAA) in an established nonhuman primate model used to clarify the association between depression and CAA. Methods 42 adult female cynomolgus macaques consuming a Western diet were characterized during an 18-month pretreatment phase, and assigned to SSRI (sertraline HCl 20 mg/kg, po, once/day) or Placebo balanced on pretreatment depression, body weight (BW), and iliac artery atherosclerosis extent measured via biopsy. After 18 months CAA extent was measured using histomorphometry. Results Before and during treatment depressed monkeys had lower BW, body mass index (BMI), and plasma high density lipoprotein cholesterol, and higher heart rates during the pretreatment (p<0.01) but not the treatment phase (p=0.17). There were no pretreatment differences between the sertraline and placebo groups. Sertraline reduced anxious behavior but had no effect on BW, BMI, heart rate, plasma lipids, or depression. CAA, analyzed by a 2 (Depressed, Nondepressed) × 2 (Placebo, Sertraline) × 3 (coronary arteries) analysis of covariance adjusted for pretreatment iliac atherosclerosis, was greater in depressed than nondepressed monkeys (p<0.036), and in sertraline than placebo-treated monkeys (p=0.040). The observed CAA extent in depressed monkeys treated with sertraline was 4.9 times higher than in untreated depressed monkeys, and 6.5 times higher than in non-depressed monkeys, on average. Conclusions Depressed animals develop more CAA, and that longterm treatment with sertraline promotes CAA. PMID:25829239

  7. Effect of Talbinah food consumption on depressive symptoms among elderly individuals in long term care facilities, randomized clinical trial.

    PubMed

    Badrasawi, Manal M; Shahar, Suzana; Abd Manaf, Zahara; Haron, Hasnah

    2013-01-01

    Talbinah is a barley syrup cooked with milk and sweetened by honey. In his famous Hadith on Talbinah, the Prophet Mohammad (SAW) recommended it when sad events happen for its effect on soothing hearts and relieving sadness. This 3-week crossover designed, randomized clinical trial was conducted to determine the effect of Talbinah on mood and depression among institutionalized elderly people in Seremban. A sample of 30 depressed elderly subjects (21 men and 9 women) was selected from the long term care facility. Three different interview-based validated scales (Geriatric Depression Scale, Depression Anxiety Stress Scales, and Profile of Mood States) were used to determine mood, depression, stress, and anxiety at week 0, 3, 4, and 7. The nutritional value of Talbinah was examined using proximate food analysis, minerals content analysis, and differential amino acid analysis. The results indicated that Talbinah is a high carbohydrate food (86.4%) and has a high tryptophan: branch chain amino acids ratio (1:2). A Wilcoxon nonparametric test showed that there was a statistically significant decrease on depression, stress, and mood disturbances scores among the intervention group (P < 0.05) for all parameters. In conclusion, Talbinah has the potential to reduce depression and enhance mood among the subjects. Ingestion of functional foods such as Talbinah may provide a mental health benefit to elderly people. PMID:23493965

  8. Depression, night terrors, and insomnia associated with long-term intrathecal clonidine therapy.

    PubMed

    Bevacqua, Brian K; Fattouh, Maher; Backonja, Misha

    2007-03-01

    Intraspinal clonidine is an effective adjunct to intrathecal/epidural opioid administration. We report a case of neuropathic pain treated with intraspinal analgesics in which depression, insomnia, and night terrors developed in association with intraspinal clonidine. PMID:17305677

  9. Effects of anxiety on the long-term course of depressive disorders†

    PubMed Central

    Coryell, William; Fiedorowicz, Jess G.; Solomon, David; Leon, Andrew C.; Rice, John P.; Keller, Martin B.

    2012-01-01

    Background It is well established that the presence of prominent anxiety within depressive episodes portends poorer outcomes. Important questions remain as to which anxiety features are important to outcome and how sustained their prognostic effects are over time. Aims To examine the relative prognostic importance of specific anxiety features and to determine whether their effects persist over decades and apply to both unipolar and bipolar conditions. Method Participants with unipolar (n = 476) or bipolar (n = 335) depressive disorders were intensively followed for a mean of 16.7 years (s.d. = 8.5). Results The number and severity of anxiety symptoms, but not the presence of pre-existing anxiety disorders, showed a robust and continuous relationship to the subsequent time spent in depressive episodes in both unipolar and bipolar depressive disorder. The strength of this relationship changed little over five successive 5-year periods. Conclusions The severity of current anxiety symptoms within depressive episodes correlates strongly with the persistence of subsequent depressive symptoms and this relationship is stable over decades. PMID:21984801

  10. Suicidal Career in Severe Depression among Long-Term Survivors: In a Followup after 37–53 Years Suicide Attempts Appeared to End Long before Depression

    PubMed Central

    Brådvik, Louise

    2013-01-01

    Objective. To describe the suicidal career in the long-term course of severe depression. Subjects and Method. Seventy-five former in-patients were interviewed by telephone about course of depression and suicide attempts 37–53 years after index admission. Medical records were read in many cases. Results. 29 subjects had attempted suicide, 13 repeated, 10 made severe, and 13 violent attempts. The risk of suicide attempt decreased by 10% for every decade spent depressed. Suicide attempts were made early in course of depression, and more time was spent depressed after suicide attempts than before. Conclusions. A healing process of the suicidal career, which may occur long before the end of the last depressive episode (sometimes decades), is proposed. PMID:24455226

  11. GABABR-Dependent Long-Term Depression at Hippocampal Synapses between CB1-Positive Interneurons and CA1 Pyramidal Cells.

    PubMed

    Jappy, Dave; Valiullina, Fliza; Draguhn, Andreas; Rozov, Andrei

    2016-01-01

    Activity induced long lasting modifications of synaptic efficacy have been extensively studied in excitatory synapses, however, long term plasticity is also a property of inhibitory synapses. Inhibitory neurons in the hippocampal CA1 region can be subdivided according to the compartment they target on the pyramidal cell. Some interneurons preferentially innervate the perisomatic area and axon hillock of the pyramidal cells while others preferentially target dendritic branches and spines. Another characteristic feature allowing functional classification of interneurons is cell type specific expression of different neurochemical markers and receptors. In the hippocampal CA1 region, nearly 90% of the interneurons expressing cannabinoid type 1 receptors (CB1R) also express cholecystokinin (CCK). Therefore, the functional presence of CB1 receptors can be used for identification of the inhibitory input from CCK positive (CCK+) interneurons to CA1 pyramidal cells. The goal of this study was to explore the nature of long term plasticity at the synapses between interneurons expressing CB1Rs (putative CCK+) and pyramidal neurons in the CA1 region of the hippocampus in vitro. We found that theta burst stimulation triggered robust long-term depression (LTD) at this synapse. The locus of LTD induction was postsynaptic and required activation of GABAB receptors. We also showed that LTD at this synaptic connection involves GABABR-dependent suppression of adenylyl cyclase and consequent reduction of PKA activity. In this respect, CB1+ to pyramidal cell synapses differ from the majority of the other hippocampal inhibitory connections where theta burst stimulation results in long-term potentiation. PMID:26858602

  12. GABABR-Dependent Long-Term Depression at Hippocampal Synapses between CB1-Positive Interneurons and CA1 Pyramidal Cells

    PubMed Central

    Jappy, Dave; Valiullina, Fliza; Draguhn, Andreas; Rozov, Andrei

    2016-01-01

    Activity induced long lasting modifications of synaptic efficacy have been extensively studied in excitatory synapses, however, long term plasticity is also a property of inhibitory synapses. Inhibitory neurons in the hippocampal CA1 region can be subdivided according to the compartment they target on the pyramidal cell. Some interneurons preferentially innervate the perisomatic area and axon hillock of the pyramidal cells while others preferentially target dendritic branches and spines. Another characteristic feature allowing functional classification of interneurons is cell type specific expression of different neurochemical markers and receptors. In the hippocampal CA1 region, nearly 90% of the interneurons expressing cannabinoid type 1 receptors (CB1R) also express cholecystokinin (CCK). Therefore, the functional presence of CB1 receptors can be used for identification of the inhibitory input from CCK positive (CCK+) interneurons to CA1 pyramidal cells. The goal of this study was to explore the nature of long term plasticity at the synapses between interneurons expressing CB1Rs (putative CCK+) and pyramidal neurons in the CA1 region of the hippocampus in vitro. We found that theta burst stimulation triggered robust long-term depression (LTD) at this synapse. The locus of LTD induction was postsynaptic and required activation of GABAB receptors. We also showed that LTD at this synaptic connection involves GABABR-dependent suppression of adenylyl cyclase and consequent reduction of PKA activity. In this respect, CB1+ to pyramidal cell synapses differ from the majority of the other hippocampal inhibitory connections where theta burst stimulation results in long-term potentiation. PMID:26858602

  13. Long-Term Effects of Bereavement and Caregiver Intervention on Dementia Caregiver Depressive Symptoms

    ERIC Educational Resources Information Center

    Haley, William E.; Bergman, Elizabeth J.; Roth, David L.; McVie, Theresa; Gaugler, Joseph E.; Mittelman, Mary S.

    2008-01-01

    Purpose: The purpose of this study was to examine the joint effects of bereavement and caregiver intervention on caregiver depressive symptoms. Design and Methods: Alzheimer's caregivers from a randomized trial of an enhanced caregiver support intervention versus usual care who had experienced the death of their spouse (n = 254) were repeatedly…

  14. Childhood Attachment and Abuse: Long-Term Effects on Adult Attachment, Depression, and Conflict Resolution.

    ERIC Educational Resources Information Center

    Styron, Thomas; Janoff-Bulman, Ronnie

    1997-01-01

    Analysis of questionnaire responses by 879 college students found respondents who indicated they had been abused as children reported less secure relationships, more depression, and greater use of destructive behaviors than their nonabused counterparts. Abuse history was substantially stronger than parental attachment in predicting conflict…

  15. The Long-Term Effects of War Experiences on Children's Depression in the Republic of Croatia

    ERIC Educational Resources Information Center

    Brajsa-Zganec, A.

    2005-01-01

    Objective:: The aim of the study was to investigate whether different levels of depressive symptoms in early adolescent boys and girls could be predicted on the basis of war experiences, perceived available social support (instrumental support, support to self-esteem, belonging and acceptance) and extraversion. Methods:: The sample consisted of…

  16. Alteration in plasma corticosterone levels following long term oral administration of lead produces depression like symptoms in rats.

    PubMed

    Haider, Saida; Saleem, Sadia; Tabassum, Saiqa; Khaliq, Saima; Shamim, Saima; Batool, Zehra; Parveen, Tahira; Inam, Qurat-ul-ain; Haleem, Darakhshan J

    2013-03-01

    Lead toxicity is known to induce a broad range of physiological, biochemical and behavioral dysfunctions that may result in adverse effects on several organs, including the central nervous system. Long-term exposure to low levels of lead (Pb(2+)) has been shown to produce behavioral deficits in rodents and humans by affecting hypothalamic-pituitary-adrenal (HPA) axis. These deficits are thought to be associated with altered brain monoamine neurotransmission and due to changes in glucocorticoids levels. This study was designed to investigate the effects of Pb(2+)exposure on growth rate, locomotor activity, anxiety, depression, plasma corticosterone and brain serotonin (5-HT) levels in rats. Rats were exposed to lead in drinking water (500 ppm; lead acetate) for 5 weeks. The assessment of depression was done using the forced swimming test (FST). Estimation of brain 5-HT was determined by high-performance liquid chromatography with electrochemical detection. Plasma corticosterone was determined by spectrofluorimetric method. The present study showed that long term exposure to Pb(2+) significantly decreased the food intake followed by the decrease in growth rate in Pb(2+)exposed rats as compared to control group. No significant changes in open field activity were observed following Pb(2+)exposure while significant increase in anxiogenic effect was observed. Increased plasma corticosterone and decreased 5-HT levels were exhibited by Pb(2+)exposed rats as compared to controls. A significant increase in depressive like symptoms was exhibited by Pb(2+)exposed rats as compared to control rats. The results are discussed in the context of Pb(2+) inducing a stress-like response in rats leading to changes in plasma corticosterone and brain 5-HT levels via altering tryptophan pyrrolase activity. PMID:23315312

  17. Activation of synaptic group II metabotropic glutamate receptors induces long-term depression at GABAergic synapses in CNS neurons.

    PubMed

    Tang, Zheng-Quan; Liu, Yu-Wei; Shi, Wei; Dinh, Emilie Hoang; Hamlet, William R; Curry, Rebecca J; Lu, Yong

    2013-10-01

    Metabotropic glutamate receptor (mGluR)-dependent homosynaptic long-term depression (LTD) has been studied extensively at glutamatergic synapses in the CNS. However, much less is known about heterosynaptic long-term plasticity induced by mGluRs at inhibitory synapses. Here we report that pharmacological or synaptic activation of group II mGluRs (mGluR II) induces LTD at GABAergic synapses without affecting the excitatory glutamatergic transmission in neurons of the chicken cochlear nucleus. Coefficient of variation and failure rate analysis suggested that the LTD was expressed presynaptically. The LTD requires presynaptic spike activity, but does not require the activation of NMDA receptors. The classic cAMP-dependent protein kinase A signaling is involved in the transduction pathway. Remarkably, blocking mGluR II increased spontaneous GABA release, indicating the presence of tonic activation of mGluR II by ambient glutamate. Furthermore, synaptically released glutamate induced by electrical stimulations that concurrently activated both the glutamatergic and GABAergic pathways resulted in significant and constant suppression of GABA release at various stimulus frequencies (3.3, 100, and 300 Hz). Strikingly, low-frequency stimulation (1 Hz, 15 min) of the glutamatergic synapses induced heterosynaptic LTD of GABAergic transmission, and the LTD was blocked by mGluR II antagonist, indicating that synaptic activation of mGluR II induced the LTD. This novel form of long-term plasticity in the avian auditory brainstem may play a role in the development as well as in temporal processing in the sound localization circuit. PMID:24089501

  18. Mild Concussion, but Not Moderate Traumatic Brain Injury, Is Associated with Long-Term Depression-Like Phenotype in Mice.

    PubMed

    Bajwa, Nikita M; Halavi, Shina; Hamer, Mary; Semple, Bridgette D; Noble-Haeusslein, Linda J; Baghchechi, Mohsen; Hiroto, Alex; Hartman, Richard E; Obenaus, André

    2016-01-01

    Mild traumatic brain injuries can lead to long-lasting cognitive and motor deficits, increasing the risk of future behavioral, neurological, and affective disorders. Our study focused on long-term behavioral deficits after repeated injury in which mice received either a single mild CHI (mCHI), a repeated mild CHI (rmCHI) consisting of one impact to each hemisphere separated by 3 days, or a moderate controlled cortical impact injury (CCI). Shams received only anesthesia. Behavioral tests were administered at 1, 3, 5, 7, and 90 days post-injury (dpi). CCI animals showed significant motor and sensory deficits in the early (1-7 dpi) and long-term (90 dpi) stages of testing. Interestingly, sensory and subtle motor deficits in rmCHI animals were found at 90 dpi. Most importantly, depression-like behaviors and social passiveness were observed in rmCHI animals at 90 dpi. These data suggest that mild concussive injuries lead to motor and sensory deficits and affective disorders that are not observed after moderate TBI. PMID:26796696

  19. Psychiatric Outcome Over a Decade After Electrical Injury: Depression as a Predictor of Long-Term Adjustment.

    PubMed

    Hahn-Ketter, Amanda; Aase, Darrin M; Paxton, Jessica; Fink, Joseph W; Kelley, Kathleen M; Lee, Raphael C; Pliskin, Neil H

    2015-01-01

    Electrical injury (EI) produces a variety of physical, cognitive, and emotional consequences. Psychiatric and neurocognitive symptoms may complicate survivors' psychosocial adjustment and ability to return to work. However, due to a paucity of longitudinal research, the long-term course of EI remains poorly understood. The purpose of this study was to investigate psychiatric and functional status in EI patients over a decade after injury. Fourteen EI patients who originally underwent baseline neuropsychological evaluation participated in this long-term follow-up. Participants completed a telephone survey of functional status, neuropsychological symptom checklist, and the Psychosocial Adjustment to Illness Scale Self-Report. Participants were grouped according to baseline Beck Depression Inventory (BDI) scores. After an average of 12.36 years postinjury, participants with elevated baseline BDI scores experienced difficulty across multiple domains of psychosocial adjustment at follow-up. This group was also less likely to return to work and exhibited a significant increase in psychological distress. EI results in significant chronic psychiatric complaints for many survivors. In the current sample, psychiatric sequelae of EI continue to persist over a decade after injury. Moreover, elevated baseline BDI scores predicted worse outcomes for vocational and psychosocial adjustment. Findings underscore the impact of emotional symptoms on recovery and need for specialized psychiatric intervention immediately following injury. PMID:25377863

  20. Mild Concussion, but Not Moderate Traumatic Brain Injury, Is Associated with Long-Term Depression-Like Phenotype in Mice

    PubMed Central

    Hamer, Mary; Semple, Bridgette D.; Noble-Haeusslein, Linda J.; Baghchechi, Mohsen; Hiroto, Alex; Hartman, Richard E.; Obenaus, André

    2016-01-01

    Mild traumatic brain injuries can lead to long-lasting cognitive and motor deficits, increasing the risk of future behavioral, neurological, and affective disorders. Our study focused on long-term behavioral deficits after repeated injury in which mice received either a single mild CHI (mCHI), a repeated mild CHI (rmCHI) consisting of one impact to each hemisphere separated by 3 days, or a moderate controlled cortical impact injury (CCI). Shams received only anesthesia. Behavioral tests were administered at 1, 3, 5, 7, and 90 days post-injury (dpi). CCI animals showed significant motor and sensory deficits in the early (1–7 dpi) and long-term (90 dpi) stages of testing. Interestingly, sensory and subtle motor deficits in rmCHI animals were found at 90 dpi. Most importantly, depression-like behaviors and social passiveness were observed in rmCHI animals at 90 dpi. These data suggest that mild concussive injuries lead to motor and sensory deficits and affective disorders that are not observed after moderate TBI. PMID:26796696

  1. Long-term effects from a randomized trial of two public health preventive interventions for parental depression.

    PubMed

    Bearslee, William R; Wright, Ellen J; Gladstone, Tracy R G; Forbes, Peter

    2007-12-01

    This article presents long-term effects of a randomized trial evaluating 2 standardized, manual-based prevention strategies for families with parental mood disorder: informational lectures and a brief, clinician-based approach including child assessment and a family meeting. A sample of 105 families, in which at least 1 parent suffered from a mood disorder and at least 1 nondepressed child was within the 8- to 15-year age range, was recruited. Parents and children were assessed separately at baseline and every 9 to 12 months thereafter on behavioral functioning, psychopathology, and response to intervention. Both interventions produced sustained effects through the 6th assessment point, approximately 4.5 years after enrollment, with relatively small sample loss of families (<14%). Clinician-based families had significantly more gains in parental child-related behaviors and attitudes and in child-reported understanding of parental disorder. Child and parent family functioning increased for both groups and internalizing symptoms decreased for both groups, with no significant group differences. These findings demonstrate that brief, family-centered preventive interventions for parental depression may contribute to long-term, sustained improvements in family functioning. PMID:18179342

  2. Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats.

    PubMed

    Spiga, Saturnino; Talani, Giuseppe; Mulas, Giovanna; Licheri, Valentina; Fois, Giulia R; Muggironi, Giulia; Masala, Nicola; Cannizzaro, Carla; Biggio, Giovanni; Sanna, Enrico; Diana, Marco

    2014-09-01

    Alcoholism involves long-term cognitive deficits, including memory impairment, resulting in substantial cost to society. Neuronal refinement and stabilization are hypothesized to confer resilience to poor decision making and addictive-like behaviors, such as excessive ethanol drinking and dependence. Accordingly, structural abnormalities are likely to contribute to synaptic dysfunctions that occur from suddenly ceasing the use of alcohol after chronic ingestion. Here we show that ethanol-dependent rats display a loss of dendritic spines in medium spiny neurons of the nucleus accumbens (Nacc) shell, accompanied by a reduction of tyrosine hydroxylase immunostaining and postsynaptic density 95-positive elements. Further analysis indicates that "long thin" but not "mushroom" spines are selectively affected. In addition, patch-clamp experiments from Nacc slices reveal that long-term depression (LTD) formation is hampered, with parallel changes in field potential recordings and reductions in NMDA-mediated synaptic currents. These changes are restricted to the withdrawal phase of ethanol dependence, suggesting their relevance in the genesis of signs and/or symptoms affecting ethanol withdrawal and thus the whole addictive cycle. Overall, these results highlight the key role of dynamic alterations in dendritic spines and their presynaptic afferents in the evolution of alcohol dependence. Furthermore, they suggest that the selective loss of long thin spines together with a reduced NMDA receptor function may affect learning. Disruption of this LTD could contribute to the rigid emotional and motivational state observed in alcohol dependence. PMID:25122682

  3. Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats

    PubMed Central

    Spiga, Saturnino; Talani, Giuseppe; Mulas, Giovanna; Licheri, Valentina; Fois, Giulia R.; Muggironi, Giulia; Masala, Nicola; Cannizzaro, Carla; Biggio, Giovanni; Sanna, Enrico; Diana, Marco

    2014-01-01

    Alcoholism involves long-term cognitive deficits, including memory impairment, resulting in substantial cost to society. Neuronal refinement and stabilization are hypothesized to confer resilience to poor decision making and addictive-like behaviors, such as excessive ethanol drinking and dependence. Accordingly, structural abnormalities are likely to contribute to synaptic dysfunctions that occur from suddenly ceasing the use of alcohol after chronic ingestion. Here we show that ethanol-dependent rats display a loss of dendritic spines in medium spiny neurons of the nucleus accumbens (Nacc) shell, accompanied by a reduction of tyrosine hydroxylase immunostaining and postsynaptic density 95-positive elements. Further analysis indicates that “long thin” but not “mushroom” spines are selectively affected. In addition, patch-clamp experiments from Nacc slices reveal that long-term depression (LTD) formation is hampered, with parallel changes in field potential recordings and reductions in NMDA-mediated synaptic currents. These changes are restricted to the withdrawal phase of ethanol dependence, suggesting their relevance in the genesis of signs and/or symptoms affecting ethanol withdrawal and thus the whole addictive cycle. Overall, these results highlight the key role of dynamic alterations in dendritic spines and their presynaptic afferents in the evolution of alcohol dependence. Furthermore, they suggest that the selective loss of long thin spines together with a reduced NMDA receptor function may affect learning. Disruption of this LTD could contribute to the rigid emotional and motivational state observed in alcohol dependence. PMID:25122682

  4. Metabotropic glutamate receptor 3 activation is required for long-term depression in medial prefrontal cortex and fear extinction

    PubMed Central

    Walker, Adam G.; Wenthur, Cody J.; Xiang, Zixiu; Rook, Jerri M.; Emmitte, Kyle A.; Niswender, Colleen M.; Lindsley, Craig W.; Conn, P. Jeffrey

    2015-01-01

    Clinical studies have revealed that genetic variations in metabotropic glutamate receptor 3 (mGlu3) affect performance on cognitive tasks dependent upon the prefrontal cortex (PFC) and may be linked to psychiatric conditions such as schizophrenia, bipolar disorder, and addiction. We have performed a series of studies aimed at understanding how mGlu3 influences PFC function and cognitive behaviors. In the present study, we found that activation of mGlu3 can induce long-term depression in the mouse medial PFC (mPFC) in vitro. Furthermore, in vivo administration of a selective mGlu3 negative allosteric modulator impaired learning in the mPFC-dependent fear extinction task. The results of these studies implicate mGlu3 as a major regulator of PFC function and cognition. Additionally, potentiators of mGlu3 may be useful in alleviating prefrontal impairments associated with several CNS disorders. PMID:25583490

  5. Characterizing the therapeutic response to deep brain stimulation for treatment-resistant depression: a single center long-term perspective

    PubMed Central

    Crowell, Andrea L.; Garlow, Steven J.; Riva-Posse, Patricio; Mayberg, Helen S.

    2015-01-01

    The number of depressed patients treated with deep brain stimulation (DBS) is relatively small. However, experience with this intervention now spans more than 10 years at some centers, with study subjects typically monitored closely. Here we describe one center’s evolving impressions regarding optimal patient selection for DBS of the subcallosal cingulate (SCC) as well as observations of short- and long-term patterns in antidepressant response and mood reactivity. A consistent time course of therapeutic response with distinct behavioral phases is observed. Early phases are characterized by changes in mood reactivity and a transient and predictable worsening in self ratings prior to stabilization of response. It is hypothesized that this characteristic recovery curve reflects the timeline of neuroplasticity in response to DBS. Further investigation of these emerging predictable psychiatric, biological, and psychosocial patterns will both improve treatment optimization and enhance understanding and recognition of meaningful DBS antidepressant effects. PMID:26124710

  6. Mirtazapine versus amitriptyline in the long-term treatment of depression: a double-blind placebo-controlled study.

    PubMed

    Montgomery, S A; Reimitz, P E; Zivkov, M

    1998-03-01

    Of 580 patients randomly assigned to short-term, double-blind treatment with either mirtazapine, amitriptyline or placebo, a total of 217 patients clinically judged to be responders subsequently continued on the same medication for up to 2 years in the long-term treatment study (mirtazapine, n = 74; amitriptyline, n = 86 and placebo, n = 57). The efficacy of mirtazapine in relapse prevention was seen in an analysis of the first 20 weeks data. Significantly fewer patients relapsed during treatment with mirtazapine compared with placebo (p < 0.05), and a significantly longer time to relapse was shown on the survival analysis. There was a significant advantage for amitriptyline compared with placebo in the first 20 weeks, with fewer patients relapsing. There was a significant advantage for mirtazapine compared with amitriptyline at 20 weeks seen on the survival analysis (p < 0.05). The significant advantage for mirtazapine compared with placebo was also seen in the prophylactic phase of treatment after 20 weeks. At the endpoint there were significantly more patients in the placebo group with a return of symptoms and significantly fewer showing sustained response. Amitriptyline was better than placebo with fewer patients suffering a recurrence of symptoms, but there was no difference from placebo in the proportion of patients with sustained response. Mirtazapine was well tolerated with a side-effect profile similar to that of placebo. The only adverse event reported significantly more frequently on mirtazapine than on placebo was weight gain. Objectively measured weight gain was more frequent with amitriptyline (22% of patients) compared with mirtazapine (13% of patients). Amitriptyline was associated with significantly more adverse events than either mirtazapine or placebo, in particular sedative and anticholinergic side effects. The efficacy of mirtazapine in reducing the risk of relapse and the recurrence of depression, which on some measures showed an advantage

  7. Involvement of the proteasome and caspase activation in hippocampal long-term depression induced by the serine protease subtilisin.

    PubMed

    Forrest, C M; Darlington, L G; Stone, T W

    2013-02-12

    The serine protease subtilisin-A produces a long-term depression (LTD) of synaptic potentials in hippocampal slices which differs mechanistically from classical LTD. Since caspases have been implicated in hippocampal plasticity, this study examined a possible role for these enzymes in subtilisin-induced LTD. Subtilisin produced a concentration-dependent decrease in the size of field excitatory synaptic potentials (fEPSPs), which was not prevented or modified by the caspase inhibitors Z-VAD(OMe)-fmk and Z-DEVD-fmk. Similarly Z-VAD(OMe)-fmk did not modify the selective loss of protein expression produced by subtilisin. Subtilisin reduced the expression of procaspase-3 and caspase-9 but, while caspase-9 was converted to its conventionally activated form (39 kDa), caspase-3 was metabolised along a non-canonical pathway to a 29/30 kDa protein rather than the classical 17/19 kDa fragments. Both Z-VAD(OMe)-fmk and Z-DEVD-fmk were unable to prevent the reduced expression of Postsynaptic Density Protein-95, Vesicle-Associated Membrane Protein-1 and Unco-ordinated 5H3 proteins produced by subtilisin, although MG132 did produce partial recovery from subtilisin-induced depression of fEPSPs. When tested on long-term potentiation (LTP) induced by theta stimulation in the stratum radiatum, MG132 inhibited the immediate increase in fEPSP size but generated a higher plateau LTP. Twin LTP stimulation generated a further increase in LTP amplitude in control slices but not in slices exposed to MG132. The results indicate that subtilisin does produce caspase activation but that this does not contribute to its induction of LTD. However, activation of the proteasome does contribute to subtilisin-induced LTD and may also play a modulatory role in electrically induced LTP. PMID:23206873

  8. Dimorphic changes of some features of loving relationships during long-term use of antidepressants in depressed outpatients.

    PubMed

    Marazziti, Donatella; Akiskal, Hagop S; Udo, Mieko; Picchetti, Michela; Baroni, Stefano; Massimetti, Gabriele; Albanese, Francesco; Dell'Osso, Liliana

    2014-09-01

    The present study aimed at investigating the possible changes of some features of loving relationships during long-term treatment of depression with both selective serotonin reuptake inhibitors (SSRIs) and tricyclics (TCAs), by means of a specifically designed test, the so-called "Sex, Attachment, Love" (SALT) questionnaire. The sample was composed by 192 outpatients (123 women and 69 men, mean age±SD: 41.2±10.2 years), suffering from mild or moderate depression, according to DSM-IV-TR criteria, that were selected if they were treated with one antidepressant only for at least six months and were involved in a loving relationship. The results showed that SSRIs had a significant impact on the feelings of love and attachment towards the partner especially in men, while women taking TCAs complained of more sexual side effects than men. These data were supported also by the detection of a significant interaction between drug and sex on the "Love" and "Sex" domains. The present findings, while demonstrating a dimorphic effect of antidepressants on some component of loving relationships, need to be deepened in future studies. PMID:25012424

  9. Modulatory effects of serotonin on glutamatergic synaptic transmission and long-term depression in the deep cerebellar nuclei.

    PubMed

    Murano, M; Saitow, F; Suzuki, H

    2011-01-13

    The deep cerebellar nuclei (DCN) are the terminal components of the cerebellar circuitry and constitute its primary output structure. Their activity is important for certain forms of motor learning as well as generation and control of movement. DCN neurons receive glutamatergic excitatory inputs from the pontine nuclei via mossy fibres (MFs) and concomitantly receive inputs from 5-HT-containing neurons of the raphe nuclei. We aimed to explore the roles of 5-HT at MF-DCN synapses by using cerebellar slices from 11 to 15-day-old rats. Bath application of 5-HT reversibly decreased the amplitude of stimulation-evoked excitatory postsynaptic currents (eEPSCs) via the activation of 5-HT1B receptors at the presynaptic terminals of the MFs. Burst stimulation of the MFs elicited long-term depression (LTD) at the MF-DCN synapses that require activation of the group I metabotropic glutamate receptor (mGluR). In the presence of 5-HT, the extent of burst-induced LTD of MF EPSCs was significantly reduced. Application of 5-HT also decreased the amplitude of mGluR-dependent slow EPSCs evoked by similar burst stimulation. Furthermore, (S)-3,5-dihydroxyphenylglycine (DHPG), a group I mGluR agonist, induced chemical LTD of MF EPSCs, and 5-HT had no significant effect on this LTD. Taken together, the results suggest that 5-HT not only has transitory inhibitory effects on MF EPSCs but also plays a role in regulating the long-term synaptic efficacy. PMID:20969929

  10. Induction of Long-term Depression-like Plasticity by Pairings of Motor Imagination and Peripheral Electrical Stimulation

    PubMed Central

    Jochumsen, Mads; Signal, Nada; Nedergaard, Rasmus W.; Taylor, Denise; Haavik, Heidi; Niazi, Imran K.

    2015-01-01

    Long-term depression (LTD) and long-term potentiation (LTP)-like plasticity are models of synaptic plasticity which have been associated with memory and learning. The induction of LTD and LTP-like plasticity, using different stimulation protocols, has been proposed as a means of addressing abnormalities in cortical excitability associated with conditions such as focal hand dystonia and stroke. The aim of this study was to investigate whether the excitability of the cortical projections to the tibialis anterior (TA) muscle could be decreased when dorsiflexion of the ankle joint was imagined and paired with peripheral electrical stimulation (ES) of the nerve supplying the antagonist soleus muscle. The effect of stimulus timing was evaluated by comparing paired stimulation timed to reach the cortex before, at and after the onset of imagined movement. Fourteen healthy subjects participated in six experimental sessions held on non-consecutive days. The timing of stimulation delivery was determined offline based on the contingent negative variation (CNV) of electroencephalography brain data obtained during imagined dorsiflexion. Afferent stimulation was provided via a single pulse ES to the peripheral nerve paired, based on the CNV, with motor imagination of ankle dorsiflexion. A significant decrease (P = 0.001) in the excitability of the cortical projection of TA was observed when the afferent volley from the ES of the tibial nerve (TN) reached the cortex at the onset of motor imagination based on the CNV. When TN stimulation was delivered before (P = 0.62), or after (P = 0.23) imagined movement onset there was no significant effect. Nor was a significant effect found when ES of the TN was applied independent of imagined movement (P = 0.45). Therefore, the excitability of the cortical projection to a muscle can be inhibited when ES of the nerve supplying the antagonist muscle is precisely paired with the onset of imagined movement. PMID:26648859

  11. Ethanol attenuation of long term depression in the nucleus accumbens can be overcome by activation of TRPV1 receptors

    PubMed Central

    Renteria, Rafael; Jeanes, Zachary M.; Morrisett, Richard A.

    2014-01-01

    Background Altered expression of synaptic plasticity within the nucleus accumbens (NAc) constitutes a critical neuroadaptive response to ethanol and other drugs of abuse. We have previously reported that NMDA receptor-dependent long-term depression (LTD) is markedly affected by chronic intermittent ethanol exposure in vivo; however, endocannabinoid (eCB)-dependent synaptic depression, despite being very well-documented in the dorsal striatum, is much less well understood in the NAc. Methods Whole cell patch clamp electrophysiology was used to investigate interactions between these different plasticity-induction systems. Excitatory postsynaptic currents (EPSCs) were measured in the NAc shell and NMDAR-LTD was induced by a pairing protocol (500 stimuli @ 1 Hz stimulation (LFS) paired with postsynaptic depolarization to −50 mV). AM251, a CB1 receptor antagonist, was used to determine whether this form of LTD is modulated by eCBs. To determine the effect of ethanol on a purely eCB-dependent response in the NAc, depolarization-induced suppression of excitation (DSE) was used in the presence of 40 mM ethanol. Finally, we determined whether the enhancement of eCB signaling with URB597, a fatty acid amide hydrolase inhibitor, and AM404, an anandamide reuptake inhibitor would also modulate LFS LTD in the presence of NMDA-receptor blockade or ethanol. Results In the presence of AM251, the LFS pairing protocol resulted in NMDA receptor-dependent long-term potentiation (LTP) that was blocked with either ethanol or DL-APV. We also found that DSE in the NAc shell was blocked by AM251 and suppressed by ethanol. Enhanced eCB signaling rescued NAc LTD expression in the presence of ethanol through a distinct mechanism requiring activation of TRPV1 receptors. Conclusion Ethanol modulation of synaptic plasticity in the NAc is dependent upon a complex interplay between NMDA receptors, eCBs and TRPV1 receptors. These findings demonstrate a novel form of TRPV1-dependent LTD in the NAc

  12. Synaptic P-Rex1 signaling regulates hippocampal long-term depression and autism-like social behavior

    PubMed Central

    Li, Jun; Chai, Anping; Wang, Lifang; Ma, Yuanlin; Wu, Zhiliu; Yu, Hao; Mei, Liwei; Lu, Lin; Zhang, Chen; Yue, Weihua; Xu, Lin; Rao, Yi; Zhang, Dai

    2015-01-01

    Autism spectrum disorders (ASDs) are a group of highly inheritable mental disorders associated with synaptic dysfunction, but the underlying cellular and molecular mechanisms remain to be clarified. Here we report that autism in Chinese Han population is associated with genetic variations and copy number deletion of P-Rex1 (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 1). Genetic deletion or knockdown of P-Rex1 in the CA1 region of the hippocampus in mice resulted in autism-like social behavior that was specifically linked to the defect of long-term depression (LTD) in the CA1 region through alteration of AMPA receptor endocytosis mediated by the postsynaptic PP1α (protein phosphase 1α)–P-Rex1–Rac1 (Ras-related C3 botulinum toxin substrate 1) signaling pathway. Rescue of the LTD in the CA1 region markedly alleviated autism-like social behavior. Together, our findings suggest a vital role of P-Rex1 signaling in CA1 LTD that is critical for social behavior and cognitive function and offer new insight into the etiology of ASDs. PMID:26621702

  13. Synaptic P-Rex1 signaling regulates hippocampal long-term depression and autism-like social behavior.

    PubMed

    Li, Jun; Chai, Anping; Wang, Lifang; Ma, Yuanlin; Wu, Zhiliu; Yu, Hao; Mei, Liwei; Lu, Lin; Zhang, Chen; Yue, Weihua; Xu, Lin; Rao, Yi; Zhang, Dai

    2015-12-15

    Autism spectrum disorders (ASDs) are a group of highly inheritable mental disorders associated with synaptic dysfunction, but the underlying cellular and molecular mechanisms remain to be clarified. Here we report that autism in Chinese Han population is associated with genetic variations and copy number deletion of P-Rex1 (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 1). Genetic deletion or knockdown of P-Rex1 in the CA1 region of the hippocampus in mice resulted in autism-like social behavior that was specifically linked to the defect of long-term depression (LTD) in the CA1 region through alteration of AMPA receptor endocytosis mediated by the postsynaptic PP1α (protein phosphase 1α)-P-Rex1-Rac1 (Ras-related C3 botulinum toxin substrate 1) signaling pathway. Rescue of the LTD in the CA1 region markedly alleviated autism-like social behavior. Together, our findings suggest a vital role of P-Rex1 signaling in CA1 LTD that is critical for social behavior and cognitive function and offer new insight into the etiology of ASDs. PMID:26621702

  14. Phosphorylation of delta2 glutamate receptors at serine 945 is not required for cerebellar long-term depression.

    PubMed

    Nakagami, Ryoichi; Kohda, Kazuhisa; Kakegawa, Wataru; Kondo, Tetsuro; Kato, Nobumasa; Yuzaki, Michisuke

    2008-06-01

    Long-term depression (LTD) of synaptic transmission at parallel fiber (PF)-Purkinje cell synapses is thought to regulate motor learning and memory formation in the cerebellum. Neuronal activity-evoked protein kinase C (PKC) activation is required for the induction of LTD. In addition, the delta2 glutamate receptor (GluRdelta2), which is predominantly expressed at PF-Purkinje cell synapses, is indispensable for the induction of LTD; however, the mechanisms by which GluRdelta2 regulates LTD and its relationship with PKC activation remain elusive. Interestingly, GluRdelta2 is phosphorylated by PKC on serine 945 (Ser945) near its C-terminus and a postsynaptic protein S-SCAM, which could potentially regulate glutamate receptor trafficking and synaptic plasticity, binds to the extreme C-terminus of GluRdelta2 in a phosphorylation-dependent manner on Ser945. Here, using a Sindbis-based virus expression approach, we show that a mutant GluRdelta2, in which alanine replaced Ser945 and did not undergo PKC phosphorylation, was normally localized at the postsynaptic sites of PF-Purkinje cell synapses. In addition, like wild-type GluRdelta2, the phosphorylation-disrupted GluRdelta2 successfully rescued abrogated LTD in GluRdelta2-null Purkinje cells. These results indicate that Ser945, a major PKC phosphorylation site of of GluRdelta2, may not play a crucial role in induction of LTD in the cerebellum. PMID:18677091

  15. Long-term plasticity determines the postsynaptic response to correlated afferents with multivesicular short-term synaptic depression

    PubMed Central

    Bird, Alex D.; Richardson, Magnus J. E.

    2014-01-01

    Synchrony in a presynaptic population leads to correlations in vesicle occupancy at the active sites for neurotransmitter release. The number of independent release sites per presynaptic neuron, a synaptic parameter recently shown to be modified during long-term plasticity, will modulate these correlations and therefore have a significant effect on the firing rate of the postsynaptic neuron. To understand how correlations from synaptic dynamics and from presynaptic synchrony shape the postsynaptic response, we study a model of multiple release site short-term plasticity and derive exact results for the crosscorrelation function of vesicle occupancy and neurotransmitter release, as well as the postsynaptic voltage variance. Using approximate forms for the postsynaptic firing rate in the limits of low and high correlations, we demonstrate that short-term depression leads to a maximum response for an intermediate number of presynaptic release sites, and that this leads to a tuning-curve response peaked at an optimal presynaptic synchrony set by the number of neurotransmitter release sites per presynaptic neuron. These effects arise because, above a certain level of correlation, activity in the presynaptic population is overly strong resulting in wastage of the pool of releasable neurotransmitter. As the nervous system operates under constraints of efficient metabolism it is likely that this phenomenon provides an activity-dependent constraint on network architecture. PMID:24523691

  16. Estrogen receptor KO mice study on rapid modulation of spines and long-term depression in the hippocampus.

    PubMed

    Murakami, Gen; Hojo, Yasushi; Ogiue-Ikeda, Mari; Mukai, Hideo; Chambon, Pierre; Nakajima, Kohei; Ooishi, Yuuki; Kimoto, Tetsuya; Kawato, Suguru

    2015-09-24

    Rapid modulation of hippocampal synaptic plasticity through synaptic estrogen receptors is an essential topic. We analyzed estradiol-induced modulation of CA1 dendritic spines using adult male ERαKO and ERβKO mice. A 2h treatment of estradiol particularly increased the density of middle-head spines (diameter 0.3-0.4 µm) in wild type mouse hippocampal slices. The enhancement of spinogenesis was completely suppressed by MAP kinase inhibitor. Estradiol-induced increase in middle-head spines was observed in ERβKO mice (which express ERα), but not in ERαKO, indicating that ERα is necessary for the spinogenesis. Direct observation of the dynamic estradiol-induced enhancing effect on rapid spinogenesis was performed using time-lapse imaging of spines in hippocampal live slices from yellow fluorescent protein expressed mice. Both appearance and disappearance of spines occurred, and the number of newly appeared spines was significantly greater than that of disappeared spines, resulting in the net increase of the spine density within 2h. As another type of synaptic modulation, we observed that estradiol rapidly enhanced N-methyl-D-aspartate (NMDA)-induced long-term depression (LTD) in CA1 of the wild type mouse hippocampus. In contrast, estradiol did not enhance NMDA-LTD in ERαKO mice, indicating the involvement of ERα in the estrogen signaling. This article is part of a Special Issue entitled SI: Brain and Memory. PMID:25498865

  17. Pragmatic randomized controlled trial of long-term psychoanalytic psychotherapy for treatment-resistant depression: the Tavistock Adult Depression Study (TADS)

    PubMed Central

    Fonagy, Peter; Rost, Felicitas; Carlyle, Jo-anne; McPherson, Susan; Thomas, Rachel; Pasco Fearon, RM; Goldberg, David; Taylor, David

    2015-01-01

    This pragmatic randomized controlled trial tested the effectiveness of long-term psychoanalytic psychotherapy (LTPP) as an adjunct to treatment-as-usual according to UK national guidelines (TAU), compared to TAU alone, in patients with long-standing major depression who had failed at least two different treatments and were considered to have treatment-resistant depression. Patients (N=129) were recruited from primary care and randomly allocated to the two treatment conditions. They were assessed at 6-monthly intervals during the 18 months of treatment and at 24, 30 and 42 months during follow-up. The primary outcome measure was the 17-item version of the Hamilton Depression Rating Scale (HDRS-17), with complete remission defined as a HDRS-17 score ≤8, and partial remission defined as a HDRS-17 score ≤12. Secondary outcome measures included self-reported depression as assessed by the Beck Depression Inventory - II, social functioning as evaluated by the Global Assessment of Functioning, subjective wellbeing as rated by the Clinical Outcomes in Routine Evaluation - Outcome Measure, and satisfaction with general activities as assessed by the Quality of Life Enjoyment and Satisfaction Questionnaire. Complete remission was infrequent in both groups at the end of treatment (9.4% in the LTPP group vs. 6.5% in the control group) as well as at 42-month follow-up (14.9% vs. 4.4%). Partial remission was not significantly more likely in the LTPP than in the control group at the end of treatment (32.1% vs. 23.9%, p=0.37), but significant differences emerged during follow-up (24 months: 38.8% vs. 19.2%, p=0.03; 30 months: 34.7% vs. 12.2%, p=0.008; 42 months: 30.0% vs. 4.4%, p=0.001). Both observer-based and self-reported depression scores showed steeper declines in the LTPP group, alongside greater improvements on measures of social adjustment. These data suggest that LTPP can be useful in improving the long-term outcome of treatment-resistant depression. End

  18. [Long-term effects of a cognitive-behavioral intervention on pain coping among inpatient orthopedic rehabilitation of chronic low back pain and depressive symptoms].

    PubMed

    Hampel, Petra; Gemp, Stephan; Mohr, Beate; Schulze, Julian; Tlach, Lisa

    2014-11-01

    Beneficial effects on psychological measures in orthopedic inpatient rehabilitation of patients with chronic low back pain (CLBP) and co-exist-ing depressive symptoms have been shown only for multidisciplinary approaches that incorporate psychotherapeutic interventions. Aim of this study was to verify these findings for pain coping outcomes (pain-related psychological disability, pain-related coping). Short-, mid-, and long-term effects of a standard pain management program that was either solely provided or combined with a supplemental cognitive-behavioral depression management were examined in a consecutive sample of n=84. Patients in both groups showed long-term beneficial effects in pain coping measures. Thus, the standard rehabilitation revealed specific and long-term effects on pain coping. However, further evidence suggests that diagnosis-specific psychotherapeutic treatment elements are required to improve psychological symptoms. PMID:24838435

  19. Early antipsychotic treatment in childhood/adolescent period has long-term effects on depressive-like, anxiety-like and locomotor behaviours in adult rats.

    PubMed

    De Santis, Michael; Lian, Jiamei; Huang, Xu-Feng; Deng, Chao

    2016-02-01

    Childhood/adolescent antipsychotic drug (APD) use is exponentially increasing worldwide, despite limited knowledge of the long-term effects of early APD treatment. Whilst investigations have found that early treatment has resulted in some alterations to dopamine and serotonin neurotransmission systems (essential to APD efficacy), there have only been limited studies into potential long-term behavioural changes. This study, using an animal model for childhood/adolescent APD treatment, investigated the long-term effects of aripiprazole, olanzapine and risperidone on adult behaviours of male and female rats. Open-field/holeboard, elevated plus maze (EPM), social interaction and forced swim (FS) tests were then conducted in adult rats. Our results indicated that in the male cohort, early risperidone and olanzapine treatment elicited long-term hyper-locomotor effects (open-field/holeboard and FS tests), whilst a decrease in depressive-like behaviour (in FS test) was observed in response to olanzapine treatment. Furthermore, anxiolytic-like behaviours were found following testing in the open-field/holeboard and EPM in response to all three drug treatments. Effects in the female cohort, however, were to a far lesser extent, with behavioural attributes indicative of an increased depressive-like behaviour and hypo-locomotor activity exhibited in the FS test following early risperidone and olanzapine treatment. These results suggest that various APDs have different long-term effects on the behaviours of adult rats. PMID:26577063

  20. Reassessment of long-term depression in cerebellar Purkinje cells in mice carrying mutated GluA2 C terminus.

    PubMed

    Yamaguchi, Kazuhiko; Itohara, Shigeyoshi; Ito, Masao

    2016-09-01

    Long-term depression (LTD) of synaptic transmission from parallel fibers (PFs) to a Purkinje cell (PC) in the cerebellum has been considered to be a core mechanism of motor learning. Recently, however, discrepancies between LTD and motor learning have been reported in mice with a mutation that targeted the expression of PF-PC LTD by blocking AMPA-subtype glutamate receptor internalization regulated via the phosphorylation of AMPA receptors. In these mice, motor learning behavior was normal, but no PF-PC LTD was observed. We reexamined slices obtained from these GluA2 K882A and GluA2 Δ7 knockin mutants at 3-6 mo of age. The conventional protocols of stimulation did not induce LTD in these mutant mice, as previously reported, but surprisingly, LTD was induced using certain modified protocols. Such modifications involved increases in the number of PF stimulation (from one to two or five), replacement of climbing fiber stimulation with somatic depolarization (50 ms), filling a patch pipette with a Cs(+)-based solution, or extension of the duration of conjunction. We also found that intracellular infusion of a selective PKCα inhibitor (Gö6976) blocked LTD induction in the mutants, as in WT, suggesting that functional compensation occurred downstream of PKCα. The possibility that LTD in the mutants was caused by changes in membrane resistance, access resistance, or presynaptic property was excluded. The present results demonstrate that LTD is inducible by intensified conjunctive stimulations even in K882A and Δ7 mutants, indicating no contradiction against the LTD hypothesis of motor learning. PMID:27551099

  1. Endocannabinoids Mediate Muscarinic Acetylcholine Receptor-Dependent Long-Term Depression in the Adult Medial Prefrontal Cortex

    PubMed Central

    Martin, Henry G. S.; Bernabeu, Axel; Lassalle, Olivier; Bouille, Clément; Beurrier, Corinne; Pelissier-Alicot, Anne-Laure; Manzoni, Olivier J.

    2015-01-01

    Cholinergic inputs into the prefrontal cortex (PFC) are associated with attention and cognition; however there is evidence that acetylcholine also has a role in PFC dependent learning and memory. Muscarinic acetylcholine receptors (mAChR) in the PFC can induce synaptic plasticity, but the underlying mechanisms remain either opaque or unresolved. We have characterized a form of mAChR mediated long-term depression (LTD) at glutamatergic synapses of layer 5 principal neurons in the adult medial PFC. This mAChR LTD is induced with the mAChR agonist carbachol and inhibited by selective M1 mAChR antagonists. In contrast to other cortical regions, we find that this M1 mAChR mediated LTD is coupled to endogenous cannabinoid (eCB) signaling. Inhibition of the principal eCB CB1 receptor blocked carbachol induced LTD in both rats and mice. Furthermore, when challenged with a sub-threshold carbachol application, LTD was induced in slices pretreated with the monoacylglycerol lipase (MAGL) inhibitor JZL184, suggesting that the eCB 2-arachidonylglyerol (2-AG) mediates M1 mAChR LTD. Yet, when endogenous acetylcholine was released from local cholinergic afferents in the PFC using optogenetics, it failed to trigger eCB-LTD. However coupling patterned optical and electrical stimulation to generate local synaptic signaling allowed the reliable induction of LTD. The light—electrical pairing induced LTD was M1 mAChR and CB1 receptor mediated. This shows for the first time that connecting excitatory synaptic activity with coincident endogenously released acetylcholine controls synaptic gain via eCB signaling. Together these results shed new light on the mechanisms of synaptic plasticity in the adult PFC and expand on the actions of endogenous cholinergic signaling. PMID:26648844

  2. The effects of comorbidity in defining major depression subtypes associated with long-term course and severity

    PubMed Central

    Wardenaar, K. J.; van Loo, H. M.; Cai, T.; Fava, M.; Gruber, M. J.; Li, J.; de Jonge, P.; Nierenberg, A. A.; Petukhova, M. V.; Rose, S.; Sampson, N. A.; Schoevers, R. A.; Wilcox, M. A.; Alonso, J.; Bromet, E. J.; Bunting, B.; Florescu, S. E.; Fukao, A.; Gureje, O.; Hu, C.; Huang, Y. Q.; Karam, A. N.; Levinson, D.; Medina Mora, M. E.; Posada-Villa, J.; Scott, K. M.; Taib, N. I.; Viana, M. C.; Xavier, M.; Zarkov, Z.; Kessler, R. C.

    2014-01-01

    Background Although variation in long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods. However, it is not known whether these distinctions can be refined by added information about comorbid conditions. The current report presents results on this question. Methods Data come from 8,261 respondents with lifetime DSM-IV MDD in the WHO World Mental Health (WMH) Surveys. Outcomes include four retrospectively-reported measures of persistence-severity of course (years in episode; years in chronic episodes, hospitalization for MDD; disability due to MDD). Machine learning methods (regression tree analysis; lasso, ridge, and elastic net penalized regression) followed by k-means cluster analysis were used to augment previously-detected subtypes with information about prior comorbidity to predict these outcomes. Results Predicted values were strongly correlated across outcomes. Cluster analysis of predicted values found 3 clusters with consistently high, intermediate, or low values. The high-risk cluster (32.4% of cases) accounted for 56.6–72.9% of high persistence, high chronicity, hospitalization, and disability. This high-risk cluster had both higher sensitivity and likelihood-ratio positive (relative proportions of cases in the high-risk cluster versus other clusters having the adverse outcomes) than in a parallel analysis that excluded measures of comorbidity as predictors. Conclusions Although results using the retrospective data reported here suggest that useful MDD subtyping distinctions can be made with machine learning and clustering across multiple indicators of illness persistence-severity, replication is need with prospective data to confirm this preliminary conclusion. PMID:25066141

  3. The metabotropic glutamate receptor mGluR3 is critically required for hippocampal long-term depression and modulates long-term potentiation in the dentate gyrus of freely moving rats.

    PubMed

    Pöschel, Beatrice; Wroblewska, Barbara; Heinemann, Uwe; Manahan-Vaughan, Denise

    2005-09-01

    Group II metabotropic glutamate receptors (mGluRs) play an important role in the regulation of hippocampal synaptic plasticity in vivo: long-term potentiation (LTP) is inhibited and long-term depression (LTD) is enhanced by activation of these receptors. The contribution, in vivo, of the individual group II mGluR subtypes has not been characterized. We analysed the involvement of the subtype mGluR3 in LTD and LTP. Rats were implanted with electrodes to enable chronic measurement of evoked potentials from medial perforant path-dentate gyrus synapses. Neither the selective mGluR3 agonist, N-acetylaspartylglutamate (NAAG), nor the antagonist beta-NAAG, given intracerebrally, affected basal synaptic transmission. beta-NAAG significantly inhibited LTD expression. NAAG exhibited transient inhibitory effects on the intermediate phase of LTD. Whereas NAAG altered paired-pulse responses, beta-NAAG had no effect, suggesting that antagonism of mGluR3 prevents LTD via a postsynaptic mechanism, whereas agonist activation of mGluR3 modulates LTD at a presynaptic locus. NAAG impaired the expression of LTP, whereas beta-NAAG had no effect. NAAG effects on LTP were blocked by EGLU, a selective group II mGluR antagonist. Our data suggest an essential role for mGluR3 in LTD, and a modulatory role for mGluR3 in LTP, with effects being mediated by distinct pre- and post-synaptic loci. PMID:15635057

  4. Potential long-term effects of a mind-body intervention for women with major depressive disorder: sustained mental health improvements with a pilot yoga intervention.

    PubMed

    Kinser, Patricia Anne; Elswick, R K; Kornstein, Susan

    2014-12-01

    Despite pharmacologic and psychotherapeutic advances over the past decades, many individuals with major depressive disorder (MDD) experience recurrent depressive episodes and persistent depressive symptoms despite treatment with the usual care. Yoga is a mind-body therapeutic modality that has received attention in both the lay and research literature as a possible adjunctive therapy for depression. Although promising, recent findings about the positive mental health effects of yoga are limited because few studies have used standardized outcome measures and none of them have involved long-term follow-up beyond a few months after the intervention period. The goal of our research study was to evaluate the feasibility, acceptability, and effects of a yoga intervention for women with MDD using standardized outcome measures and a long follow-up period (1year after the intervention). The key finding is that previous yoga practice has long-term positive effects, as revealed in both qualitative reports of participants' experiences and in the quantitative data about depression and rumination scores over time. Although generalizability of the study findings is limited because of a very small sample size at the 1-year follow-up assessment, the trends in the data suggest that exposure to yoga may convey a sustained positive effect on depression, ruminations, stress, anxiety, and health-related quality of life. Whether an individual continues with yoga practice, simple exposure to a yoga intervention appears to provide sustained benefits to the individual. This is important because it is rare that any intervention, pharmacologic or non-pharmacologic, for depression conveys such sustained effects for individuals with MDD, particularly after the treatment is discontinued. PMID:25457687

  5. Long-term corticosterone exposure decreases insulin sensitivity and induces depressive-like behaviour in the C57BL/6NCrl mouse.

    PubMed

    van Donkelaar, Eva L; Vaessen, Koen R D; Pawluski, Jodi L; Sierksma, Annerieke S; Blokland, Arjan; Cañete, Ramón; Steinbusch, Harry W M

    2014-01-01

    Chronic stress or long-term administration of glucocorticoids disrupts the hypothalamus-pituitary-adrenal system leading to continuous high levels of glucocorticoids and insulin resistance (IR). This pre-diabetic state can eventually develop into type 2 diabetes mellitus and has been associated with a higher risk to develop depressive disorders. The mechanisms underlying the link between chronic stress, IR and depression remains unclear. The present study aimed to establish a stress-depression model in mice to further study the effects of stress-induced changes upon insulin sensitivity and behavioural consequences. A pilot study was conducted to establish the optimal administration route and a pragmatic measurement of IR. Subsequently, 6-month-old C57BL/6NCrl mice were exposed to long-term oral corticosterone treatment via the drinking water. To evaluate insulin sensitivity changes, blood glucose and plasma insulin levels were measured at different time-points throughout treatment and mice were behaviourally assessed in the elevated zero maze (EZM), forced swimming test (FST) and open field test to reveal behavioural changes. Long-term corticosterone treatment increased body weight and decreased insulin sensitivity. The latter was revealed by a higher IR index and increased insulin in the plasma, whereas blood glucose levels remained unchanged. Corticosterone treatment induced longer immobility times in the FST, reflecting depressive-like behaviour. No effects were observed upon anxiety as measured in the EZM. The effect of the higher body weight of the CORT treated animals at time of testing did not influence behaviour in the EZM or FST, as no differences were found in general locomotor activity. Long-term corticosterone treatment via the drinking water reduces insulin sensitivity and induces depressive-like behaviour in the C57BL/6 mouse. This mouse model could thus be used to further explore the underlying mechanisms of chronic stress-induced T2DM and its

  6. Long-Term Corticosterone Exposure Decreases Insulin Sensitivity and Induces Depressive-Like Behaviour in the C57BL/6NCrl Mouse

    PubMed Central

    van Donkelaar, Eva L.; Vaessen, Koen R. D.; Pawluski, Jodi L.; Sierksma, Annerieke S.; Blokland, Arjan; Cañete, Ramón; Steinbusch, Harry W. M.

    2014-01-01

    Chronic stress or long-term administration of glucocorticoids disrupts the hypothalamus-pituitary-adrenal system leading to continuous high levels of glucocorticoids and insulin resistance (IR). This pre-diabetic state can eventually develop into type 2 diabetes mellitus and has been associated with a higher risk to develop depressive disorders. The mechanisms underlying the link between chronic stress, IR and depression remains unclear. The present study aimed to establish a stress-depression model in mice to further study the effects of stress-induced changes upon insulin sensitivity and behavioural consequences. A pilot study was conducted to establish the optimal administration route and a pragmatic measurement of IR. Subsequently, 6-month-old C57BL/6NCrl mice were exposed to long-term oral corticosterone treatment via the drinking water. To evaluate insulin sensitivity changes, blood glucose and plasma insulin levels were measured at different time-points throughout treatment and mice were behaviourally assessed in the elevated zero maze (EZM), forced swimming test (FST) and open field test to reveal behavioural changes. Long-term corticosterone treatment increased body weight and decreased insulin sensitivity. The latter was revealed by a higher IR index and increased insulin in the plasma, whereas blood glucose levels remained unchanged. Corticosterone treatment induced longer immobility times in the FST, reflecting depressive-like behaviour. No effects were observed upon anxiety as measured in the EZM. The effect of the higher body weight of the CORT treated animals at time of testing did not influence behaviour in the EZM or FST, as no differences were found in general locomotor activity. Long-term corticosterone treatment via the drinking water reduces insulin sensitivity and induces depressive-like behaviour in the C57BL/6 mouse. This mouse model could thus be used to further explore the underlying mechanisms of chronic stress-induced T2DM and its

  7. Remission and Recovery in the Treatment for Adolescents with Depression Study (TADS): Acute and Long-Term Outcomes

    ERIC Educational Resources Information Center

    Kennard, Betsy D.; Silva, Susan G.; Tonev, Simon; Rohde, Paul; Hughes, Jennifer L.; Vitiello, Benedetto; Kratochvil, Christopher J.; Curry, John F.; Emslie, Graham J.; Reinecke, Mark; March, John

    2009-01-01

    The remission and recovery rates of adolescent patients with depression who were treated with fluoxetine, cognitive-behavioral therapy, their combination, and placebos were examined through a multisite clinical trial. It is concluded that most depressed adolescents who received such therapies achieved remission at the end of nine months.

  8. The cost-effectiveness of short-term and long-term psychotherapy in the treatment of depressive and anxiety disorders during a 5-year follow-up.

    PubMed

    Maljanen, Timo; Knekt, Paul; Lindfors, Olavi; Virtala, Esa; Tillman, Päivi; Härkänen, Tommi

    2016-01-15

    Both short-term and long-term psychotherapies are used extensively in treating different mental disorders, but there have been practically no attempts to compare their cost-effectiveness. The aim of this study, which is part of the Helsinki Psychotherapy Study, is to assess the cost-effectiveness of two short-term therapies compared to that of a long-term therapy. In this study 326 outpatients suffering from mood or anxiety disorder were randomized to solution-focused therapy (SFT), short-term psychodynamic psychotherapy (SPP) or to long-term psychodynamic psychotherapy (LPP). Psychiatric symptoms and working ability were assessed at baseline and then 4-9 times during a 5-year follow-up using eight widely used measures including e.g. Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HDRS), Symptom Check List, anxiety scale (SCL-90-Anx), Hamilton Anxiety Rating Scale (HARS), Symptom Check List, Global Severity Index (SCL-90-GSI), and the Work-subscale (SAS-Work) of the Social Adjustment Scale (SAS-SR). Both direct and indirect costs were measured. During the 5-year follow-up period statistically significant improvements were observed in all health indicators in all therapy groups. At first the recovery was faster in the short-term therapy groups than in the LPP group, but taking the whole follow-up period into account, the effectiveness of the LPP was somewhat greater than that of the short-term therapies. Especially the direct costs were, however, much higher in the LPP group than in the short-term therapy groups. Thus the long-term therapy can hardly be regarded as cost-effective compared to short-term therapies when patients are randomized to the therapy groups. PMID:26540079

  9. Gender differences in the long-term associations between post-traumatic stress disorder and depression symptoms: Findings from the Detroit Neighborhood Health Study

    PubMed Central

    Horesh, Danny; Lowe, Sarah R.; Galea, Sandro; Uddin, Monica; Koenen, Karestan C.

    2014-01-01

    Objective Post-traumatic stress disorder (PTSD) and depression are known to be highly co-morbid. However, previous findings regarding the nature of this co-morbidity have been inconclusive. This study prospectively examined whether PTSD and depression are distinct constructs in an epidemiologic sample, as well as assessed the directionality of the PTSD-depression association across time. Methods 942 Detroit residents (males: n = 387; females: n = 555) were interviewed by phone at three time points, one year apart. At each time point, they were assessed for PTSD (using the PCL-C), depression (PHQ-9), trauma exposure, and stressful life events. Results First, a confirmatory factor analysis showed PTSD and depression to be two distinct factors at all 3 waves of assessments (W1, W2, and W3). Second, chi-square analysis detected significant differences between observed and expected rates of comorbidity at each time point, with significantly more no-disorder and comorbid cases, and significantly fewer PTSD only and depression only cases, than would be expected by chance alone. Finally, a cross-lagged analysis revealed a bidirectional association between PTSD and depression symptoms across time for the entire sample, as well as for women separately, wherein PTSD symptoms at an early wave predicted later depression symptoms, and vice versa. For men, however, only the paths from PTSD symptoms to subsequent depression symptoms were significant. Conclusions Across time, PTSD and depression are distinct, but correlated, constructs among a highly-exposed epidemiologic sample. Women and men differ in both the risk of these conditions, and the nature of the long-term associations between them. PMID:25044027

  10. Long-term consequences of pubertal timing for youth depression: Identifying personal and contextual pathways of risk.

    PubMed

    Rudolph, Karen D; Troop-Gordon, Wendy; Lambert, Sharon F; Natsuaki, Misaki N

    2014-11-01

    This research explored sex differences in the pathways linking pubertal timing to depression across 4 years. A sample of 167 youth (M age = 12.41 years, SD = 1.19) and their caregivers completed measures of puberty and semistructured interviews of interpersonal stress and youth depression. Youth reported on psychological (negative self-focus, anxious arousal) and social-behavioral (coping) characteristics; parents reported on youths' social-behavioral characteristics (withdrawal/social problems) and deviant peer affiliations. Early maturation predicted stable high trajectories of depression in girls; although early maturing boys showed low initial levels of depression, they did not differ from girls by the final wave of the study. Latent growth curve analyses identified several psychological, social-behavioral, and interpersonal pathways accounting for the contribution of pubertal timing to initial and enduring risk for depression in girls as well as emerging risk for depression in boys. These findings provide novel insight into multilevel processes accounting for sex differences in depression across the adolescent transition. PMID:25422971

  11. Long-term consequences of pubertal timing for youth depression: Identifying personal and contextual pathways of risk

    PubMed Central

    RUDOLPH, KAREN D.; TROOP-GORDON, WENDY; LAMBERT, SHARON F.; NATSUAKI, MISAKI N.

    2015-01-01

    This research explored sex differences in the pathways linking pubertal timing to depression across 4 years. A sample of 167 youth (M age = 12.41 years, SD = 1.19) and their caregivers completed measures of puberty and semistructured interviews of interpersonal stress and youth depression. Youth reported on psychological (negative self-focus, anxious arousal) and social–behavioral (coping) characteristics; parents reported on youths’ social–behavioral characteristics (withdrawal/social problems) and deviant peer affiliations. Early maturation predicted stable high trajectories of depression in girls; although early maturing boys showed low initial levels of depression, they did not differ from girls by the final wave of the study. Latent growth curve analyses identified several psychological, social–behavioral, and interpersonal pathways accounting for the contribution of pubertal timing to initial and enduring risk for depression in girls as well as emerging risk for depression in boys. These findings provide novel insight into multilevel processes accounting for sex differences in depression across the adolescent transition. PMID:25422971

  12. Long-term postpartum anxiety and depression-like behavior in mother rats subjected to maternal separation are ameliorated by palatable high fat diet.

    PubMed

    Maniam, Jayanthi; Morris, Margaret J

    2010-03-17

    While the effects of maternal separation on pups are well studied, the impact on dams has attracted little attention. The consumption of palatable food is known to dampen stress responses in animals, and emotions influence food choice in humans. Here we examined the early- and long-term impacts of maternal separation on behavioral profile of the dams, and the effects of palatable cafeteria high-fat diet (HFD). After littering, Sprague-Dawley female rats were subjected to prolonged separation, S180 (180 min) or brief separation, S15 (15 min/day) from postnatal days (PND) 2-14. At 4 weeks postpartum, half the dams were assigned to HFD. Anxiety and depression-like behaviors were assessed pre- and post-diet. Compared to S15 dams, S180 dams consuming chow demonstrated increased anxiety and depression-like behaviors assessed by elevated plus maze (EPM) and forced swim (FST) tests, respectively. These behavioral deficits were observed at 4 weeks, and persisted until 17 weeks postpartum. The S180 dams also had increased plasma corticosterone concentration compared to S15 dams, which coincided with increased hypothalamic CRH mRNA and reduced hippocampal GR mRNA expression, suggesting possible dysregulation of hypothalamic-pituitary-adrenal axis activity. Interestingly, continuous provision of HFD improved the behavioral deficits observed in S180 dams with significant reduction of hypothalamic CRH mRNA expression. These data are the first to describe long-term detrimental behavioral impacts of separation in dams, suggesting this may provide a model of postpartum depression. Moreover, they support the notion of long-term beneficial effects of 'comfort food' on stress responses. PMID:19896506

  13. SCRAPPER regulates the thresholds of long-term potentiation/depression, the bidirectional synaptic plasticity in hippocampal CA3-CA1 synapses.

    PubMed

    Takagi, Hiroshi; Setou, Mitsutoshi; Ito, Seiji; Yao, Ikuko

    2012-01-01

    SCRAPPER, which is an F-box protein encoded by FBXL20, regulates the frequency of the miniature excitatory synaptic current through the ubiquitination of Rab3-interacting molecule 1. Here, we recorded the induction of long-term potentiation/depression (LTP/LTD) in CA3-CA1 synapses in E3 ubiquitin ligase SCRAPPER-deficient hippocampal slices. Compared to wild-type mice, Scrapper-knockout mice exhibited LTDs with smaller magnitudes after induction with low-frequency stimulation and LTPs with larger magnitudes after induction with tetanus stimulation. These findings suggest that SCRAPPER regulates the threshold of bidirectional synaptic plasticity and, therefore, metaplasticity. PMID:23316391

  14. mGluR-mediated and endocannabinoid-dependent long-term depression in the hilar region of the rat dentate gyrus

    PubMed Central

    Nahir, Ben; Lindsly, Casie; Frazier, Charles J.

    2010-01-01

    We report that bath application of the group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) causes acute inhibition of evoked IPSCs recorded from hilar mossy cells, and that significant long-term depression (LTD) of synaptic transmission remains following washout of DHPG. Subsequent experiments using minimal stimulation techniques revealed that expression of both acute and long-term effects of DHPG are restricted to a subset of GABAergic afferents that are also sensitive to depolarization-induced suppression of inhibition (DSI). Experiments with a selective CB1 antagonist and with transgenic animals lacking CB1 receptors indicate that all effects of DHPG, like DSI, depend on activation of CB1 receptors. Further work with selective mGluR antagonists suggests a direct involvement of mGluR1 receptors. Interestingly, we also report that induction of LTD under our experimental conditions does not require prior direct somatic depolarization via the patch pipette and does not appear to depend critically on the level of activity in incoming GABAergic afferents. Collectively, these results represent the first characterization of mGluR-mediated and endocannabinoid dependent LTD in the hilar region of the dentate gyrus. The dentate gyrus is thus one of relatively few areas where this mechanism has clearly been demonstrated to induce long term modulation of inhibitory synaptic transmission. PMID:20045707

  15. O-GlcNAcylation of AMPA Receptor GluA2 Is Associated with a Novel Form of Long-Term Depression at Hippocampal Synapses

    PubMed Central

    Taylor, Erica W.; Wang, Kai; Nelson, Amy R.; Bredemann, Teruko M.; Fraser, Kyle B.; Clinton, Sarah M.; Puckett, Rosemary; Marchase, Richard B.; Chatham, John C.

    2014-01-01

    Serine phosphorylation of AMPA receptor (AMPAR) subunits GluA1 and GluA2 modulates AMPAR trafficking during long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory. The post-translational addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) also occurs on serine residues. This, together with the high expression of the enzymes O-GlcNAc transferase (OGT) and β-N-acetylglucosamindase (O-GlcNAcase), suggests a potential role for O-GlcNAcylation in modifying synaptic efficacy and cognition. Furthermore, because key synaptic proteins are O-GlcNAcylated, this modification may be as important to brain function as phosphorylation, yet its physiological significance remains unknown. We report that acutely increasing O-GlcNAcylation in Sprague Dawley rat hippocampal slices induces an NMDA receptor and protein kinase C-independent long-term depression (LTD) at hippocampal CA3–CA1 synapses (O-GcNAc LTD). This LTD requires AMPAR GluA2 subunits, which we demonstrate are O-GlcNAcylated. Increasing O-GlcNAcylation interferes with long-term potentiation, and in hippocampal behavioral assays, it prevents novel object recognition and placement without affecting contextual fear conditioning. Our findings provide evidence that O-GlcNAcylation dynamically modulates hippocampal synaptic function and learning and memory, and suggest that altered O-GlcNAc levels could underlie cognitive dysfunction in neurological diseases. PMID:24381264

  16. An essential role for UBE2A/HR6A in learning and memory and mGLUR-dependent long-term depression.

    PubMed

    Bruinsma, Caroline F; Savelberg, Sanne M C; Kool, Martijn J; Jolfaei, Mehrnoush Aghadavoud; Van Woerden, Geeske M; Baarends, Willy M; Elgersma, Ype

    2016-01-01

    UBE2A deficiency syndrome (also known as X-linked intellectual disability type Nascimento) is an intellectual disability syndrome characterized by prominent dysmorphic features, impaired speech and often epilepsy. The syndrome is caused by Xq24 deletions encompassing the UBE2A (HR6A) gene or by intragenic UBE2A mutations. UBE2A encodes an E2 ubiquitin-conjugating enzyme involved in DNA repair and female fertility. A recent study in Drosophila showed that dUBE2A binds to the E3 ligase Parkin, which is required for mitochondrial function and responsible for juvenile Parkinson's disease. In addition, these studies showed impairments in synaptic transmission in dUBE2A mutant flies. However, a causal role of UBE2A in of cognitive deficits has not yet been established. Here, we show that Ube2a knockout mice have a major deficit in spatial learning tasks, whereas other tested phenotypes, including epilepsy and motor coordination, were normal. Results from electrophysiological measurements in the hippocampus showed no deficits in synaptic transmission nor in the ability to induce long-term synaptic potentiation. However, a small but significant deficit was observed in mGLUR-dependent long-term depression, a pathway previously implied in several other mouse models for neurodevelopmental disorders. Our results indicate a causal role of UBE2A in learning and mGLUR-dependent long-term depression, and further indicate that the Ube2a knockout mouse is a good model to study the molecular mechanisms underlying UBE2A deficiency syndrome. PMID:26476408

  17. The GABAA receptor agonist muscimol induces an age- and region-dependent form of long-term depression in the mouse striatum.

    PubMed

    Zhang, Xiaoqun; Yao, Ning; Chergui, Karima

    2016-09-01

    Several forms of long-term depression (LTD) of glutamatergic synaptic transmission have been identified in the dorsal striatum and in the nucleus accumbens (NAc). Such experience-dependent synaptic plasticity might play important roles in reward-related learning. The GABAA receptor agonist muscimol was recently found to trigger a long-lasting depression of glutamatergic synaptic transmission in the NAc of adolescent mice, but the mechanisms that underlie this novel form of LTD were not studied. Here we examined the effect of muscimol applied in the perfusion solution on the amplitude of field excitatory postsynaptic potentials/population spikes (fEPSP/PSs) in mouse brain slices. We found that muscimol depressed the fEPSP/PS in the NAc of adolescent mice but not adult mice, through both postsynaptic and presynaptic mechanisms. Indeed, muscimol altered the fEPSP/PS paired-pulse ratio, depolarized the membrane of projection neurons, and decreased the frequency, but not amplitude, of spontaneous excitatory postsynaptic currents in the NAc of adolescent mice. The LTD induced by muscimol likely involved endocannabinoids, metabotropic glutamate receptors (mGluRs), but not TRPV1 receptors. Muscimol-LTD was occluded by prior induction of LTD through low-frequency stimulation (LFS) of the slice, demonstrating a common pathway in the induction of LFS-LTD and muscimol-LTD. We also found that muscimol induced a form of LTD in the dorsolateral striatum of adult but not adolescent mice. This LTD was mediated by endocannabinoids but did not involve mGluRs or TRPV1 receptors. These results identify a novel form of synaptic plasticity, and its mechanisms of induction, which is age and region dependent. These findings may contribute to a better understanding of the increased susceptibility of the adolescent brain to long-term synaptic changes in regions associated with reward mechanisms. PMID:27531838

  18. Consequences of long-term treatment with agomelatine on depressive-like behavior and neurobiological abnormalities in pinealectomized rats.

    PubMed

    Tchekalarova, Jana; Nenchovska, Zlatina; Atanasova, Dimitrina; Atanasova, Milena; Kortenska, Lidia; Stefanova, Miroslava; Alova, Liana; Lazarov, Nikolai

    2016-04-01

    Previous data have shown that the rat model of melatonin deficit can cause a number of neurobiological aberrations. The aim of the present study was to determine whether the antidepressant drug agomelatine, a MT1/MT2 melatoninergic receptor agonist/5-HT2C receptor antagonist is able to prevent some of the behavioral, biochemical and cellular abnormalities induced by pinealectomy. The injection of agomelatine (40 mg/kg, i.p. for 5 weeks)/vehicle started after pinealectomy/sham procedure in Wistar rats. Animals were tested in different behavioral tests for anxiety and depression during the period of agomelatine treatment (chronic effect) and two months later (plastic effect). The effect of agomelatine on KCl-evoked serotonin (5-HT) release from the hippocampus, the activity of the hypothalamic-pituitary-adrenal (HPA) axis and neuronal loss in pinealectomized rats were assessed. Our results showed that agomelatine not only did not prevent the disturbed emotional arousal/anxiety behavior in pinealectomized rats during the treatment but the enhanced motor activity and decreased anxiety state was still observed two months after the discontinuation of treatment. However, the drug corrected a depressive-like behavior (chronic and plastic effect), alleviated the enhanced KCl-evoked 5-HT release in the hippocampus, recovered the suppressed negative feedback inhibition of HPA axis and exerted a neuroprotection in pinealectomized rats. Our findings suggest that pinealectomy can model melancholic depression disorder while the antidepressant action of agomelatine is associated with a correction of 5-HT release in the hippocampus, dysregulated HPA system and neuroprotection in limbic structures. PMID:26779670

  19. Long-term course of severe depression: late remission and recurrence may be found in a follow-up after 38–53 years

    PubMed Central

    Crona, Lisa; Brådvik, Louise

    2012-01-01

    This study is a follow-up of inpatients diagnosed with severe depression/melancholia between 1956 and 1969. During this period, all inpatients at the Department of Psychiatry, University Hospital, Lund, were rated on a multidimensional diagnostic schedule on discharge. There were 471 patients born from 1920 onward. In the present follow-up, 2006 to 2010, 169 survivors could be traced. They were asked to participate in the study involving a telephone interview, in which a structured life chart was used. Of the patients contacted, 16 were ill or confused and 3 did not remember ever being depressed, leaving 150 who could participate. Seventy-five of these agreed to participate in the study. Long-term course of depression was evaluated by cluster analysis and compared to background variables, such as heredity for depression, perceived parental rearing behaviour, and treatment of index depressive episode. Using a cluster analysis the patients could be separated into six clusters describing the course: i) single or few episodes followed by long-lasting remission; ii) single or few episodes followed by long-lasting remission, although shorter; iii) single or few episodes followed by late recurrence; iv) single or few episodes, but more frequently ill, followed by late recurrence; v) several episodes followed by lasting remission; vi) chronic course of episodes. Remission or recurrence could therefore occur even after more than a decade. In summary, there was a short-term course with or without recurrence or a chronic course with or without late remission. Heredity for depression was significantly related to a chronic course with or without late remission. PMID:25478118

  20. Long-Term Care

    MedlinePlus

    ... this page please turn Javascript on. Long-Term Care What Is Long-Term Care? Long-term care involves a variety of services ... the Escape (Esc) button on your keyboard.) Most Care Provided at Home Long-term care is provided ...

  1. Neo-synthesis of estrogenic or androgenic neurosteroids determine whether long-term potentiation or depression is induced in hippocampus of male rat

    PubMed Central

    Di Mauro, Michela; Tozzi, Alessandro; Calabresi, Paolo; Pettorossi, Vito Enrico; Grassi, Silvarosa

    2015-01-01

    Estrogenic and androgenic steroids synthesized in the brain may rapidly modulate synaptic plasticity interacting with specific membrane receptors. We explored by electrophysiological recordings in hippocampal slices of male rat the influence of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT) neo-synthesis on the synaptic changes induced in the CA1 region. Induction of long-term depression (LTD) and depotentiation (DP) by low frequency stimulation (LFS, 15 min-1 Hz) and of long-term potentiation (LTP) by high frequency stimulation (HFS, 1 s-100 Hz), medium (MFS, 1 s-50 Hz), or weak (WFS, 1 s-25 Hz) frequency stimulation was assayed under inhibitors of enzymes converting testosterone (T) into DHT (5α-reductase) and T into E2 (P450-aromatase). We found that LFS-LTD depends on DHT synthesis, since it was fully prevented under finasteride, an inhibitor of DHT synthesis, and rescued by exogenous DHT, while the E2 synthesis was not involved. Conversely, the full development of HFS-LTP requires the synthesis of E2, as demonstrated by the LTP reduction observed under letrozole, an inhibitor of E2 synthesis, and its full rescue by exogenous E2. For intermediate stimulation protocols DHT, but not E2 synthesis, was involved in the production of a small LTP induced by WFS, while the E2 synthesis was required for the MFS-dependent LTP. Under the combined block of DHT and E2 synthesis all stimulation frequencies induced partial LTP. Overall, these results indicate that DHT is required for converting the partial LTP into LTD whereas E2 is needed for the full expression of LTP, evidencing a key role of the neo-synthesis of sex neurosteroids in determining the direction of synaptic long-term effects. PMID:26483631

  2. Induction of long-term potentiation and depression is reflected by corresponding changes in secretion of endogenous brain-derived neurotrophic factor

    PubMed Central

    Aicardi, Giorgio; Argilli, Emanuela; Cappello, Silvia; Santi, Spartaco; Riccio, Massimo; Thoenen, Hans; Canossa, Marco

    2004-01-01

    Neurotrophins play an important role in modulating activity-dependent neuronal plasticity. In particular, threshold levels of brain-derived neurotrophic factor (BDNF) are required to induce long-term potentiation (LTP) in acute hippocampal slices. Conversely, the administration of exogenous BDNF prevents the induction of long-term depression (LTD) in the visual cortex. A long-standing missing link in the analysis of this modulatory role of BDNF was the determination of the time-course of endogenous BDNF secretion in the same organotypic preparation in which LTP and LTD are elicited. Here, we fulfilled this requirement in slices of perirhinal cortex. Classical theta-burst stimulation patterns evoking LTP lasting >180 min elicited a large increase in BDNF secretion that persisted 5-12 min beyond the stimulation period. Weaker theta-burst stimulation patterns leading only to the initial phase of LTP (≈35 min) were accompanied by a smaller increase in BDNF secretion lasting <1 min. Sequestration of BDNF by TrkB-IgG receptor bodies prevented LTP. Low-frequency stimulations leading to LTD were accompanied by reductions in BDNF secretion that never lasted beyond the duration of the stimulation. PMID:15505222

  3. Long-term Effectiveness of Modified Electroconvulsive Therapy Compared With Repetitive Transcranial Magnetic Stimulation for the Treatment of Recurrent Major Depressive Disorder.

    PubMed

    Jin, Xi-Long; Xu, Wei-Qin; Le, Ya-Juan; Dai, Xiong-Kai

    2016-06-01

    This retrospective study recruited 150 patients with recurrent major depressive disorder (MDD) who received modified electroconvulsive therapy (MECT) and 150 cases treated with repetitive transcranial magnetic stimulation (rTMS), which aimed to compare the short- and long-term effectiveness, as well as economic outcomes, of MECT and rTMS with a large sample size in patients with recurrent MDD. The results showed that the response rate of patients in the rTMS group was lower than that in the MECT group (46.0% vs 58.7%, p < 0.05). Patients in the rTMS group had elevated rate of dizziness, but reduced rates of poor memory and headache, as well as lower costs compared with the MECT group (p < 0.05). Importantly, we found that the relapse-free survival of patients was similar between the rTMS and MECT groups in the long term. In conclusion, rTMS is an alternative method for MECT in the treatment of patients with recurrent MDD. PMID:26915018

  4. Comparison of depression, anxiety and long-term quality of health in patients with a history of either primary closure or Limberg flap reconstruction for pilonidal sinus

    PubMed Central

    Duman, Kazim; Ozdemir, Yavuz; Yucel, Ergun; Akin, Mehmet L

    2014-01-01

    OBJECTİVE: Pilonidal sinus is characterized by high operative morbidity mainly due to wound problems. We aimed to compare the quality of health, comfort and psychological status in patients who underwent surgery for pilonidal sinus. METHODS: A total of 205 pilonidal sinus patients operated on with either primary closure or Limberg flap reconstruction were compared in terms of depression, anxiety, and long-term quality of health by using Short Form 36, Beck Depression Inventory, and Beck Anxiety Inventory scales. RESULTS: There were 107 patients in the primary closure group with a mean follow-up of 29.6±7.7 months and 98 patients in the Limberg flap group with a mean follow-up of 34.1±7.3 months. In the SF-36 analysis, the mental health and bodily pain scores (59±6 and 56±11 in the primary closure group and 62±8 and 61±10 in the Limberg flap group) were significantly higher in the Limberg flap group (p = 0.014 and p = 0.002, respectively). The mean Beck Depression Inventory (19±6.13 vs. 16±4.90 p<0.001) and Beck Anxiety Inventory (19±6.27 vs. 16±4.90 p<0.001) scores were lower in the Limberg flap group. CONCLUSION: Limberg flap reconstruction produced better quality of health scores according to the SF 36, especially in terms of mental health and bodily pain. There was a higher tendency towards anxiety and depression in the primary closure group. PMID:24964301

  5. Long-term depression of glutamate-induced gamma-aminobutyric acid release in cerebellum by insulin-like growth factor I.

    PubMed Central

    Castro-Alamancos, M A; Torres-Aleman, I

    1993-01-01

    We tested the possibility that insulin-like growth factor I (IGF-I) acts as a neuromodulator in the adult cerebellar cortex since previous observations indicated that IGF-I is located in the olivo-cerebellar system encompassing the inferior olive and Purkinje cells. We found that conjoint administration of IGF-I and glutamate through a microdialysis probe stereotaxically implanted into the cerebellar cortex and deep cerebellar nuclei greatly depressed the release of gamma-aminobutyric acid (GABA), which normally follows a glutamate pulse. This inhibition was dose-dependent and long-lasting. Moreover, the effect was specific for glutamate since KCl-induced GABA release was not modified by IGF-I. Basic fibroblast growth factor, another growth-related peptide present in the cerebellum, did not alter the response of GABA to glutamate stimulation. In addition, electrical stimulation of the inferior olivary complex significantly raised IGF-I levels in the cerebellar cortex. Interestingly, when the inferior olive was stimulated in conjunction with glutamate administration, GABA release by cerebellar cells in response to subsequent glutamate pulses was depressed in a manner reminiscent of that seen after IGF-I. These findings indicate that IGF-I produces a long-lasting depression of GABA release by Purkinje cells in response to glutamate. IGF-I might be present in climbing fiber terminals and/or cells within the cerebellar cortex and thereby might affect Purkinje cell function. Whether this IGF-I-induced impairment of glutamate stimulation of Purkinje cells underlies functionally plastic processes such as long-term depression is open to question. Images Fig. 1 PMID:8346260

  6. Single fluoxetine treatment before but not after stress prevents stress-induced hippocampal long-term depression and spatial memory retrieval impairment in rats.

    PubMed

    Han, Huili; Dai, Chunfang; Dong, Zhifang

    2015-01-01

    A growing body of evidence has shown that chronic treatment with fluoxetine, a widely prescribed medication for treatment of depression, can affect synaptic plasticity in the adult central nervous system. However, it is not well understood whether acute fluoxetine influences synaptic plasticity, especially on hippocampal CA1 long-term depression (LTD), and if so, whether it subsequently impacts hippocampal-dependent spatial memory. Here, we reported that LTD facilitated by elevated-platform stress in hippocampal slices was completely prevented by fluoxetine administration (10 mg/kg, i.p.) 30 min before stress. The LTD was not, however, significantly inhibited by fluoxetine administration immediately after stress. Similarly, fluoxetine incubation (10 μM) during electrophysiological recordings also displayed no influence on the stress-facilitated LTD. In addition, behavioral results showed that a single fluoxetine treatment 30 min before but not after acute stress fully reversed the impairment of spatial memory retrieval in the Morris water maze paradigm. Taken together, these results suggest that acute fluoxetine treatment only before, but not after stress, can prevent hippocampal CA1 LTD and spatial memory retrieval impairment caused by behavioral stress in adult animals. PMID:26218751

  7. Long-term depression and suicidal ideation outcomes subsequent to emancipation from foster care: pathways to psychiatric risk in the Métis population.

    PubMed

    Kaspar, Violet

    2014-02-28

    Major depressive episode (MDE) and suicidal ideation (SI) associated with history of foster care placement (HxFCP), and mediating effects of psychosocial and socioeconomic factors through which placement may confer psychiatric risks in the years subsequent to emancipation were examined in a national sample of 7534 Métis. More than one third of emancipated respondents reported past year MDE, a prevalence rate nearly 50% higher than the rate of MDE among Métis respondents without a history of placement in foster care. The 25% lifetime prevalence rate of SI in the emancipated group was more than twice the rate observed in the non-fostered group. Direct effects of HxFCP on post placement MDE and SI were significant in multivariate logistic regression analyses, even when effects of childhood predispositional risk factors were controlled statistically. Emancipated individuals were unduly affected by psychosocial and socioeconomic disadvantages signifying pathways that linked foster care placement history and psychiatric status. Main mediators of the effects demonstrated using effect decomposition procedures were self-esteem, income, and community adversity. The findings warrant consideration of foster care history in clarifying the complex etiologies of suicidal ideation and major depressive episode in the Métis population and risk factors ensuing in the intervening years as integral to the process linking placement to long-term psychiatric outcomes. PMID:24373554

  8. Protein Synthesis Inhibitors Did Not Interfere with Long-Term Depression Induced either Electrically in Juvenile Rats or Chemically in Middle-Aged Rats

    PubMed Central

    2016-01-01

    In testing the hypothesis that long-term potentiation (LTP) maintenance depends on triggered protein synthesis, we found no effect of protein synthesis inhibitors (PSIs) on LTP stabilization. Similarly, some studies reported a lack of effect of PSIs on long-term depression (LTD); the lack of effect on LTD has been suggested to be resulting from the short time recordings. If this proposal were true, LTD might exhibit sensitivity to PSIs when the recording intervals were enough long. We firstly induced LTD by a standard protocol involving low frequency stimulation, which is suitable for eliciting NMDAR-LTD in CA1 area of hippocampal slices obtained from juvenile Sprague-Dawley rats. This LTD was persistent for intervals in range of 8–10 h. Treating slices with anisomycin, however, did not interfere with the magnitude and persistence of this form of LTD. The failure of anisomycin to block synaptic-LTD might be relied on the age of animal, the type of protein synthesis inhibitors and/or the inducing protocol. To verify whether those variables altogether were determinant, NMDA or DHPG was used to chemically elicit LTD recorded up to 10 h on hippocampal slices obtained from middle-aged rats. In either form of LTD, cycloheximide did not interfere with LTD stabilization. Furthermore, DHPG application did show an increase in the global protein synthesis as assayed by radiolabeled methodology indicating that though triggered protein synthesis can occur but not necessarily required for LTD expression. The findings confirm that stabilized LTD in either juvenile, or middle-aged rats can be independent of triggered protein synthesis. Although the processes responsible for the independence of LTD stabilization on the triggered protein synthesis are not yet defined, these findings raise the possibility that de novo protein synthesis is not universally necessary. PMID:27517693

  9. Protein Synthesis Inhibitors Did Not Interfere with Long-Term Depression Induced either Electrically in Juvenile Rats or Chemically in Middle-Aged Rats.

    PubMed

    Abbas, Abdul-Karim

    2016-01-01

    In testing the hypothesis that long-term potentiation (LTP) maintenance depends on triggered protein synthesis, we found no effect of protein synthesis inhibitors (PSIs) on LTP stabilization. Similarly, some studies reported a lack of effect of PSIs on long-term depression (LTD); the lack of effect on LTD has been suggested to be resulting from the short time recordings. If this proposal were true, LTD might exhibit sensitivity to PSIs when the recording intervals were enough long. We firstly induced LTD by a standard protocol involving low frequency stimulation, which is suitable for eliciting NMDAR-LTD in CA1 area of hippocampal slices obtained from juvenile Sprague-Dawley rats. This LTD was persistent for intervals in range of 8-10 h. Treating slices with anisomycin, however, did not interfere with the magnitude and persistence of this form of LTD. The failure of anisomycin to block synaptic-LTD might be relied on the age of animal, the type of protein synthesis inhibitors and/or the inducing protocol. To verify whether those variables altogether were determinant, NMDA or DHPG was used to chemically elicit LTD recorded up to 10 h on hippocampal slices obtained from middle-aged rats. In either form of LTD, cycloheximide did not interfere with LTD stabilization. Furthermore, DHPG application did show an increase in the global protein synthesis as assayed by radiolabeled methodology indicating that though triggered protein synthesis can occur but not necessarily required for LTD expression. The findings confirm that stabilized LTD in either juvenile, or middle-aged rats can be independent of triggered protein synthesis. Although the processes responsible for the independence of LTD stabilization on the triggered protein synthesis are not yet defined, these findings raise the possibility that de novo protein synthesis is not universally necessary. PMID:27517693

  10. Translational control of mGluR-dependent long-term depression and object-place learning by eIF2α

    PubMed Central

    Viana Di Prisco, Gonzalo; Huang, Wei; Buffington, Shelly A; Hsu, Chih-Chun; Bonnen, Penelope E; Placzek, Andon N; Sidrauski, Carmela; Krnjević, Krešimir; Kaufman, Randal J; Walter, Peter; Costa-Mattioli, Mauro

    2015-01-01

    At hippocampal synapses, activation of group I metabotropic glutamate receptors (mGluRs) induces long-term depression (LTD), which requires new protein synthesis. However, the underlying mechanism remains elusive. Here we describe the translational program that underlies mGluR-LTD and identify the translation factor eIF2α as its master effector. Genetically reducing eIF2α phosphorylation, or specifically blocking the translation controlled by eIF2α phosphorylation, prevented mGluR-LTD and the internalization of surface AMPA receptors (AMPARs). Conversely, direct phosphorylation of eIF2α, bypassing mGluR activation, triggered a sustained LTD and removal of surface AMPARs. Combining polysome profiling and RNA sequencing, we identified the mRNAs translationally upregulated during mGluR-LTD. Translation of one of these mRNAs, oligophrenin-1, mediates the LTD induced by eIF2α phosphorylation. Mice deficient in phospho-eIF2α–mediated translation are impaired in object-place learning, a behavioral task that induces hippocampal mGluR-LTD in vivo. Our findings identify a new model of mGluR-LTD, which promises to be of value in the treatment of mGluR-LTD-linked cognitive disorders. PMID:24974795

  11. Lgr4 protein deficiency induces ataxia-like phenotype in mice and impairs long term depression at cerebellar parallel fiber-Purkinje cell synapses.

    PubMed

    Guan, Xin; Duan, Yanhong; Zeng, Qingwen; Pan, Hongjie; Qian, Yu; Li, Dali; Cao, Xiaohua; Liu, Mingyao

    2014-09-19

    Cerebellar dysfunction causes ataxia characterized by loss of balance and coordination. Until now, the molecular and neuronal mechanisms of several types of inherited cerebellar ataxia have not been completely clarified. Here, we report that leucine-rich G protein-coupled receptor 4 (Lgr4/Gpr48) is highly expressed in Purkinje cells (PCs) in the cerebellum. Deficiency of Lgr4 leads to an ataxia-like phenotype in mice. Histologically, no obvious morphological changes were observed in the cerebellum of Lgr4 mutant mice. However, the number of PCs was slightly but significantly reduced in Lgr4(-/-) mice. In addition, in vitro electrophysiological analysis showed an impaired long term depression (LTD) at parallel fiber-PC (PF-PC) synapses in Lgr4(-/-) mice. Consistently, immunostaining experiments showed that the level of phosphorylated cAMP-responsive element-binding protein (Creb) was significantly decreased in Lgr4(-/-) PCs. Furthermore, treatment with forskolin, an adenylyl cyclase agonist, rescued phospho-Creb in PCs and reversed the impairment in PF-PC LTD in Lgr4(-/-) cerebellar slices, indicating that Lgr4 is an upstream regulator of Creb signaling, which is underlying PF-PC LTD. Together, our findings demonstrate for first time an important role for Lgr4 in motor coordination and cerebellar synaptic plasticity and provide a potential therapeutic target for certain types of inherited cerebellar ataxia. PMID:25063812

  12. miR-191 and miR-135 are required for long-lasting spine remodelling associated with synaptic long-term depression

    NASA Astrophysics Data System (ADS)

    Hu, Zhonghua; Yu, Danni; Gu, Qin-Hua; Yang, Yanqin; Tu, Kang; Zhu, Jun; Li, Zheng

    2014-02-01

    Activity-dependent modification of dendritic spines, subcellular compartments accommodating postsynaptic specializations in the brain, is an important cellular mechanism for brain development, cognition and synaptic pathology of brain disorders. NMDA receptor-dependent long-term depression (NMDAR-LTD), a prototypic form of synaptic plasticity, is accompanied by prolonged remodelling of spines. The mechanisms underlying long-lasting spine remodelling in NMDAR-LTD, however, are largely unclear. Here we show that LTD induction causes global changes in miRNA transcriptomes affecting many cellular activities. Specifically, we show that expression changes of miR-191 and miR-135 are required for maintenance but not induction of spine restructuring. Moreover, we find that actin depolymerization and AMPA receptor exocytosis are regulated for extended periods of time by miRNAs to support long-lasting spine plasticity. These findings reveal a miRNA-mediated mechanism and a role for AMPA receptor exocytosis in long-lasting spine plasticity, and identify a number of candidate miRNAs involved in LTD.

  13. Prophylactic efficacy of fluoxetine, escitalopram, sertraline, paroxetine, and concomitant psychotherapy in major depressive disorder: outcome after long-term follow-up.

    PubMed

    Peselow, Eric D; Tobia, Gabriel; Karamians, Reneh; Pizano, Demetria; IsHak, Waguih William

    2015-02-28

    The acute efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depressive disorder (MDD) is well established; however their role in longer-term prevention of recurrence remains unconfirmed. This study aims at examining: the prophylactic efficacy of four commonly used SSRIs in MDD in a naturalistic setting with long-term follow-up, the effect of concomitant cognitive behavioral therapy (CBT), and the predictors of outcome. In a prospective cohort study, 387 patients who either remitted or responded following treatment with four different SSRIs-fluoxetine, escitalopram, sertraline and paroxetine-were followed up over several years. During an average follow-up period of 34.5 months, 76.5% of patients experienced MDD recurrence. Escitalopram and fluoxetine showed a numerically higher prophylactic efficacy than paroxetine and sertraline but the difference was statistically insignificant. The prophylactic efficacy for SSRI-only treatment was limited, with a recurrence rate of 82.0%, compared to 59.0% of patient recurrence rate in concomitant Cognitive Behavioral Therapy (CBT). The relatively small size of the CBT group and the lack of randomization may undermine the extrapolation of its findings to clinical practice. Nevertheless, the study preliminary data may help in defining the clinical utility of antidepressants and CBT in the prophylaxis from MDD recurrence. PMID:25496869

  14. The small-conductance calcium-activated potassium channel is a key modulator of firing and long-term depression in the dorsal striatum

    PubMed Central

    Hopf, F. Woodward; Seif, Taban; Mohamedi, Maysha L.; Chen, Billy T.; Bonci, Antonello

    2011-01-01

    The striatum is considered to be critical for the control of goal-directed action, with the lateral dorsal striatum (latDS) being implicated in modulation of habits and the nucleus accumbens thought to represent a limbic–motor interface. Although medium spiny neurons from different striatal subregions exhibit many similar properties, differential firing and synaptic plasticity could contribute to the varied behavioral roles across subregions. Here, we examined the contribution of small-conductance calcium-activated potassium channels (SKs) to action potential generation and synaptic plasticity in adult rat latDS and nucleus accumbens shell (NAS) projection neurons in vitro. The SK-selective antagonist apamin exerted a prominent effect on latDS firing, significantly decreasing the interspike interval. Furthermore, prolonged latDS depolarization increased the interspike interval and reduced firing, and this enhancement was reversed by apamin. In contrast, NAS neurons exhibited greater basal firing rates and less regulation of firing by SK inhibition and prolonged depolarization. LatDS neurons also had greater SK currents than NAS neurons under voltage-clamp. Importantly, SK inhibition with apamin facilitated long-term depression (LTD) induction in the latDS but not the NAS, without alterations in glutamate release. In addition, SK activation in the latDS prevented LTD induction. Greater SK function in the latDS than in the NAS was not secondary to differences in sodium or inwardly rectifying potassium channel function, and apamin enhancement of firing did not reflect indirect action through cholinergic interneurons. Thus, these data demonstrate that SKs are potent modulators of action potential generation and LTD in the dorsal striatum, and could represent a fundamental cellular mechanism through which habits are regulated. PMID:20497469

  15. Gene-environment interactions affect long-term depression (LTD) through changes in dopamine receptor affinity in Snap25 deficient mice

    PubMed Central

    Baca, Michael; Allan, Andrea M.; Partridge, L. Donald; Wilson, Michael C.

    2013-01-01

    Genes and environmental conditions interact in the development of cognitive capacities and each plays an important role in neuropsychiatric disorders such as attention deficit/hyperactivity disorder (ADHD) and schizophrenia. Multiple studies have indicated that the gene for the SNARE protein SNAP-25 is a candidate susceptibility gene for ADHD, as well as schizophrenia, while maternal smoking is a candidate environmental risk factor for ADHD. We utilized mice heterozygous for a Snap25 null allele and deficient in SNAP-25 expression to model genetic effects in combination with prenatal exposure to nicotine to explore genetic and environmental interactions in synaptic plasticity and behavior. We show that SNAP-25 deficient mice exposed to prenatal nicotine exhibit hyperactivity and deficits in social interaction. Using a high frequency stimulus electrophysiological paradigm for long-term depression (LTD) induction, we examined the roles of dopaminergic D2 receptors (D2Rs) and cannabinoid CB1 receptors (CB1Rs), both critical for LTD induction in the striatum. We found that prenatal exposure to nicotine in Snap25 heterozygote null mice produced a deficit in the D2R-dependent induction of LTD, although CB1R regulation of plasticity was not impaired. We also show that prenatal nicotine exposure altered the affinity and/or receptor coupling of D2Rs, but not the number of these receptors in heterozygote null Snap25 mutants. These results refine the observations made in the coloboma mouse mutant, a proposed mouse model of ADHD, and illustrate how gene × environmental influences can interact to perturb neural functions that regulate behavior. PMID:23939223

  16. Effects of short-term and long-term treatment with medium- and long-chain triglycerides ketogenic diet on cortical spreading depression in young rats.

    PubMed

    de Almeida Rabello Oliveira, Marcela; da Rocha Ataíde, Terezinha; de Oliveira, Suzana Lima; de Melo Lucena, Ana Luíza; de Lira, Carla Emmanuela Pereira Rodrigues; Soares, Anderson Acioli; de Almeida, Clarissa Beatriz Santos; Ximenes-da-Silva, Adriana

    2008-03-21

    The ketogenic diet (KD) is a high fat and low carbohydrate and protein diet. It is used in the clinical treatment of epilepsy, in order to decrease cerebral excitability. KD is usually composed by long-chain triglycerides (LCT) while medium-chain triglycerides (MCT) diet is beginning to be used in some clinical treatment of disorders of pyruvate carboxylase enzyme and long-chain fatty acid oxidation. Our study aimed to analyze the effects of medium- and long-chain KD on cerebral electrical activity, analyzing the propagation of the phenomenon of cortical spreading depression (CSD). Three groups of weaned rats (21 days old) received, for 7 weeks, either a control (AIN-93G diet), or a MCT-KD (rich in triheptanoin oil), or a LCT-KD (rich in soybean oil). They were compared to another three groups (21 days old) receiving the same diets for just 10 days. CSD propagation was evaluated just after ending the dietary treatments. Results showed that short-term KD treatment resulted in a significant reduction of the CSD velocity of propagation (control group: 4.02+/-1.04mm/min; MCT-KD: 0.81+/-1.46mm/min and LCT-KD: 2.26+/-0.41mm/min) compared to the control group. However, long-term treatment with both KDs had no effect on the CSD velocity (control group: 3.10+/-0.41mm/min, MCT-KD: 2.91+/-1.62mm/min, LCT-KD: 3.02+/-2.26mm/min) suggesting that both short-term KDs have a positive effect in decreasing brain cerebral excitability in young animals. These data show for the first time that triheptanoin has an effect on central nervous system. PMID:18281154

  17. Necessary, but not Sufficient: Insights into the Mechanisms of mGluR Mediated Long Term Depression from a Rat Model of Early Life Seizures

    PubMed Central

    Bernard, Paul B.; Castano, Anna M.; Bayer, K. Ulrich; Benke, Tim. A.

    2014-01-01

    Using the rat model of early life seizures (ELS), which has exaggerated mGluR mediated long-term depression of synaptic strength (mGluR-LTD) in adulthood, we probed the signaling cascades underlying mGluR-LTD induction. Several inhibitors completely blocked mGluR-LTD in control but not in ELS rats: the proteasome, the mammalian target of rapamycin (mTOR), S6 kinase (S6K), or L-type voltage-gated calcium channels (L-type VGCC). Inhibition of the Ca2+/calmodulin-dependent protein kinase II (CaMKII) resulted in a near complete block of mGluR-LTD in control rats and a slight reduction of mGluR-LTD in ELS rats. “Autonomous” CaMKII was found to be upregulated in ELS rats, while elevated S6K activity, which is stimulated by mTOR, was described previously. Thus, modulation of each of these factors was necessary for mGluR-LTD induction in control rats, but even their combined, permanent activation in the ELS rats was not sufficient to individually support mGluR-LTD induction following ELS. This implies that while these factors may act sequentially in controls to mediate mGluR-LTD, this is no longer the case after ELS. In contrast, activated ERK was found to be significantly down-regulated in ELS rats. Inhibition of MEK/ERK activation in control rats elevated mGluR-LTD to the exaggerated levels seen in ELS rats. Together, these results elucidate both the mechanisms that persistently enhance mGluR-LTD after ELS and the mechanisms underlying normal mGluR-LTD by providing evidence for multiple, convergent pathways that mediate mGluR-LTD induction. With our prior work, this ties these signaling cascades to the ELS behavioral phenotype that includes abnormal working memory, fear conditioning and socialization. PMID:24780380

  18. Synergistic action of GABA-A and NMDA receptors in the induction of long-term depression in glutamatergic synapses in the newborn rat hippocampus.

    PubMed

    Pavlov, Ivan; Riekki, Ruusu; Taira, Tomi

    2004-12-01

    We show that activation of GABA(A) receptors (GABA(A)Rs) promotes induction of N-methyl-D-aspartate (NMDA) receptor (NMDAR)-dependent long-term depression (LTD) of glutamatergic synapses in the newborn rat hippocampal area CA1 in a developmentally restricted manner. In the newborn rat hippocampus two mechanistically different types of LTD of glutamatergic synapses could be induced under similar experimental conditions. The form of the LTD induced depended on the stimulation protocol and on the age of the animal. Low-frequency stimulation (1 Hz) with 100 stimuli induced a robust homosynaptic, reversible LTD at postnatal days 2-8 (P2-P8) but not at P14. This LTD was blocked by the NMDAR antagonist AP5 or by the GABA(A)R antagonist picrotoxin. Use of a low-chloride solution in the patch pipette resulting in E(GABA-A) < -70 mV blocked the NMDAR-dependent LTD, whereas clamping the cell to -40 mV during induction rescued it. In addition, it was possible to induce LTD at P14 with 100 stimuli if the cells were clamped to -40 mV during induction. Low-frequency stimulation with 900 stimuli induced a robust homosynaptic, reversible LTD both at P2-P8 and at P14. However, neither AP5 nor picrotoxin affected the LTD induced by 900 pulses at P2-P8. Instead, the 900 stimuli-induced LTD was blocked by the metabotropic glutamate receptor antagonists when co-applied with AP5. We suggest that during the first postnatal week postsynaptic depolarization provided by the activation of GABA(A)Rs shifts the threshold for the LTD induction, making the synapses more prone to activity-induced plasticity. From the second postnatal week onwards, when the GABA(A) responses are already hyperpolarizing, different mechanisms for LTD induction prevail. PMID:15579156

  19. Life Stress and the Long-Term Treatment Course of Recurrent Depression: III. Nonsevere Life Events Predict Recurrence for Medicated Patients over 3 Years

    ERIC Educational Resources Information Center

    Monroe, Scott M.; Torres, Leandro D.; Guillaumot, Julien; Harkness, Kate L.; Roberts, John E.; Frank, Ellen; Kupfer, David

    2006-01-01

    Research has consistently documented the significance of severe life events for onset of major depression. Theory, however, suggests other forms of stress are relevant for depression's recurrence. Nonsevere life events were tested in relation to depression for 126 patients with recurrent depression in a 3-year randomized maintenance protocol. Life…

  20. A single amino acid difference between the intracellular domains of amyloid precursor protein and amyloid-like precursor protein 2 enables induction of synaptic depression and block of long-term potentiation.

    PubMed

    Trillaud-Doppia, Emilie; Paradis-Isler, Nicolas; Boehm, Jannic

    2016-07-01

    Alzheimer disease (AD) is initially characterized as a disease of the synapse that affects synaptic transmission and synaptic plasticity. While amyloid-beta and tau have been traditionally implicated in causing AD, recent studies suggest that other factors, such as the intracellular domain of the amyloid-precursor protein (APP-ICD), can also play a role in the development of AD. Here, we show that the expression of APP-ICD induces synaptic depression, while the intracellular domain of its homolog amyloid-like precursor protein 2 (APLP2-ICD) does not. We are able to show that this effect by APP-ICD is due to a single alanine vs. proline difference between APP-ICD and APLP2-ICD. The alanine in APP-ICD and the proline in APLP2-ICD lie directly behind a conserved caspase cleavage site. Inhibition of caspase cleavage of APP-ICD prevents the induction of synaptic depression. Finally, we show that the expression of APP-ICD increases and facilitates long-term depression and blocks induction of long-term potentiation. The block in long-term potentiation can be overcome by mutating the aforementioned alanine in APP-ICD to the proline of APLP2. Based on our results, we propose the emergence of a new APP critical domain for the regulation of synaptic plasticity and in consequence for the development of AD. PMID:26921470

  1. Staufen 2 Regulates mGluR Long-Term Depression and Map1b mRNA Distribution in Hippocampal Neurons

    ERIC Educational Resources Information Center

    Lebeau, Genevieve; Miller, Linda C.; Tartas, Maylis; McAdam, Robyn; Laplante, Isabel; Badeaux, Frederique; DesGroseillers, Luc; Sossin, Wayne S.; Lacaille, Jean-Claude

    2011-01-01

    The two members of the Staufen family of RNA-binding proteins, Stau1 and Stau2, are present in distinct ribonucleoprotein complexes and associate with different mRNAs. Stau1 is required for protein synthesis-dependent long-term potentiation (L-LTP) in hippocampal pyramidal cells. However, the role of Stau2 in synaptic plasticity remains…

  2. Effects of long-term AA attendance and spirituality on the course of depressive symptoms in individuals with alcohol use disorder.

    PubMed

    Wilcox, Claire E; Pearson, Matthew R; Tonigan, J Scott

    2015-06-01

    Alcohol use disorder (AUD) is associated with depression. Although attendance at Alcoholics Anonymous (AA) meetings predicts reductions in drinking, results have been mixed about the salutary effects of AA on reducing depressive symptoms. In this single-group study, early AA affiliates (n = 253) were recruited, consented, and assessed at baseline, 3, 6, 9, 12, 18, and 24 months. Lagged growth models were used to investigate the predictive effect of AA attendance on depression, controlling for concurrent drinking and treatment attendance. Depression was measured using the Beck Depression Inventory (BDI) and was administered at baseline 3, 6, 12, 18, and 24 months. Additional predictors of depression tested included spiritual gains (Religious Background and Behavior questionnaire [RBB]) and completion of 12-step work (Alcoholics Anonymous Inventory [AAI]). Eighty-five percent of the original sample provided follow-up data at 24 months. Overall, depression decreased over the 24 month follow-up period. AA attendance predicted later reductions in depression (slope = -3.40, p = .01) even after controlling for concurrent drinking and formal treatment attendance. Finally, increased spiritual gains (RBB) also predicted later reductions in depression (slope = -0.10, p = .02) after controlling for concurrent drinking, treatment, and AA attendance. In summary, reductions in alcohol consumption partially explained decreases in depression in this sample of early AA affiliates, and other factors such as AA attendance and increased spiritual practices also accounted for reductions in depression beyond that explained by drinking. (PsycINFO Database Record PMID:26076099

  3. Effects of Long-Term AA Attendance and Spirituality on the Course of Depressive Symptoms in Individuals with Alcohol Use Disorder

    PubMed Central

    Wilcox, Claire E.; Pearson, Matthew R.; Tonigan, J. Scott

    2016-01-01

    Alcohol use disorder (AUD) is associated with depression. Although attendance at Alcoholics Anonymous (AA) meetings predicts reductions in drinking, results have been mixed about the salutary effects of AA on reducing depressive symptoms. In this single-group study, early AA affiliates (n=253) were recruited, consented, and assessed at baseline, 3, 6, 9, 12, 18 and 24 months. Lagged growth models were used to investigate the predictive effect of AA attendance on depression, controlling for concurrent drinking and treatment attendance. Depression was measured using the Beck Depression Inventory (BDI) and was administered at baseline 3, 6, 12, 18 and 24 months. Additional predictors of depression tested included spiritual gains, [Religious Background and Behavior questionnaire (RBB)] and completion of 12-step work [(Alcoholics Anonymous Inventory (AAI)]. Eighty-five percent of the original sample provided follow-up data at 24 months. Overall, depression decreased over the 24 month follow-up period. AA attendance predicted later reductions in depression (slope=−3.40, p= 0.01) even after controlling for concurrent drinking and formal treatment attendance. Finally, increased spiritual gains (RBB) also predicted later reductions in depression (slope=−0.10, p=0.02) after controlling for concurrent drinking, treatment, and AA attendance. In sum, reductions in alcohol consumption partially explained decreases in depression in this sample of early AA affiliates, and other factors such as AA attendance and increased spiritual practices also accounted for reductions in depression beyond that explained by drinking. PMID:26076099

  4. The Clinical Research Center for Depression Study: Baseline Characteristics of a Korean Long-Term Hospital-Based Observational Collaborative Prospective Cohort Study

    PubMed Central

    Kim, Tae-Suk; Jeong, Seung Hee; Kim, Jung-Bum; Lee, Min-Soo; Kim, Jae-Min; Yim, Hyeon-Woo

    2011-01-01

    Objective The Clinical Research Center for Depression (CRESCEND) study is a 9-year observational collaborative prospective cohort study for the clinical outcomes in participants with depressive disorders in Korea. In this study, we examined the baseline characteristics of the depressive participants as the hospital-based cohort. Methods Participants were assessed using various instruments including the Clinical Global Impression scale, 17-item Hamilton Depression Rating Scale (HDRS-17), Hamilton Anxiety Rating Scale, Brief Psychiatric Rating Scale, Social and Occupational Functioning Assessment Scale, Beck Depression Inventory-Second Edition, Scale for Suicide Ideation, and World Health Organization Quality of Life assessment instruments-abbreviated version. Also, personal histories of medical and psychiatric illnesses and the range of socio-epidemiologic and clinical data were collected from each participant. Results One thousand one hundred eighty three participants were recruited from 18 hospitals. The mean age of the participants was 47.9±15.9 year-old, 74.4% were female, 82.9% had been diagnosed of major depressive disorder, 40.9% were experiencing their first depressive episode, and 21.4% had a past history of suicide attempts. The majority (85.3%) of the participants were moderately to severely ill. The average HDRS-17 was 19.8±6.1. Significant gender differences at baseline were shown in age, education, marriage, employment, religion, and first depressive episode. Conclusion The baseline findings in the CRESCEND study showed some different characteristics of depression in Korea, suggesting a possibility of ethnic and cultural factors in depression. PMID:21519530

  5. Standardized web-based cognitive behavioural therapy of mild to moderate depression: a randomized controlled trial with a long-term follow-up.

    PubMed

    Ruwaard, Jeroen; Schrieken, Bart; Schrijver, Menno; Broeksteeg, Janneke; Dekker, Jack; Vermeulen, Hans; Lange, Alfred

    2009-01-01

    Depression is common but undertreated. Web-based self-help provides a widely accessible treatment alternative for mild to moderate depression. However, the lack of therapist guidance may limit its efficacy. The authors assess the efficacy of therapist-guided web-based cognitive behavioural treatment (web-CBT) of mild to moderate depression. Fifty-four individuals with chronic, moderate depression participated in a randomized wait-list controlled trial, with an 18-month follow-up (immediate treatment: n = 36, wait-list control: n = 18). Primary outcome measures were the Beck Depression Inventory (BDI-IA) and the Depression scale of the Symptom Checklist-90-Revised (SCL-90-R. DEP). Secondary outcome measures were the Depression Anxiety Stress Scales and the Well-Being Questionnaire. Five participants (9%) dropped out. Intention-to-treat analyses of covariance revealed that participants in the treatment condition improved significantly more than those in the wait-list control condition (.011 < p < .015). With regard to the primary measures, between-group effects (d) were 0.7 for the BDI-IA and 1.1 for the SCL-90-R DEP. Posttest SCL-90- R DEP scores indicated recovery of 49% of the participants in the treatment group compared with 6% in the control group (odds ratio = 14.5; p < .004). On average, the effects were stable up to 18 months (n = 39), although medication was a strong predictor of relapse. The results demonstrate the efficacy of web-CBT for mild to moderate depression and the importance of therapist guidance in psychological interventions. PMID:19221919

  6. Child protection and adult depression: evaluating the long-term consequences of evacuating children to foster care during World War II.

    PubMed

    Santavirta, Nina; Santavirta, Torsten

    2014-03-01

    This paper combined data collected from war time government records with survey data including background characteristics, such as factors that affected eligibility, to examine the adult depression outcomes of individuals who were evacuated from Finland to temporary foster care in Sweden during World War II. Using war time government records and survey data for a random sample of 723 exposed individuals and 1321 matched unexposed individuals, the authors conducted least squares adjusted means comparison to examine the association between evacuation and adult depression (Beck Depression Inventory). The random sample was representative for the whole population of evacuees who returned to their biological families after World War II. The authors found no statistically significant difference in depressive symptoms during late adulthood between the two groups; for example, the exposed group had a 0.41 percentage points lower average Beck Depression Inventory score than the unexposed group (p = 0.907). This study provides no support for family disruption during early childhood because of the onset of sudden shocks elevating depressive symptoms during late adulthood. PMID:23456990

  7. Oral health-related quality of life and depression/anxiety in long-term recurrence-free patients after treatment for advanced oral squamous cell cancer.

    PubMed

    Hassel, Alexander J; Danner, Daniel; Freier, Kolja; Hofele, Christof; Becker-Bikowski, Kirsten; Engel, Michael

    2012-06-01

    This report focuses on the association between oral health-related quality of life (OHRQoL) and depression/anxiety of a homogeneous group of cancer patients who were recurrence-free for 8 years after treatment for advanced oral squamous cell. Participants were 24 patients (mean age 55 years, 75% men) treated with neoadjuvant concurrent radiochemotherapy followed by surgery with a mean recurrence-free period of 95 months (from 39 to 164 months). The OHRQoL (OHIP) and the anxiety/depression (HADS) were assessed twice (1 year between t1 and t2). OHRQoL was impaired in this group (mean OHIP score 65 units). In cross-lagged correlation analysis, the correlation between OHRQoL to t1 and depression to t2 was significant and greater than the non-significant correlation for depression to t1 and OHRQoL to t2 indicating that OHRQoL predicts depression better than vice versa. However, the difference in the correlation coefficients was not significant (ZPF-test). The same was true for OHRQoL and anxiety. The OHRQoL measured with the OHIP was impaired in comparison to the normal population. In the limitations of the study design and bearing the small sample size in mind, the results give evidence that OHRQoL predicts psychological outcomes, namely depression and anxiety, better than vice versa. PMID:21733701

  8. Long-Term Results of a Web-Based Guided Self-Help Intervention for Employees With Depressive Symptoms: Randomized Controlled Trial

    PubMed Central

    2014-01-01

    Background Depressive disorders are highly prevalent in the working population and are associated with excessive costs. The evidence for effective worker-directed interventions for employees with depressive symptoms is limited. Treating employees with depressive symptoms via the Internet before they report sick from work could be beneficial and cost saving. Objective In this study, we tested the effectiveness over the period of 1 year of a Web-based guided self-help intervention, called Happy@Work, for employees with depressive symptoms who were not on sick leave. Methods A two-arm randomized controlled trial comparing a worker-directed, Web-based, guided self-help intervention to care as usual (CAU) was carried out. We recruited employees from 6 companies via the company’s Intranet and by putting up posters. The inclusion criteria were elevated depressive symptoms as measured by a score ≥16 on the Center for Epidemiologic Studies Depression scale (CES-D) and not being on sick leave. The intervention contained 6 lessons and consisted of problem-solving treatment and cognitive therapy. Participants were asked to submit weekly assignments via the website after completion of a lesson and they received feedback from a coach via the website. Self-report questionnaires on depressive symptoms (CES-D; primary outcome), burnout (Maslach Burnout Inventory, MBI), work performance (Health and Work Performance Questionnaire, HPQ), duration of absenteeism, and anxiety (Hospital Anxiety and Depression Scale, HADS; secondary outcomes), were completed at baseline, posttreatment, and at 6-, and 12-month follow-up. Several subgroup and per-protocol analyses were performed. Results A total of 231 employees were randomized to either the intervention group (n=116) or to CAU (n=115). Completion of assessments varied between 54%-74%. Improvement in depressive symptoms between baseline and posttreatment was shown in all participants and these effects sustained over time. However, there

  9. Long-Term Ketamine Self-Injections in Major Depressive Disorder: Focus on Tolerance in Ketamine's Antidepressant Response and the Development of Ketamine Addiction.

    PubMed

    Bonnet, Udo

    2015-01-01

    Sub-anaesthetic ketamine is of special interest for depression research due to its rapid and potent but short-lived antidepressant response (after-effect). The presented case is the first one in the literature which deals in detail with the transfer from ketamine's antidepressant action to ketamine addiction. A 50-year-old anaesthetic nurse, who had never been treated with antidepressants before, started with self-injecting ketamine racemate 50 mg IM once a week to cope with her major depression. She continuously stole ketamine from hospital stocks. Due to a gradually developing tolerance to ketamine's antidepressant action, she stepwise increased dose and frequency of ketamine self-injections up to daily 2 g IM (three-fold her anaesthetic dose) over six months. This was accompanied by the development of ketamine addiction, loss of consciousness, dissociative immobility, and amnesia. Inpatient detoxification treatment was characterized by a strong craving for ketamine and, later on, by the occurrence of a severe depressive episode remitting on venlafaxine. A 14-week follow-up documented a normal condition without any ketamine sequelae, such as craving, psychosis, depression, or cognitive abnormalities. Thus, awareness of ketamine addiction potential, even in patients who received ketamine for antidepressant purposes, is important. PMID:26317449

  10. The noradrenaline metabolite MHPG is a candidate biomarker between the depressive, remission, and manic states in bipolar disorder I: two long-term naturalistic case reports

    PubMed Central

    Kurita, Masatake; Nishino, Satoshi; Numata, Yukio; Okubo, Yoshiro; Sato, Tadahiro

    2015-01-01

    Background Treatment of the depressive and manic states in bipolar disorder I (BDI) is a challenge for psychiatrists. Despite the recognized importance of the switch phenomenon, the precise mechanisms underlying this process are yet to be shown. We conducted a naturalistic study in two BDI patients to determine whether biological markers (monoamine metabolites and brain-derived neurotrophic factor [BDNF]) are associated with the switch between depressive and manic states. Case presentation and methods Blood sampling and mood assessments were performed at 2-week intervals over a period of 2 (Case 1, n=72) and 6 (Case 2, n=183) years. Plasma concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were analyzed by high-performance liquid chromatography with electrochemical detection. Plasma BDNF was assayed by sandwich ELISA (enzyme-linked immunosorbent assay). Results MHPG had the highest standardized coefficient (β) in the multiple regression analysis. We found a significant positive correlation between Young Mania Rating Scale scores and plasma MHPG levels (Case 1: ρ=0.429; Case 2: ρ=0.488), and a significant negative correlation between Montgomery–Asberg Depression Rating Scale scores and MHPG levels (Case 1: ρ=−0.542; Case 2: ρ=−0.465). Conversely, no significant correlation was found between the level of BDNF and the presence of a manic or depressive state, and although HVA had a slightly stronger correlation than MHPG, the levels of neither of these were found to significantly correlate with the symptoms. Conclusion These data suggest that peripheral MHPG levels (which is related to noradrenaline levels in the brain) could be used as a biomarker of mood states in BDI. The noradrenaline level in the brain is likely to reflect the clinical characteristics of the switch process in BDI, and has prognostic significance for the treatment of both manic and depressive states. PMID:25709459

  11. Long-term testing

    NASA Astrophysics Data System (ADS)

    Ferber, M.; Graves, G. A., Jr.

    Land-based gas turbines are significantly different from automotive gas turbines in that they are designed to operate for 50,000 h or greater (compared to 5,000-10,000 h). The primary goal of this research is to determine the long-term survivability of ceramic materials for industrial gas turbine applications. Research activities in this program focus on the evaluation of the static tensile creep and stress rupture (SR) behavior of three commercially available structural ceramics which have been identified by the gas turbine manufacturers as leading candidates for use in industrial gas turbines. For each material investigated, a minimum of three temperatures and four stresses will be used to establish the stress and temperature sensitivities of the creep and SR behavior. Because existing data for many candidate structural ceramics are limited to testing times less than 2,000 h, this program will focus on extending these data to times on the order of 10,000 h, which represents the lower limit of operating time anticipated for ceramic blades and vanes in gas turbine engines. A secondary goal of the program will be to investigate the possibility of enhancing life prediction estimates by combining interrupted tensile SR tests and tensile dynamic fatigue tests in which tensile strength is measured as a function of stressing rate. The third goal of this program will be to investigate the effects of water vapor upon the SR behavior of the three structural ceramics chosen for the static tensile studies by measuring the flexural strength as a function of stressing rate at three temperatures.

  12. Long-term testing

    SciTech Connect

    Ferber, M.; Graves, G.A. Jr.

    1994-12-31

    Land-based gas turbines are significantly different from automotive gas turbines in that they are designed to operate for 50,000 h or greater (compared to 5,000--10,000 h). The primary goal of this research is to determine the long-term survivability of ceramic materials for industrial gas turbine applications. Research activities in this program focus on the evaluation of the static tensile creep and stress rupture (SR) behavior of three commercially available structural ceramics which have been identified by the gas turbine manufacturers as leading candidates for use in industrial gas turbines. For each material investigated, a minimum of three temperatures and four stresses will be used to establish the stress and temperature sensitivities of the creep and SR behavior. Because existing data for many candidate structural ceramics are limited to testing times less than 2,000 h, this program will focus on extending these data to times on the order of 10,000 h, which represents the lower limit of operating time anticipated for ceramic blades and vanes in gas turbine engines. A secondary goal of the program will be to investigate the possibility of enhancing life prediction estimates by combining interrupted tensile SR tests and tensile dynamic fatigue tests in which tensile strength is measured as a function of stressing rate. The third goal of this program will be to investigate the effects of water vapor upon the SR behavior of the three structural ceramics chosen for the static tensile studies by measuring the flexural strength as a function of stressing rate at three temperatures.

  13. Acute renal failure induced by markedly decreased appetite secondary to a depressive episode after discontinuation of long-term lithium therapy in an elderly patient with bipolar disorder

    PubMed Central

    Okada, Akira

    2014-01-01

    Some elderly patients on chronic lithium therapy for bipolar disorder and their doctors may be faced with a therapeutic dilemma over whether or not to continue prescribing/taking lithium given their increased risk of reduced renal function. We present the case of a 78-year-old woman with bipolar disorder who discontinued lithium therapy due to increased risk factors for renal injury. After discontinuation, she experienced markedly decreased appetite secondary to a depressive episode, and developed acute renal failure, which subsequently progressed to a more advanced stage of chronic kidney disease. This case suggests that extreme care must be taken to prevent the recurrence of depression in elderly patients with bipolar disorder who discontinue lithium therapy, even when they had been emotionally stable for a long time while receiving lithium. Medications other than lithium for bipolar disorder may be needed at the time lithium therapy is discontinued. PMID:24835805

  14. Sustained Implementation of Cognitive-Behavioral Therapy for Youth Anxiety and Depression: Long-term Effects of Structured Training and Consultation on Therapist Practice in the Field

    PubMed Central

    Chu, Brian C.; Crocco, Sofia Talbott; Arnold, Cassidy C.; Brown, Ruth; Southam-Gerow, Michael A.; Weisz, John R.

    2015-01-01

    Identifying factors that promote sustained implementation of evidence-based treatments (EBTs) after therapists receive training is critical for professional psychology. To address the field's minimal knowledge in this area, we interviewed community-based therapists (N = 23) who had completed intensive training in cognitive behavioral therapy (CBT) for either anxiety or depression as part of a randomized effectiveness trial (Southam-Gerow et al., 2010; Weisz et al., 2009). Therapists were interviewed three to five years after completion of the initial trial, representing one of the longest-term follow-ups of therapist practices after training. Therapists viewed each protocol and their individual CBT strategies as effective and appropriate for the majority of their current anxiety and depression caseloads. However, therapists used parts of each protocol much more frequently than the protocol as a whole (i.e., 78.5% used parts of the Coping Cat, and 7.5% used the whole protocol; 58.6% used parts of the PASCET, and 20% used the whole protocol). Therapists reported using problem-solving the most and exposure exercises the least for current anxious cases; they used cognitive restructuring the most and homework the least for current depression cases. Interventions that were more difficult to implement in usual care settings were less likely to be sustained. Future efforts should evaluate the characteristics and structure of EBTs that are most acceptable to therapists and should investigate which kinds of ongoing learning supports will maintain therapist skills in and continued use of EBTs. PMID:26366037

  15. Low-frequency stimulation induces a durable long-term depression in young adult hyperthyroid rats: the role of p38 mitogen-activated protein kinase and protein phosphatase 1.

    PubMed

    Tan, Burak; Bitiktaş, Soner; Kavraal, Şehrazat; Dursun, Nurcan; Dönmez Altuntaş, Hamiyet; Suer, Cem

    2016-06-15

    Long-term potentiation and long-term depression (LTD) are cellular mechanisms of learning and memory in the mammalian brain. We have previously shown that adult hyperthyroid rats showed a delay in the acquisition of a place learning task and attenuated long-term potentiation. However, changes in LTD in hyperthyroidism remain unclear. Rats were administered 0.2 mg/kg/day of L-thyroxine for 21 days starting at postnatal day 40 to induce hyperthyroidism. LTD was induced in the dentate gyrus using low-frequency stimulation (LFS) of the perforant pathway. The mRNA expressions of p38 mitogen-activated protein kinase (p38-MAPK) and protein phosphatase 1 (PP1) were evaluated using a quantitative reverse transcriptase PCR. In control rats, a standard LFS protocol induced a slight depression of the population spike (PS) amplitude during the induction phase of LTD (76±13% vs. baseline), but a small potentiation of the PS amplitude was observed in the early (107±18%) and late (111±20%) phases of LTD. Interestingly, in the hyperthyroid rats, the same LFS protocol induced a reliable LTD in the dentate gyrus of the hippocampus as evidenced by a marked depression in the PS amplitude during the induction (54±6% vs. baseline) and the early phases (56±8%) of LTD. Elevated mRNA levels of p38-MAPK and PP1 were observed in the hippocampus of the LFS-treated hyperthyroid rats compared with the hippocampus of the vehicle-treated hyperthyroid rats. No significant change in p38-MAPK or PP1 mRNA expression was observed in the euthyroid rats. The present study shows that a standard LFS protocol can induce a durable depression of synaptic strength and an upregulation of PP1 and p38-MAPK mRNA in hyperthyroid rats. We conclude that hyperthyroidism can induce molecular changes associated with degeneration of the hippocampus. The relationship between the levels of thyroid hormone and dementia requires further investigation. PMID:27128724

  16. Depressants

    MedlinePlus

    ... system. Doctors use them to treat things like insomnia or anxiety . But if depressant drugs (like sedatives, ... Other long-term effects include: impaired sexual function insomnia and other sleep problems breathing problems convulsions (similar ...

  17. Long-term characterization of the Flinders Sensitive Line rodent model of human depression: Behavioral and PET evidence of a dysfunctional entorhinal cortex.

    PubMed

    Thiele, S; Spehl, T S; Frings, L; Braun, F; Ferch, M; Rezvani, A H; Furlanetti, L L; Meyer, P T; Coenen, V A; Döbrössy, M D

    2016-03-01

    The etiology of depression is unknown but has been associated with dysregulation of neuronal activity at numerous loci on the limbic-cortical circuitry. The Flinders Sensitive Line (FSL) is a validated rodent model of human depression with spontaneously emerging behavioral and physiological phenotype, however, the durability and robustness of the phenotypes have not been described. The objective of the current study was to evaluate longitudinal dynamics of the depressive-like symptoms in this animal model. FSL and control rats of both genders were assessed over 8 months, characterizing their performance at different time points on motor, sensorimotor and complex learning/memory based tasks. Changes over time in physiological parameters, such as corticosterone and blood glucose levels, were monitored. Regional glucose metabolism, used as a marker of neuronal activity, was assessed at different time points using F18-FDG Positron Emission Tomography (PET). Results show that certain deficits at 2-3 months--on tests such as the Elevated Plus Maze, Object Recognition, and the Forced Swim Test--were transitory and the phenotype was no longer present when re-testing at 6-7 months of age. However, a stable impairment was detected on a learning and memory task, particularly indicating dysfunction in retention of spatial information. Furthermore, at multiple time points, the PET scan indicated a significate bilateral, hypo-metabolism in the temporal lobes in the FSL rats compared to healthy controls. The data suggests possible alterations of entorhinal cortex metabolism concomitant with specific behavioral changes and supports the importance of understanding the dynamics and the time and gender dependence of the phenotypes present. PMID:26658515

  18. Tailored lighting intervention improves measures of sleep, depression, and agitation in persons with Alzheimer’s disease and related dementia living in long-term care facilities

    PubMed Central

    Figueiro, Mariana G; Plitnick, Barbara A; Lok, Anna; Jones, Geoffrey E; Higgins, Patricia; Hornick, Thomas R; Rea, Mark S

    2014-01-01

    Background Light therapy has shown great promise as a nonpharmacological method to improve symptoms associated with Alzheimer’s disease and related dementias (ADRD), with preliminary studies demonstrating that appropriately timed light exposure can improve nighttime sleep efficiency, reduce nocturnal wandering, and alleviate evening agitation. Since the human circadian system is maximally sensitive to short-wavelength (blue) light, lower, more targeted lighting interventions for therapeutic purposes, can be used. Methods The present study investigated the effectiveness of a tailored lighting intervention for individuals with ADRD living in nursing homes. Low-level “bluish-white” lighting designed to deliver high circadian stimulation during the daytime was installed in 14 nursing home resident rooms for a period of 4 weeks. Light–dark and rest–activity patterns were collected using a Daysimeter. Sleep time and sleep efficiency measures were obtained using the rest–activity data. Measures of sleep quality, depression, and agitation were collected using standardized questionnaires, at baseline, at the end of the 4-week lighting intervention, and 4 weeks after the lighting intervention was removed. Results The lighting intervention significantly (P<0.05) decreased global sleep scores from the Pittsburgh Sleep Quality Index, and increased total sleep time and sleep efficiency. The lighting intervention also increased phasor magnitude, a measure of the 24-hour resonance between light–dark and rest–activity patterns, suggesting an increase in circadian entrainment. The lighting intervention significantly (P<0.05) reduced depression scores from the Cornell Scale for Depression in Dementia and agitation scores from the Cohen–Mansfield Agitation Inventory. Conclusion A lighting intervention, tailored to increase daytime circadian stimulation, can be used to increase sleep quality and improve behavior in patients with ADRD. The present field study, while

  19. Long-term Outcomes after Severe Shock

    PubMed Central

    Pratt, Cristina M.; Hirshberg, Eliotte L.; Jones, Jason P.; Kuttler, Kathryn G.; Lanspa, Michael J.; Wilson, Emily L.; Hopkins, Ramona O.; Brown, Samuel M.

    2014-01-01

    Background Severe shock is a life-threatening condition with very high short-term mortality. Whether the long-term outcomes among survivors of severe shock are similar to long-term outcomes of other critical illness survivors is unknown. We therefore sought to assess long-term survival and functional outcomes among 90-day survivors of severe shock and determine whether clinical predictors were associated with outcomes. Methods Seventy-six patients who were alive 90 days after severe shock (received ≥1 mcg/kg/min of norepinephrine equivalent) were eligible for the study. We measured three-year survival and long-term functional outcomes using the Medical Outcomes Study 36-Item Short-Form Health Survey, the EuroQOL 5-D-3L, the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised and an employment instrument. We also assessed the relationship between in-hospital predictors and long-term outcomes. Results The mean long-term survival was 5.1 years: 82% (62/76) of patients survived, of whom 49 were eligible for follow-up. Patients who died were older than patients who survived. Thirty-six patients completed a telephone interview a mean of five years after hospital admission. The patients’ Physical Functioning scores were below US population norms (p<0.001), whereas mental health scores were similar to population norms. Nineteen percent of the patients had symptoms of depression, 39% had symptoms of anxiety and 8% had symptoms of posttraumatic stress disorder. Thirty-six percent were disabled, and 17% were working full time. Conclusions Early survivors of severe shock had a high three-year survival rate. Patients’ long term physical and psychological outcomes were similar to those reported for cohorts of less severely ill ICU survivors. Anxiety and depression were relatively common, but only a few patients had symptoms of posttraumatic stress disorder. This study supports the observation that acute illness severity does not determine long-term

  20. Long-term environmental stewardship.

    SciTech Connect

    Nagy, Michael David

    2010-08-01

    The purpose of this Supplemental Information Source Document is to effectively describe Long-Term Environmental Stewardship (LTES) at Sandia National Laboratories/New Mexico (SNL/NM). More specifically, this document describes the LTES and Long-Term Stewardship (LTS) Programs, distinguishes between the LTES and LTS Programs, and summarizes the current status of the Environmental Restoration (ER) Project.

  1. Presynaptic long-term plasticity

    PubMed Central

    Yang, Ying; Calakos, Nicole

    2013-01-01

    Long-term synaptic plasticity is a major cellular substrate for learning, memory, and behavioral adaptation. Although early examples of long-term synaptic plasticity described a mechanism by which postsynaptic signal transduction was potentiated, it is now apparent that there is a vast array of mechanisms for long-term synaptic plasticity that involve modifications to either or both the presynaptic terminal and postsynaptic site. In this article, we discuss current and evolving approaches to identify presynaptic mechanisms as well as discuss their limitations. We next provide examples of the diverse circuits in which presynaptic forms of long-term synaptic plasticity have been described and discuss the potential contribution this form of plasticity might add to circuit function. Finally, we examine the present evidence for the molecular pathways and cellular events underlying presynaptic long-term synaptic plasticity. PMID:24146648

  2. Long-Term, Open-Label, Safety Study of Edivoxetine 12 to 18 mg Once Daily as Adjunctive Treatment for Patients With Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment.

    PubMed

    Ball, Susan G; Atkinson, Sarah; Sparks, JonDavid; Bangs, Mark; Goldberger, Celine; Dubé, Sanjay

    2015-06-01

    Long-term safety, tolerability, and efficacy of adjunctive edivoxetine hydrochloride (hereafter edivoxetine), a highly selective and potent norepinephrine reuptake inhibitor, was assessed in patients with major depressive disorder (MDD) experiencing partial response to selective serotonin reuptake inhibitor treatment. Data are from a multicenter, 54-week, open-label trial of adjunctive edivoxetine 12 to 18 mg once daily in patients with MDD who had experienced partial response by history to 6 or more weeks of current selective serotonin reuptake inhibitor therapy and who had a 17-item GRID Hamilton Rating Scale for Depression total score 16 or higher at study entry. Safety measures included discontinuation rate, treatment-emergent adverse events, serious adverse events, and vital signs. Efficacy measures included the Montgomery-Åsberg Depression Rating Scale. Of 608 patients, 328 (54%) completed the open-label adjunctive treatment. Study discontinuation due to adverse events occurred in 17.0%, and there were 13 serious adverse events (1 death). Treatment-emergent adverse events 5% or higher were nausea, hyperhidrosis, constipation, headache, dry mouth, dizziness, vomiting, insomnia, and upper respiratory tract infection. Mean increases were observed in systolic blood pressure (range, 0.0-2.3 mm Hg), diastolic blood pressure (range, 1.9-3.3 mm Hg), and pulse (range, 5.9-8.4 beats per minute). Mean improvements on the Montgomery-Åsberg Depression Rating Scale (-17.0) were observed from baseline to week 54. The safety profile from this study provides an overview of outcomes associated with edivoxetine and norepinephrine reuptake inhibition as an adjunctive treatment in patients with MDD who were treated up to 1 year. PMID:25815754

  3. A randomized, double-blinded, placebo-controlled study to evaluate the efficacy and safety of venlafaxine extended release and a long-term extension study for patients with major depressive disorder in Japan

    PubMed Central

    Higuchi, Teruhiko; Kamijima, Kunitoshi; Nakagome, Kazuyuki; Asami, Yuko; Kuribayashi, Kazuhiko; Imaeda, Takayuki

    2016-01-01

    The aim of this study was to assess antidepressant efficacy and safety of venlafaxine extended release in Japanese patients with major depressive disorder (MDD). We carried out a double-blinded, placebo-controlled, randomized study using fixed (75 mg/day) and flexible (75–225 mg/day, most patients attained to 225 mg/day) doses, followed by the long-term, open-labeled, extension study. Outpatients aged at least 20 years diagnosed with MDD were included. The primary efficacy measure was change from baseline in the Hamilton Rating Scale for Depression (HAM-D17) score at week 8; secondary efficacy measures included the Montgomery–Åsberg Depression Rating Scale, the Quick Inventory of Depressive Symptomatology self-report version, HAM-D6, and Clinical Global Impression scales in the double-blinded study. Overall, 538 patients were randomized; significant differences were observed in the primary efficacy variable in the fixed-dose group (−10.76; P=0.031), but not in the flexible-dose (−10.37; P=0.106) group compared with placebo (−9.25). However, the flexible-dose group showed significant efficacy in several secondary measures. Treatment-related adverse events in the treatment period were 51.7 and 67.8% in the fixed-dose and flexible-dose groups, respectively, versus 38.8% with placebo. Throughout the study period, no Japanese-specific adverse events were observed. Thus, venlafaxine extended release was efficacious and safe for MDD treatment in Japan. PMID:26513202

  4. Loss of GluN2B-containing NMDA receptors in CA1 hippocampus and cortex impairs long-term depression, reduces dendritic spine density and disrupts learning

    PubMed Central

    Brigman, Jonathan L.; Wright, Tara; Talani, Giuseppe; Prasad-Mulcare, Shweta; Jinde, Seiichiro; Seabold, Gail K.; Mathur, Poonam; Davis, Margaret I.; Bock, Roland; Gustin, Richard M.; Colbran, Roger J.; Alvarez, Veronica A.; Nakazawa, Kazu; Delpire, Eric; Lovinger, David M.; Holmes, Andrew

    2010-01-01

    N-methyl-D-aspartate receptors (NMDARs) are key mediators of certain forms of synaptic plasticity and learning. NMDAR complexes are heteromers composed of an obligatory GluN1 subunit and one or more GluN2 (GluN2A- GluN2D) subunits. Different subunits confer distinct physiological and molecular properties to NMDARs, but their contribution to synaptic plasticity and learning in the adult brain remains uncertain. Here, we generated mice lacking GluN2B in pyramidal neurons of cortex and CA1 subregion of hippocampus. We found that hippocampal principal neurons of adult GluN2B mutants had faster decaying NMDAR-mediated excitatory postsynaptic currents (EPSCs) than non-mutant controls, and were insensitive to GluN2B but not NMDAR antagonism. A sub-saturating form of hippocampal long-term potentiation (LTP) was impaired in the mutants, whereas a saturating form of LTP was intact. A NMDAR-dependent form of long-term depression (LTD) produced by low-frequency stimulation combined with glutamate transporter inhibition was abolished in the mutants. Additionally, mutants exhibited decreased dendritic spine density in CA1 hippocampal neurons as compared to controls. On multiple assays for corticohippocampal-mediated learning and memory (hidden platform Morris water maze, T-maze spontaneous alternation, Pavlovian trace fear conditioning), mutants were impaired. These data further demonstrate the importance of GluN2B for synaptic plasticity in the adult hippocampus and suggest a particularly critical role in LTD, at least the form studied here. The finding that loss of GluN2B was sufficient to cause learning deficits illustrates the contribution of GluN2B-mediated forms of plasticity to memory formation, with implications for elucidating NMDAR-related dysfunction in disease-related cognitive impairment. PMID:20357110

  5. Long term complications of diabetes

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000327.htm Long term complications of diabetes To use the sharing ... sores and infections. If it goes on too long, your toes, foot, or leg may need to ...

  6. Abdominal Pain, Long-Term

    MedlinePlus

    MENU Return to Web version Abdominal Pain, Long-term See complete list of charts. Ongoing or recurrent abdominal pain, also called chronic pain, may be difficult to diagnose, causing frustration for ...

  7. Speech signal recognition with the homotopic representation method

    NASA Astrophysics Data System (ADS)

    Bianchi, F.; Pocci, P.; Prina-Ricotti, L.

    1981-02-01

    Speech recognition by a computer, using homotopic representation, is introduced, including the algorithm and the processing mode for the speech signal, the result of a vowel recognition experiment, and the result of a phonetic transcription experiment with simple words composed of four phonemes. The signal is stored in a delay line of M elements and N = M + 1 outputs. Homotopic defines a pair of outputs symmetrical to the exit located in the central element of the delay line. When the products of sample homotopic outputs of the first sequence of pair sampling are found, they are separately summed to the products of the following processing. This procedure is repeated continuously so that at every instant the transform function is the result of the last processing and the weighted sum of the previous result. In tests a female /o/ is recognized as /a/. Of 320 test phonemes, 15 are mistaken and 7 are dubious.

  8. Novel agonists for serotonin 5-HT7 receptors reverse metabotropic glutamate receptor-mediated long-term depression in the hippocampus of wild-type and Fmr1 KO mice, a model of Fragile X Syndrome.

    PubMed

    Costa, Lara; Sardone, Lara M; Lacivita, Enza; Leopoldo, Marcello; Ciranna, Lucia

    2015-01-01

    Serotonin 5-HT7 receptors are expressed in the hippocampus and modulate the excitability of hippocampal neurons. We have previously shown that 5-HT7 receptors modulate glutamate-mediated hippocampal synaptic transmission and long-term synaptic plasticity. In particular, we have shown that activation of 5-HT7 receptors reversed metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD) in wild-type (wt) and in Fmr1 KO mice, a mouse model of Fragile X Syndrome in which mGluR-LTD is abnormally enhanced, suggesting that 5-HT7 receptor agonists might be envisaged as a novel therapeutic strategy for Fragile X Syndrome. In this perspective, we have characterized the basic in vitro pharmacokinetic properties of novel molecules with high binding affinity and selectivity for 5-HT7 receptors and we have tested their effects on synaptic plasticity using patch clamp on acute hippocampal slices. Here we show that LP-211, a high affinity selective agonist of 5-HT7 receptors, reverses mGluR-LTD in wt and Fmr1 KO mice, correcting a synaptic malfunction in the mouse model of Fragile X Syndrome. Among novel putative agonists of 5-HT7 receptors, the compound BA-10 displayed improved affinity and selectivity for 5-HT7 receptors and improved in vitro pharmacokinetic properties with respect to LP-211. BA-10 significantly reversed mGluR-LTD in the CA3-CA1 synapse in wt and Fmr1KO mice, indicating that BA-10 behaved as a highly effective agonist of 5-HT7 receptors and reduced exaggerated mGluR-LTD in a mouse model of Fragile X Syndrome. On the other side, the compounds RA-7 and PM-20, respectively arising from in vivo metabolism of LP-211 and BA-10, had no effect on mGluR-LTD thus did not behave as agonists of 5-HT7 receptors in our conditions. The present results provide information about the structure-activity relationship of novel 5-HT7 receptor agonists and indicate that LP-211 and BA-10 might be used as novel pharmacological tools for the therapy of Fragile X Syndrome

  9. Long Term Illness and Wages

    ERIC Educational Resources Information Center

    Sandy, Robert; Elliott, Robert R.

    2005-01-01

    Long-term illness (LTI) is a more prevalent workplace risk than fatal accidents but there is virtually no evidence for compensating differentials for a broad measure of LTI. In 1990 almost 3.4 percent of the U.K. adult population suffered from a LTI caused solely by their working conditions. This paper provides the first estimates of compensating…

  10. Long-term data archiving

    SciTech Connect

    Moore, David Steven

    2009-01-01

    Long term data archiving has much value for chemists, not only to retain access to research and product development records, but also to enable new developments and new discoveries. There are some recent regulatory requirements (e.g., FDA 21 CFR Part 11), but good science and good business both benefit regardless. A particular example of the benefits of and need for long term data archiving is the management of data from spectroscopic laboratory instruments. The sheer amount of spectroscopic data is increasing at a scary rate, and the pressures to archive come from the expense to create the data (or recreate it if it is lost) as well as its high information content. The goal of long-term data archiving is to save and organize instrument data files as well as any needed meta data (such as sample ID, LIMS information, operator, date, time, instrument conditions, sample type, excitation details, environmental parameters, etc.). This editorial explores the issues involved in long-term data archiving using the example of Raman spectral databases. There are at present several such databases, including common data format libraries and proprietary libraries. However, such databases and libraries should ultimately satisfy stringent criteria for long term data archiving, including readability for long times into the future, robustness to changes in computer hardware and operating systems, and use of public domain data formats. The latter criterion implies the data format should be platform independent and the tools to create the data format should be easily and publicly obtainable or developable. Several examples of attempts at spectral libraries exist, such as the ASTM ANDI format, and the JCAMP-DX format. On the other hand, proprietary library spectra can be exchanged and manipulated using proprietary tools. As the above examples have deficiencies according to the three long term data archiving criteria, Extensible Markup Language (XML; a product of the World Wide Web

  11. Slice orientation and muscarinic acetylcholine receptor activation determine the involvement of N-methyl D-aspartate receptor subunit GluN2B in hippocampal area CA1 long-term depression

    PubMed Central

    2011-01-01

    Background The contribution of different GluN2 subunits of the N-methyl D-aspartate (NMDA) receptor to the induction of bidirectional hippocampal synaptic plasticity is a controversial topic. As both supporting and refuting evidence for the hypothesis of subunit specialization in opposing directions of plasticity has accumulated since it was first proposed a few years ago, we hypothesize that differences in experimental conditions may have in part contributed to some of the inconsistent results from these studies. Here we investigate the controversial hypothesis that long-term depression (LTD) is preferentially induced by GluN2B-containing NMDA receptors in area CA1 of hippocampal slices. Results We find that brain slices from 2-3 week old rats prepared in the sagittal orientation have GluN2B-independent LTD whereas slices prepared in the coronal orientation have GluN2B-dependent LTD. There was no difference between the orientations in the fraction of the NMDAR EPSC sensitive to a GluN2B-selective antagonist, leading us to believe that the intracellular signaling properties of the NMDARs were different in the two preparations. Coronal slices had greater association of LTD-related intracellular signaling protein RasGRF1 with GluN2B relative to sagittal slices. Antagonism of muscarinic acetylcholine receptors (mAChRs) in the sagittal slices returned LTD to a GluN2B-dependent form and increased the association of GluN2B with RasGRF1. Conclusions These results suggest a novel form of NMDAR modulation by mAChRs and clarify some disagreement in the literature. PMID:22082088

  12. Suicidal Behavior in Long-Term Care Facilities.

    ERIC Educational Resources Information Center

    Osgood, Nancy J.; Brant, Barbara A.

    1990-01-01

    Surveyed administrators of 463 long-term care facilities concerning overt suicides and intentional life-threatening behaviors. Data revealed that White males were highest risk group. Refusal to eat, drink, or take medications were most common suicidal behaviors. Depression, loneliness, feelings of family rejection, and loss were significant…

  13. Clinical issues in long-term treatment with antidepressants.

    PubMed

    Zajecka, J M

    2000-01-01

    Historically, the emphasis in treating depression has been focused on the acute phase of treatment, with few published data on the continuation and maintenance phases of treatment. Yet the risk of depression increases with each episode, with a 50% to 90% chance of developing another episode after 1 or 2 prior episodes of depression. Moreover, subsequent episodes of depression are often of longer duration, more severe, and less responsive to treatment. Most patients with major depression require some form of long-term antidepressant treatment, and many need lifelong treatment. Optimizing efficacy and minimizing side effects are essential during both the acute and long-term phases of antidepressant treatment. Antidepressant side effects, including insomnia or somnolence, weight gain, asthenia, and sexual dysfunction, can significantly decrease patient compliance with long-term treatment for depression. Identification and management of side effects, combined with early and ongoing educational messages to the patient about treatment issues and the importance of sustaining illness remission, help improve compliance and reduce the potential for premature discontinuation of an otherwise optimal antidepressant. PMID:10714620

  14. Stapedectomy - long-term report.

    PubMed

    Shea, J J

    1982-01-01

    The long-term results with large fenestra stapedectomy with vein graft and Teflon piston are compared with results with the small fenestra stapedectomy with teflon piston directly into the vestibule. There were 1,943 operations in the former group and 2,155 in the latter when compared in 1970. One hundred consecutive patients from the beginning of each group with follow-up to present were compared. Results were generally the same with no great change in 15 and 20 years as compared to those at 5 years. The complication of perilymph fistula was caused by creating an opening in the footplate much larger than the prosthesis and was eliminated by interposing a living oval window seal if the opening was much larger than the prosthesis and a flap of lining membrane from the promontory when it was not. Other factors that influence a good result are discussed, including the type and the diameter of the piston used, the type of living oval window seal and the method of attachment to the incus. The small fenestra operation was found to be superior to the large, not only for the hearing gain achieved, but the case of performance and the freedom from complications due to migration of the prosthesis and/or the oval window seal. At present we have done about all that can be done for the conductive components. What remains is the sensorineural component which our studies indicate may be due to an autoimmune response. PMID:6897157

  15. Long Term Surface Salinity Measurements

    NASA Technical Reports Server (NTRS)

    Schmitt, Raymond W.; Brown, Neil L.

    2005-01-01

    Our long-term goal is to establish a reliable system for monitoring surface salinity around the global ocean. Salinity is a strong indicator of the freshwater cycle and has a great influence on upper ocean stratification. Global salinity measurements have potential to improve climate forecasts if an observation system can be developed. This project is developing a new internal field conductivity cell that can be protected from biological fouling for two years. Combined with a temperature sensor, this foul-proof cell can be deployed widely on surface drifters. A reliable in-situ network of surface salinity sensors will be an important adjunct to the salinity sensing satellite AQUARIUS to be deployed by NASA in 2009. A new internal-field conductivity cell has been developed by N Brown, along with new electronics. This sensor system has been combined with a temperature sensor to make a conductivity - temperature (UT) sensor suitable for deployment on drifters. The basic sensor concepts have been proven on a high resolution CTD. A simpler (lower cost) circuit has been built for this application. A protection mechanism for the conductivity cell that includes antifouling protection has also been designed and built. Mr. A.Walsh of our commercial partner E-Paint has designed and delivered time-release formulations of antifoulants for our application. Mr. G. Williams of partner Clearwater Instrumentation advised on power and communication issues and supplied surface drifters for testing.

  16. [Long-term evolution and complications of eating disorders].

    PubMed

    Nicolas, Isabelle

    2008-01-31

    Eating disorders long-term evolution is good in 50% of cases, middle in 25% (recovery from eating disorders, but still psychological suffering) and bad in 25% of cases, with chronic eating disorders, anxious or depressive comorbid disorder, and bad consequences in social patients' life. Anorexia nervosa has a considerably worse long-term outcome than bulimia nervosa or binge eating disorders. Never the less, purging bulimia nervosa is often associated with other impulsive symptoms, such as addictions and suicide attempts. Chronic undernutrition leads to main long-term medical complications of eating disorders: linear growth in adolescents with anorexia nervosa, infertility, and osteoporosis. These complications need a specific medical follow up, at least once a year, added to the psychiatric and psychotherapist follow-up. PMID:18361276

  17. Long-term solar-terrestrial observations

    NASA Technical Reports Server (NTRS)

    1988-01-01

    The results of an 18-month study of the requirements for long-term monitoring and archiving of solar-terrestrial data is presented. The value of long-term solar-terrestrial observations is discussed together with parameters, associated measurements, and observational problem areas in each of the solar-terrestrial links (the sun, the interplanetary medium, the magnetosphere, and the thermosphere-ionosphere). Some recommendations are offered for coordinated planning for long-term solar-terrestrial observations.

  18. Homotopic reciprocal functional connectivity between anterior human insulae.

    PubMed

    Lacuey, Nuria; Zonjy, Bilal; Kahriman, Emine S; Marashly, Ahmad; Miller, Jonathan; Lhatoo, Samden D; Lüders, Hans O

    2016-06-01

    The aim of this study was to investigate functional connectivity between right and left insulae in the human brain. We studied a patient with implanted depth electrodes for epilepsy surgery evaluation with stereotactically placed symmetric depth electrodes in both insulae. Bipolar 1 Hz electrical stimulation of the right and left posterior short gyri in the anterior insula evoked responses in the contralateral insular structures. These responses showed a latency of 8-24 ms. This report demonstrates for the first time bi-directional homotopic and heterotopic functional connectivity between right and left anterior insulae. The short latency of the evoked responses suggests mono- or oligo-synaptic connections, most likely via the corpus callosum. PMID:25993901

  19. Long-term preservation of Anammox bacteria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Deposit of useful microorganisms in culture collections requires long-term preservation and successful reactivation techniques. The goal of this study was to develop a simple preservation protocol for the long-term storage and reactivation of the anammox biomass. To achieve this, anammox biomass w...

  20. Long Term Preservation of Digital Information.

    ERIC Educational Resources Information Center

    Lorie, Raymond A.

    The preservation of digital data for the long term presents a variety of challenges from technical to social and organizational. The technical challenge is to ensure that the information, generated today, can survive long term changes in storage media, devices, and data formats. This paper presents a novel approach to the problem. It distinguishes…

  1. Virtual Models of Long-Term Care

    ERIC Educational Resources Information Center

    Phenice, Lillian A.; Griffore, Robert J.

    2012-01-01

    Nursing homes, assisted living facilities and home-care organizations, use web sites to describe their services to potential consumers. This virtual ethnographic study developed models representing how potential consumers may understand this information using data from web sites of 69 long-term-care providers. The content of long-term-care web…

  2. Paying for long-term care.

    PubMed Central

    Estes, C L; Bodenheimer, T

    1994-01-01

    Everyone agrees that insurance for long-term care is inadequate in the United States. Disagreement exists, however, on whether such insurance should be provided through the private or public sector. Private insurance generally uses the experience-rating principle that persons with higher risk of illness are charged higher premiums. For private insurance for long-term care, this principle creates a dilemma. Most policies will be purchased by the elderly; yet, because the elderly have a high risk of needing long-term care, only about 20% of them can afford the cost of premiums. A public-private partnership by which the government partially subsidizes private long-term-care insurance is unlikely to resolve this dilemma. Only a social insurance program for long-term care can provide universal, affordable, and equitable coverage. PMID:8128712

  3. Long Term Effects of Food Poisoning

    MedlinePlus

    ... develop chronic arthritis. Brain and nerve damage A Listeria infection can lead to meningitis, an inflammation of ... brain. If a newborn infant is infected with Listeria , long-term consequences may include mental retardation, seizures, ...

  4. Mental Health in Long Term Care Settings.

    ERIC Educational Resources Information Center

    Shore, Herbert

    1978-01-01

    There are many ways in which long-term care facilities attempt to cope with the mental health problems of the elderly. The author reviews five factors crucial to effective care for the aged in these facilities. (Author/RK)

  5. Asthma Medicines: Long-Term Control

    MedlinePlus

    ... Español Text Size Email Print Share Asthma Medicines: Long-term Control Page Content Article Body Corticosteroids Synthetic ... and sprinkle forms are available for young children. Long-Acting Beta2-Agonists Medications in the beta 2 - ...

  6. Long-term Synaptic Plasticity: Circuit Perturbation and Stabilization

    PubMed Central

    Jung, Sung-Cherl; Eun, Su-Yong

    2014-01-01

    At central synapses, activity-dependent synaptic plasticity has a crucial role in information processing, storage, learning, and memory under both physiological and pathological conditions. One widely accepted model of learning mechanism and information processing in the brain is Hebbian Plasticity: long-term potentiation (LTP) and long-term depression (LTD). LTP and LTD are respectively activity-dependent enhancement and reduction in the efficacy of the synapses, which are rapid and synapse-specific processes. A number of recent studies have a strong focal point on the critical importance of another distinct form of synaptic plasticity, non-Hebbian plasticity. Non-Hebbian plasticity dynamically adjusts synaptic strength to maintain stability. This process may be very slow and occur cell-widely. By putting them all together, this mini review defines an important conceptual difference between Hebbian and non-Hebbian plasticity. PMID:25598658

  7. Long-term Multiwavelength Observations of Polars

    NASA Astrophysics Data System (ADS)

    Santana, Joshua; Mason, Paul A.

    2016-06-01

    Polars are cataclysmic variables with the highest magnetic field strengths (10-250 MG). Matter is accreted after being funneled by the strong magnetic field of the white dwarf. We perform a meta-study of multi-wavelength data of polars. Many polars have been observed in surveys, such as SDSS, 2MASS, ROSAT, just to name a few. Some polars have now been detected by the JVLA, part of an expanding class of radio CVs. A large subset of polars have long-term optical light curves from CRTS and AAVSO. We suggest that the long term light curves of polars display a variety of signature behaviors and may be grouped accordingly. Additional characteristics such a binary period, magnetic field strengths, X-ray properties, and distance estimates are examined in context with long-term observations.

  8. Scenarios for long-term analysis

    SciTech Connect

    Wolbers, Stephen; /Fermilab

    2009-01-01

    Data Preservation and Long-Term Analysis of High Energy Physics (HEP) Experiments data is described and summarized in this talk. The summary covers information presented at the First Workshop on Data Preservation and Long-Term Analysis. Experiments representing e{sup +}e{sup -} collisions (LEP, B Factories and CLEO), ep collisions (H1 and ZEUS), p{bar p} collisions (CDF and D0) and others presented interesting information related to utilizing the large datasets collected over many years at these HEP facilities. Many questions and issues remain to be explored.

  9. Long-Term Use of Benzodiazepines

    PubMed Central

    Potts, Nicholas L.S.; Krishnan, K. Ranga R.

    1992-01-01

    Problems associated with physical dependence and abuse of benzodiazepines by a small percentage of patients have reduced their popularity from the most commonly prescribed psychoactive drug in the 1970s to being prescribed for mainly short periods. Patients who benefit from long-term benzodiazepine use are nearly ignored by the medical community as a whole. This article details what patient population can improve from long-term benzodiazepine therapy, the risks and benefits of treatment, and how to select appropriate candidates. PMID:21229127

  10. LONG TERM HYDROLOGICAL IMPACT ASSESSMENT (LTHIA)

    EPA Science Inventory

    LTHIA is a universal Urban Sprawl analysis tool that is available to all at no charge through the Internet. It estimates impacts on runoff, recharge and nonpoint source pollution resulting from past or proposed land use changes. It gives long-term average annual runoff for a lan...

  11. Long Term Care Aide. Course Outline.

    ERIC Educational Resources Information Center

    Wilbee, Judy

    This course outline is intended to assist the instructor in the development of a curriculum for a long-term care aide program by specifying one component of the curriculum--the objectives. These objectives, or competencies expected as outcomes for student performance on completion of the program, describe the capabilities an individual must…

  12. Who Recommends Long-Term Care Matters

    ERIC Educational Resources Information Center

    Kane, Robert L.; Bershadsky, Boris; Bershadsky, Julie

    2006-01-01

    Purpose: Making good consumer decisions requires having good information. This study compared long-term-care recommendations among various types of health professionals. Design and Methods: We gave randomly varied scenarios to a convenience national sample of 211 professionals from varying disciplines and work locations. For each scenario, we…

  13. Long-term fixed income market structure

    NASA Astrophysics Data System (ADS)

    Grilli, Luca

    2004-02-01

    Long-term fixed income market securities present a strong positive correlation in daily returns. By using a metrical approach and considering “modified” time series, I show how it is possible to show a more complex structure which depends strictly on the maturity date.

  14. Professionalism in Long-Term Care Settings

    ERIC Educational Resources Information Center

    Lubinski, Rosemary

    2006-01-01

    Speech-language pathologists who serve elders in a variety of long-term care settings have a variety of professional skills and responsibilities. Fundamental to quality service is knowledge of aging and communication changes and disorders associated with this process, institutional alternatives, and the changing nature of today's elders in…

  15. NATIONAL LONG TERM CARE SURVEY (NLTCS)

    EPA Science Inventory

    National Long Term Care Surveys (NLTCS) are surveys of the entire aged population with a particular emphasis on the functionally impaired. Longitudinal study of the health and well-being of elderly Americans. Information about the population of chronically disabled elderly person...

  16. Long-Term Memory and Learning

    ERIC Educational Resources Information Center

    Crossland, John

    2011-01-01

    The English National Curriculum Programmes of Study emphasise the importance of knowledge, understanding and skills, and teachers are well versed in structuring learning in those terms. Research outcomes into how long-term memory is stored and retrieved provide support for structuring learning in this way. Four further messages are added to the…

  17. Long-Term Stability of Social Participation

    ERIC Educational Resources Information Center

    Hyyppa, Markku T.; Maki, Juhani; Alanen, Erkki; Impivaara, Olli; Aromaa, Arpo

    2008-01-01

    The long-term stability of social participation was investigated in a representative urban population of 415 men and 579 women who had taken part in the nationwide Mini-Finland Health Survey in the years 1978-1980 and were re-examined 20 years later. Stability was assessed by means of the following tracking coefficients: kappa, proportion of…

  18. [Long-term plasticity of HVC-RA synapses in adult male zebra finches].

    PubMed

    Li, Feng-Ling; Li, Dong-Feng

    2013-12-25

    Long-term synaptic plasticity is considered as a key part of the neural mechanism of learning and memory. The production of learned vocalization of male zebra finches is closely related to high vocal center (HVC)-robust nucleus of the arcopallium (RA) pathway. However, the long-term plasticity of HVC-RA synapses is unclear. This study investigated the long-term plasticity of HVC-RA synapses in adult male zebra finches through in vivo field potential recording. The results showed that physiologic stimulation, i.e., δ rhythmic stimulation and low frequency stimulation could not effectively induce long-term synaptic plasticity. The former leaded to no change of the amplitudes of evoked population spikes, and the latter induced short-term depression (STD) of the amplitudes of the second evoked population spikes caused by paired pulses. But high frequency stimulation induced long-term depression (LTD) of the amplitudes of evoked population spikes to show out long-term synaptic plasticity. These results suggest that LTD represents the long-term plasticity of HVC-RA synapses in adult male zebra finches, which may be a key part of the neural mechanism of vocal learning and memory and can explain the plasticity of adult song to some degree. PMID:24343715

  19. Long term mortality in burned children

    PubMed Central

    Stamboulian, Daniel; Lede, Roberto

    2015-01-01

    Studies about risk factors for mortality in burn children are scarce and are even less in the follow up of this population across time. Usually, after complete event attendance, children are not follow-up as risk patients, burn injury affects all facets of life. Integration of professionals from different disciplines has enabled burn centers to develop collaborative methods of assessing the quality of care delivered to patients with burns. In this editorial we comment the paper of Duke et al. The authors highlight the importance of maintaining a long-term monitoring of children who suffered burns. The importance of this original study is to promote the reconsideration of clinical guides of long-term follow-up of burn patients. PMID:26835375

  20. Long term mortality in burned children.

    PubMed

    Rosanova, María Teresa; Stamboulian, Daniel; Lede, Roberto

    2015-07-01

    Studies about risk factors for mortality in burn children are scarce and are even less in the follow up of this population across time. Usually, after complete event attendance, children are not follow-up as risk patients, burn injury affects all facets of life. Integration of professionals from different disciplines has enabled burn centers to develop collaborative methods of assessing the quality of care delivered to patients with burns. In this editorial we comment the paper of Duke et al. The authors highlight the importance of maintaining a long-term monitoring of children who suffered burns. The importance of this original study is to promote the reconsideration of clinical guides of long-term follow-up of burn patients. PMID:26835375

  1. Long-term safety of retinoid therapy.

    PubMed

    Vahlquist, A

    1992-12-01

    The concern about long-term toxicity of oral synthetic retinoids has developed because many patients, especially those with genodermatoses, require lifelong therapy. Several organ systems are at risk, especially the hepatic, skeletal, and cardiovascular systems. Although acute hepatotoxicity is a rare side effect of etretinate and acitretin therapy, prospective studies have not demonstrated chronic liver toxicity. The frequency of bone changes induced by retinoids is difficult to estimate, because this adverse effect is usually asymptomatic and requires x-ray or scintigraphic examination for detection. Atherosclerosis develops in many patients who receive long-term retinoid therapy, but the extent to which the process is aggravated by drug-induced hyperlipidemia is not known. Many patients have now been treated with either etretinate or isotretinoin continuously for as many as 15 years and have not developed any signs of severe chronic toxicity. However, continued intense surveillance is recommended for patients expected to require lifelong therapy. PMID:1460122

  2. [Taiwan long-term care insurance and the evolution of long-term care in Japan].

    PubMed

    Huang, Hui-Wen; Liu, Shu-Hui; Pai, Yu-Chu

    2010-08-01

    The proportion of elderly (65 years of age and older) in Taiwan has exceeded 10% since 2008. With more elderly, the number of patients suffering from dementia and disabilities has also been rapidly increasing. Japan also has been facing increasing demand for long-term care due to an aging society. Prior to 2000, social welfare programs in Japan, working to cope with changing needs, typically provided insufficient services, and geriatric patients were hospitalized unnecessarily, wasting medical resources and causing undue patient hardship. In response, Japan launched its long-term care insurance program in April 2000. Under the program, city, town and village-based organizations should take responsibility for providing care to the elderly in their place of residence. The program significantly improved previous financial shortfalls and long-term care supply and demand has been met by existing social welfare organization resources. In Taiwan, the provision of long-term care by county / city authorities has proven inconsistent, with performance deemed poor after its first decade of long-term care operations. Service was found to be affected by differences in available resources and insufficient long-term care administration. The cultures of Taiwan and Japan are similar. The authors visited the Japan Long-Term Care Insurance Institute in August 2009. Main issues involved in the implementation and evolution of the Japan long-term Care Insurance are reported on in this paper. We hope such may be useful information to those working to develop long-term care programs in Taiwan. PMID:20661859

  3. Long-term orbital lifetime predictions

    NASA Astrophysics Data System (ADS)

    Dreher, P. E.; Lyons, A. T.

    1990-10-01

    Long-term orbital lifetime predictions are analyzed. Predictions were made for three satellites: the Solar Max Mission (SMM), the Long Duration Exposure Facility (LDEF), and the Pegasus Boiler Plate (BP). A technique is discussed for determining an appropriate ballistic coefficient to use in the lifetime prediction. The orbital decay rate should be monitored regularly. Ballistic coefficient updates should be done whenever there is a significant change in the actual decay rate or in the solar activity prediction.

  4. Long-term sequelae of electrical injury

    PubMed Central

    Wesner, Marni L.; Hickie, John

    2013-01-01

    Abstract Objective To summarize the current evidence-based knowledge about the long-term sequelae of injuries from electrical current. Quality of evidence MEDLINE was searched for English-language articles published in the past 20 years using the following search terms: electrical, injuries, wound, trauma, accident, sequelae, long-term, follow-up, and aftereffects. For obvious reasons, it is unethical to randomly study electrical injury in controlled clinical trials. By necessity, this topic is addressed in less-rigorous observational and retrospective work and case studies. Therefore, the strength of the literature pertaining to the long-term sequelae of electrical injury is impaired by the necessity of retrospective methods and case studies that typically describe small cohorts. Main message There are 2 possible consequences of electrical injury: the person either survives or dies. For those who survive electrical injury, the immediate consequences are usually obvious and often require extensive medical intervention. The long-term sequelae of the electrical injury might be more subtle, pervasive, and less well defined, but can include neurologic, psychological, and physical symptoms. In the field of compensation medicine, determining causation and attributing outcome to an injury that might not result in objective clinical findings becomes a considerable challenge. Conclusion The appearance of these consequences of electrical injury might be substantially delayed, with onset 1 to 5 or more years after the electrical injury. This poses a problem for patients and health care workers, making it hard to ascribe symptoms to a remote injury when they might not arise until well after the incident event. PMID:24029506

  5. Long-term home hemodialysis in children

    PubMed Central

    Borra, Sonia; Kaye, Michael

    1971-01-01

    Experience with chronic hemodialysis as a definitive form of therapy is described for six children aged 11 to 15 years at the onset. Duration on dialysis in the home has been between one and 4½ years. All patients are alive and rehabilitated without serious complications. It is concluded that although transplantation is the most desirable form of treatment for children, long-term hemodialysis is an alternative acceptable second choice. ImagesFIG. 2 PMID:5150193

  6. Long-term Variation of AGNs

    NASA Astrophysics Data System (ADS)

    Fan, J. H.; Xie, G. Z.; Adam, G.; Copin, Y.; Lin, R. G.; Bai, J. M.; Quin, Y. P.

    In this paper we will present the long-term variation in the optical and the infrared bands for some selected AGNs. 1. Some new optical data observed by us have been presented for BL Lacertae (1995-1996) and OJ 287 (1994-1995), and new infrared data are presented for OJ 287 (Nov=2E 1995), which corresponds to the second optical peak (Sillanpaa et al. 1996; Takalo et al. 1996) and during last outburst. 2. For objects with long term observations, the Jurkevich's method has been used to analyses the long-term variation period. It is interesting that the reported periods of AGNs are of the similar value of about 10 years: 3C 345 11.4 years (Webb et al. 1988), 3C 120 15 years (Belokon et al. 1987; Hagen-Thorn et al. 1997), ON 231 13.6 years (Liu et al. 1995), OJ 287 12 years (Sillanpaa et al. 1988; Kidger et al. 1992), PKS 0735+178 14 years (Fan et al. 1997), NGC 4151 15 years (Fan et al. 1998a), BL Lacertae 14.0 years (Fan et al. 1998b). Is the mechanism for the long-term variation the same for different AGNs? 3. The DCF method has been adopted to analysis the variation correlation in the optical and infrared bands for BL Lac object OJ 287, the results show that these two bands are strongly correlated, which suggest that the emission mechanism in the two bands is the same. 4. For the optical and infrared bands, the maximum variations are correlated.

  7. Long-term consequences of anorexia nervosa.

    PubMed

    Meczekalski, Blazej; Podfigurna-Stopa, Agnieszka; Katulski, Krzysztof

    2013-07-01

    Anorexia nervosa (AN) is a psychiatric disorder that occurs mainly in female adolescents and young women. The obsessive fear of weight gain, critically limited food intake and neuroendocrine aberrations characteristic of AN have both short- and long-term consequences for the reproductive, cardiovascular, gastrointestinal and skeletal systems. Neuroendocrine changes include impairment of gonadotropin releasing-hormone (GnRH) pulsatile secretion and changes in neuropeptide activity at the hypothalamic level, which cause profound hypoestrogenism. AN is related to a decrease in bone mass density, which can lead to osteopenia and osteoporosis and a significant increase in fracture risk in later life. Rates of birth complications and low birth weight may be higher in women with previous AN. The condition is associated with fertility problems, unplanned pregnancies and generally negative attitudes to pregnancy. During pregnancy, women with the condition have higher rates of hyperemesis gravidarum, anaemia and obstetric complications, as well as impaired weight gain and compromised intrauterine foetal growth. It is reported that 80% of AN patients are affected by a cardiac complications such as sinus bradycardia, a prolonged QT interval on electrocardiography, arrythmias, myocardial mass modification and hypotension. A decrease in bone mineral density (BMD) is one of the most important medical consequences of AN. Reduced BMD may subsequently lead to a three- to seven-fold increased risk of spontaneous fractures. Untreated AN is associated with a significant increase in the risk of death. Better detection and sophisticated therapy should prevent the long-term consequences of this disorder. The aims of treatment are not only recovery but also prophylaxis and relief of the long-term effects of this disorder. Further investigations of the long-term disease risk are needed. PMID:23706279

  8. Titanium for long-term tritium storage

    SciTech Connect

    Heung, L.K.

    1994-12-01

    Due to the reduction of nuclear weapon stockpile, there will be an excess of tritium returned from the field. The excess tritium needs to be stored for future use, which might be several years away. A safe and cost effective means for long term storage of tritium is needed. Storing tritium in a solid metal tritide is preferred to storing tritium as a gas, because a metal tritide can store tritium in a compact form and the stored tritium will not be released until heat is applied to increase its temperature to several hundred degrees centigrade. Storing tritium as a tritide is safer and more cost effective than as a gas. Several candidate metal hydride materials have been evaluated for long term tritium storage. They include uranium, La-Ni-Al alloys, zirconium and titanium. The criteria used include material cost, radioactivity, stability to air, storage capacity, storage pressure, loading and unloading conditions, and helium retention. Titanium has the best combination of properties and is recommended for long term tritium storage.

  9. [Long-term survival after severe trauma].

    PubMed

    Mutschler, W; Mutschler, M; Graw, M; Lefering, R

    2016-07-01

    Long-term survival after severe trauma is rarely addressed in German trauma journals although knowledge of life expectancy and identification of factors contributing to increased mortality are important for lifetime care management, development of service models, and targeting health promotion and prevention interventions. As reliable data in Germany are lacking, we compiled data mainly from the USA and Australia to describe life expectancy, risk factors, and predictors of outcome in patients experiencing traumatic spinal cord injury, traumatic brain injury, and polytrauma. Two years after trauma, life expectancy in all three categories was significantly lower than that of the general population. It depends strongly on severity of disability, age, and gender and is quantifiable. Whereas improvements in medical care have led to a marked decline in short-term mortality, surprisingly long-term survival in severe trauma has not changed over the past 30 years. Therefore, there is need to intensify long-term trauma patient care and to find new strategies to limit primary damage. PMID:27342106

  10. Homotopic approach and pseudospectral method applied jointly to low thrust trajectory optimization

    NASA Astrophysics Data System (ADS)

    Guo, Tieding; Jiang, Fanghua; Li, Junfeng

    2012-02-01

    The homotopic approach and the pseudospectral method are two popular techniques for low thrust trajectory optimization. A hybrid scheme is proposed in this paper by combining the above two together to cope with various difficulties encountered when they are applied separately. Explicitly, a smooth energy-optimal problem is first discretized by the pseudospectral method, leading to a nonlinear programming problem (NLP). Costates, especially their initial values, are then estimated from Karush-Kuhn-Tucker (KKT) multipliers of this NLP. Based upon these estimated initial costates, homotopic procedures are initiated efficiently and the desirable non-smooth fuel-optimal results are finally obtained by continuing the smooth energy-optimal results through a homotopic algorithm. Two main difficulties, one due to absence of reasonable initial costates when the homotopic procedures are being initiated and the other due to discontinuous bang-bang controls when the pseudospectral method is applied to the fuel-optimal problem, are both resolved successfully. Numerical results of two scenarios are presented in the end, demonstrating feasibility and well performance of this hybrid technique.

  11. A surface-based technique for mapping homotopic interhemispheric connectivity: Development, characterization, and clinical application.

    PubMed

    Tobyne, Sean M; Boratyn, Daria; Johnson, Jessica A; Greve, Douglas N; Mainero, Caterina; Klawiter, Eric C

    2016-08-01

    The functional organization of the human brain consists of a high degree of connectivity between interhemispheric homologous regions. The degree of homotopic organization is known to vary across the cortex and homotopic connectivity is high in regions that share cross-hemisphere structural connections or are activated by common input streams (e.g., the visual system). Damage to one or both regions, as well as damage to the connections between homotopic regions, could disrupt this functional organization. Here were introduce and test a computationally efficient technique, surface-based homotopic interhermispheric connectivity (sHIC), that leverages surface-based registration and processing techniques in an attempt to improve the spatial specificity and accuracy of cortical interhemispheric connectivity estimated with resting state functional connectivity. This technique is shown to be reliable both within and across subjects. sHIC is also characterized in a dataset of nearly 1000 subjects. We confirm previous results showing increased interhemispheric connectivity in primary sensory regions, and reveal a novel rostro-caudal functionally defined network level pattern of sHIC across the brain. In addition, we demonstrate a structural-functional relationship between sHIC and atrophy of the corpus callosum in multiple sclerosis (r = 0.2979, p = 0.0461). sHIC presents as a sensitive and reliable measure of cortical homotopy that may prove useful as a biomarker in neurologic disease. Hum Brain Mapp 37:2849-2868, 2016. © 2016 Wiley Periodicals, Inc. PMID:27219660

  12. [Long-term treatment with amiodarone].

    PubMed

    Baedeker, W; Goedel-Meinen, L; Schmidt, G; Hofmann, M; Barthel, P; Blömer, H

    1991-02-01

    The aim of this study was to investigate the efficacy and the side effects of a long-term treatment with amiodarone. We analyzed the data of 41 patients in whom amiodarone therapy had been initiated between 1974 and 1984. Twenty-one patients had dilative cardiomyopathy, 14 patients had chronic myocardial infarction, four patients suffered from WPW syndrome with intermittent atrial fibrillation, one patient had aortic valve surgery, whereas in one patient there was no clinical evidence of a heart disease. All patients had salvos of ventricular extrasystoles, ventricular tachycardia or documented intermittent ventricular fibrillation. There have been seven drop-outs up to the present time. In each patient, the lowest antiarrhythmically effective dose was applied, which was generally higher in patients with low ejection fraction. Effective treatment of the ventricular tachycardia was achieved in 55-92% of patients and did not depend on the duration of treatment. In 10 patients in whom amiodarone therapy had to be stopped for various reasons. Sudden cardiac death was slightly more frequent than in the 24 patients treated with amiodarone, though the difference was not significant. In cases with a history of syncope the prognosis was poor, even with amiodarone therapy. Due to side effects, a dosage reduction or discontinuation of amiodarone treatment became necessary in 14 patients. Amiodarone proved to be an effective drug also for the long-term treatment of ventricular tachycardia, and possibly for the prevention of sudden cardiac death. With the exception of blue skin color, there was no accumulation of side effects, even during long-term treatment of several years. PMID:1711739

  13. Long-term EARLINET dust observations

    NASA Astrophysics Data System (ADS)

    Mona, Lucia; Amiridis, Vassilis; Amodeo, Aldo; Binietoglou, Ioannis; D'Amico, Giuseppe; Schwarz, Anja; Papagiannopoulos, Nikolaos; Papayannis, Alexandros; Sicard, Michael; Comeron, Adolfo; Pappalardo, Gelsomina

    2015-04-01

    Systematic observations of Saharan dust events over Europe are performed from May 2000 by EARLINET, the European Aerosol Research LIdar NETwork. EARLINET is a coordinated network of stations that make use of advanced lidar methods for the vertical profiling of aerosols. The backbone of EARLINET network is a common schedule for performing the measurements and the quality assurance of instruments/data. Particular attention is paid to monitoring the Saharan dust intrusions over the European continent. The geographical distribution of the EARLINET stations is particularly appealing for the dust observation, with stations located all around the Mediterranean and in the center of the Mediterranean (Italian stations) where dust intrusions are frequent, and with several stations in the central Europe where dust penetrates occasionally. All aerosol backscatter and extinction profiles related to observations collected during these alerts are grouped in the devoted "Saharan dust" category of the EARLINET database. This category consists of about 4700 files (as of December 2013). Case studies involving several stations around Europe selected from this long-term database have been provided the opportunity to investigate dust modification processes during transport over the continent. More important, the long term EARLINET dust monitoring allows the investigation of the horizontal and vertical extent of dust outbreaks over Europe and the climatological analysis of dust optical intensive and extensive properties at continental scale. This long-term database is also a unique tool for a systematic comparison with dust model outputs and satellite-derived dust products. Because of the relevance for both dust modeling and satellite retrievals improvement, results about desert dust layers extensive properties as a function of season and source regions are investigated and will be presented at the conference. First comparisons with models outputs and CALIPSO dust products will be

  14. Timber beams subjected to long - term loading

    NASA Astrophysics Data System (ADS)

    Sógel, K.

    2010-09-01

    Wood is a significant structural material, which is often used for timber bearing structures. Elements of timber structures must especially satisfy safety requirements, which are expressed by the ultimate limit states in the established standards. The structure must also satisfy the serviceability limit states. Local and global deformations make it impossible for the structure to serve the purpose it was designed for. It is important to take the deflections and their possible increase into account in the design to provide a structure which can be used during the whole period of service. Based on earlier examinations, it is known that a timber element over the course of long-term loading shows creep behavior. The structure of wood is able to adapt to the conditions of the surrounding environment. The properties of wood are especially affected by the relative humidity of the air and then by the type, intensity and duration of the loading. The most important factors affecting the serviceability of timber structures are volume changes caused by humidity and additional deflections caused by the effects of long-term loading. These phenomena emphasize the importance of serviceability limit states for timber structures. The paper deals with a long-term experimental investigation of timber girders that are currently often used. The aim was to obtain the deflection curves and mark the time dependence and the final deflections. The paper will also define the approximations for simulating the time-dependent deflections and obtain the creep coefficients for calculating the final deflections of the girders investigated.

  15. Long-Term Wind Power Variability

    SciTech Connect

    Wan, Y. H.

    2012-01-01

    The National Renewable Energy Laboratory started collecting wind power data from large commercial wind power plants (WPPs) in southwest Minnesota with dedicated dataloggers and communication links in the spring of 2000. Over the years, additional WPPs in other areas were added to and removed from the data collection effort. The longest data stream of actual wind plant output is more than 10 years. The resulting data have been used to analyze wind power fluctuations, frequency distribution of changes, the effects of spatial diversity, and wind power ancillary services. This report uses the multi-year wind power data to examine long-term wind power variability.

  16. Long-term outcomes in multiple gestations.

    PubMed

    Rand, Larry; Eddleman, Keith A; Stone, Joanne

    2005-06-01

    Children born from a multiple gestation are at increased risk for cerebral palsy, learning disability, and language and neurobehavioral deficits. With the increased incidence of multiple pregnancies and use of assisted reproductive technology (ART), these issues are more commonly affecting parents. Long-term outcomes are a critical part of preconceptual and early pregnancy counseling for parents faced with a multiple gestation or considering ART, and the provider should be well versed on issues surrounding zygosity, gestational age, higher-order multiples, and the effects of options such as multifetal pregnancy reduction. PMID:15922795

  17. Long-Term Solar Irradiance Variability

    NASA Technical Reports Server (NTRS)

    Pap, J. M.

    1996-01-01

    Measurements of the solar energy throughout the solar spectrum and understanding its variability provide important information about the physical processes and structural changes in the solar interior and in the solar atmosphere...The aim of this paper is to discuss the solar-cycle-related long-term changes in solar total and UV irradiances. The spaceborne irradiance observations are compared to ground-based indices of solar magnetic activity, such as the Photometric Sunspot Index, full disk magnetic flux, and the Mt. Wilson Magnetic Plage Strength Index.

  18. Long Term Archiving and CCSDS Standards

    NASA Astrophysics Data System (ADS)

    Boucon, Danièle

    This article presents some conceptual and implementation CCSDS -Consultative Committee for Space Data Systemsstandards for long term archiving. It focuses on the most recent one, the Producer Archive Interface Specification (PAIS) standard. This standard, currently available as a draft on the CCSDS web site, will be published by the beginning of 2014. It will enable the Producer to share with the Archive a sufficiently precise and unambiguous formal definition of the Digital Objects to be produced and transferred, by means of a model. It will also enable a precise definition of the packaging of these objects in the form of Submission Information Packages (SIPs), including the order in which they should be transferred.

  19. Human Behaviour in Long-Term Missions

    NASA Technical Reports Server (NTRS)

    1997-01-01

    In this session, Session WP1, the discussion focuses on the following topics: Psychological Support for International Space Station Mission; Psycho-social Training for Man in Space; Study of the Physiological Adaptation of the Crew During A 135-Day Space Simulation; Interpersonal Relationships in Space Simulation, The Long-Term Bed Rest in Head-Down Tilt Position; Psychological Adaptation in Groups of Varying Sizes and Environments; Deviance Among Expeditioners, Defining the Off-Nominal Act in Space and Polar Field Analogs; Getting Effective Sleep in the Space-Station Environment; Human Sleep and Circadian Rhythms are Altered During Spaceflight; and Methodological Approach to Study of Cosmonauts Errors and Its Instrumental Support.

  20. Performance considerations in long-term spaceflight

    NASA Technical Reports Server (NTRS)

    Akins, F. R.

    1979-01-01

    Maintenance of skilled performance during extended space flight is of critical importance to both the health and safety of crew members and to the overall success of mission goals. An examination of long term effects and performance requirements is therefore a factor of immense importance to the planning of future missions. Factors that were investigated include: definition of performance categories to be investigated; methods for assessing and predicting performance levels; in-flight factors which can affect performance; and factors pertinent to the maintenance of skilled performance.

  1. 47 CFR 54.303 - Long term support.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Long term support. 54.303 Section 54.303... SERVICE Universal Service Support for High Cost Areas § 54.303 Long term support. (a) Beginning January 1... shall receive Long Term Support. Beginning July 1, 2004, no carrier shall receive Long Term Support....

  2. 47 CFR 54.303 - Long term support.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 3 2011-10-01 2011-10-01 false Long term support. 54.303 Section 54.303... SERVICE Universal Service Support for High Cost Areas § 54.303 Long term support. (a) Beginning January 1... shall receive Long Term Support. Beginning July 1, 2004, no carrier shall receive Long Term Support....

  3. Long-term prescribing of antidepressants in the older population: a qualitative study

    PubMed Central

    Dickinson, Rebecca; Knapp, Peter; House, Allan O; Dimri, Vandana; Zermansky, Arnold; Petty, Duncan; Holmes, John; Raynor, David K

    2010-01-01

    Background High rates of long-term antidepressant prescribing have been identified in the older population. Aims To explore the attitudes of older patients and their GPs to taking long-term antidepressant therapy, and their accounts of the influences on long-term antidepressant use. Design of study Qualitative study using in-depth semi-structured interviews. Setting One primary care trust in North Bradford. Method Thirty-six patients aged ≥75 years and 10 GPs were interviewed. Patients were sampled to ensure diversity in age, sex, antidepressant type, and home circumstances. Results Participants perceived significant benefits and expressed little apprehension about taking long-term antidepressants, despite being aware of the psychological and social factors involved in onset and persistence of depression. Barriers to discontinuation were identified following four themes: pessimism about the course and curability of depression; negative expectations and experiences of ageing; medicine discontinuation perceived by patients as a threat to stability; and passive (therapeutic momentum) and active (therapeutic maintenance) decisions to accept the continuing need for medication. Conclusion There is concern at a public health level about high rates of long-term antidepressant prescribing, but no evidence was found of a drive for change either from the patients or the doctors interviewed. Any apprehension was more than balanced by attitudes and behaviours supporting continuation. These findings will need to be incorporated into the planning of interventions aimed at reducing long-term antidepressant prescribing in older people. PMID:20353660

  4. Long term perfusion system supporting adipogenesis

    PubMed Central

    Abbott, Rosalyn D.; Raja, Waseem K.; Wang, Rebecca Y.; Stinson, Jordan A.; Glettig, Dean L.; Burke, Kelly A.; Kaplan, David L.

    2015-01-01

    Adipose tissue engineered models are needed to enhance our understanding of disease mechanisms and for soft tissue regenerative strategies. Perfusion systems generate more physiologically relevant and sustainable adipose tissue models, however adipocytes have unique properties that make culturing them in a perfusion environment challenging. In this paper we describe the methods involved in the development of two perfusion culture systems (2D and 3D) to test their applicability for long term in vitro adipogenic cultures. It was hypothesized that a silk protein biomaterial scaffold would provide a 3D framework, in combination with perfusion flow, to generate a more physiologically relevant sustainable adipose tissue engineered model than 2D cell culture. Consistent with other studies evaluating 2D and 3D culture systems for adipogenesis we found that both systems successfully model adipogensis, however 3D culture systems were more robust, providing the mechanical structure required to contain the large, fragile adipocytes that were lost in 2D perfused culture systems. 3D perfusion also stimulated greater lipogenesis and lipolysis and resulted in decreased secretion of LDH compared to 2D perfusion. Regardless of culture configuration (2D or 3D) greater glycerol was secreted with the increased nutritional supply provided by perfusion of fresh media. These results are promising for adipose tissue engineering applications including long term cultures for studying disease mechanisms and regenerative approaches, where both acute (days to weeks) and chronic (weeks to months) cultivation are critical for useful insight. PMID:25843606

  5. Sleep facilitates long-term face adaptation.

    PubMed

    Ditye, Thomas; Javadi, Amir Homayoun; Carbon, Claus-Christian; Walsh, Vincent

    2013-10-22

    Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted image of a famous person were larger in a group of participants who had slept (experiment 1) or merely napped for 90 min (experiment 2) during the interval between adaptation and test compared with controls who stayed awake. Participants' individual rapid eye movement sleep duration predicted the size of post-sleep behavioural adaptation effects. Our data suggest that sleep prevented decay of adaptation in a way that is qualitatively different from the effects of reduced visual interference known as 'storage'. In the light of the well-established link between sleep and memory consolidation, our findings link the perceptual mechanisms of sensory adaptation--which are usually not considered to play a relevant role in mnemonic processes--with learning and memory, and at the same time reveal a new function of sleep in cognition. PMID:23986109

  6. Long-term intracranial pressure monitoring.

    PubMed

    de Jong, D A; Maas, A I; den Ouden, A H; de Lange, S A

    Continuous or intermittent measurement of intracranial pressure (ICP) is important in patients at risk for raised ICP. Indications exist for short- and long-term measurements. The various methods used for short-term monitoring are discussed with their relative advantages and disadvantages. For long-term measurements of ICP use of a completely implantable telemetric epidural pressure transducer is indicated. No such device is commercially available. We have developed an inexpensive passive telemetric transducer for this purpose. Results obtained up till now have demonstrated its reliability for measurements of two to three months duration. The life span of the device is limited by degrading of the epoxy utilized for sealing of the titanium pressure sensing part to the radiolucent ceramic cap of the transducer, causing leakage of water into the transducer and false low measurements. Because of these problems new hermetic sealing techniques were tested. Both active metal brazing and glass bonding yielded good results and hermetic sealing could be obtained. The metal to ceramic bonding presented is generally applicable within the design of implants. Besides the technical progress reported, the experience with clinical use in 12 patients is presented. PMID:6674738

  7. Long-Term Care Policy: Singapore's Experience.

    PubMed

    Chin, Chee Wei Winston; Phua, Kai-Hong

    2016-01-01

    Singapore, like many developed countries, is facing the challenge of a rapidly aging population and the increasing need to provide long-term care (LTC) services for elderly in the community. The Singapore government's philosophy on care for the elderly is that the family should be the first line of support, and it has relied on voluntary welfare organizations (VWOs) or charities for the bulk of LTC service provision. For LTC financing, it has emphasized the principles of co-payment and targeting of state support to the low-income population through means-tested government subsidies. It has also instituted ElderShield, a national severe disability insurance scheme. This paper discusses some of the challenges facing LTC policy in Singapore, particularly the presence of perverse financial incentives for hospitalization, the pitfalls of over-reliance on VWOs, and the challenges facing informal family caregivers. It discusses the role of private LTC insurance in LTC financing, bearing in mind demand- and supply-side failures that have plagued the private LTC insurance market. It suggests the need for more standardized needs assessment and portable LTC benefits, with reference to the Japanese Long-Term Care Insurance program, and also discusses the need to provide more support to informal family caregivers. PMID:26808468

  8. Long Term Changes in the Polar Vortices

    NASA Astrophysics Data System (ADS)

    Braathen, Geir O.

    2016-04-01

    As the amount of halogens in the stratosphere is slowly declining and the ozone layer slowly recovers it is of interest to see how the meteorological conditions in the vortex develop over the long term since such changes might alter the foreseen ozone recovery. In conjunction with the publication of the WMO Antarctic and Arctic Ozone Bulletins, WMO has acquired the ERA Interim global reanalysis data set for several meteorological parameters. This data set goes from 1979 - present. These long time series of data can be used for several useful studies of the long term development of the polar vortices. Several "environmental indicators" for vortex change have been calculated, and a climatology, as well as trends, for these parameters will be presented. These indicators can act as yardsticks and will be useful for understanding past and future changes in the polar vortices and how these changes affect polar ozone depletion. Examples of indicators are: vortex mean temperature, vortex minimum temperature, vortex mean PV, vortex "importance" (PV*area), vortex break-up time, mean and maximum wind speed. Data for both the north and south polar vortices have been analysed at several isentropic levels from 350 to 850 K. A possible link between changes in PV and sudden stratospheric warmings will be investigated, and the results presented. The unusual meteorological conditions of the 2015 south polar vortex and the 2010/11 and 2015/16 north polar vortices will be compared to other recent years.

  9. Long term changes in the polar vortices

    NASA Astrophysics Data System (ADS)

    Braathen, Geir O.

    2015-04-01

    As the amount of halogens in the stratosphere is slowly declining and the ozone layer slowly recovers it is of interest to see how the meteorological conditions in the vortex develop over the long term since such changes might alter the foreseen ozone recovery. In conjunction with the publication of the WMO Antarctic and Arctic Ozone Bulletins, WMO has acquired the ERA Interim global reanalysis data set for several meteorological parameters. This data set goes from 1979 - present. These long time series of data can be used for several useful studies of the long term development of the polar vortices. Several "environmental indicators" for vortex change have been calculated, and a climatology, as well as trends, for these parameters will be presented. These indicators can act as yardsticks and will be useful for understanding past and future changes in the polar vortices and how these changes affect polar ozone depletion. Examples of indicators are: vortex mean temperature, vortex minimum temperature, vortex mean PV, vortex "importance" (PV*area), vortex break-up time, mean and maximum wind speed. Data for both the north and south polar vortices have been analysed at several isentropic levels from 350 to 850 K. A possible link between changes in PV and sudden stratospheric warmings will be investigated, and the results presented.

  10. Asymptomatic myocardial infarction in Kawasaki disease: Long-term prognosis

    SciTech Connect

    Shiraishi, I.; Onouchi, Z.; Hayano, T.; Hamaoka, K.; Kiyosawa, N. )

    1991-04-01

    Eight patients with Kawasaki disease who had sustained asymptomatic myocardial infarction 8-15 years ago (mean, 13.1 years) were reexamined by various noninvasive cardiac function tests to assess long-term prognosis. At present, electrocardiograms (ECGs) are normal in six patients. However, all eight patients had a prolonged preejection period (PEP) to left ventricular ejection time (LVET) ratio 30 s after amylnitrate (AN) inhalation. Six patients had perfusion defects by exercise thallium-201 myocardial scintigraphy, and two patients developed ST segment depression in treadmill exercise testing. These patients are symptom-free even though their physical activity has not been restricted. Yet they proved to have serious abnormalities suggesting sequelae of myocardial infarction or existing myocardial ischemia. Judging from the results of noninvasive cardiac function tests and recently performed coronary angiography, five of the eight patients require coronary bypass surgery.

  11. Behavioral reinforcement of long-term potentiation is impaired in aged rats with cognitive deficiencies.

    PubMed

    Bergado, J A; Almaguer, W; Ravelo, J; Rosillo, J C; Frey, J U

    2001-01-01

    Behavioral stimuli with emotional/motivational content can reinforce long-term potentiation in the dentate gyrus, if presented within a distinct time window. A similar effect can be obtained by stimulating the basolateral amygdala, a limbic structure related to emotions. We have previously shown that aging impairs amygdala-hippocampus interactions during long-term potentiation. In this report we show that behavioral reinforcement of long-term potentiation is also impaired in aged rats with cognitive deficits. While among young water-deprived animals drinking 15 min after induction of long-term potentiation leads to a significant prolongation of potentiation, cognitively impaired aged rats are devoid of such reinforcing effects. In contrast, a slight but statistically significant depression develops after drinking in this group of animals. We suggest that an impaired mechanism of emotional/motivational reinforcement of synaptic plasticity might be functionally related to the cognitive deficits shown by aged animals. PMID:11738126

  12. Managing soils for long-term productivity

    PubMed Central

    Syers, J. K.

    1997-01-01

    Meeting the goal of long-term agricultural productivity requires that soil degradation be halted and reversed. Soil fertility decline is a key factor in soil degradation and is probably the major cause of declining crop yields. There is evidence that the contribution of declining soil fertility to soil degradation has been underestimated.
    Sensitivity to soil degradation is implicit in the assessment of the sustainability of land management practices, with wide recognition of the fact that soils vary in their ability to resist change and recover subsequent to stress. The concept of resilience in relation to sustainability requires further elaboration and evaluation.
    In the context of soil degradation, a decline in soil fertility is primarily interpreted as the depletion of organic matter and plant nutrients. Despite a higher turnover rate of organic matter in the tropics there is no intrinsic difference between the organic matter content of soils from tropical and temperate regions. The level of organic matter in a soil is closely related to the above and below ground inputs. In the absence of adequate organic material inputs and where cultivation is continuous, soil organic matter declines progressively. Maintaining the quantity and quality of soil organic matter should be a guiding principle in developing management practices.
    Soil microbial biomass serves as an important reservoir of nitrogen (N), phosphorus (P) and sulphur (S), and regulates the cycling of organic matter and nutrients. Because of its high turnover rate, microbial biomass reacts quickly to changes in management and is a sensitive indicator for monitoring and predicting changes in soil organic matter. Modelling techniques have been reasonably successful in predicting changes in soil organic matter with different organic material inputs, but there is little information from the tropics.
    Nutrient depletion through harvested crop components and residue removal, and by leaching and soil

  13. Advanced long term cryogenic storage systems

    NASA Technical Reports Server (NTRS)

    Brown, Norman S.

    1987-01-01

    Long term, cryogenic fluid storage facilities will be required to support future space programs such as the space-based Orbital Transfer Vehicle (OTV), Telescopes, and Laser Systems. An orbital liquid oxygen/liquid hydrogen storage system with an initial capacity of approximately 200,000 lb will be required. The storage facility tank design must have the capability of fluid acquisition in microgravity and limit cryogen boiloff due to environmental heating. Cryogenic boiloff management features, minimizing Earth-to-orbit transportation costs, will include advanced thick multilayer insulation/integrated vapor cooled shield concepts, low conductance support structures, and refrigeration/reliquefaction systems. Contracted study efforts are under way to develop storage system designs, technology plans, test article hardware designs, and develop plans for ground/flight testing.

  14. Long term performance of radon mitigation systems

    SciTech Connect

    Prill, R.; Fisk, W.J.

    2002-03-01

    Researchers installed radon mitigation systems in 12 houses in Spokane, Washington and Coeur d'Alene, Idaho during the heating season 1985--1986 and continued to monitor indoor radon quarterly and annually for ten years. The mitigation systems included active sub-slab ventilation, basement over-pressurization, and crawlspace isolation and ventilation. The occupants reported various operational problems with these early mitigation systems. The long-term radon measurements were essential to track the effectiveness of the mitigation systems over time. All 12 homes were visited during the second year of the study, while a second set 5 homes was visited during the fifth year to determine the cause(s) of increased radon in the homes. During these visits, the mitigation systems were inspected and measurements of system performance were made. Maintenance and modifications were performed to improve system performance in these homes.

  15. Long-term U. S. energy outlook

    SciTech Connect

    Friesen, G.

    1984-01-01

    Each year Chase Econometrics offers its clients a brief summary of the assumptions underlying the long-term energy forecast for the U.S. To illustrate the uncertainty involved in forecasting for the period to the year 2000, they choose to compare forecasts with some recent projections prepared by the Department of Energy's Office of Policy, Planning and Analysis for the annual National Energy Policy Plan supplement. Particular emphasis is placed on Scenario B, which is the mid-range reference case. As the introduction to the supplement emphasizes, the NEPP projections should not be considered a statement of the policy goals of the Reagan Administration. They represent an analysis of the possible evolution of U.S. energy markets, given current information and existing policies. The purpose of providing Scenario B as a reference case as well as Scenarios A and C as alternate cases is to show the sensitivity of oil price projections to small swings in energy demand.

  16. Long-term control of root growth

    DOEpatents

    Burton, Frederick G.; Cataldo, Dominic A.; Cline, John F.; Skiens, W. Eugene

    1992-05-26

    A method and system for long-term control of root growth without killing the plants bearing those roots involves incorporating a 2,6-dinitroaniline in a polymer and disposing the polymer in an area in which root control is desired. This results in controlled release of the substituted aniline herbicide over a period of many years. Herbicides of this class have the property of preventing root elongation without translocating into other parts of the plant. The herbicide may be encapsulated in the polymer or mixed with it. The polymer-herbicide mixture may be formed into pellets, sheets, pipe gaskets, pipes for carrying water, or various other forms. The invention may be applied to other protection of buried hazardous wastes, protection of underground pipes, prevention of root intrusion beneath slabs, the dwarfing of trees or shrubs and other applications. The preferred herbicide is 4-difluoromethyl-N,N-dipropyl-2,6-dinitro-aniline, commonly known as trifluralin.

  17. Long-term control of root growth

    SciTech Connect

    Burton, F.G.; Cataldo, D.A.; Cline, J.F.; Skiens, W.E.

    1992-05-26

    A method and system for long-term control of root growth without killing the plants bearing those roots involves incorporating a 2,6-dinitroaniline in a polymer and disposing the polymer in an area in which root control is desired. This results in controlled release of the substituted aniline herbicide over a period of many years. Herbicides of this class have the property of preventing root elongation without translocating into other parts of the plant. The herbicide may be encapsulated in the polymer or mixed with it. The polymer-herbicide mixture may be formed into pellets, sheets, pipe gaskets, pipes for carrying water, or various other forms. The invention may be applied to other protection of buried hazardous wastes, protection of underground pipes, prevention of root intrusion beneath slabs, the dwarfing of trees or shrubs and other applications. The preferred herbicide is 4-difluoromethyl-N,N-dipropyl-2,6-dinitro-aniline, commonly known as trifluralin. 7 figs.

  18. Withdrawal from long-term benzodiazepine treatment.

    PubMed Central

    Petursson, H; Lader, M H

    1981-01-01

    Long-term, normal-dose benzodiazepine treatment was discontinued in 16 patients who were suspected of being dependent on their medication. The withdrawal was gradual, placebo-controlled, and double-blind. All the patients experienced some form of withdrawal reaction, which ranged from anxiety and dysphoria to moderate affective and perceptual changes. Symptom ratings rose as the drugs were discontinued, but usually subsided to prewithdrawal levels over the next two to four weeks. Other features of the withdrawal included disturbance of sleep and appetite and noticeable weight loss. Electroencephalography showed appreciable reduction in fast-wave activity as the drugs were withdrawn, and an improvement in psychological performance was recorded by the Digit Symbol Substitution Test. Because of the risk of dependence on benzodiazepines these agents should probably not be given as regular daily treatment for chronic anxiety. PMID:6114776

  19. Long term thermoelectric module testing system.

    PubMed

    D'Angelo, Jonathan; Hogan, Timothy

    2009-10-01

    Thermoelectric generators can be used for converting waste heat into electric power. Significant interest in developing new materials in recent years has led to the discovery of several promising thermoelectrics, however, there can be considerable challenges in developing the materials into working devices. Testing and feedback is needed at each step to gain valuable information for identification of difficulties, quality of the materials and modules, repeatability in fabrication, and longevity of the devices. This paper describes a long-term module testing system for monitoring the output power of a module over extended testing times. To evaluate the system, we have tested commercially available thermoelectric modules over a one month time period. PMID:19895086

  20. Managing Records for the Long Term - 12363

    SciTech Connect

    Montgomery, John V.; Gueretta, Jeanie

    2012-07-01

    The U.S. Department of Energy (DOE) is responsible for managing vast amounts of information documenting historical and current operations. This information is critical to the operations of the DOE Office of Legacy Management. Managing legacy records and information is challenging in terms of accessibility and changing technology. The Office of Legacy Management is meeting these challenges by making records and information management an organizational priority. The Office of Legacy Management mission is to manage DOE post-closure responsibilities at former Cold War weapons sites to ensure the future protection of human health and the environment. These responsibilities include environmental stewardship and long-term preservation and management of operational and environmental cleanup records associated with each site. A primary organizational goal for the Office of Legacy Management is to 'Preserve, Protect, and Share Records and Information'. Managing records for long-term preservation is an important responsibility. Adequate and dedicated resources and management support are required to perform this responsibility successfully. Records tell the story of an organization and may be required to defend an organization in court, provide historical information, identify lessons learned, or provide valuable information for researchers. Loss of records or the inability to retrieve records because of poor records management processes can have serious consequences and even lead to an organisation's downfall. Organizations must invest time and resources to establish a good records management program because of its significance to the organization as a whole. The Office of Legacy Management will continue to research and apply innovative ways of doing business to ensure that the organization stays at the forefront of effective records and information management. DOE is committed to preserving records that document our nation's Cold War legacy, and the Office of Legacy

  1. Long-term dynamics of Typha populations

    USGS Publications Warehouse

    Grace, J.B.; Wetzel, R.G.

    1998-01-01

    The zonation of Typha populations in an experimental pond in Michigan was re-examined 15 years after the original sampling to gain insight into the long-term dynamics. Current distributions of Typha populations were also examined in additional experimental ponds at the site that have been maintained for 23 years. The zonation between T. latifolia and T. angustifolia in the previously studied pond 15 years after the initial sampling revealed that the density and distribution of shoots had not changed significantly. Thus, it appears that previously reported results (based on 7- year old populations) have remained consistent over time. Additional insight into the interaction between these two taxa was sought by comparing mixed and monoculture stands in five experimental ponds that have remained undisturbed for their 23-year history. The maximum depth of T. latifolia, the shallow- water species, was not significantly reduced when growing in the presence of the more flood tolerant T. angustifolia. In contrast, the minimum depth of T. angustifolia was reduced from 0 to 37 cm when in the presence of T. latifolia. When total populations were compared between monoculture and mixed stands, the average density of T. angustifolia shoots was 59.4 percent lower in mixed stands while the density of T. latifolia was 32 percent lower, with T. angustifolia most affected at shallow depths (reduced by 92 percent) and T. latifolia most affected at the deepest depths (reduced by 60 percent). These long-term observations indicate that competitive displacement between Typha taxa has remained stable over time.

  2. A Review of the Long-Term Effects of Child Sexual Abuse.

    ERIC Educational Resources Information Center

    Beitchman, Joseph H.; And Others

    1992-01-01

    Evidence suggests that sexual abuse has serious long-term effects; but specific effects, independent of force, threatened force, or family variables such as parental psychopathology, are not yet clarified. Effects among adults in terms of their relationship to sexual dysfunction, depression, anxiety, fear, multiple or borderline personality…

  3. Examining the long-term stability of overgeneral autobiographical memory.

    PubMed

    Sumner, Jennifer A; Mineka, Susan; Zinbarg, Richard E; Craske, Michelle G; Vrshek-Schallhorn, Suzanne; Epstein, Alyssa

    2014-01-01

    Overgeneral autobiographical memory (OGM) is a proposed trait-marker for vulnerability to depression, but relatively little work has examined its long-term stability. This study investigated the stability of OGM over several years in 271 late adolescents and young adults participating in a larger longitudinal study of risk for emotional disorders. The Autobiographical Memory Test (AMT) was administered twice, with test-retest intervals ranging from approximately 3 to 6 years. There was evidence of significant but modest stability in OGM over several years. Specifically, Spearman rank correlations (ρs) between the proportions of specific and categoric memories generated on the two AMTs were .31 and .32, respectively. We did not find evidence that the stability of OGM was moderated by the length of the test-retest interval. Furthermore, the stability coefficients for OGM for individuals with and without a lifetime history of major depressive disorder (MDD) were relatively similar in magnitude and not significantly different from one another (ρs=.34 and .42 for the proportions of specific and categoric memories for those with a history of MDD; ρs=.31 for both the proportions of specific and categoric memories for those without a history of MDD). Implications for the conceptualisation of OGM are discussed. PMID:23439226

  4. Examining the Long-Term Stability of Overgeneral Autobiographical Memory

    PubMed Central

    Sumner, Jennifer A.; Mineka, Susan; Zinbarg, Richard E.; Craske, Michelle G.; Vrshek-Schallhorn, Suzanne; Epstein, Alyssa

    2013-01-01

    Overgeneral autobiographical memory (OGM) is a proposed trait-marker for vulnerability to depression, but relatively little work has examined its long-term stability. This study investigated the stability of OGM over several years in 271 late adolescents and young adults participating in a larger longitudinal study of risk for emotional disorders. The Autobiographical Memory Test (AMT) was administered twice, with test-retest intervals ranging from approximately 3 to 6 years. There was evidence of significant but modest stability in OGM over several years. Specifically, Spearman rank correlations (ρs) between the proportions of specific and categoric memories generated on the two AMTs were .31 and .32, respectively. We did not find evidence that the stability of OGM was moderated by the length of the test-retest interval. Furthermore, the stability coefficients for OGM for individuals with and without a lifetime history of major depressive disorder (MDD) were relatively similar in magnitude and not significantly different from one another (ρs = .34 and .42 for the proportions of specific and categoric memories for those with a history of MDD; ρs = .31 for both the proportions of specific and categoric memories for those without a history of MDD). Implications for the conceptualization of OGM are discussed. PMID:23439226

  5. LONG-TERM MONITORING SENSOR NETWORK

    SciTech Connect

    Stephen P. Farrington; John W. Haas; Neal Van Wyck

    2003-10-16

    Long-term monitoring (LTM) associated with subsurface contamination sites is a key element of Long Term Stewardship and Legacy Management across the Department of Energy (DOE) complex. However, both within the DOE and elsewhere, LTM is an expensive endeavor, often exceeding the costs of the remediation phase of a clean-up project. The primary contributors to LTM costs are associated with labor. Sample collection, storage, preparation, analysis, and reporting can add a significant financial burden to project expense when extended over many years. Development of unattended, in situ monitoring networks capable of providing quantitative data satisfactory to regulatory concerns has the potential to significantly reduce LTM costs. But survival and dependable operation in a difficult environment is a common obstacle to widespread use across the DOE complex or elsewhere. Deploying almost any sensor in the subsurface for extended periods of time will expose it to chemical and microbial degradation. Over the time-scales required for in situ LTM, even the most advanced sensor systems may be rendered useless. Frequent replacement or servicing (cleaning) of sensors is expensive and labor intensive, offsetting most, if not all, of the cost savings realized with unattended, in situ sensors. To enable facile, remote monitoring of contaminants and other subsurface parameters over prolonged periods, Applied Research Associates, Inc has been working to develop an advanced LTM sensor network consisting of three key elements: (1) an anti-fouling sensor chamber that can accommodate a variety of chemical and physical measurement devices based on electrochemical, optical and other techniques; (2) two rapid, cost effective, and gentle means of emplacing sensor packages either at precise locations directly in the subsurface or in pre-existing monitoring wells; and (3) a web browser-based data acquisition and control system (WebDACS) utilizing field-networked microprocessor-controlled smart

  6. Robotics for Long-Term Monitoring

    SciTech Connect

    Shahin, Sarkis; Duran, Celso

    2002-07-01

    While long-term monitoring and stewardship means many things to many people, DOE has defined it as The physical controls, institutions, information, and other mechanisms needed to ensure protection of people and the environment at sites where DOE has completed or plans to complete cleanup (e.g., landfill closures, remedial actions, and facility stabilization). Across the United States, there are thousands of contaminated sites with multiple contaminants released from multiple sources where contaminants have transported and commingled. The U.S. government and U.S. industry are responsible for most of the contamination and are landowners of many of these contaminated properties. These sites must be surveyed periodically for various criteria including structural deterioration, water intrusion, integrity of storage containers, atmospheric conditions, and hazardous substance release. The surveys, however, are intrusive, time-consuming, and expensive and expose survey personnel to radioactive contamination. In long-term monitoring, there's a need for an automated system that will gather and report data from sensors without costly human labor. In most cases, a SCADA (Supervisory Control and Data Acquisition) unit is used to collect and report data from a remote location. A SCADA unit consists of an embedded computer with data acquisition capabilities. The unit can be configured with various sensors placed in different areas of the site to be monitored. A system of this type is static, i.e., the sensors, once placed, cannot be moved to other locations within the site. For those applications where the number of sampling locations would require too many sensors, or where exact location of future problems is unknown, a mobile sensing platform is an ideal solution. In many facilities that undergo regular inspections, the number of video cameras and air monitors required to eliminate the need for human inspections is very large and far too costly. HCET's remote harsh

  7. Treatment for childhood cancer -- long-term risks

    MedlinePlus

    ... ency/patientinstructions/000849.htm Treatment for childhood cancer - long-term risks To use the sharing features on ... has. Being aware of your child's risk of long-term health problems can help you follow-up ...

  8. Long-term adequacy of metal resources

    USGS Publications Warehouse

    Singer, D.A.

    1977-01-01

    Although the earth's crust contains vast quantities of metals, extraction technologies and associated costs are inextricably bound to three fundamental geological factors - the amount of metal available in the earth's crust in each range of grades, the mineralogical form and chemical state of the metal, and the spatial distribution of the metal. The energy required to recover a given amount of metal increases substantially as grade declines. Most metal is produced from sulphide or oxide minerals, whereas most metal in the crust may be locked in the structures of the more refractory silicates. Recovery from silicate minerals could require orders of magnitude more energy than that used at present as also could exploitation of small, widely scattered or thin, deeply buried deposits. Although specific information on the fundamental factors is not available, each factor must in turn tend to further restrict exploitation. Independence of average grade and tonnage for many deposit types further reduces the availability of rock as a source of metal. In the long term, effects of these factors will be large increases in price for many metals. ?? 1977.

  9. Long-term outcome in aqueductal stenosis.

    PubMed

    Villani, R; Tomei, G; Gaini, S M; Grimoldi, N; Spagnoli, D; Bello, L

    1995-03-01

    In this study, 78 patients with aqueductal stenosis were submitted to detailed neurodevelopmental assessment with a follow-up of 5-25 years. Sixty-eight percent of patients were categorized as normal; they either attended normal school courses or had regular jobs. Among these, 34% had some motor abnormalities (ataxia, mild hemiparesis, visual disturbances). Twenty-four percent (19 cases) were moderately disabled (trainable retardation) and 8% (6 cases) were severely handicapped. Epilepsy was observed in 13% of the cases. Incidence of recurrent and generalized seizures paralleled neurodevelopmental outcome (5% in normal, 16% in moderately disabled and 50% in severely disabled patients). Endocrine dysfunctions were evident in 28% of the cases and were characterized by precocious or delayed puberty, amenorrhea and somatic underdevelopment. No patient with ventricular enlargement and a cortical mantle width below 20 mm showed a good outcome. Large ventricles were compatible with normal mental development when compensated with a corresponding cranial vault enlargement. In patients with normal mental status and motor abnormalities, long-term CT scan findings revealed the presence of focal brain abnormalities (poroencephaly, brain atrophy, calcifications, extracerebral collections). PMID:7773981

  10. Alpine Soils as long-term Bioindicators

    NASA Astrophysics Data System (ADS)

    Nestroy, O.

    2009-04-01

    Alpine soils as long-term bioindicators The introductory words concern the definitions and peculiarities of alpine soils and their position in the Austrian Soil Classification 2000 in comparison with the World Reference Base for Soil Resources 2006. The important parameters for genesis and threats for these soils in steep and high positions are discussed. It must be emphasized that the main threats are the very different kinds of erosion e.g. by water, wind and snow, and also by skiing (end of season) as well as and mountain-biking (mainly summer-sport). Due the very slow regeneration and - in this connection - due to the very slow changes of the soil entities, these soils give an utmost importance as a long-time bioindicator. With regard to the climate change one can assume an increase in the content of organic matter on site, but also an increase of erosion and mass movement on the other site, e. g. in kind of "plaiken" (soil slide) as result of an increasing intensity of rainfall. It lies partly in our hands to diminish the number and the intensity of the threats, we can influence the soil development, but the result to reach a new ecological equilibrium is very long - in case of alpine soil more than two generations.