[125I]Iodo-ASEM, a specific in vivo radioligand for α7-nAChR

PubMed Central

Gao, Yongjun; Mease, Ronnie C.; Olson, Thao T.; Kellar, Kenneth J.; Dannals, Robert F.; Pomper, Martin G.; Horti, Andrew G.

2014-01-01

[125I]Iodo-ASEM, a new radioligand with high affinity and selectivity for α7-nAChRs (Ki = 0.5 nM; α7/α4β2 = 3,414), has been synthesized in radiochemical yield of 33 ± 6% from the corresponding di-butyltriazene derivative and at high specific radioactivity (1,600 Ci/mmol; 59.2 MBq/μmol). [125I]Iodo-ASEM readily entered the brains of normal CD-1 mice and specifically and selectively labeled cerebral α7-nAChRs. [125I]iodo-ASEM is a new useful tool for studying α7-nAChR. PMID:25687449

AT–1001: a high-affinity α3β4 nAChR ligand with novel nicotine-suppressive pharmacology

PubMed Central

Cippitelli, Andrea; Wu, Jinhua; Gaiolini, Kelly A; Mercatelli, Daniela; Schoch, Jennifer; Gorman, Michelle; Ramirez, Alejandra; Ciccocioppo, Roberto; Khroyan, Taline V; Yasuda, Dennis; Zaveri, Nurulain T; Pascual, Conrado; Xie, Xinmin (Simon); Toll, Lawrence

2015-01-01

Background and Purpose The α3β4 subtype of nicotinic acetylcholine receptors (nAChRs) has been implicated in mediating nicotine reinforcement processes. AT-1001 has been recently described as a high-affinity and selective α3β4 nAChR antagonist that blocks nicotine self-administration in rats. The aim of this study was to investigate the mechanism of action underlying the nicotine-suppressive effects of AT-1001. Experimental Approach Effects of AT-1001 were determined using in vitro assays and rat models of nicotine addiction, and compared with varenicline. Key Results AT-1001 and its analogue AT-1012 were functionally selective as antagonists for α3β4 over α4β2 nAChRs, but not to the same extent as the binding selectivity, and had partial agonist activity at α3β4 nAChRs. In contrast, varenicline was a partial agonist at α4β2, a weak agonist at α3β4 and inhibited α4β2 at a much lower concentration than it inhibited α3β4 nAChRs. AT-1001 and varenicline also had very different in vivo properties. Firstly, AT-1001 did not exhibit reinforcing properties per se while varenicline was self-administered. Secondly, systemic treatment with AT-1001 did not induce reinstatement of nicotine seeking but rather attenuated reinstatement induced by varenicline, as well as nicotine. Finally, unlike varenicline, AT-1001 selectively blocked nicotine self-administration without altering alcohol lever pressing as assessed in an operant co-administration paradigm. Conclusions and Implications These findings describe a more complex AT-1001 in vitro profile than previously appreciated and provide further support for the potential of AT-1001 and congeners as clinically useful compounds for smoking cessation, with a mechanism of action distinct from currently available medications. PMID:25440006

A mutation in the extracellular domain of the α7 nAChR reduces calcium permeability.

PubMed

Colón-Sáez, José O; Yakel, Jerrel L

2014-08-01

The α7 neuronal nicotinic acetylcholine receptor (nAChR) displays the highest calcium permeability among the different subtypes of nAChRs expressed in the mammalian brain and can impact cellular events including neurotransmitter release, second messenger cascades, cell survival, and apoptosis. The selectivity for cations in nAChRs is thought to be achieved in part by anionic residues which are located on either side of the channel mouth and increase relative cationic concentration. Mutagenesis studies have improved our understanding of the role of the second transmembrane domain and the intracellular loop of the channel in ion selectivity. However, little is known about the influence that the extracellular domain (ECD) plays in ion permeation. In the α7 nAChR, it has been found that the ECD contains a ring of ten aspartates (two per subunit) that is believed to face the lumen of the pore and could attract cations for permeation. Using mutagenesis and a combination of electrophysiology and imaging techniques, we tested the possible involvement of these aspartate residues in the calcium permeability of the rat α7 nAChR. We found that one of these residues (the aspartate at position 44) appears to be essential since mutating it to alanine resulted in a decrease in amplitude for both whole cell and single-channel responses and in the complete disappearance of detectable calcium changes in most cells, which indicates that the ECD of the α7 nAChR plays a key role in calcium permeation.

A mutation in the extracellular domain of the α7 nAChR reduces calcium permeability

PubMed Central

Colón-Sáez, José O.

2013-01-01

The α7 neuronal nicotinic acetylcholine receptor (nAChR) displays the highest calcium permeability among the different subtypes of nAChRs expressed in the mammalian brain and can impact cellular events including neurotransmitter release, second messenger cascades, cell survival, and apoptosis. The selectivity for cations in nAChRs is thought to be achieved in part by anionic residues which are located on either side of the channel mouth and increase relative cationic concentration. Mutagenesis studies have improved our understanding of the role of the second transmembrane domain and the intracellular loop of the channel in ion selectivity. However, little is known about the influence that the extracellular domain (ECD) plays in ion permeation. In the α7 nAChR, it has been found that the ECD contains a ring of ten aspartates (two per subunit) that is believed to face the lumen of the pore and could attract cations for permeation. Using mutagenesis and a combination of electrophysiology and imaging techniques, we tested the possible involvement of these aspartate residues in the calcium permeability of the rat α7 nAChR. We found that one of these residues (the aspartate at position 44) appears to be essential since mutating it to alanine resulted in a decrease in amplitude for both whole cell and single-channel responses and in the complete disappearance of detectable calcium changes in most cells, which indicates that the ECD of the α7 nAChR plays a key role in calcium permeation. PMID:24177919

PPARα modulation of mesolimbic dopamine transmission rescues depression-related behaviors.

PubMed

Scheggi, Simona; Melis, Miriam; De Felice, Marta; Aroni, Sonia; Muntoni, Anna Lisa; Pelliccia, Teresa; Gambarana, Carla; De Montis, Maria Graziella; Pistis, Marco

2016-11-01

Depressive disorders cause a substantial burden for the individual and the society. Key depressive symptoms can be modeled in animals and enable the development of novel therapeutic interventions. Chronic unavoidable stress disrupts rats' competence to escape noxious stimuli and self-administer sucrose, configuring a depression model characterized by escape deficit and motivational anhedonia associated to impaired dopaminergic responses to sucrose in the nucleus accumbens shell (NAcS). Repeated treatments that restore these responses also relieve behavioral symptoms. Ventral tegmental area (VTA) dopamine neurons encode reward and motivation and are implicated in the neuropathology of depressive-like behaviors. Peroxisome proliferator-activated receptors type-α (PPARα) acutely regulate VTA dopamine neuron firing via β2 subunit-containing nicotinic acetylcholine receptors (β2*nAChRs) through phosphorylation and this effect is predictive of antidepressant-like effects. Here, by combining behavioral, electrophysiological and biochemical techniques, we studied the effects of repeated PPARα stimulation by fenofibrate on mesolimbic dopamine system. We found decreased β2*nAChRs phosphorylation levels and a switch from tonic to phasic activity of dopamine cells in the VTA, and increased phosphorylation of dopamine and cAMP-regulated phosphoprotein Mr 32,000 (DARPP-32) in the NAcS. We then investigated whether long-term fenofibrate administration to stressed rats reinstated the decreased DARPP-32 response to sucrose and whether this effect translated into antidepressant-like properties. Fenofibrate restored dopaminergic responses to appetitive stimuli, reactivity to aversive stimuli and motivation to self-administer sucrose. Overall, this study suggests PPARα as new targets for antidepressant therapies endowed with motivational anti-anhedonic properties, further supporting the role of an unbalanced mesolimbic dopamine system in pathophysiology of depressive disorders

Blockade of Neuronal α7-nAChR by α-Conotoxin ImI Explained by Computational Scanning and Energy Calculations

PubMed Central

Yu, Rilei; Craik, David J.; Kaas, Quentin

2011-01-01

α-Conotoxins potently inhibit isoforms of nicotinic acetylcholine receptors (nAChRs), which are essential for neuronal and neuromuscular transmission. They are also used as neurochemical tools to study nAChR physiology and are being evaluated as drug leads to treat various neuronal disorders. A number of experimental studies have been performed to investigate the structure-activity relationships of conotoxin/nAChR complexes. However, the structural determinants of their binding interactions are still ambiguous in the absence of experimental structures of conotoxin-receptor complexes. In this study, the binding modes of α-conotoxin ImI to the α7-nAChR, currently the best-studied system experimentally, were investigated using comparative modeling and molecular dynamics simulations. The structures of more than 30 single point mutants of either the conotoxin or the receptor were modeled and analyzed. The models were used to explain qualitatively the change of affinities measured experimentally, including some nAChR positions located outside the binding site. Mutational energies were calculated using different methods that combine a conformational refinement procedure (minimization with a distance dependent dielectric constant or explicit water, or molecular dynamics using five restraint strategies) and a binding energy function (MM-GB/SA or MM-PB/SA). The protocol using explicit water energy minimization and MM-GB/SA gave the best correlations with experimental binding affinities, with an R2 value of 0.74. The van der Waals and non-polar desolvation components were found to be the main driving force for binding of the conotoxin to the nAChR. The electrostatic component was responsible for the selectivity of the various ImI mutants. Overall, this study provides novel insights into the binding mechanism of α-conotoxins to nAChRs and the methodological developments reported here open avenues for computational scanning studies of a rapidly expanding range of wild

Menthol Enhances Nicotine Reward-Related Behavior by Potentiating Nicotine-Induced Changes in nAChR Function, nAChR Upregulation, and DA Neuron Excitability.

PubMed

Henderson, Brandon J; Wall, Teagan R; Henley, Beverley M; Kim, Charlene H; McKinney, Sheri; Lester, Henry A

2017-11-01

Understanding why the quit rate among smokers of menthol cigarettes is lower than non-menthol smokers requires identifying the neurons that are altered by nicotine, menthol, and acetylcholine. Dopaminergic (DA) neurons in the ventral tegmental area (VTA) mediate the positive reinforcing effects of nicotine. Using mouse models, we show that menthol enhances nicotine-induced changes in nicotinic acetylcholine receptors (nAChRs) expressed on midbrain DA neurons. Menthol plus nicotine upregulates nAChR number and function on midbrain DA neurons more than nicotine alone. Menthol also enhances nicotine-induced changes in DA neuron excitability. In a conditioned place preference (CPP) assay, we observed that menthol plus nicotine produces greater reward-related behavior than nicotine alone. Our results connect changes in midbrain DA neurons to menthol-induced enhancements of nicotine reward-related behavior and may help explain how smokers of menthol cigarettes exhibit reduced cessation rates.

Menthol Enhances Nicotine Reward-Related Behavior by Potentiating Nicotine-Induced Changes in nAChR Function, nAChR Upregulation, and DA Neuron Excitability

PubMed Central

Henderson, Brandon J; Wall, Teagan R; Henley, Beverley M; Kim, Charlene H; McKinney, Sheri; Lester, Henry A

2017-01-01

Understanding why the quit rate among smokers of menthol cigarettes is lower than non-menthol smokers requires identifying the neurons that are altered by nicotine, menthol, and acetylcholine. Dopaminergic (DA) neurons in the ventral tegmental area (VTA) mediate the positive reinforcing effects of nicotine. Using mouse models, we show that menthol enhances nicotine-induced changes in nicotinic acetylcholine receptors (nAChRs) expressed on midbrain DA neurons. Menthol plus nicotine upregulates nAChR number and function on midbrain DA neurons more than nicotine alone. Menthol also enhances nicotine-induced changes in DA neuron excitability. In a conditioned place preference (CPP) assay, we observed that menthol plus nicotine produces greater reward-related behavior than nicotine alone. Our results connect changes in midbrain DA neurons to menthol-induced enhancements of nicotine reward-related behavior and may help explain how smokers of menthol cigarettes exhibit reduced cessation rates. PMID:28401925

Nicotine-Induced Effects on Nicotinic Acetylcholine Receptors (nAChRs), Ca2+ and Brain-Derived Neurotrophic Factor (BDNF) in STC-1 Cells.

PubMed

Qian, Jie; Mummalaneni, Shobha K; Alkahtani, Reem M; Mahavadi, Sunila; Murthy, Karnam S; Grider, John R; Lyall, Vijay

2016-01-01

In addition to the T2R bitter taste receptors, neuronal nicotinic acetylcholine receptors (nAChRs) have recently been shown to be involved in the bitter taste transduction of nicotine, acetylcholine and ethanol. However, at present it is not clear if nAChRs are expressed in enteroendocrine cells other than beta cells of the pancreas and enterochromaffin cells, and if they play a role in the synthesis and release of neurohumoral peptides. Accordingly, we investigated the expression and functional role of nAChRs in enteroendocrine STC-1 cells. Our studies using RT-PCR, qRT-PCR, immunohistochemical and Western blotting techniques demonstrate that STC-1 cells express several α and β nAChR subunits. Exposing STC-1 cells to nicotine acutely (24h) or chronically (4 days) induced a differential increase in the expression of nAChR subunit mRNA and protein in a dose- and time-dependent fashion. Mecamylamine, a non-selective antagonist of nAChRs, inhibited the nicotine-induced increase in mRNA expression of nAChRs. Exposing STC-1 cells to nicotine increased intracellular Ca2+ in a dose-dependent manner that was inhibited in the presence of mecamylamine or dihydro-β-erythroidine, a α4β2 nAChR antagonist. Brain-derived neurotrophic factor (BDNF) mRNA and protein were detected in STC-1 cells using RT-PCR, specific BDNF antibody, and enzyme-linked immunosorbent assay. Acute nicotine exposure (30 min) decreased the cellular content of BDNF in STC-1 cells. The nicotine-induced decrease in BDNF was inhibited in the presence of mecamylamine. We also detected α3 and β4 mRNA in intestinal mucosal cells and α3 protein expression in intestinal enteroendocrine cells. We conclude that STC-1 cells and intestinal enteroendocrine cells express nAChRs. In STC-1 cells nAChR expression is modulated by exposure to nicotine in a dose- and time-dependent manner. Nicotine interacts with nAChRs and inhibits BDNF expression in STC-1 cells.

α7 nAChR mediated Fas demethylation contributes to prenatal nicotine exposure-induced programmed thymocyte apoptosis in mice.

PubMed

Liu, Han-Xiao; Liu, Sha; Qu, Wen; Yan, Hui-Yi; Wen, Xiao; Chen, Ting; Hou, Li-Fang; Ping, Jie

2017-11-07

This study aimed to investigate the effects of prenatal nicotine exposure (PNE) on thymocyte apoptosis and postnatal immune impairments in vivo and further explore the epigenetic mechanisms of the pro-apoptotic effect of nicotine in vitro . The results showed that PNE caused immune impairments in offspring on postnatal day 49, manifested as increased IL-4 production and an increased IgG1/IgG2a ratio in serum. Enhanced apoptosis of total and CD4+SP thymocytes was observed both in fetus and in offspring. Further, by exposing thymocytes to 0-100 μM of nicotine in vitro for 48 h, we found that nicotine increased α7 nicotinic acetylcholine receptor (nAChR) expression, activated the Fas apoptotic pathway, and promoted thymocyte apoptosis in concentration-dependent manners. In addition, nicotine could induce Tet methylcytosine dioxygenase (TET) 2 expression and Fas promoter demethylation, which can be abolished by TET2 siRNA transfection. Moreover, the α7 nAChR specific antagonist α-bungarotoxin can abrogate nicotine-induced TET2 increase, and the following Fas demethylation and Fas-mediated apoptosis. In conclusion, our findings showed, for the first time, that α7 nAChR activation could induce TET2-mediated Fas demethylation in thymocytes and results in the upregulation of Fas apoptotic pathway, which provide evidence for elucidating the PNE-induced programmed thymocyte apoptosis.

A positive allosteric modulator of α7 nAChRs augments neuroprotective effects of endogenous nicotinic agonists in cerebral ischaemia

PubMed Central

Kalappa, Bopanna I; Sun, Fen; Johnson, Stephen R; Jin, Kunlin; Uteshev, Victor V

2013-01-01

Background and Purpose Activation of α7 nicotinic acetylcholine receptors (nAChRs) can be neuroprotective. However, endogenous choline and ACh have not been regarded as potent neuroprotective agents because physiological levels of choline/ACh do not produce neuroprotective levels of α7 activation. This limitation may be overcome by the use of type-II positive allosteric modulators (PAMs-II) of α7 nAChRs, such as 1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-methylisoxazol-3-yl)-urea (PNU-120596). This proof-of-concept study presents a novel neuroprotective paradigm that converts endogenous choline/ACh into potent neuroprotective agents in cerebral ischaemia by inhibiting α7 nAChR desensitization using PNU-120596. Experimental Approach An electrophysiological ex vivo cell injury assay (to quantify the susceptibility of hippocampal neurons to acute injury by complete oxygen and glucose deprivation; COGD) and an in vivo middle cerebral artery occlusion model of ischaemia were used in rats. Key Results Choline (20–200 μM) in the presence, but not absence of 1 μM PNU-120596 significantly delayed anoxic depolarization/injury of hippocampal CA1 pyramidal neurons, but not CA1 stratum radiatum interneurons, subjected to COGD in acute hippocampal slices and these effects were blocked by 20 nM methyllycaconitine, a selective α7 antagonist, thus, activation of α7 nAChRs was required. PNU-120596 alone was ineffective ex vivo. In in vivo experiments, both pre- and post-ischaemia treatments with PNU-120596 (30 mg·kg−1, s.c. and 1 mg·kg−1, i.v., respectively) significantly reduced the cortical/subcortical infarct volume caused by transient focal cerebral ischaemia. PNU-120596 (1 mg·kg−1, i.v., 30 min post-ischaemia) remained neuroprotective in rats subjected to a choline-deficient diet for 14 days prior to experiments. Conclusions and Implications PNU-120596 and possibly other PAMs-II significantly improved neuronal survival in cerebral ischaemia by augmenting

Roles for N-terminal Extracellular Domains of Nicotinic Acetylcholine Receptor (nAChR) β3 Subunits in Enhanced Functional Expression of Mouse α6β2β3- and α6β4β3-nAChRs*

PubMed Central

Dash, Bhagirathi; Li, Ming D.; Lukas, Ronald J.

2014-01-01

Functional heterologous expression of naturally expressed mouse α6*-nicotinic acetylcholine receptors (mα6*-nAChRs; where “*” indicates the presence of additional subunits) has been difficult. Here we expressed and characterized wild-type (WT), gain-of-function, chimeric, or gain-of-function chimeric nAChR subunits, sometimes as hybrid nAChRs containing both human (h) and mouse (m) subunits, in Xenopus oocytes. Hybrid mα6mβ4hβ3- (∼5–8-fold) or WT mα6mβ4mβ3-nAChRs (∼2-fold) yielded higher function than mα6mβ4-nAChRs. Function was not detected when mα6 and mβ2 subunits were expressed together or in the additional presence of hβ3 or mβ3 subunits. However, function emerged upon expression of mα6mβ2mβ3V9′S-nAChRs containing β3 subunits having gain-of-function V9′S (valine to serine at the 9′-position) mutations in transmembrane domain II and was further elevated 9-fold when hβ3V9′S subunits were substituted for mβ3V9′S subunits. Studies involving WT or gain-of-function chimeric mouse/human β3 subunits narrowed the search for domains that influence functional expression of mα6*-nAChRs. Using hβ3 subunits as templates for site-directed mutagenesis studies, substitution with mβ3 subunit residues in extracellular N-terminal domain loops “C” (Glu221 and Phe223), “E” (Ser144 and Ser148), and “β2-β3” (Gln94 and Glu101) increased function of mα6mβ2*- (∼2–3-fold) or mα6mβ4* (∼2–4-fold)-nAChRs. EC50 values for nicotine acting at mα6mβ4*-nAChR were unaffected by β3 subunit residue substitutions in loop C or E. Thus, amino acid residues located in primary (loop C) or complementary (loops β2-β3 and E) interfaces of β3 subunits are some of the molecular impediments for functional expression of mα6mβ2β3- or mα6mβ4β3-nAChRs. PMID:25028511

Behavioral effects of nicotinic antagonist mecamylamine in a rat model of depression: prefrontal cortex level of BDNF protein and monoaminergic neurotransmitters.

PubMed

Aboul-Fotouh, Sawsan

2015-03-01

Several studies have pointed to the nicotinic acetylcholine receptor (nAChR) antagonists, such as mecamylamine (MEC), as a potential therapeutic target for the treatment of depression. The present study evaluated the behavioral and neurochemical effects of chronic administration of MEC (1, 2, and 4 mg/kg/day, intraperitoneally (i.p.)) in Wistar rats exposed to chronic restraint stress (CRS, 4 h × 6 W). MEC prevented CRS-induced depressive-like behavior via increasing sucrose preference, body weight, and forced swim test (FST) struggling and swimming while reducing immobility in FST and hypothalamic-pituitary-adrenal (HPA) axis hyperactivity (adrenal gland weight and serum corticosterone). At the same time, MEC amended CRS-induced anxiety as indicated by decreasing central zone duration in open field test and increasing active interaction duration. Additionally, MEC modulated the prefrontal cortex (PFC) level of brain-derived neurotrophic factor (BDNF), 5-hydroxy tryptamine (5-HT), and norepinephrine (NE). In conclusion, the present data suggest that MEC possesses antidepressant and anxiolytic-like activities in rats exposed to CRS. These behavioral effects may be in part mediated by reducing HPA axis hyperactivity and increasing PFC level of BDNF and monoamines. Accordingly, these findings further support the hypothesis that nAChRs blockade might afford a novel promising strategy for pharmacotherapy of depression.

Enhanced synthesis and release of dopamine in transgenic mice with gain-of-function α6* nAChRs.

PubMed

Wang, Yuexiang; Lee, Jang-Won; Oh, Gyeon; Grady, Sharon R; McIntosh, J Michael; Brunzell, Darlene H; Cannon, Jason R; Drenan, Ryan M

2014-04-01

α6β2* nicotinic acetylcholine receptors (nAChRs)s in the ventral tegmental area to nucleus accumbens (NAc) pathway are implicated in the response to nicotine, and recent work suggests these receptors play a role in the rewarding action of ethanol. Here, we studied mice expressing gain-of-function α6β2* nAChRs (α6L9'S mice) that are hypersensitive to nicotine and endogenous acetylcholine. Evoked extracellular dopamine (DA) levels were enhanced in α6L9'S NAc slices compared to control, non-transgenic (non-Tg) slices. Extracellular DA levels in both non-Tg and α6L9'S slices were further enhanced in the presence of GBR12909, suggesting intact DA transporter function in both mouse strains. Ongoing α6β2* nAChR activation by acetylcholine plays a role in enhancing DA levels, as α-conotoxin MII completely abolished evoked DA release in α6L9'S slices and decreased spontaneous DA release from striatal synaptosomes. In HPLC experiments, α6L9'S NAc tissue contained significantly more DA, 3,4-dihydroxyphenylacetic acid, and homovanillic acid compared to non-Tg NAc tissue. Serotonin (5-HT), 5-hydroxyindoleacetic acid, and norepinephrine (NE) were unchanged in α6L9'S compared to non-Tg tissue. Western blot analysis revealed increased tyrosine hydroxylase expression in α6L9'S NAc. Overall, these results show that enhanced α6β2* nAChR activity in NAc can stimulate DA production and lead to increased extracellular DA levels. © 2013 International Society for Neurochemistry.

Molecular modeling and structural analysis of nAChR variants uncovers the mechanism of resistance to snake toxins.

PubMed

Gunasekaran, D; Sridhar, J; Suryanarayanan, V; Manimaran, N C; Singh, Sanjeev Kumar

2017-06-01

Nicotinic acetylcholine receptors (nAChRs) are neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh). The α-neurotoxins of snake mimic the structure of ACh and attacks nAChRs, which block the flow of ACh and leads to numbness and paralysis. The toxin-binding site of alpha subunit in the nAChRs is highly conserved throughout chordate lineages with few exceptions in resistance organisms. In this study, we have analyzed the sequence and structures of toxin-binding/resistant nAChRs and their interaction stability with toxins through molecular docking and molecular dynamics simulation (MDS). We have reported the potential glycosylation residues within the toxin-binding cleft adding sugar moieties through N-linked glycosylation in resistant organisms. Residue variations at key positions alter the secondary structure of binding cleft, which might interfere with toxin binding and it could be one of the possible explanations for the resistance to snake venoms. Analysis of nAChR-α-neurotoxin complexes has confirmed the key interacting residues. In addition, drastic variation in the binding stability of Mongoose nAChR-α-Bungarotoxin (α-BTX) and human nAChR-α-BTX complexes were found at specific phase of MDS. Our findings suggest that specific mutations in the binding site of toxin are potentially preventing the formation of stable complex of receptor-toxin, which might lead to mechanism of resistance. This in silico study on the binding cleft of nAChR and the findings of interacting residues will assist in designing potential inhibitors as therapeutic targets.

Nicotine withdrawal-induced inattention is absent in alpha7 nAChR knockout mice

PubMed Central

Higa, K. K.; Grim, A.; Kamenski, M. E.; van Enkhuizen, J.; Zhou, X.; Li, K.; Naviaux, J. C.; Wang, L.; Naviaux, R. K.; Geyer, M. A.; Markou, A.; Young, J. W.

2017-01-01

Rationale Smoking is the leading cause of preventable death in the U.S., but quit attempts result in withdrawal-induced cognitive dysfunction and predicts relapse. Greater understanding of the neural mechanism(s) underlying these cognitive deficits is required to develop targeted treatments to aid quit attempts. Objectives We examined nicotine withdrawal-induced inattention in mice lacking the α7 nicotinic acetylcholine receptor (nAChR) using the 5-choice continuous performance test (5C-CPT). Methods Mice were trained in the 5C-CPT prior to osmotic minipump implantation containing saline or nicotine. Experiment 1 used 40 mg/kg/day nicotine treatment and tested C57BL/6 mice 4, 28, and 52 h after pump removal. Experiment 2 used 14 and 40 mg/kg/day nicotine treatment in α7 nAChR knockout (KO) and wildtype (WT) littermates tested 4 h after pump removal. Subsets of WT mice were sacrificed before and after pump removal to assess changes in receptor expression associated with nicotine administration and withdrawal. Results Nicotine withdrawal impaired attention in the 5C-CPT, driven by response inhibition and target detection deficits. The overall attentional deficit was absent in α7 nAChR KO mice despite response disinhibition in these mice. Synaptosomal glutamate mGluR5 and dopamine D4 receptor expression were reduced during chronic nicotine but increased during withdrawal, potentially contributing to cognitive deficits. Conclusions The α7 nAChR may underlie nicotine withdrawal-induced deficits in target detection but is not required for response disinhibition deficits. Alterations to the glutamatergic and dopaminergic pathways may also contribute to withdrawal-induced attentional deficits, providing novel targets to alleviate the cognitive symptoms of withdrawal during quit attempts. PMID:28243714

nAChR dysfunction as a common substrate for schizophrenia and comorbid nicotine addiction: current trends and perspectives

PubMed Central

Parikh, Vinay; Kutlu, Munir Gunes; Gould, Thomas J.

2016-01-01

Introduction The prevalence of tobacco use in the population with schizophrenia is enormously high. Moreover, nicotine dependence is found to be associated with symptom severity and poor outcome in patients with schizophrenia. The neurobiological mechanisms that explain schizophrenia-nicotine dependence comorbidity are not known. This study systematically reviews the evidence highlighting the contribution of nicotinic acetylcholine receptors (nAChRs) to nicotine abuse in schizophrenia. Methods Electronic data bases (Medline, Google Scholar, and Web of Science) were searched using the selected key words that match the aims set forth for this review. A total of 275 articles were used for the qualitative synthesis of this review. Results Substantial evidence from preclinical and clinical studies indicated that dysregulation of α7 and β2-subunit containing nAChRs account for the cognitive and affective symptoms of schizophrenia and nicotine use may represent a strategy to remediate these symptoms. Additionally, recent meta-analyses proposed that early tobacco use may itself increase the risk of developing schizophrenia. Genetic studies demonstrating that nAChR dysfunction that may act as a shared vulnerability factor for comorbid tobacco dependence and schizophrenia were found to support this view. The development of nAChR modulators was considered an effective therapeutic strategy to ameliorate psychiatric symptoms and to promote smoking cessation in schizophrenia patients. Conclusions The relationship between schizophrenia and smoking is complex. While the debate for the self-medication versus addiction vulnerability hypothesis continues, it is widely accepted that a dysfunction in the central nAChRs represent a common substrate for various symptoms of schizophrenia and comorbid nicotine dependence. PMID:26803692

The binding properties of cycloxaprid on insect native nAChRs partially explain the low cross-resistance with imidacloprid in Nilaparvata lugens.

PubMed

Zhang, Yixi; Xu, Xiaoyong; Bao, Haibo; Shao, Xusheng; Li, Zhong; Liu, Zewen

2018-06-06

Neonicotinoids, such as imidacloprid, are selective agonists of insect nicotinic acetylcholine receptors (nAChRs) to control Nilaparvata lugens, a major rice insect pest. High imidacloprid resistance has been reported in N. lugens in laboratory and in fields. Cycloxaprid, an oxabridged cis-nitromethylene neonicotinoid, showed high insecticidal activity against N. lugens and low cross-resistance in the imidacloprid resistant strains and field populations. Binding studies have demonstrated that imidacloprid had two binding sites with different affinities (Kd = 3.18 ± 0.43 pM and 1.78 ± 0.19 nM) in N. lugens nAChRs. Cycloxaprid was poor at displacing [ 3 H]imidacloprid at its high-affinity binding site (Ki = 159.38±20.43 nM), but quite efficient at the low-affinity binding site (Ki = 1.27±0.35 nM). These data showed that cycloxaprid had overlapping binding sites with imidacloprid only at its low-affinity binding site. Therefore, the low displacement ability of cycloxaprid against imidacloprid binding at its high affinity site could partially explain the low cross-resistance of cycloxaprid in the imidacloprid resistant populations. The high insecticidal activity, low cross-resistance and different binding properties on insect nAChRs of cycloxaprid demonstrating it a potential insecticide to control N. lugens and related insect pests, especially the ones with high resistance to neonicotinoids. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

α7 Nicotinic Acetylcholine Receptor (α7nAChR) Expression in Bone Marrow–Derived Non–T Cells Is Required for the Inflammatory Reflex

PubMed Central

Olofsson, Peder S; Katz, David A; Rosas-Ballina, Mauricio; Levine, Yaakov A; Ochani, Mahendar; Valdés-Ferrer, Sergio I; Pavlov, Valentin A; Tracey, Kevin J; Chavan, Sangeeta S

2012-01-01

The immune response to infection or injury coordinates host defense and tissue repair, but also has the capacity to damage host tissues. Recent advances in understanding protective mechanisms have found neural circuits that suppress release of damaging cytokines. Stimulation of the vagus nerve protects from excessive cytokine production and ameliorates experimental inflammatory disease. This mechanism, the inflammatory reflex, requires the α7 nicotinic acetylcholine receptor (α7nAChR), a ligand-gated ion channel expressed on macrophages, lymphocytes, neurons and other cells. To investigate cell-specific function of α7nAChR in the inflammatory reflex, we created chimeric mice by cross-transferring bone marrow between wild-type (WT) and α7nAChR-deficient mice. Deficiency of α7nAChR in bone marrow–derived cells significantly impaired vagus nerve–mediated regulation of tumor necrosis factor (TNF), whereas α7nAChR deficiency in neurons and other cells had no significant effect. In agreement with recent work, the inflammatory reflex was not functional in nude mice, because functional T cells are required for the integrity of the pathway. To investigate the role of T-cell α7nAChR, we adoptively transferred α7nAChR-deficient or WT T cells to nude mice. Transfer of WT and α7nAChR-deficient T cells restored function, indicating that α7nAChR expression on T cells is not necessary for this pathway. Together, these results indicate that α7nAChR expression in bone marrow–derived non–T cells is required for the integrity of the inflammatory reflex. PMID:22183893

Effect of a nicotine vaccine on nicotine binding to the beta2-nAChRs in vivo in human tobacco smokers

PubMed Central

Esterlis, Irina; Hannestad, Jonas O.; Perkins, Evgenia; Bois, Frederic; D’Souza, D. Cyril; Tyndale, Rachel F.; Seibyl, John P.; Hatsukami, Dorothy M.; Cosgrove, Kelly P.; O’Malley, Stephanie S.

2013-01-01

Objective Nicotine acts in the brain to promote smoking in part by binding to the beta2-containing nicotinic acetylcholine receptors (β2*-nAChRs) and acting in the mesolimbic reward pathway. The effects of nicotine from smoking one tobacco cigarette are significant (80% of β2*-nAChRs occupied for >6h). This likely contributes to the maintenance of smoking dependence and low cessation outcomes. Development of nicotine vaccines provides potential for alternative treatments. We used [123I]5IA-85380 SPECT to evaluate the effect of 3′-AmNic-rEPA on the amount of nicotine that binds to the β2*-nAChRs in the cortical and subcortical regions in smokers. Method Eleven smokers (36years (SD=13); 19cig/day (SD=11) for 10years (SD=7) who were dependent on nicotine (Fagerström Test of Nicotine Dependence score =5.5 (SD=3); plasma nicotine 9.1 ng/mL (SD=5)) participated in 2 SPECT scan days: before and after immunization with 4–400μg doses of 3′-AmNic-rEPA. On SPECT scan days, 3 30-min baseline emission scans were obtained, followed by administration of IV nicotine (1.5mg/70kg) and up to 9 30-min emission scans. Results β2*-nAChR availability was quantified as VT/fP and nicotine binding was derived using the Lassen plot approach. Immunization led to a 12.5% reduction in nicotine binding (F=5.19, df=1,10, p=0.05). Significant positive correlations were observed between nicotine bound to β2*-nAChRs and nicotine injected before but not after vaccination (p=0.05 vs. p=0.98). There was a significant reduction in the daily number of cigarettes and desire for a cigarette (p=.01 and p=.04, respectively). Conclusions This proof-of-concept study demonstrates that immunization with nicotine vaccine can reduce the amount of nicotine binding to β2*-nAChRs and disrupt the relationship between nicotine administered vs. nicotine available to occupy β2*-nAChRs. PMID:23429725

RAGE mediates the inactivation of nAChRs in sympathetic neurons under high glucose conditions.

PubMed

Chandna, Andrew R; Nair, Manoj; Chang, Christine; Pennington, Paul R; Yamamoto, Yasuhiko; Mousseau, Darrell D; Campanucci, Verónica A

2015-02-01

Autonomic dysfunction is a serious complication of diabetes and can lead to cardiovascular abnormalities and premature death. It was recently proposed that autonomic dysfunction is triggered by oxidation-mediated inactivation of neuronal nicotinic acetylcholine receptors (nAChRs), impairing synaptic transmission in sympathetic ganglia and resulting in autonomic failure. We investigated whether the receptor for advanced glycation end products (RAGE) and its role in the generation of reactive oxygen species (ROS) could be contributing to the events that initiate sympathetic malfunction under high glucose conditions. Using biochemical, live imaging and electrophysiological tools we demonstrated that exposure of sympathetic neurons to high glucose increases RAGE expression and oxidative markers, and that incubation with RAGE ligands (e.g. AGEs, S100 and HMGB1) mimics both ROS elevation and nAChR inactivation. In contrast, co-treatment with either antioxidants or an anti-RAGE IgG prevented the inactivation of nAChRs. Lastly, a role for RAGE in this context was corroborated by the lack of sensitivity of sympathetic neurons from RAGE knock-out mice to high glucose. These data define a pivotal role for RAGE in initiating the events associated with exposure of sympathetic neurons to high glucose, and strongly support RAGE signaling as a potential therapeutic target in the autonomic complications associated with diabetes. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Foccα6, a truncated nAChR subunit, positively correlates with spinosad resistance in the western flower thrips, Frankliniella occidentalis (Pergande).

PubMed

Wan, Yanran; Yuan, Guangdi; He, Bingqing; Xu, Baoyun; Xie, Wen; Wang, Shaoli; Zhang, Youjun; Wu, Qingjun; Zhou, Xuguo

2018-08-01

Nicotinic acetylcholine receptors (nAChRs), a molecular target for spinosyns and neonicotinoids, mediate rapid cholinergic transmission in insect central nervous system by binding acetylcholine. Previous studies have shown that mutations in nAChRs contribute to the high level of resistance to these two classes of insecticides. In this study, we identified nine nAChR subunits from a transcriptome of the western flower thrips, Frankliniella occidentalis, including α1-7, β1, and β2. Exon 4 of α4 and exons 3 and 8 of α6 each have two splicing variants, respectively. In addition, altered or incorrect splicing leads to truncated forms of α3, α5, and α6 subunits. The abundance of every nAChRs in both spinosad susceptible and resistant strains was highest in the 1st instar nymph. Significantly more truncated forms of α6 subunit were detected in spinosad resistant strains, whereas, hardly any full-length form was found in the two highly resistant F. occidentalis strains (resistance ratio >10 4 -fold). Under laboratory conditions, spinosad resistance was positively correlated with truncated α6 transcripts. The correlation was later confirmed under the field conditions using five field strains. As the molecular target of spinosad, the percentage of truncated nAChR α6 subunits can be used as a diagnostic tool to detect and quantify spinosad resistance in the field. Copyright © 2018. Published by Elsevier Ltd.

Cigarette smoking during pregnancy regulates the expression of specific nicotinic acetylcholine receptor (nAChR) subunits in the human placenta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Machaalani, R., E-mail: rita.machaalani@sydney.edu.au; Bosch Institute, The University of Sydney, NSW 2006; The Children's Hospital at Westmead, NSW 2145

Smoking during pregnancy is associated with low birth weight, premature delivery, and neonatal morbidity and mortality. Nicotine, a major pathogenic compound of cigarette smoke, binds to the nicotinic acetylcholine receptors (nAChRs). A total of 16 nAChR subunits have been identified in mammals (9 α, 4 β, and 1 δ, γ and ε subunits). The effect of cigarette smoking on the expression of these subunits in the placenta has not yet been determined, thus constituting the aim of this study. Using RT-qPCR and western blotting, this study investigated all 16 mammalian nAChR subunits in the normal healthy human placenta, and comparedmore » mRNA and protein expressions in the placentas from smokers (n = 8) to controls (n = 8). Our data show that all 16 subunit mRNAs are expressed in the normal, non-diseased human placenta and that the expression of α2, α3, α4, α9, β2 and β4 subunits is greater than the other subunits. For mRNA, cigarette smoke exposure was associated with increased expression of the α9 subunit, and decreased expression of the δ subunit. At the protein level, expression of both α9 and δ was increased. Thus, cigarette smoking in pregnancy is sufficient to regulate nAChR subunits in the placenta, specifically α9 and δ subunits, and could contribute to the adverse effects of vasoconstriction and decreased re-epithelialisation (α9), and increased calcification and apoptosis (δ), seen in the placentas of smoking women. - Highlights: • All 16 mammalian nAChR subunits are expressed in the human placenta. • Cigarette smoking increases α9 mRNA and protein in the placenta. • Cigarette smoking decreases δ mRNA but increases δ protein in the placenta.« less

The possible role of maternal bonding style and CHRNB2 gene polymorphisms in nicotine dependence and related depressive phenotype.

PubMed

Csala, Iren; Egervari, Luca; Dome, Peter; Faludi, Gabor; Dome, Balazs; Lazary, Judit

2015-06-03

Neuronal nicotinic acetylcholinergic receptors (nAChR) and especially α4β2 nAChRs are the major targets for cessation medications and also for some promising antidepressant agents. Furthermore, depressive symptoms pose multifacet difficulties during cessation therapy. However, gene encoding for the β2 subunit of nAChRs has been poorly investigated in association with depression. Since both nicotine dependence (ND) and depressive phenotype are complex disorders, we investigated the effects of a significant early life experience, maternal bonding style (MB) and CHRNB2 gene SNPs on smoking-related depression. We recruited two hundred and thirty-two treatment-seeking smokers in our study. Phenotypic variants were evaluated using the Fagerstrom Test for Nicotine Dependence (FTND), the Zung Self-Rating Depression Scale (ZSDS) and the Parental Bonding Instrument (PBI). Besides the total score (TS) of ZSDS, impulsivity (ZSDS-I) and suicidal ideation (ZSDS-S) were distinguished as phenotypic variable. DNAs were extracted from buccal mucosa samples and one SNP in promoter and two SNPs in 3' UTR of CHRNB2 gene were genotyped. GLM and ANOVA tests were performed for genotype associations and interaction analyses. Maternal bonding had a significant impact on depressive phenotypes. Low care, high protection and affectionless control (ALC) were associated with ZSDS-TS and all subphenotypes of ZSDS. One SNP, the rs2072660 in 3' UTR, had a significant effect on the FTND score (p=0.010). Direct association of CHRNB2 variants and depressive phenotypes were not significant. However, in interaction with ALC, rs2072660 was significantly associated with ZSDS-S (p=0.005). MB had no significant effect on smoking-related phenotype. Our results highlight the important role of 3' UTR in the CHRNB2 gene in the shared molecular background of ND and depressive phenotype. Parental bonding style can be suggested as a significant environmental factor in further GxE studies of depression. The

Recent Developments in Novel Antidepressants Targeting α4β2-Nicotinic Acetylcholine Receptors

PubMed Central

2015-01-01

Nicotinic acetylcholine receptors (nAChRs) have been investigated for developing drugs that can potentially treat various central nervous system disorders. Considerable evidence supports the hypothesis that modulation of the cholinergic system through activation and/or desensitization/inactivation of nAChR holds promise for the development of new antidepressants. The introductory portion of this Miniperspective discusses the basic pharmacology that underpins the involvement of α4β2-nAChRs in depression, along with the structural features that are essential to ligand recognition by the α4β2-nAChRs. The remainder of this Miniperspective analyzes reported nicotinic ligands in terms of drug design considerations and their potency and selectivity, with a particular focus on compounds exhibiting antidepressant-like effects in preclinical or clinical studies. This Miniperspective aims to provide an in-depth analysis of the potential for using nicotinic ligands in the treatment of depression, which may hold some promise in addressing an unmet clinical need by providing relief from depressive symptoms in refractory patients. PMID:24901260

Vagus nerve stimulation mediates protection from kidney ischemia-reperfusion injury through α7nAChR+ splenocytes.

PubMed

Inoue, Tsuyoshi; Abe, Chikara; Sung, Sun-Sang J; Moscalu, Stefan; Jankowski, Jakub; Huang, Liping; Ye, Hong; Rosin, Diane L; Guyenet, Patrice G; Okusa, Mark D

2016-05-02

The nervous and immune systems interact in complex ways to maintain homeostasis and respond to stress or injury, and rapid nerve conduction can provide instantaneous input for modulating inflammation. The inflammatory reflex referred to as the cholinergic antiinflammatory pathway regulates innate and adaptive immunity, and modulation of this reflex by vagus nerve stimulation (VNS) is effective in various inflammatory disease models, such as rheumatoid arthritis and inflammatory bowel disease. Effectiveness of VNS in these models necessitates the integration of neural signals and α7 nicotinic acetylcholine receptors (α7nAChRs) on splenic macrophages. Here, we sought to determine whether electrical stimulation of the vagus nerve attenuates kidney ischemia-reperfusion injury (IRI), which promotes the release of proinflammatory molecules. Stimulation of vagal afferents or efferents in mice 24 hours before IRI markedly attenuated acute kidney injury (AKI) and decreased plasma TNF. Furthermore, this protection was abolished in animals in which splenectomy was performed 7 days before VNS and IRI. In mice lacking α7nAChR, prior VNS did not prevent IRI. Conversely, adoptive transfer of VNS-conditioned α7nAChR splenocytes conferred protection to recipient mice subjected to IRI. Together, these results demonstrate that VNS-mediated attenuation of AKI and systemic inflammation depends on α7nAChR-positive splenocytes.

Physical Activity, Gender Difference, and Depressive Symptoms.

PubMed

Zhang, Jun; Yen, Steven T

2015-10-01

To investigate the roles of physical activity (exercise) and sociodemographic factors in depressive symptoms among men and women in the United States. 2011 U.S. Behavioral Risk Factor Surveillance System (BRFSS). Patient Health Questionnaire Depression Scale (PHQ-8) scores are aggregated and divided into five categories. An ordered switching probability model with binary endogenous physical activity is developed to accommodate ordinality of depression categories and ameliorate statistical biases due to endogeneity of physical activity. Average treatment effects suggest physical activity ameliorates depressive symptoms among mildly and moderately depressed individuals, most notably among mildly depressed women. Gender differences exist in the roles of sociodemographic factors, with age, income, race, education, employment status, and recent mental health condition playing differentiated roles in affecting depressive symptoms. Regular physical activity reduces depressive symptoms among both men and women with mild to moderate depression, notably among women. © Health Research and Educational Trust.

NMR resolved multiple anesthetic binding sites in the TM domains of the α4β2 nAChR

PubMed Central

Bondarenko, Vasyl; Mowrey, David; Liu, Lu Tian; Xu, Yan; Tang, Pei

2012-01-01

The α4β2 nicotinic acetylcholine receptor (nAChR) has significant roles in nervous system function and disease. It is also a molecular target of general anesthetics. Anesthetics inhibit the α4β2 nAChR at clinically relevant concentrations, but their binding sites in α4β2 remain unclear. The recently determined NMR structures of the α4β2 nAChR transmembrane (TM) domains provide valuable frameworks for identifying the binding sites. In this study, we performed solution NMR experiments on the α4β2 TM domains in the absence and presence of halothane and ketamine. Both anesthetics were found in an intra-subunit cavity near the extracellular end of the 2 transmembrane helices, homologous to a common anesthetic binding site observed in X-ray structures of anesthetic-bound GLIC (Nury, et. al. 2011). Halothane, but not ketamine, was also found in cavities adjacent to the common anesthetic site at the interface of α4 and β2. In addition, both anesthetics bound to cavities near the ion selectivity filter at the intracellular end of the TM domains. Anesthetic binding induced profound changes in protein conformational exchanges. A number of residues, close to or remote from the binding sites, showed resonance signal splitting from single to double peaks, signifying that anesthetics decreased conformation exchange rates. It was also evident that anesthetics shifted population of two conformations. Altogether, the study comprehensively resolved anesthetic binding sites in the α4β2 nAChR. Furthermore, the study provided compelling experimental evidence of anesthetic-induced changes in protein dynamics, especially near regions of the hydrophobic gate and ion selectivity filter that directly regulate channel functions. PMID:23000369

NMR resolved multiple anesthetic binding sites in the TM domains of the α4β2 nAChR.

PubMed

Bondarenko, Vasyl; Mowrey, David; Liu, Lu Tian; Xu, Yan; Tang, Pei

2013-02-01

The α4β2 nicotinic acetylcholine receptor (nAChR) has significant roles in nervous system function and disease. It is also a molecular target of general anesthetics. Anesthetics inhibit the α4β2 nAChR at clinically relevant concentrations, but their binding sites in α4β2 remain unclear. The recently determined NMR structures of the α4β2 nAChR transmembrane (TM) domains provide valuable frameworks for identifying the binding sites. In this study, we performed solution NMR experiments on the α4β2 TM domains in the absence and presence of halothane and ketamine. Both anesthetics were found in an intra-subunit cavity near the extracellular end of the β2 transmembrane helices, homologous to a common anesthetic binding site observed in X-ray structures of anesthetic-bound GLIC (Nury et al., [32]). Halothane, but not ketamine, was also found in cavities adjacent to the common anesthetic site at the interface of α4 and β2. In addition, both anesthetics bound to cavities near the ion selectivity filter at the intracellular end of the TM domains. Anesthetic binding induced profound changes in protein conformational exchanges. A number of residues, close to or remote from the binding sites, showed resonance signal splitting from single to double peaks, signifying that anesthetics decreased conformation exchange rates. It was also evident that anesthetics shifted population of two conformations. Altogether, the study comprehensively resolved anesthetic binding sites in the α4β2 nAChR. Furthermore, the study provided compelling experimental evidence of anesthetic-induced changes in protein dynamics, especially near regions of the hydrophobic gate and ion selectivity filter that directly regulate channel functions. Copyright © 2012 Elsevier B.V. All rights reserved.

The 3,7-diazabicyclo[3.3.1]nonane scaffold for subtype selective nicotinic acetylcholine receptor (nAChR) ligands. Part 1: the influence of different hydrogen bond acceptor systems on alkyl and (hetero)aryl substituents.

PubMed

Eibl, Christoph; Tomassoli, Isabelle; Munoz, Lenka; Stokes, Clare; Papke, Roger L; Gündisch, Daniela

2013-12-01

3,7-Diazabicyclo[3.3.1]nonane is a naturally occurring scaffold interacting with nicotinic acetylcholine receptors (nAChRs). When one nitrogen of the 3,7-diazabicyclo[3.3.1]nonane scaffold was implemented in a carboxamide motif displaying a hydrogen bond acceptor (HBA) functionality, compounds with higher affinities and subtype selectivity for α4β2(∗) were obtained. The nature of the HBA system (carboxamide, sulfonamide, urea) had a strong impact on nAChR interaction. High affinity ligands for α4β2(∗) possessed small alkyl chains, small un-substituted hetero-aryl groups or para-substituted phenyl ring systems along with a carboxamide group. Electrophysiological responses of selected 3,7-diazabicyclo[3.3.1]nonane derivatives to Xenopus oocytes expressing various nAChR subtypes showed diverse activation profiles. Compounds with strongest agonistic profiles were obtained with small alkyl groups whereas a shift to partial agonism/antagonism was observed for aryl substituents. Copyright © 2013 Elsevier Ltd. All rights reserved.

Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induce cyclooxygenase-2 activity in human gastric cancer cells: Involvement of nicotinic acetylcholine receptor (nAChR) and {beta}-adrenergic receptor signaling pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shin, Vivian Yvonne; Jin, H.C.; Ng, Enders K.O.

Induction of cyclooxygenase-2 (COX-2) associates with cigarette smoke exposure in many malignancies. Nicotine and its derivative, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are the two important components in cigarette smoke that contributes to cancer development. However, the molecular mechanism(s) by which nicotine or NNK promotes gastric carcinogenesis remains largely unknown. We found that nicotine and NNK significantly enhanced cell proliferation in AGS cells that expressed both alpha7 nicotinic acetylcholine receptor ({alpha}7 nAChR) and {beta}-adrenergic receptors. Treatment of cells with {alpha}-bungarotoxin ({alpha}-BTX, {alpha}7nAChR antagonist) or propranolol ({beta}-adrenergic receptor antagonist) blocked NNK-induced COX-2/PGE{sub 2} and cell proliferation, while nicotine-mediated cell growth and COX-2/PGE{sub 2} induction canmore » only be suppressed by propranolol, but not {alpha}-BTX. Moreover, in contrast to the dependence of growth promoting effect of nicotine on Erk activation, inhibitor of p38 mitogen-activated protein kinase (MAPK) repressed NNK-induced COX-2 upregulation and resulted in suppression of cell growth. In addition, nicotine and NNK mediated COX-2 induction via different receptors to modulate several G1/S transition regulatory proteins and promote gastric cancer cell growth. Selective COX-2 inhibitor (SC-236) caused G1 arrest and abrogated nicotine/NNK-induced cell proliferation. Aberrant expression of cyclin D1 and other G1 regulatory proteins are reversed by blockade of COX-2. These results pointed to the importance of adrenergic and nicotinic receptors in gastric tumor growth through MAPK/COX-2 activation, which may perhaps provide a chemoprevention strategy for cigarette smoke-related gastric carcinogenesis.« less

Increased Spreading Activation in Depression

ERIC Educational Resources Information Center

Foster, Paul S.; Yung, Raegan C.; Branch, Kaylei K.; Stringer, Kristi; Ferguson, Brad J.; Sullivan, William; Drago, Valeria

2011-01-01

The dopaminergic system is implicated in depressive disorders and research has also shown that dopamine constricts lexical/semantic networks by reducing spreading activation. Hence, depression, which is linked to reductions of dopamine, may be associated with increased spreading activation. However, research has generally found no effects of…

Electrophysiological investigation of the effect of structurally different bispyridinium non-oxime compounds on human α7-nicotinic acetylcholine receptor activity-An in vitro structure-activity analysis.

PubMed

Scheffel, Corinna; Niessen, Karin V; Rappenglück, Sebastian; Wanner, Klaus T; Thiermann, Horst; Worek, Franz; Seeger, Thomas

2018-09-01

Organophosphorus compounds, including nerve agents and pesticides, exert their toxicity through irreversible inhibition of acetylcholinesterase (AChE) resulting in an accumulation of acetylcholine and functional impairment of muscarinic and nicotinic acetylcholine receptors. Current therapy comprises oximes to reactivate AChE and atropine to antagonize effects induced by muscarinic acetylcholine receptors. Nicotinic malfunction leading to depression of the central and peripheral respiratory system is not directly treated calling for alternative therapeutic interventions. In the present study, we investigated the electrophysiological properties of the human nAChR subtype α7 (hα7-nAChR) and the functional effect of the 4-tert-butyl bispyridinium (BP) compound MB327 and of a series of novel substituted bispyridinium compounds on the receptors by an automated patch clamp technique. Activation of hα7-nAChRs was induced by nicotine and acetylcholine demonstrating rapid cationic influx up to 100μM. Agonist-induced currents decayed within a few milliseconds revealing fast desensitization of the receptors. Application of higher agonist concentrations led to a decline of current amplitudes which seemed to be due to increasing receptor desensitization. When 100μM of agonist was coapplied with low concentrations of the well characterized α7-specific positive allosteric modulator PNU-120596 (1μM-10μM), the maximum response and duration of nAChR activation were markedly augmented indicating an elongated mean open-time of receptors and prevention of receptor desensitization. However, co-application of increasing PNU-120596 concentrations (>10μM) with agonist induced a decline of potentiated current responses. Although less pronounced than PNU-120596, six of the twenty tested substituted BP compounds, in particular those with a substituent at 3-position and 4-position at the pyridinium moieties, were found to potentiate current responses of hα7-nAChRs, most pronounced MB

Cracking the Betel Nut: Cholinergic Activity of Areca Alkaloids and Related Compounds.

PubMed

Horenstein, Nicole A; Quadri, Marta; Stokes, Clare; Shoaib, Mohammed; Papke, Roger L

2017-10-03

The use of betel quid is the most understudied major addiction in the world. The neuropsychological activity of betel quid has been attributed to alkaloids of Areca catechu. With the goal of developing novel addiction treatments, we evaluate the muscarinic and nicotinic activity of the four major Areca alkaloids: arecoline, arecaidine, guvacoline, and guvacine and four structurally related compounds. Acetylcholine receptors were expressed in Xenopus oocytes and studied with two-electrode voltage clamp. Both arecoline- and guvacoline-activated muscarinic acetylcholine receptors (mAChR), while only arecoline produced significant activation of nicotinic AChR (nAChR). We characterized four additional arecoline-related compounds, seeking an analog that would retain selective activity for a α4* nAChR, with diminished effects on mAChR and not be a desensitizer of α7 nAChR. We show that this profile is largely met by isoarecolone. Three additional arecoline analogs were characterized. While the quaternary dimethyl analog had a broad range of activities, including activation of mAChR and muscle-type nAChR, the methyl analog only activated a range of α4* nAChR, albeit with low potency. The ethyl analog had no detectable cholinergic activity. Evidence indicates that α4* nAChR are at the root of nicotine addiction, and this may also be the case for betel addiction. Our characterization of isoarecolone and 1-(4-methylpiperazin-1-yl) ethanone as truly selective α4*nAChR selective partial agonists with low muscarinic activity may point toward a promising new direction for the development of drugs to treat both nicotine and betel addiction. Nearly 600 million people use Areca nut, often with tobacco. Two of the Areca alkaloids are muscarinic acetylcholine receptor agonists, and one, arecoline, is a partial agonist for the α4* nicotinic acetylcholine receptors (nAChR) associated with tobacco addiction. The profile of arecoline activity suggested its potential to be used as a

GaAs laser therapy reestablishes the morphology of the NMJ and nAChRs after injury due to bupivacaine.

PubMed

Pissulin, Cristiane Neves Alessi; de Souza Castro, Paula Aiello Tomé; Codina, Flávio; Pinto, Carina Guidi; Vechetti-Junior, Ivan Jose; Matheus, Selma Maria Michelin

2017-02-01

Local anesthetics are used to relieve pre- and postoperative pain, acting on both sodium channels and nicotinic acetylcholine receptors (nAChR) at the neuromuscular junction (NMJ). Bupivacaine acts as a non-competitive antagonist and has limitations, such as myotoxicity, neurotoxicity, and inflammation. Low-level laser therapy (LLLT) has anti-inflammatory, regenerative, and analgesic effects. The aim of the present study was to evaluate the effects of a gallium arsenide laser (GaAs) on the morphology of the NMJ and nAChRs after application of bupivacaine in the sternomastoid muscle. Thirty-two adult male Wistar rats received injections of bupivacaine 0.5% (Bupi: right antimere) and 0.9% sodium chloride (Cl: left antimere). Next, the animals were divided into a Control group (C) and a Laser group (LLLT). The laser group received LLLT (GaAs 904nm, 50mW, 4,8J) in both antimeres for five consecutive days. After seven days, the animals were euthanized and the surface portion of the sternomastoid muscle was removed, frozen, and subjected to morphological and morphometric analyses of the NMJs (nonspecific esterase reaction), confocal laser scanning, and an ultrastructural analysis. The nAChRs were quantified by Western blotting. In the chloride group, the morphology and morphometry of the NMJs remained stable. The maximum diameters of the NMJs were lower in the Bupi (15.048±1.985) and LLLT/Bupi subgroups (15.456±1.983) compared to the Cl (18.502±2.058) and LLLT/Cl subgroups (19.356±2.522) (p<0.05). Ultrastructurally, LLLT reduced myonecrosis observed after application of bupivacaine, with recovery in the junctional folds and active zone. There was an increase in the perimeter of the LLLT/Bupi subgroup (150.33) compared to the Bupi subgroup (74.69) (p<0.01) observed by confocal microscopy. There was also an increase in the relative planar area of the NMJ after LBI (8.75) compared to CBupi (4.80) (p<0.01). An analysis of the protein expression of nAChRα1 showed no

Physical activity and depression symptom profiles in young men and women with major depression.

PubMed

McKercher, Charlotte; Patton, George C; Schmidt, Michael D; Venn, Alison J; Dwyer, Terence; Sanderson, Kristy

2013-05-01

This study explored whether young adults with major depression who are physically active differ in their depression symptom profile from those physically inactive. Analyses included data from 950 (47.6%) men and 1045 women (mean [standard deviation] age = 31.5 [2.6] years) participating in a national study. Participants reported leisure physical activity (International Physical Activity Questionnaire) and ambulatory activity (pedometer steps per day). Diagnosis and symptoms of major depression were assessed using the Composite International Diagnostic Interview. Prevalence of major depression was 5.5% (n = 52) for men and 11.6% (n = 121) for women. Interactions between physical activity and sex were observed for depressed mood, appetite changes, vacillating thoughts, and suicidality (all, p < .050). Among those with major depression, physically active men were significantly less likely to endorse the presence of insomnia (prevalence ratio [PR] = 0.78, 95% confidence interval [CI] = 0.63-0.96), fatigue (PR = 0.82, 95% CI = 0.69-0.99), and suicidality (PR = 0.69, 95% CI = 0.49-0.96) compared with inactive men. Physically active women were significantly less likely to endorse hypersomnia (PR = 0.50, 95% CI = 0.27-0.95), excessive/irrational guilt (PR = 0.76, 95% CI = 0.59-0.97), vacillating thoughts (PR = 0.74, 95% CI = 0.58-0.95), and suicidality (PR = 0.43, 95% CI = 0.20-0.89) compared with inactive women. Associations were adjusted for age, physical health, educational attainment, depression severity, and other depressive symptoms. Among adults with major depression, those physically active seem to differ in their depression symptom profile from those physically inactive.

Concomitant alpha7 and beta2 nicotinic AChR subunit deficiency leads to impaired energy homeostasis and increased physical activity in mice.

PubMed

Somm, Emmanuel; Guérardel, Audrey; Maouche, Kamel; Toulotte, Audrey; Veyrat-Durebex, Christelle; Rohner-Jeanrenaud, Françoise; Maskos, Uwe; Hüppi, Petra S; Schwitzgebel, Valérie M

2014-05-01

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated cation channels well characterized in neuronal signal transmission. Moreover, recent studies have revealed nAChR expression in nonneuronal cell types throughout the body, including tissues involved in metabolism. In the present study, we screen gene expression of nAChR subunits in pancreatic islets and adipose tissues. Mice pancreatic islets present predominant expression of α7 and β2 nAChR subunits but at a lower level than in central structures. Characterization of glucose and energy homeostasis in α7β2nAChR(-/-) mice revealed no major defect in insulin secretion and sensitivity but decreased glycemia apparently unrelated to gluconeogenesis or glycogenolysis. α7β2nAChR(-/-) mice presented an increase in lean and bone body mass and a decrease in fat storage with normal body weight. These observations were associated with elevated spontaneous physical activity in α7β2nAChR(-/-) mice, mainly due to elevation in fine vertical (rearing) activity while their horizontal (ambulatory) activity remained unchanged. In contrast to α7nAChR(-/-) mice presenting glucose intolerance and insulin resistance associated to excessive inflammation of adipose tissue, the present metabolic phenotyping of α7β2nAChR(-/-) mice revealed a metabolic improvement possibly linked to the increase in spontaneous physical activity related to central β2nAChR deficiency. Copyright © 2014 Elsevier Inc. All rights reserved.

[The bidirectional relationship between physical activity and sleep in depressed versus non-depressed individuals].

PubMed

Oude Oosterik, N A M; Bouwmans, M E J; de Groot, I W; Bos, E H; de Jonge, P

Sleep and physical activity are related, but the direction of this relationship is unclear and it is not known whether the direction differs in depressed and non-depressed persons. To study the bidirectional relationship between physical activity and sleep in daily life by making repeated measurements in depressed and non-depressed people. Every day for 30 consecutive days each depressed (N = 27) and non-depressed (N = 27) participant in our study had to complete an electronic questionnaire relating to subjective sleep quality and sleep duration and were required to wear an accelerometer that recorded physical activity. Multi-level analysis showed that an increase in subjective sleep duration resulted in a decrease in physical activity. The differences between individuals with regard to the direction and strength of this relationship were significant. Changes in physical activity did not predict changes in sleep quality or sleep duration. We did not find any differences in the relationships for depressed and non-depressed participants. Change in sleep duration predicts change in physical activity, although there was significant heterogeneity in the results for individuals. Our findings underline the importance of further research and of the development of interventions that are tailored to the precise needs of the individual patient.

Covariation of depressive mood and spontaneous physical activity in major depressive disorder: toward continuous monitoring of depressive mood.

PubMed

Kim, Jinhyuk; Nakamura, Toru; Kikuchi, Hiroe; Yoshiuchi, Kazuhiro; Sasaki, Tsukasa; Yamamoto, Yoshiharu

2015-07-01

The objective evaluation of depressive mood is considered to be useful for the diagnosis and treatment of depressive disorders. Thus, we investigated psychobehavioral correlates, particularly the statistical associations between momentary depressive mood and behavioral dynamics measured objectively, in patients with major depressive disorder (MDD) and healthy subjects. Patients with MDD ( n = 14) and healthy subjects ( n = 43) wore a watch-type computer device and rated their momentary symptoms using ecological momentary assessment. Spontaneous physical activity in daily life, referred to as locomotor activity, was also continuously measured by an activity monitor built into the device. A multilevel modeling approach was used to model the associations between changes in depressive mood scores and the local statistics of locomotor activity simultaneously measured. We further examined the cross validity of such associations across groups. The statistical model established indicated that worsening of the depressive mood was associated with the increased intermittency of locomotor activity, as characterized by a lower mean and higher skewness. The model was cross validated across groups, suggesting that the same psychobehavioral correlates are shared by both healthy subjects and patients, although the latter had significantly higher mean levels of depressive mood scores. Our findings suggest the presence of robust as well as common associations between momentary depressive mood and behavioral dynamics in healthy individuals and patients with depression, which may lead to the continuous monitoring of the pathogenic processes (from healthy states) and pathological states of MDD.

The impact of a parkinsonian lesion on dynamic striatal dopamine transmission depends on nicotinic receptor activation

PubMed Central

Jennings, Katie A.; Platt, Nicola J.; Cragg, Stephanie J.

2015-01-01

Dopamine function is disturbed in Parkinson's disease (PD), but whether and how release of dopamine from surviving neurons is altered has long been debated. Nicotinic acetylcholine receptors (nAChRs) on dopamine axons powerfully govern dopamine release and could be critical contributing factors. We revisited whether fundamental properties of dopamine transmission are changed in a parkinsonian brain and tested the potentially profound masking effects of nAChRs. Using real-time detection of dopamine in mouse striatum after a partial 6-hydroxydopamine lesion and under nAChR inhibition, we reveal that dopamine signals show diminished sensitivity to presynaptic activity. This effect manifested as diminished contrast between DA release evoked by the lowest versus highest frequencies. This reduced activity-dependence was underpinned by loss of short-term facilitation of dopamine release, consistent with an increase in release probability (Pr). With nAChRs active, the reduced activity-dependence of dopamine release after a parkinsonian lesion was masked. Consequently, moment-by-moment variation in activity of nAChRs may lead to dynamic co-variation in dopamine signal impairments in PD. PMID:26117304

Bipolar I disorder and major depressive disorder show similar brain activation during depression.

PubMed

Cerullo, Michael A; Eliassen, James C; Smith, Christopher T; Fleck, David E; Nelson, Erik B; Strawn, Jeffrey R; Lamy, Martine; DelBello, Melissa P; Adler, Caleb M; Strakowski, Stephen M

2014-11-01

Despite different treatments and courses of illness, depressive symptoms appear similar in major depressive disorder (MDD) and bipolar I disorder (BP-I). This similarity of depressive symptoms suggests significant overlap in brain pathways underlying neurovegetative, mood, and cognitive symptoms of depression. These shared brain regions might be expected to exhibit similar activation in individuals with MDD and BP-I during functional magnetic resonance imaging (fMRI). fMRI was used to compare regional brain activation in participants with BP-I (n = 25) and MDD (n = 25) during a depressive episode as well as 25 healthy comparison (HC) participants. During the scans, participants performed an attentional task that incorporated emotional pictures. During the viewing of emotional images, subjects with BP-I showed decreased activation in the middle occipital gyrus, lingual gyrus, and middle temporal gyrus compared to both subjects with MDD and HC participants. During attentional processing, participants with MDD had increased activation in the parahippocampus, parietal lobe, and postcentral gyrus. However, among these regions, only the postcentral gyrus also showed differences between MDD and HC participants. No differences in cortico-limbic regions were found between participants with BP-I and MDD during depression. Instead, the major differences occurred in primary and secondary visual processing regions, with decreased activation in these regions in BP-I compared to major depression. These differences were driven by abnormal decreases in activation seen in the participants with BP-I. Posterior activation changes are a common finding in studies across mood states in participants with BP-I. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Interactions of Sexual Activity, Gender, and Depression with Immunity

PubMed Central

Lorenz, Tierney; van Anders, Sari

2015-01-01

Introduction Depression can suppress immune function, leading to lower resistance against infection and longer healing times in depressed individuals. Sexuality may also influence immune function, with evidence that sexual activity is associated with lowered immune function in women and mixed results in men. Immune mediators like immunoglobulin A (IgA) are immediately relevant to sexual health, since they are the first line of defense against pathogens at mucous membranes like the vagina. Aim This study aims to determine if and how depression, sexual activity, and their interaction impact salivary IgA (SIgA) in men and women. Methods In Study 1, a community-based sample of 84 women and 88 men provided saliva samples and completed questionnaires on their demographic background, level of depression, and frequency of partnered and solitary sexual activity. Study 2, conducted separately in an undergraduate student sample of 54 women and 52 men, had similar methods. Main Outcome Measures The main outcome measures were scores on the General Well-Being Schedule depression subscale, reported frequency of sexual activity, and SIgA levels as measured by enzyme immunoassay. Results Across studies, higher levels of partnered sexual activity were associated with lower SIgA for women with high depression scores, but not for women with low depression scores. In contrast, higher levels of partnered sexual activity were associated with higher SIgA for men with high depression scores, but not for men with low depression scores. Conclusion Our results show that partnered sexual activity is a risk factor for lowered immunity in women with depressive symptoms but a possible resilience factor for men with depressive symptoms. This suggests a role for sexual activity in determining the impact of depression on physical health parameters. PMID:23448297

24-h activity rhythm and sleep in depressed outpatients.

PubMed

Hori, Hiroaki; Koga, Norie; Hidese, Shinsuke; Nagashima, Anna; Kim, Yoshiharu; Higuchi, Teruhiko; Kunugi, Hiroshi

2016-06-01

Disturbances in sleep and circadian rest-activity rhythms are key features of depression. Actigraphy, a non-invasive method for monitoring motor activity, can be used to objectively assess circadian rest-activity rhythms and sleep patterns. While recent studies have measured sleep and daytime activity of depressed patients using wrist-worn actigraphy, the actigraphic 24-h rest-activity rhythm in depression has not been well documented. We aimed to examine actigraphically measured sleep and circadian rest-activity rhythms in depressed outpatients. Twenty patients with DSM-IV major depressive episode and 20 age- and sex-matched healthy controls participated in this study. Participants completed 7 consecutive days of all-day actigraphic activity monitoring while engaging in usual activities. For sleep parameters, total sleep time, wake after sleep onset, and sleep fragmentation index were determined. Circadian rhythms were estimated by fitting individual actigraphy data to a cosine curve of a 24-h activity rhythm using the cosinor method, which generated three circadian activity rhythm parameters, i.e., MESOR (rhythm-adjusted mean), amplitude, and acrophase. Subjective sleep was also assessed using a sleep diary and the Pittsburgh Sleep Quality Index. Patients showed significantly lower MESOR and more dampened amplitude along with significant sleep disturbances. Logistic regression analysis revealed that lower MESOR and more fragmented sleep emerged as the significant predictors of depression. Correlations between subjectively and actigraphically measured parameters demonstrated the validity of actigraphic measurements. These results indicate marked disturbances in sleep and circadian rest-activity rhythms of depression. By simultaneously measuring sleep and rest-activity rhythm parameters, actigraphy might serve as an objective diagnostic aid for depression. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impairment of contextual fear extinction by chronic nicotine and withdrawal from chronic nicotine is associated with hippocampal nAChR upregulation

PubMed Central

Kutlu, Munir Gunes; Oliver, Chicora; Huang, Peng; Liu-Chen, Lee-Yuan; Gould, Thomas J.

2017-01-01

Chronic nicotine and withdrawal from chronic nicotine have been shown to be major modulators of fear learning behavior. Moreover, recent studies from our laboratory have shown that acute nicotine impaired fear extinction and safety learning in mice. However, the effects of chronic nicotine and withdrawal on fear extinction are unknown. Therefore, the current experiments were conducted to investigate the effects of chronic nicotine as well as withdrawal from chronic nicotine on contextual fear extinction in mice. C57BL6/J mice were given contextual fear conditioning training and retention testing during chronic nicotine administration. Mice then received contextual fear extinction either during chronic nicotine or during withdrawal from chronic nicotine. Our results showed that contextual fear extinction was impaired both during chronic nicotine administration and subsequent withdrawal. However, it was also observed that the effects of prior chronic nicotine disappeared after 72 h in withdrawal, a timeline that closely matches with the timing of the chronic nicotine-induced upregulation of hippocampal nicotinic acetylcholine receptor (nAChR) density. Additional experiments found that 4 days, but not 1 day, of continuous nicotine administration upregulated hippocampal nAChRs and impaired contextual fear extinction. These effects disappeared following 72 h withdrawal. Overall, these experiments provide a potential link between nicotine-induced upregulation of hippocampal nAChRs and fear extinction deficits observed in patients with anxiety disorders, which may lead to advancements in the pharmacological treatment methods for this disorder. PMID:27378334

Activation of muscle nicotinic acetylcholine receptor channels by nicotinic and muscarinic agonists

PubMed Central

Akk, Gustav; Auerbach, Anthony

1999-01-01

The dose-response parameters of recombinant mouse adult neuromuscular acetylcholine receptor channels (nAChR) activated by carbamylcholine, nicotine, muscarine and oxotremorine were measured. Rate constants for agonist association and dissociation, and channel opening and closing, were estimated from single-channel kinetic analysis.The dissociation equilibrium constants were (mM): ACh (0.16)carbamylcholine (5.1)>oxotremorine M (0.6)>nicotine (0.5)>muscarine (0.15).Rat neuronal α4β2 nAChR can be activated by all of the agonists. However, detailed kinetic analysis was impossible because the recordings lacked clusters representing the activity of a single receptor complex. Thus, the number of channels in the patch was unknown and the activation rate constants could not be determined.Considering both receptor affinity and agonist efficacy, muscarine and oxotremorine are significant agonists of muscle-type nAChR. The results are discussed in terms of structure-function relationships at the nAChR transmitter binding site. PMID:10602325

Spinal activation of alpha7-nicotinic acetylcholine receptor attenuates posttraumatic stress disorder-related chronic pain via suppression of glial activation.

PubMed

Sun, Rao; Zhang, Wei; Bo, Jinhua; Zhang, Zuoxia; Lei, Yishan; Huo, Wenwen; Liu, Yue; Ma, Zhengliang; Gu, Xiaoping

2017-03-06

The high prevalence of chronic pain in posttraumatic stress disorder (PTSD) individuals has been widely reported by clinical studies, which emphasized an urgent need to uncover the underlying mechanisms and identify potential therapeutic targets. Recent studies suggested that targeting activated glia and their pro-inflammatory products may provide a novel and effective therapy for the stress-related pain. In this study, we investigated whether activation of alpha-7 nicotinic acetylcholine receptor (α7 nAChR), a novel anti-inflammatory target, could attenuate PTSD-related chronic pain. The experiments were conducted in a rat model of single prolonged stress (SPS), an established model of PTSD-pain comorbidity. We found that SPS exposure produced persistent mechanical allodynia. Immunohistochemical and enzyme-linked immuno sorbent assay analysis showed that SPS also induced elevated activation of glia cells (including microglia and astrocytes) and accumulation of pro-inflammatory cytokines in spinal cord. In another experiment, we found that intrathecal injection of PHA-543613, a selective α7 nAchR agonist, attenuated the SPS-evoked allodynia in a dose dependent manner. However, this anti-hyperalgesic effect was blocked by pretreatment with methyllycaconitine (MLA), a selective α7 nAchR antagonist. Further analyses showed that PHA-543613 suppressed SPS-induced spinal glial activation and SPS-elevated spinal pro-inflammatory cytokines, and these were abolished by MLA. Taken together, the present study showed that spinal activation of α7 nAChR by PHA-543613 attenuated mechanical allodynia induced by PTSD-like stress, and the suppression of spinal glial activation may underlie this anti-hyperalgesic effect. Our study demonstrated the therapeutic potential of targeting α7 nAChR in the treatment of PTSD-related chronic pain. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Nicotine-Induced Airway Smooth Muscle Cell Proliferation Involves TRPC6-Dependent Calcium Influx Via α7 nAChR.

PubMed

Hong, Wei; Peng, Gongyong; Hao, Binwei; Liao, Baoling; Zhao, Zhuxiang; Zhou, Yumin; Peng, Fang; Ye, Xiuqin; Huang, Lingmei; Zheng, Mengning; Pu, Jinding; Liang, Chunxiao; Yi, Erkang; Peng, Huanhuan; Li, Bing; Ran, Pixin

2017-01-01

The proliferation of human bronchial smooth muscle cells (HBSMCs) is a key pathophysiological component of airway remodeling in chronic obstructive pulmonary disease (COPD) for which pharmacotherapy is limited, and only slight improvements in survival have been achieved in recent decades. Cigarette smoke is a well-recognized risk factor for COPD; however, the pathogenesis of cigarette smoke-induced COPD remains incompletely understood. This study aimed to investigate the mechanisms by which nicotine affects HBSMC proliferation. Cell viability was assessed with a CCK-8 assay. Proliferation was measured by cell counting and EdU immunostaining. Fluorescence calcium imaging was performed to measure intracellular Ca2+ concentration ([Ca2+]i). The results showed that nicotine promotes HBSMC proliferation, which is accompanied by elevated store-operated calcium entry (SOCE), receptor-operated calcium entry (ROCE) and basal [Ca2+]i in HBSMCs. Moreover, we also confirmed that canonical transient receptor potential protein 6 (TRPC6) and α7 nicotinic acetylcholine receptor (α7 nAChR) are involved in nicotine-induced upregulation of cell proliferation. Furthermore, we verified that activation of the PI3K/Akt signaling pathway plays a pivotal role in nicotine-enhanced proliferation and calcium influx in HBSMCs. Inhibition of α7 nAChR significantly decreased Akt phosphorylation levels, and LY294002 inhibited the protein expression levels of TRPC6. Herein, these data provide compelling evidence that calcium entry via the α7 nAChR-PI3K/Akt-TRPC6 signaling pathway plays an important role in the physiological regulation of airway smooth muscle cell proliferation, representing an important target for augmenting airway remodeling. © 2017 The Author(s). Published by S. Karger AG, Basel.

α4α6β2* nicotinic acetylcholine receptor activation on ventral tegmental area dopamine neurons is sufficient to stimulate a depolarizing conductance and enhance surface AMPA receptor function.

PubMed

Engle, Staci E; Shih, Pei-Yu; McIntosh, J Michael; Drenan, Ryan M

2013-09-01

Tobacco addiction is a serious threat to public health in the United States and abroad, and development of new therapeutic approaches is a major priority. Nicotine activates and/or desensitizes nicotinic acetylcholine receptors (nAChRs) throughout the brain. nAChRs in ventral tegmental area (VTA) dopamine (DA) neurons are crucial for the rewarding and reinforcing properties of nicotine in rodents, suggesting that they may be key mediators of nicotine's action in humans. However, it is unknown which nAChR subtypes are sufficient to activate these neurons. To test the hypothesis that nAChRs containing α6 subunits are sufficient to activate VTA DA neurons, we studied mice expressing hypersensitive, gain-of-function α6 nAChRs (α6L9'S mice). In voltage-clamp recordings in brain slices from adult mice, 100 nM nicotine was sufficient to elicit inward currents in VTA DA neurons via α6β2* nAChRs. In addition, we found that low concentrations of nicotine could act selectively through α6β2* nAChRs to enhance the function of 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid (AMPA) receptors on the surface of these cells. In contrast, α6β2* activation did not enhance N-methyl-D-aspartic acid receptor function. Finally, AMPA receptor (AMPAR) function was not similarly enhanced in brain slices from α6L9'S mice lacking α4 nAChR subunits, suggesting that α4α6β2* nAChRs are important for enhancing AMPAR function in VTA DA neurons. Together, these data suggest that activation of α4α6β2* nAChRs in VTA DA neurons is sufficient to support the initiation of cellular changes that play a role in addiction to nicotine. α4α6β2* nAChRs may be a promising target for future smoking cessation pharmacotherapy.

Impairment of contextual fear extinction by chronic nicotine and withdrawal from chronic nicotine is associated with hippocampal nAChR upregulation.

PubMed

Kutlu, Munir Gunes; Oliver, Chicora; Huang, Peng; Liu-Chen, Lee-Yuan; Gould, Thomas J

2016-10-01

Chronic nicotine and withdrawal from chronic nicotine have been shown to be major modulators of fear learning behavior. Moreover, recent studies from our laboratory have shown that acute nicotine impaired fear extinction and safety learning in mice. However, the effects of chronic nicotine and withdrawal on fear extinction are unknown. Therefore, the current experiments were conducted to investigate the effects of chronic nicotine as well as withdrawal from chronic nicotine on contextual fear extinction in mice. C57BL6/J mice were given contextual fear conditioning training and retention testing during chronic nicotine administration. Mice then received contextual fear extinction either during chronic nicotine or during withdrawal from chronic nicotine. Our results showed that contextual fear extinction was impaired both during chronic nicotine administration and subsequent withdrawal. However, it was also observed that the effects of prior chronic nicotine disappeared after 72 h in withdrawal, a timeline that closely matches with the timing of the chronic nicotine-induced upregulation of hippocampal nicotinic acetylcholine receptor (nAChR) density. Additional experiments found that 4 days, but not 1 day, of continuous nicotine administration upregulated hippocampal nAChRs and impaired contextual fear extinction. These effects disappeared following 72 h withdrawal. Overall, these experiments provide a potential link between nicotine-induced upregulation of hippocampal nAChRs and fear extinction deficits observed in patients with anxiety disorders, which may lead to advancements in the pharmacological treatment methods for this disorder. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chronic Nicotine Treatment Increases nAChRs and Microglial Expression in Monkey Substantia Nigra after Nigrostriatal Damage

PubMed Central

Campos, Carla; Parameswaran, Neeraja; William Langston, J.; Michael McIntosh, J.; Yeluashvili, Michael

2010-01-01

Our previous work had shown that long-term nicotine administration improved dopaminergic markers and nicotinic receptors (nAChRs) in the striatum of monkeys with nigrostriatal damage. The present experiments were done to determine whether nicotine treatment also led to changes in the substantia nigra, the region containing dopaminergic cell bodies. Monkeys were chronically treated with nicotine in the drinking water for 6 months after which they were injected with low dose MPTP for a further 6-month period. Nicotine was administered until the monkeys were euthanized 2 months after the last MPTP injection. Nicotine treatment did not affect the dopamine transporter or the number of tyrosine hydroxylase positive cells in the substantia nigra of lesioned monkeys. However, nicotine administration did lead to a greater increase in α3/α6β2* and α4β2* nAChRs in lesioned monkeys compared to controls. Nicotine also significantly elevated microglia and reduced the number of extracellular neuromelanin deposits in the substantia nigra of MPTP-lesioned monkeys. These findings indicate that long-term nicotine treatment modulates expression of several molecular measures in monkey substantia nigra that may result in an improvement in nigral integrity and/or function. These observations may have therapeutic implications for Parkinson’s disease. PMID:19685015

In vivo Interactions between α7 Nicotinic Acetylcholine Receptor and Nuclear Peroxisome Proliferator-Activated Receptor-α: Implication for Nicotine Dependence

PubMed Central

Jackson, Asti; Bagdas, Deniz; Muldoon, Pretal P.; Lichtman, Aron H.; Carroll, F. Ivy; Greenwald, Mark; Miles, Michael F.; Damaj, M. Imad

2017-01-01

Chronic tobacco use dramatically increases health burdens and financial costs. Limitations of current smoking cessation therapies indicate the need for improved molecular targets. The main addictive component of tobacco, nicotine, exerts its dependency effects via nicotinic acetylcholine receptors (nAChRs). Activation of the homomeric α7 nAChR reduces nicotine's rewarding properties in conditioned place preference (CPP) test and i.v. self-administration models, but the mechanism underlying these effects is unknown. Recently, the nuclear receptor peroxisome proliferator-activated receptor type-α (PPARα) has been implicated as a downstream signaling target of the α7 nAChR in ventral tegmental area dopamine cells. The present study investigated PPARα as a possible mediator of the effect of α7 nAChR activation in nicotine dependence. Our results demonstrate the PPARα antagonist GW6471 blocks actions of the α7 nAChR agonist PNU282987 on nicotine reward in an unbiased CPP test in male ICR adult mice. These findings suggests that α7 nAChR activation attenuates nicotine CPP in a PPARα-dependent manner. To evaluate PPARα activation in nicotine dependence we used the selective and potent PPARα agonist, WY-14643 and the clinically used PPARα activator, fenofibrate, in nicotine CPP and we observed attenuation of nicotine preference, but fenofibrate was less potent. We also studied PPARα in nicotine dependence by evaluating its activation in nicotine withdrawal. WY-14643 reversed nicotine withdrawal signs whereas fenofibrate had modest efficacy. This suggests that PPARα plays a role in nicotine reward and withdrawal and that further studies are warranted to elucidate its function in mediating the effects of α7 nAChRs in nicotine dependence. PMID:28279662

Anaerobic muscle strengthening physical activity and depression severity among USA adults.

PubMed

Cangin, Causenge; Harris, Randall; Binkley, Philip; Schwartzbaum, Judith; Focht, Brian

2018-06-01

We investigated the association between depression and anaerobic physical activity (while controlling aerobic physical activity), using a nationally representative sample of USA adults ( n  = 7354) who participated in the cross sectional National Health and Nutrition Examination Survey (NHANES, 1999-2006). We defined depression using the validated "Patient Health Questionnaire" (PHQ 9 ) scale of 0-27 as PHQ 9   ≥  10. Severity of depression was classified by clinically established PHQ 9 levels: mild (5-9), dysthymic (10-14), moderate (15-19), and major depression ( ≥ 20). We used logistic regression to estimate adjusted odds ratios of depression associated with distinct types of activity (only aerobic, only anaerobic, combined regime). We used multinomial logistic regression to examine associations of anaerobic activity with various severity levels of depression (mild, dysthymic, moderate, and major depression) with adjustment for aerobic activity. Women had higher prevalence of depression than men (8.4% versus 5.7%), whereas anaerobic muscle strengthening activity was more common in men than women (35% versus 24%). Adjusting for aerobic activity , anaerobic activity was inversely associated with depression (PHQ 9   ≥  10) in women under 50 (OR = 0.57; 95%CI = 0.41-0.81), all women (OR = 0.59; 0.43-0.80), men under 50 (OR = 0.85; 0.58-1.2), and all men (OR = 0.72; 0.51-1.01). Anaerobic activity was inversely associated with severity level of depressive symptoms in women and men. The combined regimen of anaerobic muscle strengthening activity and meeting the Physical Activity Guideline for America (PAGA) was related to the lowest odds ratio of depression in women (OR = 0.50; 95%CI = 0.33-0.75) and men (OR = 0.39; 95%CI = 0.23-0.62). Independent of aerobic physical activity, anaerobic muscle strengthening activity is significantly and inversely associated with depression among USA adults.

In vivo interactions between α7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α: Implication for nicotine dependence.

PubMed

Jackson, Asti; Bagdas, Deniz; Muldoon, Pretal P; Lichtman, Aron H; Carroll, F Ivy; Greenwald, Mark; Miles, Michael F; Damaj, M Imad

2017-05-15

Chronic tobacco use dramatically increases health burdens and financial costs. Limitations of current smoking cessation therapies indicate the need for improved molecular targets. The main addictive component of tobacco, nicotine, exerts its dependency effects via nicotinic acetylcholine receptors (nAChRs). Activation of the homomeric α7 nAChR reduces nicotine's rewarding properties in conditioned place preference (CPP) test and i.v. self-administration models, but the mechanism underlying these effects is unknown. Recently, the nuclear receptor peroxisome proliferator-activated receptor type-α (PPARα) has been implicated as a downstream signaling target of the α7 nAChR in ventral tegmental area dopamine cells. The present study investigated PPARα as a possible mediator of the effect of α7 nAChR activation in nicotine dependence. Our results demonstrate the PPARα antagonist GW6471 blocks actions of the α7 nAChR agonist PNU282987 on nicotine reward in an unbiased CPP test in male ICR adult mice. These findings suggests that α7 nAChR activation attenuates nicotine CPP in a PPARα-dependent manner. To evaluate PPARα activation in nicotine dependence we used the selective and potent PPARα agonist, WY-14643 and the clinically used PPARα activator, fenofibrate, in nicotine CPP and we observed attenuation of nicotine preference, but fenofibrate was less potent. We also studied PPARα in nicotine dependence by evaluating its activation in nicotine withdrawal. WY-14643 reversed nicotine withdrawal signs whereas fenofibrate had modest efficacy. This suggests that PPARα plays a role in nicotine reward and withdrawal and that further studies are warranted to elucidate its function in mediating the effects of α7 nAChRs in nicotine dependence. Copyright © 2017 Elsevier Ltd. All rights reserved.

Agonist activation of α7 nicotinic acetylcholine receptors via an allosteric transmembrane site

PubMed Central

Gill, JasKiran K.; Savolainen, Mari; Young, Gareth T.; Zwart, Ruud; Sher, Emanuele; Millar, Neil S.

2011-01-01

Conventional nicotinic acetylcholine receptor (nAChR) agonists, such as acetylcholine, act at an extracellular “orthosteric” binding site located at the interface between two adjacent subunits. Here, we present evidence of potent activation of α7 nAChRs via an allosteric transmembrane site. Previous studies have identified a series of nAChR-positive allosteric modulators (PAMs) that lack agonist activity but are able to potentiate responses to orthosteric agonists, such as acetylcholine. It has been shown, for example, that TQS acts as a conventional α7 nAChR PAM. In contrast, we have found that a compound with close chemical similarity to TQS (4BP-TQS) is a potent allosteric agonist of α7 nAChRs. Whereas the α7 nAChR antagonist metyllycaconitine acts competitively with conventional nicotinic agonists, metyllycaconitine is a noncompetitive antagonist of 4BP-TQS. Mutation of an amino acid (M253L), located in a transmembrane cavity that has been proposed as being the binding site for PAMs, completely blocks agonist activation by 4BP-TQS. In contrast, this mutation had no significant effect on agonist activation by acetylcholine. Conversely, mutation of an amino acid located within the known orthosteric binding site (W148F) has a profound effect on agonist potency of acetylcholine (resulting in a shift of ∼200-fold in the acetylcholine dose-response curve), but had little effect on the agonist dose-response curve for 4BP-TQS. Computer docking studies with an α7 homology model provides evidence that both TQS and 4BP-TQS bind within an intrasubunit transmembrane cavity. Taken together, these findings provide evidence that agonist activation of nAChRs can occur via an allosteric transmembrane site. PMID:21436053

Rest-Activity Cycles in Childhood and Adolescent Depression.

ERIC Educational Resources Information Center

Armitage, Roseanne; Hoffmann, Robert; Emslie, Graham; Rintelman, Jeanne; Moore, Jarrette; Lewis, Kelly

2004-01-01

Objective: To quantify circadian rhythms in rest-activity cycles in depressed children and adolescents. Method: Restactivity cycles were evaluated by actigraphy over five consecutive 24-hour periods in 100 children and adolescents, including 59 outpatients with major depressive disorder (MDD) and 41 healthy normal controls. Total activity, total…

Neurobiology of nAChRs and cognition: A mini review of Dr. Jerry J. Buccafusco's contributions over a 25 year career

PubMed Central

Terry, Alvin V.; Decker, Michael W.

2011-01-01

This review highlights some of the many contributions of the late Dr. Jerry J. Buccafusco to the neurobiology of nicotinic acetylcholine receptors (nAChRs) and cognition over a 25 year period. The article is written by two of Dr. Buccafusco's professional colleagues, one from academia and one from the pharmaceutical industry. While Dr. Buccafusco's expertise in the cholinergic field was extensive, his insights into the practical relevance of his work (with a long-term goal of formulating new drug development strategies) were unique, and a great asset to both the basic science community and pharmaceutical companies. In 1988, Dr. Buccafusco's laboratory was the first to report the cognitive enhancing action of low doses of nicotine in non-human primates. Since that time he studied a large number of novel pro-cognitive agents from several pharmacological classes in rodents as well as monkeys. Based on years of observing paradoxical effects of nicotinic ligands in vitro and in vivo, Dr. Buccafusco made the provocative argument that it might be possible to develop new chemical entities (with pro-cognitive actions) that have the ability to desensitize nAChRs without producing an antecedent agonist action. Some of his more recent work focused on development of single molecular entities that act on multiple CNS targets (including nAChRs) to enhance cognition, provide neuroprotection, and/or provide additional therapeutic actions (e.g., antipsychotic effects). Dr. Buccafusco's influence will live on in the work of the numerous graduate students, postdoctoral fellows, and junior faculty that he mentored over the years who now serve in prestigious positions throughout the world. PMID:21684265

Platelet GSK3B activity in patients with late-life depression: marker of depressive episode severity and cognitive impairment?

PubMed

Diniz, Breno Satler; Talib, Leda Leme; Joaquim, Helena Passarelli Giroud; de Paula, Vanessa Rodrigues Jesus; Gattaz, Wagner Farid; Forlenza, Orestes Vicente

2011-04-01

Increased GSK3B activity has been reported as a state marker of major affective episodes in patients with depression and bipolar disorder. No study so far has addressed GSK3B activity in late-life depression. The aims of the present study were to determine GSK3B activity in platelets of elderly patients with major depression, and the association between GSK3B activity and the severity of depressive symptoms and cognitive impairment. Forty drug-free elderly patients with major depressive episode were compared to healthy older adults (n = 13). Severity of the depressive episode and current cognitive state were determined by the Hamilton Depression Scale (HAM-D) and the Cambridge Cognitive Test (CAMCOG), respectively. Total- and ser-9-phosphorylated GSK3B (tGSK3B and pGSK3B) were determined in platelets by enzyme immunometric assays (EIA). GSK3B activity was indirectly inferred by the GSK3B ratio (i.e. pGSK3B/tGSK3B). Elderly depressed patients had significantly lower pGSK3B levels (P = 0.03) and GSK3B ratio (P = 0.03), indicating higher GSK3B activity. Higher GSK3B activity were observed in patients with severe depressive episode (HAM-D scores >22, P = 0.03) and with cognitive impairment (CAMCOG scores <86, P = 0.01). The present findings provide additional evidence of the involvement of GSK3B in the pathophysiology of late-life major depression. Higher GSK3B activity may be more relevant in those patients with more severe depressive symptoms and cognitive impairment.

Behavioral Activation for Depressed Teens: A Pilot Study

ERIC Educational Resources Information Center

Ritschel, Lorie A.; Ramirez, Cynthia L.; Jones, Meredith; Craighead, W. Edward

2011-01-01

Behavioral activation (BA) is a psychosocial intervention that has shown promising treatment outcome results with depressed adults. The current pilot study evaluated a version of BA adapted for depressed adolescents. Six teens (3 male, 3 female, ages 14-17) who met criteria for major depressive disorder participated in the study. Participants were…

Physical activity and depressive symptoms after stillbirth: informing future interventions.

PubMed

Huberty, Jennifer; Leiferman, Jenn A; Gold, Katherine J; Rowedder, Lacey; Cacciatore, Joanne; McClain, Darya Bonds

2014-11-29

In the United States, approximately one in 110 pregnancies end in stillbirth affecting more than 26,000 women annually. Women experiencing stillbirth have a threefold greater risk of developing depressive symptoms compared to women experiencing live birth. Depression contributes negatively to health outcomes for both mothers and babies subsequent to stillbirth. Physical activity may improve depression in these women, however, little is known about acceptable physical activity interventions for women after stillbirth. This is the purpose of this descriptive exploratory study. Eligible women were between ages 19 and 45, and experienced stillbirth within one year of the study. An online survey was used to ask questions related to 1) pregnancy and family information (i.e., time since stillbirth, weight gain during pregnancy, number of other children) 2) physical activity participation, 3) depressive symptomatology, and 4) demographics. One hundred seventy-five women participated in the study (M age = 31.26 ± 5.52). Women reported participating in regular physical activity (at least 150 minutes of moderate activity weekly) before (60%) and during (47%) their pregnancy, as well as after their stillbirth (61%). Only 37% were currently meeting physical activity recommendations. Approximately 88% reported depression (i.e., score of >10 on depression scale). When asked how women cope with depression, anxiety, or grief, 38% said physical activity. Of those that reported using physical activity to cope after stillbirth, they did so to help with depression (58%), weight loss (55%), and better overall physical health (52%). To cope with stillbirth, women used walking (67%), followed by jogging (35%), and yoga (23%). Women who participated in physical activity after stillbirth reported significantly lower depressive symptoms (M = 15.10, SD = 5.32) compared to women who did not participate in physical activity (M = 18.06, SD = 5.57; t = -3.45, p = .001). Physical activity may

Changes in physical activity, self-efficacy and depressive symptoms in adolescent girls.

PubMed

Neissaar, Inga; Raudsepp, Lennart

2011-08-01

The purpose of this study was to examine the longitudinal relationships between naturally occurring changes in leisure-time physical activity, depressive symptoms and self-efficacy in adolescent girls. We also aimed to test whether depressive symptoms would moderate the self-efficacy-physical activity relationship. Participants were 181 urban adolescent girls. Physical activity was measured using the 3-Day Physical Activity Recall. Self-efficacy and depressive symptoms were assessed using questionnaires. Body height and body mass were measured and body mass index (BMI) was calculated. Data were collected on three occasions over a 2-year period. There was a decrease in physical activity and self-efficacy and increase in depressive symptoms across three measurement occasions. There were statistically significant and negative relationships between initial level and change for physical activity and depressive symptoms. Initially higher levels of physical activity were related with initially lower levels of depressive symptoms, and change in physical activity across time was inversely associated with change in levels of depressive symptoms across measurements. There were statistically significant and positive relationships between initial level and change for physical activity and self-efficacy after controlling effect of BMI. Latent growth modeling (LGM) also indicated a moderating effect of depressive symptoms on the self-efficacy-physical activity relationship. Girls who had high initial levels of self-efficacy and smaller increases in depressive symptoms had the lowest decline in physical activity participation. Our results encourage the design of interventions that reduce depressive symptoms and increase self-efficacy as a possible of means of increasing adolescent girls' physical activity.

Co-occurring anxiety influences patterns of brain activity in depression.

PubMed

Engels, Anna S; Heller, Wendy; Spielberg, Jeffrey M; Warren, Stacie L; Sutton, Bradley P; Banich, Marie T; Miller, Gregory A

2010-03-01

Brain activation associated with anhedonic depression and co-occurring anxious arousal and anxious apprehension was measured by fMRI during performance of an emotion word Stroop task. Consistent with EEG findings, depression was associated with rightward frontal lateralization in the dorsolateral prefrontal cortex (DLPFC), but only when anxious arousal was elevated and anxious apprehension was low. Activity in the right inferior frontal gyrus (IFG) was also reduced for depression under the same conditions. In contrast, depression was associated with more activity in the anterior cingulate cortex (dorsal ACC and rostral ACC) and the bilateral amygdala. Results imply that depression, particularly when accompanied by anxious arousal, may result in a failure to implement top-down processing by appropriate brain regions (left DLPFC, right IFG) due to increased activation in regions associated with responding to emotionally salient information (right DLPFC, amygdala).

Co-occurring Anxiety Influences Patterns of Brain Activity in Depression

PubMed Central

Engels, Anna S.; Heller, Wendy; Spielberg, Jeffrey M.; Warren, Stacie L.; Sutton, Bradley P.; Banich, Marie T.; Miller, Gregory A.

2011-01-01

Brain activation associated with anhedonic depression and co-occurring anxious arousal and anxious apprehension was measured by fMRI during performance of an emotion-word Stroop task. Consistent with EEG findings, depression was associated with rightward frontal lateralization in dorsolateral prefrontal cortex (DLPFC), but only when anxious arousal was elevated and anxious apprehension was low. Activity in right inferior frontal gyrus (IFG) was also reduced for depression under the same conditions. In contrast, depression was associated with more activity in anterior cingulate cortex (dACC and rACC) and bilateral amygdala. Results imply that depression, particularly when accompanied by anxious arousal, may result in a failure to implement top-down processing by appropriate brain regions (left DLPFC, right IFG) due to increased activation in regions associated with responding to emotionally salient information (right DLPFC, amygdala). PMID:20233962

Effects of the specific α4β2 nAChR antagonist, 2-fluoro-3-(4-nitrophenyl) deschloroepibatidine, on nicotine reward-related behaviors in rats and mice.

PubMed

Tobey, K M; Walentiny, D M; Wiley, J L; Carroll, F I; Damaj, M I; Azar, M R; Koob, G F; George, O; Harris, L S; Vann, R E

2012-09-01

Alleviating addiction to tobacco products could prevent millions of deaths. Investigating novel compounds selectively targeting α4β2 nAChRs hypothesized to have a key role in the rewarding effects of nicotine may be a useful approach for future treatment. The present study was designed to evaluate 2-fluoro-3-(4-nitrophenyl) deschloroepibatidine (4-nitro-PFEB), a potent competitive antagonist of neuronal α4β2 nAChRs, in several animal models related to nicotine reward: drug discrimination, intracranial self-stimulation (ICSS), conditioned place preference, and limited access to self-administration. Long Evans rats were trained in a two-lever discrimination procedure to discriminate 0.4 mg/kg nicotine (s.c.) from saline. Male Sprague-Dawley rats were stereotaxically implanted with electrodes and trained to respond for direct electrical stimulation of the medial forebrain bundle. ICR mice were evaluated using an unbiased place preference paradigm, and finally, male Wistar rats were implanted with intrajugular catheters and tested for nicotine self-administration under limited access (1 h/day). 4-Nitro-PFEB attenuated the discriminative stimulus effects of nicotine, but alone did not produce nicotine-like discriminative stimulus effects. Nicotine-induced facilitation of ICSS reward thresholds was reversed by 4-nitro-PFEB, which alone had no effect on thresholds. 4-Nitro-PFEB also blocked the conditioned place preference produced by nicotine, but alone had no effect on conditioned place preference. Finally, 4-nitro-PFEB dose-dependently decreased nicotine self-administration. These results support the hypothesis that neuronal α4β2 nAChRs play a key role in mediating the rewarding effects of nicotine and further suggest that targeting α4β2 nAChRs may yield a potential candidate for the treatment of nicotine dependence.

Beyond METs: types of physical activity and depression among older adults

PubMed Central

Joshi, Spruha; Mooney, Stephen J.; Kennedy, Gary J.; Benjamin, Ebele O.; Ompad, Danielle; Rundle, Andrew G.; Beard, John R.; Cerdá, Magdalena

2016-01-01

Background/Objectives: physical activity may be beneficial in reducing depression incidence among the elderly. A key unanswered question is whether certain types of physical activity are particularly associated with decreased depression incidence. We examined the relationship between quantity and type of physical activity and subsequent depression using longitudinal data from elderly adults in New York City (NYC). Methods: we followed 3,497 adults aged 65–75 living in NYC for three years. Total physical activity was measured using the Physical Activity Scale for the Elderly (PASE) and type of physical activity was measured using a latent class analysis of PASE item responses. We used generalised estimating equations to measure the relationship between quantity and latent class of physical activity at waves 1–2 and depression at waves 2–3, controlling for wave-1 depression. Results: individuals in the second highest quartile (50–75%) (odds ratio (OR) = 0.45; 95% confidence interval (CI) = 0.23, 0.88) and highest quartile of activity (OR = 0.31; 95% CI = 0.16, 0.63) had lower odds of depression. Among all subjects, athletic types (OR = 0.25; 95% CI = 0.12, 0.51) and walker types (OR = 0.58; 95% CI = 0.34, 0.99) had lower odds of depression. Among non-disabled participants, walkers (OR = 0.36; 95% CI = 0.18, 0.73), athletic types (OR = 0.14; 95% CI = 0.06, 0.32), domestic/gardening types (OR = 0.29; 95% CI = 0.12, 0.73) and domestic/gardening athletic types (OR = 0.13; 95% CI = 0.02, 0.75) had lower odds of depression. Conclusion: respondents who practised the highest levels of physical activity and who performed athletic activities were at lower risk for depression. Interventions aimed at promoting athletic physical activity among older adults may generate benefits for mental health. PMID:26764399

Role of tissue-type plasminogen activator and plasminogen activator inhibitor-1 in psychological stress and depression.

PubMed

Tsai, Shih-Jen

2017-12-22

Major depressive disorder is a common illness worldwide, but the pathogenesis of the disorder remains incompletely understood. The tissue-type plasminogen activator-plasminogen proteolytic cascade is highly expressed in the brain regions involved in mood regulation and neuroplasticity. Accumulating evidence from animal and human studies suggests that tissue-type plasminogen activator and its chief inhibitor, plasminogen activator inhibitor-1, are related to stress reaction and depression. Furthermore, the neurotrophic hypothesis of depression postulates that compromised neurotrophin brain-derived neurotrophic factor (BDNF) function is directly involved in the pathophysiology of depression. In the brain, the proteolytic cleavage of proBDNF, a BDNF precursor, to mature BDNF through plasmin represents one mechanism that can change the direction of BDNF action. We also discuss the implications of tissue-type plasminogen activator and plasminogen activator inhibitor-1 alterations as biomarkers for major depressive disorder. Using drugs that increase tissue-type plasminogen activator or decrease plasminogen activator inhibitor-1 levels may open new avenues to develop conceptually novel therapeutic strategies for depression treatment.

Rapid relief of block by mecamylamine of neuronal nicotinic acetylcholine receptors of rat chromaffin cells in vitro: an electrophysiological and modeling study.

PubMed

Giniatullin, R A; Sokolova, E M; Di Angelantonio, S; Skorinkin, A; Talantova, M V; Nistri, A

2000-10-01

The mechanism responsible for the blocking action of mecamylamine on neuronal nicotinic acetylcholine receptors (nAChRs) was studied on rat isolated chromaffin cells recorded under whole-cell patch clamp. Mecamylamine strongly depressed (IC(50) = 0.34 microM) inward currents elicited by short pulses of nicotine, an effect slowly reversible on wash. The mecamylamine block was voltage-dependent and promptly relieved by a protocol combining membrane depolarization with a nicotine pulse. Either depolarization or nicotine pulses were insufficient per se to elicit block relief. Block relief was transient; response depression returned in a use-dependent manner. Exposure to mecamylamine failed to block nAChRs if they were not activated by nicotine or if they were activated at positive membrane potentials. These data suggest that mecamylamine could not interact with receptors either at rest or at depolarized level. Other nicotinic antagonists like dihydro-beta-erythroidine or tubocurarine did not share this action of mecamylamine although proadifen partly mimicked it. Mecamylamine is suggested to penetrate and block open nAChRs that would subsequently close and trap this antagonist. Computer modeling indicated that the mechanism of mecamylamine blocking action could be described by assuming that 1) mecamylamine-blocked receptors possessed a much slower, voltage-dependent isomerization rate, 2) the rate constant for mecamylamine unbinding was large and poorly voltage dependent. Hence, channel reopening plus depolarization allowed mecamylamine escape and block relief. In the presence of mecamylamine, therefore, nAChRs acquire the new property of operating as coincidence detectors for concomitant changes in membrane potential and receptor occupancy.

Major depression in mothers predicts reduced ventral striatum activation in adolescent female offspring with and without depression.

PubMed

Sharp, Carla; Kim, Sohye; Herman, Levi; Pane, Heather; Reuter, Tyson; Strathearn, Lane

2014-05-01

Prior research has identified reduced reward-related brain activation as a promising endophenotype for the early identification of adolescents with major depressive disorder (MDD). However, it is unclear whether reduced reward-related brain activation constitutes a true vulnerability for MDD. One way of studying vulnerability is through a high-risk design. Therefore, the aim of the current study was to determine whether reward-related activation of the ventral striatum is reduced in nondepressed daughters of mothers with a history of MDD (high-risk) similarly to currently depressed adolescent girls, compared with healthy controls. By directly comparing groups with a shared risk profile during differing states, we aimed to shed light on the endophenotypic nature of reduced reward processing for adolescent depression. We compared reward-related neural activity through functional magnetic resonance imaging (fMRI) between three groups of female biological offspring (N = 52) of mothers with differential MDD status: (a) currently depressed daughters of mothers with a history of MDD (MDD group; n = 14), (b) age- and socioeconomic status (SES)-matched never-depressed daughters of mothers with a history of MDD (high-risk group; n = 19), and (c) age- and SES-matched control daughters of mothers with no past or current psychopathology in either the mother or the daughter (healthy control group; n = 19). For the outcome phase of the reward task, right-sided ventral striatum activation was reduced for both currently depressed and high-risk girls compared with healthy controls. This ventral striatal activity correlated significantly with maternal depression scores. These findings provide further evidence of aberrant functioning for the United States Department of Health & Human Services, National Institutes of Health, National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC)-defined domain of positive valence systems as a vulnerability factor for MDD and a

Depressive mood and disease activity in inflammatory bowel disease.

PubMed

Besharat, Sima; Amiriani, Taghi; Roshandel, Gholamreza; Besharat, Mahsa; Semnani, Shahryar; Kamkar, Mohammadzaman

2012-09-01

Some mood disorders are more prevalent in chronic medical conditions compared with the general population. The relationship between inflammatory bowel disease (IBD) and psychiatric disorders has been raised as an area of interest for investigation. In this study, we aimed to assess the probable relationship between depression and disease activity in IBD patients in Golestan province, northeast of Iran. During February 2008 to February 2010, 50 patients recently diagnosed as IBD cases attended the Golestan Research Center of Gastroenterology and Hepatology (GRCGH), northeast of Iran. The Simple Clinical Colitis Activity Index (SCCAI) was used to evaluate the disease activity. The Beck Depression Inventory (BDI) was used to assess the severity of depressive symptoms. Depression was assumed when the BDI score was 13 points or higher. Sixteen cases (32%) had depressive characteristics. SCCAI and the Beck score were not significantly different between the two sexes. There was a non-significant correlation between SCCAI, Beck score, age and body mass index (BMI). We reported a relatively high percent of depression in IBD patients, although no significant relationship was seen. Copyright © 2012 Arab Journal of Gastroenterology. Published by Elsevier Ltd. All rights reserved.

The Adolescent Behavioral Activation Program: Adapting Behavioral Activation as a Treatment for Depression in Adolescence.

PubMed

McCauley, Elizabeth; Gudmundsen, Gretchen; Schloredt, Kelly; Martell, Christopher; Rhew, Isaac; Hubley, Samuel; Dimidjian, Sona

2016-01-01

This study aimed to examine implementation feasibility and initial treatment outcomes of a behavioral activation (BA) based treatment for adolescent depression, the Adolescent Behavioral Activation Program (A-BAP). A randomized, controlled trial was conducted with 60 clinically referred adolescents with a depressive disorder who were randomized to receive either 14 sessions of A-BAP or uncontrolled evidenced-based practice for depression. The urban sample was 64% female, predominantly Non-Hispanic White (67%), and had an average age of 14.9 years. Measures of depression, global functioning, activation, and avoidance were obtained through clinical interviews and/or through parent and adolescent self-report at preintervention and end of intervention. Intent-to-treat linear mixed effects modeling and logistic regression analysis revealed that both conditions produced statistically significant improvement from pretreatment to end of treatment in depression, global functioning, and activation and avoidance. There were no significant differences across treatment conditions. These findings provide the first step in establishing the efficacy of BA as a treatment for adolescent depression and support the need for ongoing research on BA as a way to enhance the strategies available for treatment of depression in this population.

Maternal depressive symptoms and physical activity in very low-income children

PubMed Central

Fernald, Lia C.H.; Jones-Smith, Jessica C.; Ozer, Emily J.; Neufeld, Lynnette M.; DiGirolamo, Ann M.

2009-01-01

Objective To test the contribution of maternal depression during late infancy to physical activity in children five years later. Method Children (n=168) from very low-income households in semi-urban Mexico were assessed as toddlers (15 mo, Time 1) and at pre-school age (4–6 y, Time 2). Child low activity level (<20 minutes of activity daily for <7 d/wk) at Time 2 was the primary outcome measure and maternal depressive symptoms (Center for Epidemiologic Studies – Depression Scale) by self report at Time 1 was the primary independent variable. Covariates tested included child age, sex, BMI percentile, television viewing and behavior (Behavior Problem Index sub-scales), current maternal depressive symptoms, age, BMI and physical activity level, and family socio-economic status; all covariates were assessed at Time 2 except for socio-economic status. Results At 4–6 years old, 27.5% of children were categorized with low activity level. Exposure to high maternal depressive symptoms at child age 15 months was associated with an increased risk of having a low activity level at age 4–6 years (OR, 2.38; 95% CI, 1.05–5.40); results were unchanged with the inclusion of current maternal depressive symptoms. High child TV-viewing was significantly associated with low activity level (OR, 5.44; 95% CI, 2.06–14.3), but did not change the effect of maternal depressive symptoms in early childhood. Tests of mediation revealed that current child internalizing behavior, but not externalizing behavior, significantly attenuated the association between early high maternal depressive symptoms and later childhood activity level. Conclusion Exposure to maternal depressive symptoms in late infancy is a risk factor for low activity level in later childhood and the association may be mediated by child internalizing factors. PMID:18714208

Pancreatic and snake venom presynaptically active phospholipases A2 inhibit nicotinic acetylcholine receptors.

PubMed

Vulfius, Catherine A; Kasheverov, Igor E; Kryukova, Elena V; Spirova, Ekaterina N; Shelukhina, Irina V; Starkov, Vladislav G; Andreeva, Tatyana V; Faure, Grazyna; Zouridakis, Marios; Tsetlin, Victor I; Utkin, Yuri N

2017-01-01

Phospholipases A2 (PLA2s) are enzymes found throughout the animal kingdom. They hydrolyze phospholipids in the sn-2 position producing lysophospholipids and unsaturated fatty acids, agents that can damage membranes. PLA2s from snake venoms have numerous toxic effects, not all of which can be explained by phospholipid hydrolysis, and each enzyme has a specific effect. We have earlier demonstrated the capability of several snake venom PLA2s with different enzymatic, cytotoxic, anticoagulant and antiproliferative properties, to decrease acetylcholine-induced currents in Lymnaea stagnalis neurons, and to compete with α-bungarotoxin for binding to nicotinic acetylcholine receptors (nAChRs) and acetylcholine binding protein. Since nAChRs are implicated in postsynaptic and presynaptic activities, in this work we probe those PLA2s known to have strong presynaptic effects, namely β-bungarotoxin from Bungarus multicinctus and crotoxin from Crotalus durissus terrificus. We also wished to explore whether mammalian PLA2s interact with nAChRs, and have examined non-toxic PLA2 from porcine pancreas. It was found that porcine pancreatic PLA2 and presynaptic β-bungarotoxin blocked currents mediated by nAChRs in Lymnaea neurons with IC50s of 2.5 and 4.8 μM, respectively. Crotoxin competed with radioactive α-bungarotoxin for binding to Torpedo and human α7 nAChRs and to the acetylcholine binding protein. Pancreatic PLA2 interacted similarly with these targets; moreover, it inhibited radioactive α-bungarotoxin binding to the water-soluble extracellular domain of human α9 nAChR, and blocked acetylcholine induced currents in human α9α10 nAChRs heterologously expressed in Xenopus oocytes. These and our earlier results show that all snake PLA2s, including presynaptically active crotoxin and β-bungarotoxin, as well as mammalian pancreatic PLA2, interact with nAChRs. The data obtained suggest that this interaction may be a general property of all PLA2s, which should be proved by

APS8, a Polymeric Alkylpyridinium Salt Blocks α7 nAChR and Induces Apoptosis in Non-Small Cell Lung Carcinoma

PubMed Central

Zovko, Ana; Viktorsson, Kristina; Lewensohn, Rolf; Kološa, Katja; Filipič, Metka; Xing, Hong; Kem, William R.; Paleari, Laura; Turk, Tom

2013-01-01

Naturally occurring 3-alkylpyridinium polymers (poly-APS) from the marine sponge Reniera sarai, consisting of monomers containing polar pyridinium and nonpolar alkyl chain moieties, have been demonstrated to exert a wide range of biological activities, including a selective cytotoxicity against non-small cell lung cancer (NSCLC) cells. APS8, an analog of poly-APS with defined alkyl chain length and molecular size, non-competitively inhibits α7 nicotinic acetylcholine receptors (nAChRs) at nanomolar concentrations that are too low to be acetylcholinesterase (AChE) inhibitory or generally cytotoxic. In the present study we show that APS8 inhibits NSCLC tumor cell growth and activates apoptotic pathways. APS8 was not toxic for normal lung fibroblasts. Furthermore, in NSCLC cells, APS8 reduced the adverse anti-apoptotic, proliferative effects of nicotine. Our results suggest that APS8 or similar compounds might be considered as lead compounds to develop antitumor therapeutic agents for at least certain types of lung cancer. PMID:23880932

Activities on Facebook Reveal the Depressive State of Users

PubMed Central

Kwak, Jinah

2013-01-01

Background As online social media have become prominent, much effort has been spent on identifying users with depressive symptoms in order to aim at early diagnosis, treatment, and even prevention by using various online social media. In this paper, we focused on Facebook to discern any correlations between the platform’s features and users’ depressive symptoms. This work may be helpful in trying to reach and detect large numbers of depressed individuals more easily. Objective Our goal was to develop a Web application and identify depressive symptom–related features from users of Facebook, a popular social networking platform. Methods 55 Facebook users (male=40, female=15, mean age 24.43, SD 3.90) were recruited through advertisement fliers distributed to students in a large university in Korea. Using EmotionDiary, the Facebook application we developed, we evaluated depressive symptoms using the Center for Epidemiological Studies-Depression (CES-D) scale. We also provided tips and facts about depression to participants and measured their responses using EmotionDiary. To identify the Facebook features related to depression, correlation analyses were performed between CES-D and participants’ responses to tips and facts or Facebook social features. Last, we interviewed depressed participants (CES-D≥25) to assess their depressive symptoms by a psychiatrist. Results Facebook activities had predictive power in distinguishing depressed and nondepressed individuals. Participants’ response to tips and facts, which can be explained by the number of app tips viewed and app points, had a positive correlation (P=.04 for both cases), whereas the number of friends and location tags had a negative correlation with the CES-D scale (P=.08 and P=.045 respectively). Furthermore, in finding group differences in Facebook social activities, app tips viewed and app points resulted in significant differences (P=.01 and P=.03 respectively) between probably depressed and

Activities on Facebook reveal the depressive state of users.

PubMed

Park, Sungkyu; Lee, Sang Won; Kwak, Jinah; Cha, Meeyoung; Jeong, Bumseok

2013-10-01

As online social media have become prominent, much effort has been spent on identifying users with depressive symptoms in order to aim at early diagnosis, treatment, and even prevention by using various online social media. In this paper, we focused on Facebook to discern any correlations between the platform's features and users' depressive symptoms. This work may be helpful in trying to reach and detect large numbers of depressed individuals more easily. Our goal was to develop a Web application and identify depressive symptom-related features from users of Facebook, a popular social networking platform. 55 Facebook users (male=40, female=15, mean age 24.43, SD 3.90) were recruited through advertisement fliers distributed to students in a large university in Korea. Using EmotionDiary, the Facebook application we developed, we evaluated depressive symptoms using the Center for Epidemiological Studies-Depression (CES-D) scale. We also provided tips and facts about depression to participants and measured their responses using EmotionDiary. To identify the Facebook features related to depression, correlation analyses were performed between CES-D and participants' responses to tips and facts or Facebook social features. Last, we interviewed depressed participants (CES-D≥25) to assess their depressive symptoms by a psychiatrist. Facebook activities had predictive power in distinguishing depressed and nondepressed individuals. Participants' response to tips and facts, which can be explained by the number of app tips viewed and app points, had a positive correlation (P=.04 for both cases), whereas the number of friends and location tags had a negative correlation with the CES-D scale (P=.08 and P=.045 respectively). Furthermore, in finding group differences in Facebook social activities, app tips viewed and app points resulted in significant differences (P=.01 and P=.03 respectively) between probably depressed and nondepressed individuals. Our results using Emotion

Beyond METs: types of physical activity and depression among older adults.

PubMed

Joshi, Spruha; Mooney, Stephen J; Kennedy, Gary J; Benjamin, Ebele O; Ompad, Danielle; Rundle, Andrew G; Beard, John R; Cerdá, Magdalena

2016-01-01

physical activity may be beneficial in reducing depression incidence among the elderly. A key unanswered question is whether certain types of physical activity are particularly associated with decreased depression incidence. We examined the relationship between quantity and type of physical activity and subsequent depression using longitudinal data from elderly adults in New York City (NYC). we followed 3,497 adults aged 65-75 living in NYC for three years. Total physical activity was measured using the Physical Activity Scale for the Elderly (PASE) and type of physical activity was measured using a latent class analysis of PASE item responses. We used generalised estimating equations to measure the relationship between quantity and latent class of physical activity at waves 1-2 and depression at waves 2-3, controlling for wave-1 depression. individuals in the second highest quartile (50-75%) (odds ratio (OR) = 0.45; 95% confidence interval (CI) = 0.23, 0.88) and highest quartile of activity (OR = 0.31; 95% CI = 0.16, 0.63) had lower odds of depression. Among all subjects, athletic types (OR = 0.25; 95% CI = 0.12, 0.51) and walker types (OR = 0.58; 95% CI = 0.34, 0.99) had lower odds of depression. Among non-disabled participants, walkers (OR = 0.36; 95% CI = 0.18, 0.73), athletic types (OR = 0.14; 95% CI = 0.06, 0.32), domestic/gardening types (OR = 0.29; 95% CI = 0.12, 0.73) and domestic/gardening athletic types (OR = 0.13; 95% CI = 0.02, 0.75) had lower odds of depression. respondents who practised the highest levels of physical activity and who performed athletic activities were at lower risk for depression. Interventions aimed at promoting athletic physical activity among older adults may generate benefits for mental health. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Behavioral Activation Is an Evidence-Based Treatment for Depression

ERIC Educational Resources Information Center

Sturmey, Peter

2009-01-01

Recent reviews of evidence-based treatment for depression did not identify behavioral activation as an evidence-based practice. Therefore, this article conducted a systematic review of behavioral activation treatment of depression, which identified three meta-analyses, one recent randomized controlled trial and one recent follow-up of an earlier…

Prevalence of depressive symptoms among college students and the influence of sport activity.

PubMed

Uglesić, Boran; Lasić, Davor; Zuljan-Cvitanović, Marija; Buković, Damir; Karelović, Deni; Delić-Brkljacić, Diana; Buković, Nevia; Radan, Mirjana

2014-03-01

The present study asses the prevalence of depressive symptoms among college students in Split, Croatia, and positive influence of sport activity on decreasing the depression symptoms. Authors screened all 664 college students of the first year of study. All of them were over the 18 years and the mean age was 19.4 +/- 1.2 years. There were 466 females (70.2%) and 178 (26.8%) males. They answered The Beck Depression Inventory (BDI) and questionnaire about their sport activity (no sport activity, recreational and active in sports). For the purpose of the analysis depressive symptoms were defined as a score of > 11. Chi-square and Mann-Whitney test were used for data analysis. 9.4% of the students had significant depression symptoms (score > 11). No one student had score > 26 (symptoms of major depression). Statistically significant lower score on BDI have students who are active in sports (score median = 3) compared to group of recreational (score median = 4) and in correlation to group who are not active in sports (score median = 5) (Kruskal-Wallis: p < 0.001). In the group of active in sports (N = 254) there are only 5.5% with depressions symptoms, while in the group of non active in sports (N = 60) are 18 depressive (chi2-test: p = 0,005). Females are statistically more depressed than males (chi2-test: p = 0.01). In the female group 49 (10.5%) are depressed, and in the male group are 9 (5%). Compared to gender in separate analysis we did not find correlation of decreasing depression symptoms and sport activity among males (chi2-test: p = 0.47), while in females we find that sport activity has significant effect (chi2-test: p = 0.026). Our results shoved moderate values of depression symptoms among college population in Split, Croatia. More females than males experienced depressive symptoms. While sport activity did not have significant influence on the depression in male population, it has significant influence in reducing the depression symptoms among females.

Major depression in mothers predict reduced ventral striatum activation in adolescent female offspring with and without depression

USDA-ARS?s Scientific Manuscript database

Prior research has identified reduced reward-related brain activation as a promising endophenotype for the early identification of adolescents with major depressive disorder. However, it is unclear whether reduced reward-related brain activation constitutes a true vulnerability for major depressive ...

Differential Links Between Leisure Activities and Depressive Symptoms in Unemployed Individuals

PubMed Central

Goodman, William K.; Geiger, Ashley M.; Wolf, Jutta M.

2016-01-01

Objective Unemployment has consistently been linked to an elevated risk for depression. Exercise, specifically leisure-based physical activities, has received increasing attention as alternative treatment options. However, because leisure activities are pursued during discretionary time, it is unclear if the mental health benefits of physical and leisure activities apply during times of unemployment as well. Method Depressive symptoms and participation in recreational activities were assessed in 142 employed and 158 unemployed participants (age = 34 ± 11 years; male = 150). Results Independent of employment status, all recreational activities were inversely associated with depressive symptoms. However, social (employed: ηp2 = .21; unemployed: ηp2 = .11) and self-focused (employed: ηp2 = .19; unemployed: ηp2 = .10) recreational activities were more strongly related to depressive symptoms than exercise (employed: ηp2 = .12; unemployed: ηp2 > .05). Conclusion These findings highlight the strong mental health associations of recreational activities and suggest that, particularly for unemployed individuals, promoting recreational activities, rather than exercise, may leverage the stronger negative relationship with risk of depression. PMID:26443982

Differential Links Between Leisure Activities and Depressive Symptoms in Unemployed Individuals.

PubMed

Goodman, William K; Geiger, Ashley M; Wolf, Jutta M

2016-01-01

Unemployment has consistently been linked to an elevated risk for depression. Exercise, specifically leisure-based physical activities, has received increasing attention as alternative treatment options. However, because leisure activities are pursued during discretionary time, it is unclear if the mental health benefits of physical and leisure activities apply during times of unemployment as well. Depressive symptoms and participation in recreational activities were assessed in 142 employed and 158 unemployed participants (age = 34 ± 11 years; male = 150). Independent of employment status, all recreational activities were inversely associated with depressive symptoms. However, social (employed: ηp (2) = .21; unemployed: ηp (2) = .11) and self-focused (employed: ηp (2) = .19; unemployed: ηp (2) = .10) recreational activities were more strongly related to depressive symptoms than exercise (employed: ηp (2) = .12; unemployed: ηp (2) > .05). These findings highlight the strong mental health associations of recreational activities and suggest that, particularly for unemployed individuals, promoting recreational activities, rather than exercise, may leverage the stronger negative relationship with risk of depression. © 2015 Wiley Periodicals, Inc.

From the Cover: Prenatal Nicotinic Exposure Attenuates Respiratory Chemoreflexes Associated With Downregulation of Tyrosine Hydroxylase and Neurokinin 1 Receptor in Rat Pup Carotid Body.

PubMed

Zhao, Lei; Zhuang, Jianguo; Gao, Xiuping; Ye, Chunyan; Lee, Lu-Yuan; Xu, Fadi

2016-09-01

Maternal cigarette smoke is the major risk of sudden infant death syndrome (SIDS). A depressed ventilatory response to hypoxia (HVR) and hypercapnia (HCVR) is thought to be responsible for the pathogenesis of SIDS and the carotid body is critically involved in these responses. We have recently reported that prenatal nicotinic exposure (PNE) over the full gestation induces depressed HVR in rat pups. Here, we asked whether PNE (1) depressed not only HVR but also HCVR that were dependent on the carotid body, (2) affected some important receptors and neurochemicals expressed in the carotid body, such as tyrosine hydroxylase (TH), neurokinin-1 receptor (NK1R), and α7 nicotinic acetylcholine receptor (α7nAChR), and (3) blunted the ventilatory responses to activation of these receptors. To this end, HVR and HCVR in Ctrl and PNE pups were measured with plethysmography before and after carotid body ablation (Series I), mRNA expression and/or immunoreactivity (IR) of TH, NK1R, and α7nAChR in the carotid body were examined by RT-PCR and immunohistochemistry (Series II), and the ventilatory responses were tested before and after intracarotid injection of substance P (NK1R agonist) and AR-R17779 (α7nAChR agonist) (Series III). Our results showed that PNE (1) significantly depressed both HVR and HCVR and these depressions were abolished by carotid body ablation, (2) reduced the relative population of glomus cells, mRNA NK1R, and α7nAChR and IR of NK1R and TH in the carotid body, and (3) decreased ventilatory responses to intracarotid injection of substance P or AR-R17779. These results suggest that PNE acting via the carotid body could strikingly blunt HVR and HCVR, likely through downregulating TH and NK1R. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Medial cortex activity, self-reflection and depression.

PubMed

Johnson, Marcia K; Nolen-Hoeksema, Susan; Mitchell, Karen J; Levin, Yael

2009-12-01

Using functional magnetic resonance imaging, we investigated neural activity associated with self-reflection in depressed [current major depressive episode (MDE)] and healthy control participants, focusing on medial cortex areas previously shown to be associated with self-reflection. Both the MDE and healthy control groups showed greater activity in anterior medial cortex (medial frontal gyrus, anterior cingulate gyrus) when cued to think about hopes and aspirations compared with duties and obligations, and greater activity in posterior medial cortex (precuneus, posterior cingulate) when cued to think about duties and obligations (Experiment 1). However, the MDE group showed less activity than controls in the same area of medial frontal cortex when self-referential cues were more ambiguous with respect to valence (Experiment 2), and less deactivation in a non-self-referential condition in both experiments. Furthermore, individual differences in rumination were positively correlated with activity in both anterior and posterior medial cortex during non-self-referential conditions. These results provide converging evidence for a dissociation of anterior and posterior medial cortex depending on the focus of self-relevant thought. They also provide neural evidence consistent with behavioral findings that depression is associated with disruption of positively valenced thoughts in response to ambiguous cues, and difficulty disengaging from self-reflection when it is appropriate to do so.

Medial cortex activity, self-reflection and depression

PubMed Central

Nolen-Hoeksema, Susan; Mitchell, Karen J.; Levin, Yael

2009-01-01

Using functional magnetic resonance imaging, we investigated neural activity associated with self-reflection in depressed [current major depressive episode (MDE)] and healthy control participants, focusing on medial cortex areas previously shown to be associated with self-reflection. Both the MDE and healthy control groups showed greater activity in anterior medial cortex (medial frontal gyrus, anterior cingulate gyrus) when cued to think about hopes and aspirations compared with duties and obligations, and greater activity in posterior medial cortex (precuneus, posterior cingulate) when cued to think about duties and obligations (Experiment 1). However, the MDE group showed less activity than controls in the same area of medial frontal cortex when self-referential cues were more ambiguous with respect to valence (Experiment 2), and less deactivation in a non-self-referential condition in both experiments. Furthermore, individual differences in rumination were positively correlated with activity in both anterior and posterior medial cortex during non-self-referential conditions. These results provide converging evidence for a dissociation of anterior and posterior medial cortex depending on the focus of self-relevant thought. They also provide neural evidence consistent with behavioral findings that depression is associated with disruption of positively valenced thoughts in response to ambiguous cues, and difficulty disengaging from self-reflection when it is appropriate to do so. PMID:19620180

Prospective Reciprocal Relations between Physical Activity and Depression in Female Adolescents

ERIC Educational Resources Information Center

Jerstad, Sarah J.; Boutelle, Kerri N.; Ness, Kirsten K.; Stice, Eric

2010-01-01

Objective: Although an inverse correlation between physical activity and depression among adolescents has been found in research, this relation has seldom been examined prospectively. Thus, we tested whether physical activity reduces risk for future escalations in depression and whether depression decreases likelihood of future change in physical…

Longitudinal associations between physical activity and depression scores in Swedish women followed 32 years.

PubMed

Gudmundsson, P; Lindwall, M; Gustafson, D R; Östling, S; Hällström, T; Waern, M; Skoog, I

2015-12-01

Physical activity is negatively associated with depressive symptoms. However, few studies consider dynamic associations of changes in physical activity and reciprocal relationships. This study aimed to perform comprehensive evaluations of relationships between physical activity and depression scores in women followed from mid- to late life. The Prospective Population Study of Women in Gothenburg, Sweden, provided repeated measures of self-reported physical activity and depressive symptoms between 1974 and 2005 (baseline N = 676, 84.5% response rate). Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale, and physical activity was evaluated by the Saltin-Grimby Physical Activity Level Scale. Latent growth curve analyses were used to evaluate associations of change, and cross-lagged models were used to study the reciprocal relationship between physical activity and depression scores. At baseline, lower levels of physical activity were related to higher depression scores. Individuals with decreasing physical activity over time evidenced higher depression scores at 32-year follow-up. Higher average baseline depression score was related to declining levels of physical activity at subsequent examinations. Reduced physical activity may be a long-term consequence of depression. It is important to address individual changes in physical activity and not merely absolute levels of physical activity in relationship to depression. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Physical Activity in Depressed Elderly. A Systematic Review

PubMed Central

Mura, Gioia; Carta, Mauro Giovanni

2013-01-01

Background: exercise may reduce depressive symptoms both in healthy aged populations and in old patients diagnosed with MDD, but few specific analysis were conducted on the efficacy of exercise as an adjunctive treatment with antidepressants, which may be probably more useful in clinical practice, considered the high prevalence of treatment resistant depression in late life, the low cost and safety of physical activity interventions. Objective: to establish the new findings on the effectiveness of exercise on depression in elderlies, with particular focus on the efficacy of the exercise as an adjunctive treatment with antidepressants drug therapy. Method: the search of significant articles was carried out in PubMed/Medline with the following key words: “exercise”, “physical activity”, “physical fitness”, “depressive disorder”, “depression”, “depressive symptoms”, “late life”, “old people”, and “elderly”. Results: 44 papers were retrieved by the search. Among the 10 included randomized controlled trials, treatment allocation was adequately conceived in 4 studies, intention-to-treat analysis was performed in 6 studies, but no study had a double-blinded assessment. We examined and discussed the results of all these trials. Conclusion: in the last 20 years, few progresses were done in showing the efficacy of exercise on depression, due in part to the persistent lack of high quality research, in part to clinical issues of management of depression in late life, in part to the difficult to establish the real effectiveness of exercise on depressive symptoms in elderlies. However, there are some promising findings on physical activity combined with antidepressants in treatment resistant late life depression. PMID:24009640

The lymphocytic cholinergic system and its contribution to the regulation of immune activity.

PubMed

Kawashima, Koichiro; Fujii, Takeshi

2003-12-26

Lymphocytes express most of the cholinergic components found in the nervous system, including acetylcholine (ACh), choline acetyltransferase (ChAT), high affinity choline transporter, muscarinic and nicotinic ACh receptors (mAChRs and nAChRs, respectively), and acetylcholinesterase. Stimulation of T and B cells with ACh or another mAChR agonist elicits intracellular Ca2+ signaling, up-regulation of c-fos expression, increased nitric oxide synthesis and IL-2-induced signal transduction, probably via M3 and M5 mAChR-mediated pathways. Acute stimulation of nAChRs with ACh or nicotine causes rapid and transient Ca2+ signaling in T and B cells, probably via alpha7 nAChR subunit-mediated pathways. Chronic nicotine stimulation, by contrast, down-regulates nAChR expression and suppresses T cell activity. Activation of T cells with phytohemagglutinin or antibodies against cell surface molecules enhances lymphocytic cholinergic transmission by activating expression of ChAT and M5 mAChR, which is suggestive of local cholinergic regulation of immune system activity. This idea is supported by the facts that lymphocytic cholinergic activity reflects well the changes in immune system function seen in animal models of immune deficiency and immune acceleration. Collectively, these data provide a compelling picture in which lymphocytes constitute a cholinergic system that is independent of cholinergic nerves, and which is involved in the regulation of immune function.

Depressive and anxiety disorders and the association with obesity, physical, and social activities.

PubMed

de Wit, Leonore M; Fokkema, Marjolein; van Straten, Annemieke; Lamers, Femke; Cuijpers, Pim; Penninx, Brenda W J H

2010-11-01

There is evidence of more obesity among persons with depressive and depressive and anxiety disorders. However, the nature and the underlying mechanisms of the association are still unclear. This study examines the association between depressive and anxiety disorders and obesity, physical activity, and social activity, and examines whether social and physical activity are potential influencing factors in the association between depressive and anxiety disorders and obesity. Cross-sectional data were used from the Netherlands Study of Depression and Anxiety. A total of 1,854 women and 955 men aged 18-65 years were recruited from the community, general practices, and specialized mental health care. Depressive and anxiety disorders were determined with the Composite International Diagnostic Interview. Body mass index (BMI<30 kg/m(2) ) was used to determine obesity. Physical and social activities were measured by self-report. The odds of obesity adjusted for covariates was significantly higher among those with a current pure Major Depressive Disorder (MDD;odds ratio [OR] OR:1.43; 95% CI:1.07-1.92) compared to controls. Physical activity and social activities were lower among persons with depressive and anxiety disorders compared to controls. The association between MDD and obesity was influenced by social and physical activities. This study confirmed a link between depressive disorders and obesity that was influenced by lower social and physical activities among the depressed. © 2010 Wiley-Liss, Inc.

Naturally occurring disulfide-bound dimers of three-fingered toxins: a paradigm for biological activity diversification.

PubMed

Osipov, Alexey V; Kasheverov, Igor E; Makarova, Yana V; Starkov, Vladislav G; Vorontsova, Olga V; Ziganshin, Rustam Kh; Andreeva, Tatyana V; Serebryakova, Marina V; Benoit, Audrey; Hogg, Ronald C; Bertrand, Daniel; Tsetlin, Victor I; Utkin, Yuri N

2008-05-23

Disulfide-bound dimers of three-fingered toxins have been discovered in the Naja kaouthia cobra venom; that is, the homodimer of alpha-cobratoxin (a long-chain alpha-neurotoxin) and heterodimers formed by alpha-cobratoxin with different cytotoxins. According to circular dichroism measurements, toxins in dimers retain in general their three-fingered folding. The functionally important disulfide 26-30 in polypeptide loop II of alpha-cobratoxin moiety remains intact in both types of dimers. Biological activity studies showed that cytotoxins within dimers completely lose their cytotoxicity. However, the dimers retain most of the alpha-cobratoxin capacity to compete with alpha-bungarotoxin for binding to Torpedo and alpha7 nicotinic acetylcholine receptors (nAChRs) as well as to Lymnea stagnalis acetylcholine-binding protein. Electrophysiological experiments on neuronal nAChRs expressed in Xenopus oocytes have shown that alpha-cobratoxin dimer not only interacts with alpha7 nAChR but, in contrast to alpha-cobratoxin monomer, also blocks alpha3beta2 nAChR. In the latter activity it resembles kappa-bungarotoxin, a dimer with no disulfides between monomers. These results demonstrate that dimerization is essential for the interaction of three-fingered neurotoxins with heteromeric alpha3beta2 nAChRs.

Affective mediators of a physical activity intervention for depression in multiple sclerosis.

PubMed

Kratz, Anna L; Ehde, Dawn M; Bombardier, Charles H

2014-02-01

Previous analyses showed that a telephone-based intervention to increase physical activity in individuals with multiple sclerosis (MS) and depression resulted in significantly improved depressive symptoms compared to a wait-list control group. The aim of this study was to test positive affect and negative affect as mediators of the effect of the physical activity counseling on depressive symptoms. Ninety-two adults with MS, who met diagnostic criteria for either major depression or dysthymia and who reported low levels of physical activity, were randomized 1:1 to a 12-week telephone-based motivational interviewing (MI) intervention to improve physical activity (n = 44) or to a 12-week wait-list control group (n = 48). Self-reported positive and negative affect, physical activity, and depressive symptoms were gathered at baseline and postintervention. Path-analysis was used to test whether positive affect and negative affect mediated the positive effects of the intervention on depressive symptoms. Both positive and negative affect were significant mediators of the effects of the intervention on depressive symptoms; however, only positive affect mediated the association between changes in physical activity and improved depressive symptoms. Findings support physical activity and positive affect as key mediators of the MI treatment effect on improved mood. Decreases in negative affect were also evident in the treatment group, but were not related to improved physical activity. Findings may suggest the use of exercise-based interventions in conjunction with treatments that specifically target negative affective mechanisms for depression. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Zingiberis Siccatum Rhizoma, the active component of the Kampo formula Daikenchuto, induces anti-inflammatory actions through α7 nicotinic acetylcholine receptor activation.

PubMed

Endo, M; Hori, M; Mihara, T; Ozaki, H; Oikawa, T; Odaguchi, H; Hanawa, T

2017-12-01

We previously reported that Daikenchuto (DKT), a gastrointestinal prokinetic Japanese herbal (Kampo) medicine used for the treatment of postoperative ileus (POI), has characteristic potent anti-inflammatory activity. This effect may be partly mediated by the activation of α7 nicotinic acetylcholine receptor (nAChR). In this study, we identified the specific herbs in DKT that induce anti-inflammatory action. The herbal components of DKT were individually administered orally to each mouse four times before and after intestinal manipulation (IM) was carried out on the distal ileum. The anti-inflammatory activity of each crude drug was subsequently evaluated using immunohistochemical analyses of relevant molecules. Treatment with Zingiberis Siccatum Rhizoma (ZSR) but not the other components inhibited the infiltration of cluster of differentiation 68 (CD68)-positive macrophages as effectively as DKT treatment. Selective α7nAChR antagonists, such as methyllycaconitine citrate, or transient receptor potential ankyrin 1 (TRPA1) antagonists, such as HC-030031, significantly inhibited the amelioration of macrophage infiltration by ZSR. The inhibition of macrophage infiltration by ZSR was abolished in both α7nAChR and 5-hydroxytryptamine 4 receptor (5-HT 4 R) knockout mice. Daikenchuto-induced anti-inflammatory activity, which was mediated by inhibiting macrophage infiltration in POI, is dependent on the effects of ZSR. Zingiberis Siccatum Rhizoma activates TRPA1 channels possibly in enterochromaffin (EC) cells to release 5-HT, which stimulates 5-HT 4 R in the myenteric plexus neurons to release ACh, which in turn activates α7nAChR on macrophages to inhibit inflammation in POI. © 2017 John Wiley & Sons Ltd.

The p38 mitogen activated protein kinase regulates β-amyloid protein internalization through the α7 nicotinic acetylcholine receptor in mouse brain.

PubMed

Ma, Kai-Ge; Lv, Jia; Yang, Wei-Na; Chang, Ke-Wei; Hu, Xiao-Dan; Shi, Li-Li; Zhai, Wan-Ying; Zong, Hang-Fan; Qian, Yi-Hua

2018-03-01

Alzheimer's disease (AD) is one of the most devastating neurodegenerative disorders. Intracellular β-amyloid protein (Aβ) is an early event in AD. It induces the formation of amyloid plaques and neuron damage. The α7 nicotinic acetylcholine receptor (α7nAChR) has been suggested to play an important role in Aβ caused cognition. It has high affinity with Aβ and could mediate Aβ internalization in vitro. However, whether in mouse brain the p38 MAPK signaling pathway is involved in the regulation of the α7nAChR mediated Aβ internalization and their role in mitochondria remains little known. Therefore, in this study, we revealed that Aβ is internalized by cholinergic and GABAergic neurons. The internalized Aβ were found deposits in lysosomes/endosomes and mitochondria. Aβ could form Aβ-α7nAChR complex with α7nAChR, activates the p38 mitogen activated protein kinase (MAPK). And the increasing of α7nAChR could in return mediate Aβ internalization in the cortex and hippocampus. In addition, by using the α7nAChR agonist PNU282987, the p38 phosphorylation level decreases, rescues the biochemical changes which are tightly associated with Aβ-induced apoptosis, such as Bcl2/Bax level, cytochrome c (Cyt c) release. Collectively, the p38 MAPK signaling pathway could regulate the α7nAChR-mediated internalization of Aβ. The activation of α7nAChR or the inhibition of p38 MAPK signaling pathway may be a beneficial therapy to AD. Copyright © 2017 Elsevier Inc. All rights reserved.

Effort Deficits and Depression: The Influence of Anhedonic Depressive Symptoms on Cardiac Autonomic Activity During a Mental Challenge

PubMed Central

Silvia, Paul J.; Nusbaum, Emily C.; Eddington, Kari M.; Beaty, Roger E.; Kwapil, Thomas R.

2014-01-01

Motivational approaches to depression emphasize the role of dysfunctional motivational dynamics, particularly diminished reward and incentive processes associated with anhedonia. A study examined how anhedonic depressive symptoms, measured continuously across a wide range of severity, influenced the physiological mobilization of effort during a cognitive task. Using motivational intensity theory as a guide, we expected that the diminished incentive value associated with anhedonic depressive symptoms would reduce effort during a “do your best” challenge (also known as an unfixed or self-paced challenge), in which effort is a function of the value of achieving the task’s goal. Using impedance cardiography, two cardiac autonomic responses were assessed: pre-ejection period (PEP), a measure of sympathetic activity and our primary measure of interest, and respiratory sinus arrhythmia (RSA), a measure of parasympathetic activity. As expected, PEP slowed from baseline to task as anhedonic depressive symptoms increased (as measured with the DASS Depression scale), indicating diminished effort-related sympathetic activity. No significant effects appeared for RSA. The findings support motivational intensity theory as a translational model of effort processes in depression and clarify some inconsistent effects of depressive symptoms on effort-related physiology found in past work. PMID:25431505

Neuroimmune Interactions in Schizophrenia: Focus on Vagus Nerve Stimulation and Activation of the Alpha-7 Nicotinic Acetylcholine Receptor

PubMed Central

Corsi-Zuelli, Fabiana Maria das Graças; Brognara, Fernanda; Quirino, Gustavo Fernando da Silva; Hiroki, Carlos Hiroji; Fais, Rafael Sobrano; Del-Ben, Cristina Marta; Ulloa, Luis; Salgado, Helio Cesar; Kanashiro, Alexandre; Loureiro, Camila Marcelino

2017-01-01

Schizophrenia is one of the most debilitating mental disorders and is aggravated by the lack of efficacious treatment. Although its etiology is unclear, epidemiological studies indicate that infection and inflammation during development induces behavioral, morphological, neurochemical, and cognitive impairments, increasing the risk of developing schizophrenia. The inflammatory hypothesis of schizophrenia is also supported by clinical studies demonstrating systemic inflammation and microglia activation in schizophrenic patients. Although elucidating the mechanism that induces this inflammatory profile remains a challenge, mounting evidence suggests that neuroimmune interactions may provide therapeutic advantages to control inflammation and hence schizophrenia. Recent studies have indicated that vagus nerve stimulation controls both peripheral and central inflammation via alpha-7 nicotinic acetylcholine receptor (α7nAChR). Other findings have indicated that vagal stimulation and α7nAChR-agonists can provide therapeutic advantages for neuropsychiatric disorders, such as depression and epilepsy. This review analyzes the latest results regarding: (I) the immune-to-brain pathogenesis of schizophrenia; (II) the regulation of inflammation by the autonomic nervous system in psychiatric disorders; and (III) the role of the vagus nerve and α7nAChR in schizophrenia. PMID:28620379

Increased autoimmune activity against 5-HT: a key component of depression that is associated with inflammation and activation of cell-mediated immunity, and with severity and staging of depression.

PubMed

Maes, Michael; Ringel, Karl; Kubera, Marta; Berk, Michael; Rybakowski, Janusz

2012-02-01

Depression is characterized by inflammation and cell-mediated immune (CMI) activation and autoimmune reactions directed against a multitude of self-epitopes. There is evidence that the inflammatory response in depression causes dysfunctions in the metabolism of 5-HT, e.g. lowering the 5-HT precursor tryptophan, and upregulating 5-HT receptor mRNA. This study has been undertaken to examine autoimmune activity directed against 5-HT in relation to CMI activation and inflammation. 5-HT antibodies were examined in major depressed patients (n=109) versus normal controls (n=35) in relation to serum neopterin and lysozyme, and plasma pro-inflammatory cytokines (PIC), i.e. interleukin-1 (IL-1) and tumor necrosis factor-α (TNFα). Severity of depression was assessed with the Hamilton Depression Rating Scale (HDRS) and severity of fatigue and somatic symptoms with the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale. The incidence of anti-5-HT antibody activity was significantly higher in depressed patients (54.1%), and in particular in those with melancholia (82.9%), than in controls (5.7%). Patients with positive 5-HT antibodies showed increased serum neopterin and lysozyme, and plasma TNFα and IL-1; higher scores on the HDRS and FF scales, and more somatic symptoms, including malaise and neurocognitive dysfunctions. There was a significant association between autoimmune activity to 5-HT and the number of previous depressive episodes. The autoimmune reactions directed against 5-HT might play a role in the pathophysiology of depression and the onset of severe depression. The strong association between autoimmune activity against 5-HT and inflammation/CMI activation is explained by multiple, reciprocal pathways between these factors. Exposure to previous depressive episodes increases the incidence of autoimmune activity directed against 5-HT, which in turn may increase the likelihood to develop new depressive episodes. These findings suggest that sensitization

Association between Physical Activity and Depressive Symptoms: Midlife Women in SWAN

PubMed Central

Dugan, Sheila A.; Bromberger, Joyce T.; Segawa, Eisuke; Avery, Elizabeth; Sternfeld, Barbara

2014-01-01

Introduction The relationship of physical activity (PA) and positive mood has been the focus of considerable research, primarily cross-sectional. This study was done to evaluate the relationship between PA and high depressive symptoms across time and to examine whether being physically active attenuates the risk of depressive symptoms in midlife women. Methods The present study is a longitudinal observation study of the menopausal transition in a multiethnic population. Ten years of data on 2891 women were analyzed. The participants were women from seven geographic areas nationwide, aged 42 to 52 years at baseline, still menstruating and not using exogenous reproductive hormones. Physical activity was measured with the Kaiser Permanente Physical Activity Scale (KPAS). The main outcome measure, depressive symptoms, was assessed with the Center for Epidemiological Studies Depression Scale (CES-D) with primary outcome CES-D score of 16 or higher. Results In mixed effect logistic regression models adjusted for covariates, compared to inactivity, physical activity Meeting PA Guidelines (approximating public health guidelines) and physical activity Below PA Guidelines were each associated with lower risk of High Depressive Symptoms (CES-D score of 16 or higher) [odds ratio (OR) =0.52, 95% confidence intervals (CI) 0.40-0.70; OR =0.81, 95% CI 0.67-0.98, respectively] across 10 years. Being married, Japanese and Hispanic ethnicity, current smoking, reporting very upsetting life events, using anti-depressive medications, having hot flashes, and high BMI were all positively associated with High Depressive Symptoms, while high social support was negatively associated. Conclusions Higher PA was associated with lower levels of depressive symptoms persistently over ten years independent of potential confounders. Our findings suggest that reaching moderate intensity PA levels during midlife may be protective against depressive symptoms. PMID:24914519

Decreased Resting-State Activity in the Precuneus Is Associated With Depressive Episodes in Recurrent Depression.

PubMed

Liu, Chun-Hong; Ma, Xin; Yuan, Zhen; Song, Lu-Ping; Jing, Bing; Lu, Hong-Yu; Tang, Li-Rong; Fan, Jin; Walter, Martin; Liu, Cun-Zhi; Wang, Lihong; Wang, Chuan-Yue

2017-04-01

To investigate alterations in resting-state spontaneous brain activity in patients with major depressive disorder (MDD) experiencing multiple episodes. Between May 2007 and September 2014, 24 recurrent and 22 remitted patients diagnosed with MDD with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), and 69 healthy controls matched for age, sex, and educational level participated in this study. Among them, 1 healthy control was excluded due to excessive head motion. The fractional amplitude of low-frequency fluctuation (fALFF) was assessed for all recruited subjects during the completion of resting-state functional magnetic resonance imaging. Relationships between fALFF and clinical measurements, including number of depressive episodes and illness duration, were examined. Compared to patients with remitted MDD and to healthy controls, patients with recurrent MDD exhibited decreased fALFF in the right posterior insula and right precuneus and increased fALFF in the left ventral anterior cingulate cortex. Decreased fALFF in the right precuneus and increased fALFF in the right middle insula were correlated with the number of depressive episodes in the recurrent MDD groups (r = -0.75, P < .01 and r = 0.78, P < .01, respectively) and remitted MDD groups (r = -0.63, P < .01 and r = 0.41, P = .03, respectively). In addition to regions in the default mode network (DMN) and salience network, the altered resting-state activity in the middle temporal and visual cortices was also identified. Altered resting-state activity was observed across several neural networks in patients with recurrent MDD. Consistent with the emerging theory that altered DMN activity is a risk factor for depression relapses, the association between reduced fALFF in the right precuneus and number of depressive episodes supports the role of the DMN in the pathology of recurrent depression. © Copyright 2017 Physicians Postgraduate Press, Inc.

Selective activation of α7 nicotinic acetylcholine receptor by PHA-543613 improves Aβ25-35-mediated cognitive deficits in mice.

PubMed

Sadigh-Eteghad, S; Talebi, M; Mahmoudi, J; Babri, S; Shanehbandi, D

2015-07-09

Agonists of α7 nicotinic acetylcholine receptors (nAChRs) are currently being considered as therapeutic approaches for managing cognitive deficits in Alzheimer's disease (AD). Present study was designed to evaluate the effect of α7 nAChR selective activation by PHA-543613 (PHA) on beta-amyloid (Aβ)25-35-mediated cognitive deficits in mice. For this purpose, PHA (1mg/kg, i.p.), a selective α7 nAChR agonist, and galantamine (Gal) (3mg/kg, s.c.), an acetylcholine-esterase inhibitor (AChEI) effects on α7 nAChR were tested in Aβ25-35-received (intracerebroventricular, 10 nmol) mice model of AD. Methyllycaconitine (MLA) (1mg/kg, i.p.), a α7 nAChR antagonist, was used for receptor blockage effects evaluation. Working and reference memory in animals was assessed by the Morris water maze (MWM) task. The mRNA and protein levels of α7 subunit were analyzed by real-time PCR and Western blotting, respectively. PHA and Gal, ameliorate Aβ-impaired working and reference memory. However, Gal had less effect than PHA in this regard. Pretreatment with MLA reverses both Gal and PHA effects in MWM. PHA and Gal treatment prevent Aβ-induced α7 subunit protein reduction, but Gal has lesser effect than PHA. This effect blocked by pretreatment with MLA. In neither the pretreatment nor treatment group, the mRNA levels of nAChR α7 subunit were significantly changed. Therefore, α7 nAChR activation, reduces Aβ-induced cognitive deficits and increases the α7 protein level and subsequent neuron survival. However, blockage of receptor, increases Aβ toxicity and cognitive impairment and reduces the α7 nAChR protein level and flowing neuroprotection. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Coincident postsynaptic activity gates presynaptic dopamine release to induce plasticity in Drosophila mushroom bodies

PubMed Central

Ueno, Kohei; Suzuki, Ema; Naganos, Shintaro; Ofusa, Kyoko; Horiuchi, Junjiro; Saitoe, Minoru

2017-01-01

Simultaneous stimulation of the antennal lobes (ALs) and the ascending fibers of the ventral nerve cord (AFV), two sensory inputs to the mushroom bodies (MBs), induces long-term enhancement (LTE) of subsequent AL-evoked MB responses. LTE induction requires activation of at least three signaling pathways to the MBs, mediated by nicotinic acetylcholine receptors (nAChRs), NMDA receptors (NRs), and D1 dopamine receptors (D1Rs). Here, we demonstrate that inputs from the AL are transmitted to the MBs through nAChRs, and inputs from the AFV are transmitted by NRs. Dopamine signaling occurs downstream of both nAChR and NR activation, and requires simultaneous stimulation of both pathways. Dopamine release requires the activity of the rutabaga adenylyl cyclase in postsynaptic MB neurons, and release is restricted to MB neurons that receive coincident stimulation. Our results indicate that postsynaptic activity can gate presynaptic dopamine release to regulate plasticity. DOI: http://dx.doi.org/10.7554/eLife.21076.001 PMID:28117664

Physical Activity and Depressive Symptoms in Four Ethnic Groups of Midlife Women

PubMed Central

Im, Eun-Ok; Ham, Ok Kyung; Chee, Eunice; Chee, Wonshik

2014-01-01

The purpose of this study was to determine the associations between physical activity and depression and the multiple contextual factors influencing these associations in four major ethnic-groups of midlife women in the U.S. This was a secondary analysis of the data from 542 midlife women. The instruments included questions on background characteristics and health and menopausal status; the Depression Index for Midlife Women; and the Kaiser Physical Activity Survey. The data were analyzed using chi-square tests, the ANOVA, twoway ANOVA, correlation analyses, and hierarchical multiple regression analyses. The women's depressive symptoms were negatively correlated with active living and sports/exercise physical activities whereas they were positively correlated with occupational physical activities (p < .01). Family income was the strongest predictor of their depressive symptoms. Increasing physical activity may improve midlife women's depressive symptoms, but the types of physical activity and multiple contextual factors need to be considered in intervention development. PMID:24879749

Physical activity and depressive symptoms in four ethnic groups of midlife women.

PubMed

Im, Eun-Ok; Ham, Ok Kyung; Chee, Eunice; Chee, Wonshik

2015-06-01

The purpose of this study was to determine the associations between physical activity and depression and the multiple contextual factors influencing these associations in four major ethnic groups of midlife women in the United States. This was a secondary analysis of the data from 542 midlife women. The instruments included questions on background characteristics and health and menopausal status; the Depression Index for Midlife Women (DIMW); and the Kaiser Physical Activity Survey (KPAS). The data were analyzed using chi-square tests, the ANOVA, two-way ANOVA, correlation analyses, and hierarchical multiple regression analyses. The women's depressive symptoms were negatively correlated with active living and sports/exercise physical activities whereas they were positively correlated with occupational physical activities (p < .01). Family income was the strongest predictor of their depressive symptoms. Increasing physical activity may improve midlife women's depressive symptoms, but the types of physical activity and multiple contextual factors need to be considered in intervention development. © The Author(s) 2014.

Distribution of Active and Resting Periods in the Motor Activity of Patients with Depression and Schizophrenia

PubMed Central

Hauge, Erik; Berle, Jan Øystein; Dilsaver, Steven; Oedegaard, Ketil J.

2016-01-01

Objective Alterations of activity are prominent features of the major functional psychiatric disorders. Motor activity patterns are characterized by bursts of activity separated by periods with inactivity. The purpose of the present study has been to analyze such active and inactive periods in patients with depression and schizophrenia. Methods Actigraph registrations for 12 days from 24 patients with schizophrenia, 23 with depression and 29 healthy controls. Results Patients with schizophrenia and depression have distinctly different profiles with regard to the characterization and distribution of active and inactive periods. The mean duration of active periods is lowest in the depressed patients, and the duration of inactive periods is highest in the patients with schizophrenia. For active periods the cumulative probability distribution, using lengths from 1 to 35 min, follows a straight line on a log-log plot, suggestive of a power law function, and a similar relationship is found for inactive periods, using lengths from 1 to 20 min. For both active and inactive periods the scaling exponent is higher in the depressed compared to the schizophrenic patients. Conclusion The present findings add to previously published results, with other mathematical methods, suggesting there are important differences in control systems regulating motor behavior in these two major groups of psychiatric disorders. PMID:26766953

Gating of Long-Term Potentiation by Nicotinic Acetylcholine Receptors at the Cerebellum Input Stage

PubMed Central

Prestori, Francesca; Bonardi, Claudia; Mapelli, Lisa; Lombardo, Paola; Goselink, Rianne; De Stefano, Maria Egle; Gandolfi, Daniela; Mapelli, Jonathan; Bertrand, Daniel; Schonewille, Martijn; De Zeeuw, Chris; D’Angelo, Egidio

2013-01-01

The brain needs mechanisms able to correlate plastic changes with local circuit activity and internal functional states. At the cerebellum input stage, uncontrolled induction of long-term potentiation or depression (LTP or LTD) between mossy fibres and granule cells can saturate synaptic capacity and impair cerebellar functioning, which suggests that neuromodulators are required to gate plasticity processes. Cholinergic systems innervating the cerebellum are thought to enhance procedural learning and memory. Here we show that a specific subtype of acetylcholine receptors, the α7-nAChRs, are distributed both in cerebellar mossy fibre terminals and granule cell dendrites and contribute substantially to synaptic regulation. Selective α7-nAChR activation enhances the postsynaptic calcium increase, allowing weak mossy fibre bursts, which would otherwise cause LTD, to generate robust LTP. The local microperfusion of α7-nAChR agonists could also lead to in vivo switching of LTD to LTP following sensory stimulation of the whisker pad. In the cerebellar flocculus, α7-nAChR pharmacological activation impaired vestibulo-ocular-reflex adaptation, probably because LTP was saturated, preventing the fine adjustment of synaptic weights. These results show that gating mechanisms mediated by specific subtypes of nicotinic receptors are required to control the LTD/LTP balance at the mossy fibre-granule cell relay in order to regulate cerebellar plasticity and behavioural adaptation. PMID:23741401

Sit, step, sweat: longitudinal associations between physical activity patterns, anxiety and depression.

PubMed

Hiles, S A; Lamers, F; Milaneschi, Y; Penninx, B W J H

2017-06-01

Physical inactivity has been identified as a risk factor for depression and, less often, as a long-term consequence of depression. Underexplored is whether similar bi-directional longitudinal relationships are observed for anxiety disorders, particularly in relation to three distinct indicators of activity levels - sports participation, general physical activity and sedentary behavior. Participants were from the Netherlands Study of Depression and Anxiety (NESDA; N = 2932, 18-65 years old; 57% current anxiety or depressive disorder, 21% remitted disorder, 22% healthy controls). At baseline, 2, 4, and 6 years, participants completed a diagnostic interview and self-report questionnaires assessing psychopathology symptom severity, physical activity indicators, and sociodemographic and health covariates. Consistently across assessment waves, people with anxiety and/or depressive disorders had lower sports participation and general physical activity compared to healthy controls. Greater anxiety or depressive symptoms were associated with lower activity according to all three indicators. Over time, a diagnosis or greater symptom severity at one assessment was associated with poorer sports participation and general physical activity 2 years later. In the opposite direction, only low sports participation was associated with greater symptom severity and increased odds of disorder onset 2 years later. Stronger effects were observed for chronicity, with lower activity according to all indicators increasing the odds of disorder chronicity after 2 years. Over time, there seems to a mutually reinforcing, bidirectional relationship between psychopathology and lower physical activity, particularly low sports participation. People with anxiety are as adversely affected as those with depression.

Spatiotemporal psychopathology I: No rest for the brain's resting state activity in depression? Spatiotemporal psychopathology of depressive symptoms.

PubMed

Northoff, Georg

2016-01-15

Despite intense neurobiological investigation in psychiatric disorders like major depressive disorder (MDD), the basic disturbance that underlies the psychopathological symptoms of MDD remains, nevertheless, unclear. Neuroimaging has focused mainly on the brain's extrinsic activity, specifically task-evoked or stimulus-induced activity, as related to the various sensorimotor, affective, cognitive, and social functions. Recently, the focus has shifted to the brain's intrinsic activity, otherwise known as its resting state activity. While various abnormalities have been observed during this activity, their meaning and significance for depression, along with its various psychopathological symptoms, are yet to be defined. Based on findings in healthy brain resting state activity and its particular spatial and temporal structure - defined in a functional and physiological sense rather than anatomical and structural - I claim that the various depressive symptoms are spatiotemporal disturbances of the resting state activity and its spatiotemporal structure. This is supported by recent findings that link ruminations and increased self-focus in depression to abnormal spatial organization of resting state activity. Analogously, affective and cognitive symptoms like anhedonia, suicidal ideation, and thought disorder can be traced to an increased focus on the past, increased past-focus as basic temporal disturbance o the resting state. Based on these findings, I conclude that the various depressive symptoms must be conceived as spatiotemporal disturbances of the brain's resting state's activity and its spatiotemporal structure. Importantly, this entails a new form of psychopathology, "Spatiotemporal Psychopathology" that directly links the brain and psyche, therefore having major diagnostic and therapeutic implications for clinical practice. Copyright © 2015 Elsevier B.V. All rights reserved.

Substituted 2-Aminopyrimidines Selective for α7-Nicotinic Acetylcholine Receptor Activation and Association with Acetylcholine Binding Proteins.

PubMed

Kaczanowska, Katarzyna; Camacho Hernandez, Gisela Andrea; Bendiks, Larissa; Kohs, Larissa; Cornejo-Bravo, Jose Manuel; Harel, Michal; Finn, M G; Taylor, Palmer

2017-03-15

Through studies with ligand binding to the acetylcholine binding protein (AChBP), we previously identified a series of 4,6-substituted 2-aminopyrimidines that associate with this soluble surrogate of the nicotinic acetylcholine receptor (nAChR) in a cooperative fashion, not seen for classical nicotinic agonists and antagonists. To examine receptor interactions of this structural family on ligand-gated ion channels, we employed HEK cells transfected with cDNAs encoding three requisite receptor subtypes: α7-nAChR, α4β2-nAChR, and a serotonin receptor (5-HT 3A R), along with a fluorescent reporter. Initial screening of a series of over 50 newly characterized 2-aminopyrimidines with affinity for AChBP showed only two to be agonists on the α7-nAChR below 10 μM concentration. Their unique structural features were incorporated into design of a second subset of 2-aminopyrimidines yielding several congeners that elicited α7 activation with EC 50 values of 70 nM and K d values for AChBP in a similar range. Several compounds within this series exhibit specificity for the α7-nAChR, showing no activation or antagonism of α4β2-nAChR or 5-HT3AR at concentrations up to 10 μM, while others were weaker antagonists (or partial agonists) on these receptors. Analysis following cocrystallization of four ligand complexes with AChBP show binding at the subunit interface, but with an orientation or binding pose that differs from classical nicotinic agonists and antagonists and from the previously analyzed set of 2-aminopyrimidines that displayed distinct cooperative interactions with AChBP. Orientations of aromatic side chains of these complexes are distinctive, suggesting new modes of binding at the agonist-antagonist site and perhaps an allosteric action for heteromeric nAChRs.

Adolescent Sexual Activity: Links between Relational Context and Depressive Symptoms

ERIC Educational Resources Information Center

Monahan, Kathryn C.; Lee, Joanna M.

2008-01-01

Little is known about the impact of the relational context of adolescent sexual activity on depressive symptoms. The present study examined trajectories of depressive symptoms among 6,602 adolescents (44% male, 60% White) taken from a nationally representative study (Add Health). Sexually active youth in romantic and casual relationships were…

Depression, Activity, and Evaluation of Reinforcement

ERIC Educational Resources Information Center

Hammen, Constance L.; Glass, David R., Jr.

1975-01-01

This research attempted to find the causal relation between mood and level of reinforcement. An effort was made to learn what mood change might occur if depressed subjects increased their levels of participation in reinforcing activities. (Author/RK)

[Indicators of the persistent pro-inflammatory activation of the immune system in depression].

PubMed

Cubała, Wiesław Jerzy; Godlewska, Beata; Trzonkowski, Piotr; Landowski, Jerzy

2006-01-01

The aetiology of depression remains tentative. Current hypotheses on the aetiology of the depressive disorder tend to integrate monoaminoergic, neuroendocrine and immunological concepts of depression. A number of research papers emphasise the altered hormonal and immune status of patients with depression with pronounced cytokine level variations. Those studies tend to link the variable course of depression in relation to the altered proinflammatory activity of the immune system. The results of the studies on the activity of the selected elements of the immune system are ambiguous indicating both increased and decreased activities of its selected elements. However, a number of basic and psychopharmacological studies support the hypothesis of the increased proinflammatory activity of the immune system in the course of depression which is the foundation for the immunological hypothesis of depression. The aim of this paper is to review the functional abnormalities that are observed in depression focusing on the monoaminoergic deficiency and increased immune activation as well as endocrine dysregulation. This paper puts together and discusses current studies related to this subject with a detailed insight into interactions involving nervous, endocrine and immune systems.

Fetal-muscle type nicotinic acetylcholine receptor activation in TE-671 cells, and inhibition of fetal movement in a day 40 pregnant goat model by optical isomers of the piperidine alkaloid coniine

USDA-ARS?s Scientific Manuscript database

Coniine is an optically active toxic piperidine alkaloid and nicotinic acetylcholine receptor (nAChR) agonist found in poison hemlock (Conium maculatum L.). Coniine teratogenicity is hypothesized to be due to the binding, activation, and prolonged desensitization of fetal muscle-type nAChR which re...

Isotemporal Substitution Analysis for Physical Activity, Television Watching, and Risk of Depression

PubMed Central

Mekary, Rania A.; Lucas, Michel; Pan, An; Okereke, Olivia I.; Willett, Walter C.; Hu, Frank B.; Ding, Eric L.

2013-01-01

The isotemporal substitution model (ISM) was previously developed as a methodology to study the time-substitution effects of 1 type of activity for another in a data setting with continuous outcomes. To demonstrate the application of ISM with a dichotomous outcome, we prospectively examined the associations of different activities with various activity displacements with depression risk among 32,900 US women from the Nurses' Health Study who were free from depressive symptoms at baseline (in 1996). During a 10-year follow-up, 5,730 incident depression cases were documented. Results from the ISMs indicated that for each physical activity, differences in magnitude of effects of each activity type were observed, dependent on the activity being displaced/substituted. Notably, an isotemporal substitution gradient was found for television watching, in which its association with depression risk varied by its substitution for slow-, average-, or brisk-paced walking in a gradient toward high depression risk when television watching replaced a faster walking pace (relative risk = 1.18, 95% confidence interval: 1.05, 1.31). Conversely, no association with depression was found for replacement of television watching with 60 minutes/day of slow walking, whereas a lower depression risk (relative risk = 0.85, 95% confidence interval: 0.76, 0.95) was found when 60 minutes/day of brisk walking replaced 60 minutes/day of television watching. Thus, the ISM could offer a more meaningful alternative to the standard nonsubstitution models to support public health recommendations. PMID:23785112

Depression and physical activity in a sample of nigerian adolescents: levels, relationships and predictors

PubMed Central

2011-01-01

Background Physical inactivity is related to many morbidities but the evidence of its link with depression in adolescents needs further investigation in view of the existing conflicting reports. Methods The data for this cross-sectional study were collected from 1,100 Nigerian adolescents aged 12-17 years. Depressive symptomatology and physical activity were assessed using the Children's Depression Inventory (CDI) and the Physical Activity Questionnaire-Adolescent version (PAQ-A) respectively. Independent t tests, Pearson's Moment Correlation and Multi-level logistic regression analyses for individual and school area influences were carried out on the data at p < 0.05. Results The mean age of the participants was 15.20 ± 1.435 years. The prevalence of mild to moderate depression was 23.8%, definite depression was 5.7% and low physical activity was 53.8%. More severe depressive symptoms were linked with lower levels of physical activity (r = -0.82, p < 0.001) and moderate physical activity was linked with reduced risk of depressive symptoms (OR = 0.42, 95% CI = 0.29-0.71). The odds of having depressive symptoms were higher in older adolescents (OR = 2.16, 95% CI = 1.81-3.44) and in females (OR = 2.92, 95% CI = 1.82-3.54). Females had a higher risk of low physical activity than male adolescents (OR = 2.91, 95% CI = 1.51-4.26). Being in Senior Secondary class three was a significant predictor of depressive symptoms (OR = 3.4, 95% CI = 2.55-4.37) and low physical activity. Conclusions A sizable burden of depression and low physical activity existed among the studied adolescents and these were linked to both individual and school factors. Future studies should examine the effects of physical activity among clinical samples of adolescents with depression. PMID:21569581

The α3β4 nAChR partial agonist AT-1001 attenuates stress-induced reinstatement of nicotine seeking in a rat model of relapse and induces minimal withdrawal in dependent rats.

PubMed

Yuan, Menglu; Malagon, Ariana M; Yasuda, Dennis; Belluzzi, James D; Leslie, Frances M; Zaveri, Nurulain T

2017-08-30

The strong reinforcing effects of nicotine and the negative symptoms such as anxiety experienced during a quit attempt often lead to relapse and low success rates for smoking cessation. Treatments that not only block the reinforcing effects of nicotine but also attenuate the motivation to relapse are needed to improve cessation rates. Recent genetic and preclinical studies have highlighted the involvement of the α3, β4, and α5 nicotinic acetylcholine receptor (nAChR) subunits and the α3β4 nAChR subtype in nicotine dependence and withdrawal. However, the involvement of these nAChR in relapse is not fully understood. We previously reported that the α3β4 nAChR partial agonist AT-1001 selectively decreases nicotine self-administration in rats without affecting food responding. In the present experiments, we examined the efficacy of AT-1001 in attenuating reinstatement of nicotine-seeking behavior in a model of stress-induced relapse. Rats extinguished from nicotine self-administration were treated with the pharmacological stressor yohimbine prior to AT-1001 treatment and reinstatement testing. We also examined whether AT-1001 produced any withdrawal-related effects when administered to nicotine-dependent rats. We found that AT-1001 dose-dependently reduced yohimbine stress-induced reinstatement of nicotine seeking. When administered to nicotine-dependent rats at the dose that significantly blocked nicotine reinstatement, AT-1001 elicited minimal somatic withdrawal signs in comparison to the nicotinic antagonist mecamylamine, which is known to produce robust withdrawal. Our data suggest that α3β4 nAChR-targeted compounds may be a promising approach for nicotine addiction treatment because they can not only block nicotine's reinforcing effects, but also decrease motivation to relapse without producing significant withdrawal effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Activation and inhibition of mouse muscle and neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes.

PubMed

Papke, Roger L; Wecker, Lynn; Stitzel, Jerry A

2010-05-01

Transgenic mouse models with nicotinic acetylcholine receptor (nAChR) knockouts and knockins have provided important insights into the molecular substrates of addiction and disease. However, most studies of heterologously expressed neuronal nAChR have used clones obtained from other species, usually human or rat. In this work, we use mouse clones expressed in Xenopus oocytes to provide a relatively comprehensive characterization of the three primary classes of nAChR: muscle-type receptors, heteromeric neuronal receptors, and homomeric alpha7-type receptors. We evaluated the activation of these receptor subtypes with acetylcholine and cytisine-related compounds, including varenicline. We also characterized the activity of classic nAChR antagonists, confirming the utility of mecamylamine and dihydro-beta-erythroidine as selective antagonists in mouse models of alpha3beta4 and alpha4beta2 receptors, respectively. We also conducted an in-depth analysis of decamethonium and hexamethonium on muscle and neuronal receptor subtypes. Our data indicate that, as with receptors cloned from other species, pairwise expression of neuronal alpha and beta subunits in oocytes generates heterogeneous populations of receptors, most likely caused by variations in subunit stoichiometry. Coexpression of the mouse alpha5 subunit had varying effects, depending on the other subunits expressed. The properties of cytisine-related compounds are similar for mouse, rat, and human nAChR, except that varenicline produced greater residual inhibition of mouse alpha4beta2 receptors than with human receptors. We confirm that decamethonium is a partial agonist, selective for muscle-type receptors, but also note that it is a nondepolarizing antagonist for neuronal-type receptors. Hexamethonium was a relatively nonselective antagonist with mixed competitive and noncompetitive activity.

Activation and Inhibition of Mouse Muscle and Neuronal Nicotinic Acetylcholine Receptors Expressed in Xenopus Oocytes

PubMed Central

Wecker, Lynn; Stitzel, Jerry A.

2010-01-01

Transgenic mouse models with nicotinic acetylcholine receptor (nAChR) knockouts and knockins have provided important insights into the molecular substrates of addiction and disease. However, most studies of heterologously expressed neuronal nAChR have used clones obtained from other species, usually human or rat. In this work, we use mouse clones expressed in Xenopus oocytes to provide a relatively comprehensive characterization of the three primary classes of nAChR: muscle-type receptors, heteromeric neuronal receptors, and homomeric α7-type receptors. We evaluated the activation of these receptor subtypes with acetylcholine and cytisine-related compounds, including varenicline. We also characterized the activity of classic nAChR antagonists, confirming the utility of mecamylamine and dihydro-β-erythroidine as selective antagonists in mouse models of α3β4 and α4β2 receptors, respectively. We also conducted an in-depth analysis of decamethonium and hexamethonium on muscle and neuronal receptor subtypes. Our data indicate that, as with receptors cloned from other species, pairwise expression of neuronal α and β subunits in oocytes generates heterogeneous populations of receptors, most likely caused by variations in subunit stoichiometry. Coexpression of the mouse α5 subunit had varying effects, depending on the other subunits expressed. The properties of cytisine-related compounds are similar for mouse, rat, and human nAChR, except that varenicline produced greater residual inhibition of mouse α4β2 receptors than with human receptors. We confirm that decamethonium is a partial agonist, selective for muscle-type receptors, but also note that it is a nondepolarizing antagonist for neuronal-type receptors. Hexamethonium was a relatively nonselective antagonist with mixed competitive and noncompetitive activity. PMID:20100906

Genetic Moderators of the Impact of Physical Activity on Depressive Symptoms.

PubMed

Dotson, V M; Hsu, F C; Langaee, T Y; McDonough, C W; King, A C; Cohen, R A; Newman, A B; Kritchevsky, S B; Myers, V; Manini, T M; Pahor, M

2016-01-01

Converging evidence suggests that physical activity is an effective intervention for both clinical depression and sub-threshold depressive symptoms; however, findings are not always consistent. These mixed results might reflect heterogeneity in response to physical activity, with some subgroups of individuals responding positively, but not others. 1) To examine the impact of genetic variation and sex on changes in depressive symptoms in older adults after a physical activity (PA) intervention, and 2) to determine if PA differentially improves particular symptom dimensions of depression. Randomized controlled trial. Four field centers (Cooper Institute, Stanford University, University of Pittsburgh, and Wake Forest University). 396 community-dwelling adults aged 70-89 years who participated in the Lifestyle Interventions and Independence for Elders Pilot Study (LIFE-P). 12-month PA intervention compared to an education control. Polymorphisms in the serotonin transporter (5-HTT), brain-derived neurotrophic factor (BDNF), and apolipoprotein E (APOE) genes; 12-month change in the Center for Epidemiologic Studies Depression Scale total score, as well as scores on the depressed affect, somatic symptoms, and lack of positive affect subscales. Men randomized to the PA arm showed the greatest decreases in somatic symptoms, with a preferential benefit in male carriers of the BDNF Met allele. Symptoms of lack of positive affect decreased more in men compared to women, particularly in those possessing the 5-HTT L allele, but the effect did not differ by intervention arm. APOE status did not affect change in depressive symptoms. Results of this study suggest that the impact of PA on depressive symptoms varies by genotype and sex, and that PA may mitigate somatic symptoms of depression more than other symptoms. The results suggest that a targeted approach to recommending PA therapy for treatment of depression is viable.

Choline induces opposite changes in pyramidal neuron excitability and synaptic transmission through a nicotinic receptor-independent process in hippocampal slices.

PubMed

Albiñana, E; Luengo, J G; Baraibar, A M; Muñoz, M D; Gandía, L; Solís, J M; Hernández-Guijo, J M

2017-06-01

Choline is present at cholinergic synapses as a product of acetylcholine degradation. In addition, it is considered a selective agonist for α5 and α7 nicotinic acetylcholine receptors (nAChRs). In this study, we determined how choline affects action potentials and excitatory synaptic transmission using extracellular and intracellular recording techniques in CA1 area of hippocampal slices obtained from both mice and rats. Choline caused a reversible depression of evoked field excitatory postsynaptic potentials (fEPSPs) in a concentration-dependent manner that was not affected by α7 nAChR antagonists. Moreover, this choline-induced effect was not mimicked by either selective agonists or allosteric modulators of α7 nAChRs. Additionally, this choline-mediated effect was not prevented by either selective antagonists of GABA receptors or hemicholinium, a choline uptake inhibitor. The paired pulse facilitation paradigm, which detects whether a substance affects presynaptic release of glutamate, was not modified by choline. On the other hand, choline induced a robust increase of population spike evoked by orthodromic stimulation but did not modify that evoked by antidromic stimulation. We also found that choline impaired recurrent inhibition recorded in the pyramidal cell layer through a mechanism independent of α7 nAChR activation. These choline-mediated effects on fEPSP and population spike observed in rat slices were completely reproduced in slices obtained from α7 nAChR knockout mice, which reinforces our conclusion that choline modulates synaptic transmission and neuronal excitability by a mechanism independent of nicotinic receptor activation.

Body esteem is a mediator of the association between physical activity and depression in Korean adolescents.

PubMed

Chae, Sun-Mi; Kang, Hee Sun; Ra, Jin Suk

2017-02-01

This study examined whether body-esteem would mediate the association between physical activity and depression in adolescents. A total of 848 Korean high school students aged 15 to 18years completed a questionnaire on body-esteem, physical activity recall, and depression. Path analysis was used to test mediating effects of body-esteem on the association between physical activity and depression. Girls showed a significantly higher level of depressive symptoms than boys. Boys showed significantly higher levels of physical activity and body-esteem than girls. Body-esteem mediated the relation of physical activity with depression. Physical activity might reduce the risk of depression in addition to supporting body-esteem in adolescents. Interventions that reinforce healthy body-esteem and encourage physical activity would help prevent depression in adolescents. Future studies should examine the effects of programs addressing physical activity and body-esteem among adolescents with depressive symptoms. Copyright © 2016 Elsevier Inc. All rights reserved.

Nicotine Addiction and Psychiatric Disorders

PubMed Central

Kutlu, Munir Gunes; Parikh, Vinay; Gould, Thomas J.

2017-01-01

Even though smoking rates have long been on the decline, nicotine addiction still affects 20% of the US population today. Moreover, nicotine dependence shows high comorbidity with many mental illnesses including, but are not limited to, attention deficit hyperactivity disorder, anxiety disorders, and depression. The reason for the high rates of smoking in patients with mental illnesses may relate to attempts to self-medicate with nicotine. While nicotine may alleviate the symptoms of mental disorders, nicotine abstinence has been shown to worsen the symptoms of these disorders. In this chapter, we review the studies from animal and human research examining the bidirectional relationship between nicotine and attention deficit hyperactivity disorder, anxiety disorders, and depression as well as studies examining the roles of specific subunits of nicotinic acetylcholine receptors (nAChRs) in the interaction between nicotine and these mental illnesses. The results of these studies suggest that activation, desensitization, and upregulation of nAChRs modulate the effects of nicotine on mental illnesses. PMID:26472530

Social stress, obesity, and depression among women: clarifying the role of physical activity.

PubMed

Lincoln, Karen D

2017-07-01

This study examined the role of stress in the association among physical activity, obesity, and depression among women. The extent to which physical activity moderated these relationships was also examined. Data from the National Survey of American Life (N = 3235) and multivariable regression analyses were used to examine the effects of chronic stress, material hardship, racial discrimination, and physical activity on obesity and depression among African American, Caribbean Black and White women. Stress was not related to body mass index (BMI) for African American or White women, but chronic stress was associated with higher BMI for Caribbean Black women. Stress was associated with depressive symptoms, but there was variation by the type of stressor under consideration. Physical activity was associated with fewer depressive symptoms and lower BMI, but the relationships varied by type of stressor and race/ethnicity. Physical activity moderated the effect of chronic stress on depressive symptoms and BMI, but only for African American women who reported high levels of chronic stress. Among White women, physical activity moderated the effect of racial discrimination on BMI for those who reported experiencing both high and low levels of discrimination. This study was the first to document physical activity as a moderator in the relationship among stress, depression, and obesity using a nationally representative sample of racially/ethnically diverse women. Findings provide insight into the role of stress in relation to depression and obesity while highlighting heterogeneity among Black Americans.

Relationship between physical activity and depression and anxiety symptoms: a population study.

PubMed

De Mello, Marco Tulio; Lemos, Valdir de Aquino; Antunes, Hanna Karen Moreira; Bittencourt, Lia; Santos-Silva, Rogerio; Tufik, Sergio

2013-07-01

There are few studies evaluating the association between practice of physical activity and mood in a population sample. This study evaluated the frequency of symptoms of depression and anxiety in the population of the city of Sao Paulo and their association with the report of practice of regular physical activity. This survey was conducted with the adult population of Sao Paulo between July and December of 2007. The sample was composed of 1042 volunteers (both genders) with a mean age of 41.9±14.4 years. The volunteers were evaluated using the Beck Depression Inventory, the Beck Anxiety Inventory, and two simple questions designed to evaluate and classify physical activity. Socioeconomic status was also determined according to Brazil's Economic Classification Criterion. People who do not engage in physical activity are two times more likely to exhibit symptoms of depression (PR: 2.1) and anxiety (PR: 2.5) compared with those who regularly practice physical activity and a higher prevalence of symptoms for anxiety (9.8%) and depression (10.9%) was observed among those claiming to not practice regular physical activity and 63.2% related did not practice any physical activity regularly. Altogether, these results suggest that people who do not practice physical activity have a higher chance of exhibiting symptoms of depression and anxiety when compared to those who perform physical activity regularly. In this sense, regular physical activity must be encouraged, and this incentive should be routine in both current and future public health policies. Although the methodology in the present study does not allow assigning a relation of cause and effect, we observed associations between symptoms of depression, anxiety and physical activity. Copyright © 2013 Elsevier B.V. All rights reserved.

Facial recognition of happiness among older adults with active and remitted major depression.

PubMed

Shiroma, Paulo R; Thuras, Paul; Johns, Brian; Lim, Kelvin O

2016-09-30

Biased emotion processing in depression might be a trait characteristic independent of mood improvement and a vulnerable factor to develop further depressive episodes. This phenomenon of among older adults with depression has not been adequately examined. In a 2-year cross-sectional study, 59 older patients with either active or remitted major depression, or never-depressed, completed a facial emotion recognition task (FERT) to probe perceptual bias of happiness. The results showed that depressed patients, compared with never depressed subjects, had a significant lower sensitivity to identify happiness particularly at moderate intensity of facial stimuli. Patients in remission from a previous major depressive episode but with none or minimal symptoms had similar sensitivity rate to identify happy facial expressions as compared to patients with an active depressive episode. Further studies would be necessary to confirm whether recognition of happy expression reflects a persistent perceptual bias of major depression in older adults. Published by Elsevier Ireland Ltd.

Associations between Dementia Outcomes and Depressive Symptoms, Leisure Activities, and Social Support

PubMed Central

Heser, Kathrin; Wagner, Michael; Wiese, Birgitt; Prokein, Jana; Ernst, Annette; König, Hans-Helmut; Brettschneider, Christian; Riedel-Heller, Steffi G.; Luppa, Melanie; Weyerer, Siegfried; Eifflaender-Gorfer, Sandra; Bickel, Horst; Mösch, Edelgard; Pentzek, Michael; Fuchs, Angela; Maier, Wolfgang; Scherer, Martin; Eisele, Marion

2014-01-01

Background Social relations and depressive symptoms are intertwined. They both predict subsequent dementia, but only few studies on the association between social life aspects and subsequent dementia exist. Methods The risk of subsequent dementia was estimated over 2 follow-up assessments, each 18 months apart, depending on leisure activity, social support (general scale and the 3 factors emotional support, practical support, and social integration), and depressive symptoms, using proportional hazard models in a cohort of elderly patients (n = 2,300, with a mean age of 82.45 years) recruited for the study by their general practitioners. Results Higher depressive symptoms and lower cognitive and physical activity were associated with an increased risk of subsequent all-cause dementia and Alzheimer's dementia (AD). While neither social engagement nor the general social support scale was associated with subsequent dementia, a higher level of social integration was associated with a lower dementia risk. In combined models, the results for activity variables remained similar, but the strength of the association between depressive symptoms and the subsequent risk of dementia decreased, and the association with social integration disappeared. Conclusions Depressive symptoms increased and activity variables decreased the risk of subsequent dementia; however, activity variables, namely cognitive and physical activity, partly mediated the effect of depressive symptoms on the subsequent risk of all-cause dementia and AD. In many cases, social support was not associated with a risk of subsequent dementia. PMID:25685139

Brief Report: Relationships between Physical Activity and Depressive Symptoms in Adolescent Girls

ERIC Educational Resources Information Center

Raudsepp, Lennart; Neissaar, Inga

2012-01-01

This study examined the relationships between changes in physical activity and depressive symptoms in adolescent girls. Participants were 277 urban adolescent girls. Physical activity was measured using the 3-Day Physical Activity Recall and depressive symptoms were assessed using questionnaire. Data were collected on three occasions over a 3-year…

Assessing the relationship between quality of life and behavioral activation using the Japanese Behavioral Activation for Depression Scale-Short Form.

PubMed

Shudo, Yusuke; Yamamoto, Tatsuya

2017-01-01

Quality of life (QOL) is an important health-related concept. Identifying factors that affect QOL can help develop and improve health-promotion interventions. Previous studies suggest that behavioral activation fosters subjective QOL, including well-being. However, the mechanism by which behavioral activation improves QOL is not clear. Considering that QOL improves when depressive symptoms improve post-treatment and that behavioral activation is an effective treatment for depression, it is possible that behavioral activation affects QOL indirectly rather than directly. To clarify the mechanism of the influence of behavioral activation on QOL, it is necessary to examine the relationships between factors related to behavioral activation, depressive symptoms, and QOL. Therefore, we attempted to examine the relationship between these factors. Participants comprised 221 Japanese undergraduate students who completed questionnaires on behavioral activation, QOL, and depressive symptoms: the Japanese versions of the Behavioral Activation for Depression Scale-Short Form (BADS-SF), WHO Quality of Life-BREF (WHOQOL-26), and Center for Epidemiologic Studies Depression Scale (CES-D). The BADS-SF comprises two subscales, Activation and Avoidance, and the WHOQOL-26 measures overall QOL and four domains, Physical Health, Psychological Health, Social Relationships, and Environment. Mediation analyses were conducted with BADS-SF activation and avoidance as independent variables, CES-D as a mediator variable, and each WHO-QOL as an outcome variable. Results indicated that depression completely mediated the relationship between Avoidance and QOL, and partially mediated the relationship between Activation and QOL. In addition, analyses of each domain of QOL showed that Activation positively affected all aspects of QOL directly and indirectly, but Avoidance had a negative influence on only part of QOL mainly through depression. The present study provides behavioral activation strategies

Differential Expression of P450 Genes and nAChR Subunits Associated With Imidacloprid Resistance in Laodelphax striatellus (Hemiptera: Delphacidae).

PubMed

Zhang, Yueliang; Liu, Baosheng; Zhang, Zhichun; Wang, Lihua; Guo, Huifang; Li, Zhong; He, Peng; Liu, Zewen; Fang, Jichao

2018-05-28

Imidacloprid is a key insecticide used for controlling sucking insect pests, including the small brown planthopper (Laodelphax striatellus, Fallén) (Hemiptera: Delphacidae), an important agricultural pest of rice. A strain of L. striatellus (YN-ILR) developed 21-fold resistance when selected with imidacloprid on a susceptible YN strain. An in vitro study on piperonyl butoxide synergism indicated that enhanced detoxification mediated by cytochrome P450s contributed to imidacloprid resistance to some extent, and multiple P450 genes showed altered expression in the imidacloprid-resistant YN-ILR strain compared with the susceptible YN strain (CYP425B1-CYP6BD10 had 1.51- to 11.45-fold higher expression, CYP4CE2-CYP4DD1V2 had 0.12- to 0.57-fold lower expression). While there were no mutations in target nicotinic acetylcholine receptor (nAChR) genes, subunits of Lsα1, Lsβ1, and Lsβ3 in the YN-ILR strain showed 3.86-, 4.39-, and 2.59-fold higher expression and Lsa8 displayed 0.38-fold lower expression than the YN strain. Moreover, 21-fold moderate imidacloprid resistance in individuals of L. striatellus did not produce a fitness cost. The findings suggest that L. striatellus has the capacity to develop resistance to imidacloprid through P450 detoxification and potential target nAChR expression changes, and moderate imidacloprid resistance was not associated with a fitness cost.

Abnormal brain activation during directed forgetting of negative memory in depressed patients.

PubMed

Yang, Wenjing; Chen, Qunlin; Liu, Peiduo; Cheng, Hongsheng; Cui, Qian; Wei, Dongtao; Zhang, Qinglin; Qiu, Jiang

2016-01-15

The frequent occurrence of uncontrollable negative thoughts and memories is a troubling aspect of depression. Thus, knowledge on the mechanism underlying intentional forgetting of these thoughts and memories is crucial to develop an effective emotion regulation strategy for depressed individuals. Behavioral studies have demonstrated that depressed participants cannot intentionally forget negative memories. However, the neural mechanism underlying this process remains unclear. In this study, participants completed the directed forgetting task in which they were instructed to remember or forget neutral or negative words. Standard univariate analysis based on the General Linear Model showed that the depressed participants have higher activation in the inferior frontal gyrus (IFG), superior frontal gyrus (SFG), superior parietal gyrus (SPG), and inferior temporal gyrus (ITG) than the healthy individuals. The results indicated that depressed participants recruited more frontal and parietal inhibitory control resources to inhibit the TBF items, but the attempt still failed because of negative bias. We also used the Support Vector Machine to perform multivariate pattern classification based on the brain activation during directed forgetting. The pattern of brain activity in directed forgetting of negative words allowed correct group classification with an overall accuracy of 75% (P=0.012). The brain regions which are critical for this discrimination showed abnormal activation when depressed participants were attempting to forget negative words. These results indicated that the abnormal neural circuitry when depressed individuals tried to forget the negative words might provide neurobiological markers for depression. Copyright © 2015 Elsevier B.V. All rights reserved.

Walk on the bright side: physical activity and affect in major depressive disorder.

PubMed

Mata, Jutta; Thompson, Renee J; Jaeggi, Susanne M; Buschkuehl, Martin; Jonides, John; Gotlib, Ian H

2012-05-01

Although prescribed exercise has been found to improve affect and reduce levels of depression, we do not know how self-initiated everyday physical activity influences levels of positive affect (PA) and negative affect (NA) in depressed persons. Fifty-three individuals diagnosed with Major Depressive Disorder (MDD) and 53 never-depressed controls participated in a seven-day experience sampling study. Participants were prompted randomly eight times per day and answered questions about their physical activity and affective state. Over the week, the two groups of participants did not differ in average level of physical activity. As expected, participants with MDD reported lower average PA and higher average NA than did never-depressed controls. Both participants with MDD and controls reported higher levels of PA at prompts after physical activity than at prompts after inactive periods; moreover, for both groups of participants, PA increased from a prompt after an inactive period to a subsequent prompt at which activity was reported. Depressed participants in particular showed a dose-response effect of physical activity on affect: longer duration and/or higher intensity of physical activity increased their PA significantly more than did short duration and/or lower intensity physical activity. Physical activity did not influence NA in either group. In contrast to previous treatment studies that examined the effects of prescribed structured exercise, this investigation showed that self-initiated physical activity influences PA. These findings also underscore the importance of distinguishing between PA and NA to gain a more comprehensive understanding of the effects of physical activity on affect in MDD.

Physical activity moderates the association between nicotine dependence and depression among U.S. smokers.

PubMed

Loprinzi, Paul D; Walker, Jerome F; Kane, Christy; Cardinal, Bradley J

2014-01-01

Research demonstrates that nicotine dependence and depression are associated and that physical activity is effective in reducing depression symptoms. However, our understanding of the potential beneficial effects of physical activity on depression in current smokers is more limited. The purpose of this study was to examine whether physical activity moderates the association between nicotine dependence and depression in U.S. smokers. Cross-sectional. National Health and Nutrition Examination Survey 2005-2006. Four hundred forty-one current adult smokers. Participants wore an accelerometer for at least 4 days and completed questionnaires to assess nicotine dependence and depression. Effect modification and statistical interaction models were used. Both models were significant. With regard to the statistical interaction model, and after controlling for age, gender, race/ethnicity, education, comorbidity index, homocysteine, cotinine, total cholesterol, sedentary behavior, and vitamins C, D, and E, objectively measured physical activity moderated the association between nicotine dependence and depression (interaction variable: odds ratio = 3.43; 95% confidence interval: 1.02-11.51; p = .04). In this national sample of current smokers, physical activity moderated the association between nicotine dependence and depression. These results suggest that those individuals with nicotine dependence and who are less physically active are more likely to be depressed than what would be expected on the basis of the individual effects of nicotine and physical inactivity separately.

Mediating role of activity level in the depressive realism effect.

PubMed

Blanco, Fernando; Matute, Helena; A Vadillo, Miguel

2012-01-01

Several classic studies have concluded that the accuracy of identifying uncontrollable situations depends heavily on depressive mood. Nondepressed participants tend to exhibit an optimistic illusion of control, whereas depressed participants tend to better detect a lack of control. Recently, we suggested that the different activity levels (measured as the probability of responding during a contingency learning task) exhibited by depressed and nondepressed individuals is partly responsible for this effect. The two studies presented in this paper provide further support for this mediational hypothesis, in which mood is the distal cause of the illusion of control operating through activity level, the proximal cause. In Study 1, the probability of responding, P(R), was found to be a mediator variable between the depressive symptoms and the judgments of control. In Study 2, we intervened directly on the mediator variable: The P(R) for both depressed and nondepressed participants was manipulated through instructions. Our results confirm that P(R) manipulation produced differences in the participants' perceptions of uncontrollability. Importantly, the intervention on the mediator variable cancelled the effect of the distal cause; the participants' judgments of control were no longer mood dependent when the P(R) was manipulated. This result supports the hypothesis that the so-called depressive realism effect is actually mediated by the probability of responding.

Husbands’ and Wives’ Physical Activity and Depressive Symptoms: Longitudinal Findings from the Cardiovascular Health Study

PubMed Central

Monin, Joan K.; Levy, Becca; Chen, Baibing; Fried, Terri; Stahl, Sarah T.; Schulz, Richard; Doyle, Margaret; Kershaw, Trace

2015-01-01

Background When examining older adults’ health behaviors and psychological health it is important to consider the social context. Purpose To examine in older adult marriages whether each spouse’s physical activity predicted changes in their own (actor effects) and their partner’s (partner effects) depressive symptoms. Gender differences were also examined. Method Each spouse within 1,260 married couples (at baseline) in the Cardiovascular Health Study completed self-report measures at wave 1 (1989–1990), wave 3 (1992–1993), and wave 7 (1996–1997). Dyadic path analyses were performed. Results Husbands’ physical activity significantly predicted own decreased depressive symptoms (actor effect). For both spouses, own physical activity did not significantly predict the spouse’s depressive symptoms (partner effects). However, husbands’ physical activity and depressive symptoms predicted wives’ physical activity and depressive symptoms (partner effects), respectively. Depressive symptoms did not predict physical activity. Conclusion Findings suggest that husbands’ physical activity is particularly influential for older married couples’ psychological health. PMID:25868508

Physical Activity and Incident Depression: A Meta-Analysis of Prospective Cohort Studies.

PubMed

Schuch, Felipe B; Vancampfort, Davy; Firth, Joseph; Rosenbaum, Simon; Ward, Philip B; Silva, Edson S; Hallgren, Mats; Ponce De Leon, Antonio; Dunn, Andrea L; Deslandes, Andrea C; Fleck, Marcelo P; Carvalho, Andre F; Stubbs, Brendon

2018-04-25

The authors examined the prospective relationship between physical activity and incident depression and explored potential moderators. Prospective cohort studies evaluating incident depression were searched from database inception through Oct. 18, 2017, on PubMed, PsycINFO, Embase, and SPORTDiscus. Demographic and clinical data, data on physical activity and depression assessments, and odds ratios, relative risks, and hazard ratios with 95% confidence intervals were extracted. Random-effects meta-analyses were conducted, and the potential sources of heterogeneity were explored. Methodological quality was assessed using the Newcastle-Ottawa Scale. A total of 49 unique prospective studies (N=266,939; median proportion of males across studies, 47%) were followed up for 1,837,794 person-years. Compared with people with low levels of physical activity, those with high levels had lower odds of developing depression (adjusted odds ratio=0.83, 95% CI=0.79, 0.88; I 2 =0.00). Furthermore, physical activity had a protective effect against the emergence of depression in youths (adjusted odds ratio=0.90, 95% CI=0.83, 0.98), in adults (adjusted odds ratio=0.78, 95% CI=0.70, 0.87), and in elderly persons (adjusted odds ratio=0.79, 95% CI=0.72, 0.86). Protective effects against depression were found across geographical regions, with adjusted odds ratios ranging from 0.65 to 0.84 in Asia, Europe, North America, and Oceania, and against increased incidence of positive screen for depressive symptoms (adjusted odds ratio=0.84, 95% CI=0.79, 0.89) or major depression diagnosis (adjusted odds ratio=0.86, 95% CI=0.75, 0.98). No moderators were identified. Results were consistent for unadjusted odds ratios and for adjusted and unadjusted relative risks/hazard ratios. Overall study quality was moderate to high (Newcastle-Ottawa Scale score, 6.3). Although significant publication bias was found, adjusting for this did not change the magnitude of the associations. Available evidence supports

Habitual emotion regulation strategies and depressive symptoms in healthy subjects predict fMRI brain activation patterns related to major depression.

PubMed

Abler, Birgit; Hofer, Christian; Walter, Henrik; Erk, Susanne; Hoffmann, Holger; Traue, Harald C; Kessler, Henrik

2010-08-30

The response-focused emotion regulation style 'Expressive suppression' has been associated with symptoms of lower psychological well-being and increased function magnetic resonance imaging (fMRI) activation of the sublenticular extended amygdala (SLEA) in patients with major depression. Extending prior studies on active emotion regulation, we were interested in effects of habitual emotion regulation on neurobiology. Thirty subjects with either relatively high or low suppression scores as assessed with the Emotion Regulation Questionnaire without symptoms of clinical depression participated in the study. They were instructed to expect and then perceive emotionally unpleasant, pleasant or neutral stimuli selected from the International Affective Picture System that were announced by a congruent cue during fMRI. In the subjects with high suppression scores, decreased activation of the orbital medial prefrontal cortex (oMFC) when expecting negative pictures and increased activation of the SLEA upon presentation of neutral stimuli were found. Subclinical depression ratings independently of suppression scores in the healthy subjects were positively correlated with brain activation in the SLEA when expecting negative pictures. SLEA hyperactivity may represent an emotional responsivity that involves less successful habitual emotion regulation and a tendency to depressed mood in healthy subjects, as shown in patients with major depression. Decreased anticipatory oMFC activation may parallel a lack of antecedent emotion regulation in subjects with high suppression scores, representing another neurobiological predictor of lower mental well-being. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Decrease in neuronal nicotinic acetylcholine receptor subunit and PSD-93 transcript levels in the male mouse MPG after cavernous nerve injury or explant culture.

PubMed

Girard, Beatrice M; Merriam, Laura A; Tompkins, John D; Vizzard, Margaret A; Parsons, Rodney L

2013-11-15

Quantitative real-time PCR was used to test whether cavernous nerve injury leads to a decrease in major pelvic ganglia (MPG) neuronal nicotinic ACh receptor (nAChR) subunit and postsynaptic density (PSD)-93 transcript levels. Subunits α3, β4, and α7, commonly expressed in the MPG, were selected for analysis. After 72 h in explant culture, MPG transcript levels for α3, β4, α7, and PSD-93 were significantly depressed. Three days after cavernous nerve axotomy or crush in vivo, transcript levels for α3, β4, and PSD-93, but not for α7, were significantly depressed. Three days after dissection of the cavernous nerve free of underlying tissue and application of a 5-mm lateral stretch (manipulation), transcript levels for α3 and PSD-93 were also significantly decreased. Seven days after all three surgical procedures, α3 transcript levels remained depressed, but PSD-93 transcript levels were still decreased only after axotomy or nerve crush. At 30 days postsurgery, transcript levels for the nAChR subunits and PSD-93 had recovered. ACh-induced currents were significantly smaller in MPG neurons dissociated from 3-day explant cultured ganglia than from those recorded in neurons dissociated from acutely isolated ganglia; this observation provides direct evidence showing that a decrease in nAChR function was coincident with a decrease in nAChR subunit transcript levels. We conclude that a downregulation of nAChR subunit and PSD-93 expression after cavernous nerve injury, or even manipulation, could interrupt synaptic transmission within the MPG and thus contribute to the loss of neural control of urogenital organs after pelvic surgeries.

Protective Effect of Regular Physical Activity on Depression After Myocardial Infarction: The HUNT Study.

PubMed

Ernstsen, Linda; Rangul, Vegar; Nauman, Javaid; Nes, Bjarne M; Dalen, Håvard; Krokstad, Steinar; Lavie, Carl J; Blair, Steven N; Wisløff, Ulrik

2016-01-01

To study if physical activity within the recommended level over time was associated with risk of developing depression after the first myocardial infarction in older adults. Men (n = 143) and women (n = 46) who had reached the age of 60 years in 2006-2008 who participated in the Nord-Trøndelag Health Study (HUNT1, 1984-1986; HUNT2, 1995-1997; HUNT3, 2006-2008) without any mental illness or cardiovascular disease at baseline in HUNT2 and who experienced their first myocardial infarction before HUNT3 were included. Based on the patterns of physical activity from HUNT1 to HUNT2, the sample was divided into 4 groups: persistently inactive, from active to inactive, from inactive to active, and persistently active. The primary outcome, post-myocardial infarction depression symptoms, was measured with the Hospital, Anxiety and Depression Scale in HUNT3. In HUNT3, 11% of participants had depression. After multivariable adjustment, those who were persistently active had significantly lower odds of being depressed (odds ratio 0.28; 95% confidence interval, 0.08-0.98) compared with those who were persistently inactive. Additionally, a significant test for trend (P = .033) of lowering odds of depression was observed across all 4 categories of physical activity patterns at baseline. In this small sample of initially healthy adults, we observed a long-term protective effect of regular physical activity on the development of depression following myocardial infarction. Copyright © 2016 Elsevier Inc. All rights reserved.

Multiple Sclerosis: Associations Between Physical Disability and Depression Are Not Mediated by Self-Reported Physical Activity.

PubMed

Sadeghi Bahmani, Dena; Calabrese, Pasquale; Merkt, Helene; Naegelin, Yvonne; Gerber, Markus; Pühse, Uwe; Holsboer-Trachsler, Edith; Brand, Serge

2017-10-01

This study investigated the interrelatedness of physical disability, physical activity, and depression among patients with multiple sclerosis (MS). We hypothesized that self-reported physical activity would mediate the effect of disability on depressive symptoms. Twenty-seven patients with MS (mean age: 49 years; 44.5% females) completed self-rating scales covering sociodemographic variables, intake of antidepressants, physical activity, and symptoms of depression; disability was measured by the Expanded Disability Status Scale. We found a higher level of disability to be significantly associated with more symptoms of depression. While higher reported physical activity was descriptively associated with lower depression scores and unrelated to Expanded Disability Status Scale, physical activity levels did not mediate the effect of disability on depressive symptoms.

A pragmatic randomised controlled trial to evaluate the cost-effectiveness of a physical activity intervention as a treatment for depression: the treating depression with physical activity (TREAD) trial.

PubMed

Chalder, M; Wiles, N J; Campbell, J; Hollinghurst, S P; Searle, A; Haase, A M; Taylor, A H; Fox, K R; Baxter, H; Davis, M; Thorp, H; Winder, R; Wright, C; Calnan, M; Lawlor, D A; Peters, T J; Sharp, D J; Turner, K M; Montgomery, A A; Lewis, G

2012-01-01

The TREAting Depression with physical activity (TREAD) study investigated the cost-effectiveness of a physical activity intervention, in addition to usual general practitioner care, as a treatment for people with depression. An individually randomised, pragmatic, multicentre randomised controlled trial with follow-up at 4, 8 and 12 months. A subset of participants took part in a qualitative study that investigated the acceptability and perceived benefits of the intervention. General practices in the Bristol and Exeter areas. Aged 18-69 years with an International Statistical Classification of Diseases and Related Health Problems, 10th Edition (ICD-10) diagnosis of depression and scoring ≥ 14 on the Beck Depression Inventory (BDI). Those who were unable to complete self-administered questionnaires in English, with medical contraindications to physical activity or with psychosis, bipolar disorder or serious drug abuse were excluded. We devised an intervention designed to encourage choice and autonomy in the adoption of physical activity. It consisted of up to three face-to-face and ten telephone contacts delivered by a trained physical activity facilitator over an 8-month period. The primary outcome was the BDI score measured at 4 months. Secondary outcomes included depressive symptoms over the 12 months and quality of life, antidepressant use and level of physical activity. The study recruited 361 patients, with 182 randomised to the intervention arm and 179 to the usual care arm; there was 80% retention at the 4-month follow-up. The intervention group had a slightly lower BDI score at 4 months [-0.54, 95% confidence interval (CI) -3.06 to 1.99] but there was no evidence that the intervention improved outcome for depression. Neither was there any evidence to suggest a difference in the prescription of or self-reported use of antidepressants. However, the amount of physical activity undertaken by those who had received the intervention was increased (odds ratio 2

Activation and Self-Efficacy in a Randomized Trial of a Depression Self-Care Intervention.

PubMed

McCusker, Jane; Lambert, Sylvie D; Cole, Martin G; Ciampi, Antonio; Strumpf, Erin; Freeman, Ellen E; Belzile, Eric

2016-12-01

In a sample of primary care participants with chronic physical conditions and comorbid depressive symptoms: to describe the cross-sectional and longitudinal associations of activation and self-efficacy with demographic, physical and mental health status, health behaviors, depression self-care, health care utilization, and use of self-care tools; and to examine the effects of a depression self-care coaching intervention on these two outcomes. Design/Study Setting. A secondary analysis of activation and self-efficacy data collected as part of a randomized trial to compare the effects of a telephone-based coached depression self-care intervention with a noncoached intervention. Activation (Patient Activation Measure) was measured at baseline and 6 months. Depression self-care self-efficacy was assessed at baseline, at 3 months, and at 6 months. In multivariable cross-sectional analyses (n = 215), activation and/or self-efficacy were associated with language, birthplace, better physical and mental health, individual exercise, specialist visits, and antidepressant nonuse. In longitudinal analyses (n = 158), an increase in activation was associated with increased medication adherence; an increase in self-efficacy was associated with use of cognitive self-care strategies and increases in social and solitary activities. There were significant improvements from baseline to 6 months in activation and self-efficacy scores both among coached and noncoached groups. The self-care coaching intervention did not affect 6-month activation or self-efficacy but was associated with quicker improvement in self-efficacy. Overall, the results for activation and self-efficacy were similar, although self-efficacy correlated more consistently than activation with depression-specific behaviors and was responsive to a depression self-care coaching intervention. © 2016 Society for Public Health Education.

Physical activity and depression in older adults with and without cognitive impairment.

PubMed

Yuenyongchaiwat, Kornanong; Pongpanit, Khajonsak; Hanmanop, Somrudee

2018-01-01

Low physical activity and depression may be related to cognitive impairment in the elderly. To determine depression and physical activity (PA) among older adults with and without cognitive impairment. 156 older adults, both males and females, aged ≥60 years, were asked to complete the Thai Mini-Mental State Examination (Thai-MMSE), a global cognitive impairment screening tool. Seventy-eight older adults with cognitive impairment and 78 older adults without cognitive impairment were then separately administered two questionnaires (i.e., the Thai Geriatric Depression Scale; TGDS and Global Physical Activity Questionnaire; GPAQ). Logistic regression analysis was used to determine the risk of developing cognitive impairment in the groups of older individuals with and without cognitive impairment. A cross-sectional study of elderly with a mean age of 74.47 ± 8.14 years was conducted. There were significant differences on the depression scale and in PA between older adults with and without cognitive impairment. Further, participants with low PA and high level of depressive symptoms had an increased risk of cognitive impairment (Odds ratio = 4.808 and 3.298, respectively). Significant differences were noted in PA and on depression scales between older adults with and without cognitive impairment. Therefore, increased PA and decreased depressive symptoms (i.e., having psychological support) are suggested to reduce the risks of cognitive impairment in older adults.

Depressive symptoms negate the beneficial effects of physical activity on mortality risk.

PubMed

Lee, Pai-Lin

2013-01-01

The aim of this study is to: (1) compare the association between various levels of physical activity (PA) and mortality; and (2) examine the potential modifying effect of depressive symptoms on the PA-mortality associations. Previous large scale randomized studies rarely assess the association in conjunction with modifying effects of depressive symptoms. In this study, participants consisted of 624 (mean age = 77.35 years) non-institutionalized elderly from the Americans' Changing Lives Longitudinal Study. Depression was measured using the Center for Epidemiological Studies' Depression Scale. Participants in gardening, walking, and sports were first classified into four PA frequency levels, "never," "rarely," "sometimes," and "often." Those who self-reported "often" engaged in activities of gardening and walking and had reduced odds of mortality of 77% and 83%, adjusted odds ratio (ORadj) = .23 and .17, 95% confidence interval (CI) = .09-.59 and.07-.41 when compared to those who reported "never." However, mortality risk was not linked to sports activity. The modifying effects of depressive symptoms on PA (depressive symptoms x PA) were then tested, PA was not associated with increased risk for mortality for gardening (parameter estimates, PE = -.03 +/- .62, p = .958), and for walking (PE = .04 +/- .57, p = .948). Elderly people who engaged in gardening and walking might have protection effects on later risk of mortality. Depressive symptoms showed negative modifying effects that prevent PA predicting later mortality.

Adolescents' social environment and depression: social networks, extracurricular activity, and family relationship influences.

PubMed

Mason, Michael J; Schmidt, Christopher; Abraham, Anisha; Walker, Leslie; Tercyak, Kenneth

2009-12-01

The present study examined components of adolescents' social environment (social network, extracurricular activities, and family relationships) in association with depression. A total of 332 adolescents presenting for a routine medical check-up were self-assessed for social network risk (i.e., smoking habits of best male and female friends), extracurricular activity level (i.e., participation in organized sports teams, clubs, etc.), family relationship quality (i.e., cohesion and conflict), and symptoms of depression (i.e., minimal, mild, moderate/severe). Results of a forward linear regression modeling indicate that social environment components were associated with a significant proportion of the variance in adolescent depression (Adjusted R (2) = .177, p < or = .05). Specifically, adolescent females (beta = .166, p < .01) and those having more smokers in their social network (beta = .107, p < .05) presented with significantly greater depression symptoms. Conversely, adolescents who engaged in more extracurricular activities (beta = -.118, p < .05) and experienced higher quality family relationships (beta = -.368, p < .001) presented with significantly lower depressive symptoms. These findings highlight the important role that the social environment plays in adolescent depression, as well as yields new insights into socially-based intervention targets that may ameliorate adolescent depression. These intervention targets may be gender-specific, include positive social network skills training, increase adolescents' engagement in organized activities, and attend to the quality of their family relationships.

Effect of upper extremity nerve damage on activity participation, pain, depression, and quality of life.

PubMed

Bailey, Ryan; Kaskutas, Vicki; Fox, Ida; Baum, Carolyn M; Mackinnon, Susan E

2009-11-01

To explore the relationship between upper extremity nerve damage and activity participation, pain, depression, and perceived quality of life. A total of 49 patients with upper extremity nerve damage completed standardized measures of activity participation, pain, depression, and quality of life. We analyzed scores for all subjects and for 2 diagnostic groups: patients with compressive neuropathy and patients with nerve injury (laceration, tumor, and brachial plexus injury), and explored predictors of overall quality of life. Participants had given up 21% of their previous daily activities; greater activity loss was reported in patients with nerve injury. Pain was moderate and 39% had signs of clinical depression. Physical and psychological quality of life ratings were below the norms. Activity loss was strongly associated with higher levels of depression and lower physical and psychological quality of life. Higher depression scores correlated strongly with lower overall quality of life. Greater pain correlated moderately with higher depression scores and weakly with quality of life; no statistical relationship was found between pain and physical quality of life. Activity participation and depression predicted 61% of the variance in overall quality of life in patients with nerve damage. The results of this study suggest that hand surgeons and therapists caring for patients with nerve compression and nerve injury should discuss strategies to improve activity participation, and decrease pain and depression, to improve overall effect on quality of life throughout the recovery process. Depression screening and referral when indicated should be included in the overall treatment plan for patients with upper extremity nerve damage. Prognostic IV.

Dispositional Mindfulness and Depressive Symptomatology: Correlations with Limbic and Self-Referential Neural Activity during Rest

PubMed Central

Way, Baldwin M.; Creswell, J. David; Eisenberger, Naomi I.; Lieberman, Matthew D.

2010-01-01

To better understand the relationship between mindfulness and depression, we studied normal young adults (n=27) who completed measures of dispositional mindfulness and depressive symptomatology, which were then correlated with: a) Rest: resting neural activity during passive viewing of a fixation cross, relative to a simple goal-directed task (shape-matching); and b) Reactivity: neural reactivity during viewing of negative emotional faces, relative to the same shape-matching task. Dispositional mindfulness was negatively correlated with resting activity in self-referential processing areas, while depressive symptomatology was positively correlated with resting activity in similar areas. In addition, dispositional mindfulness was negatively correlated with resting activity in the amygdala, bilaterally, while depressive symptomatology was positively correlated with activity in the right amygdala. Similarly, when viewing emotional faces, amygdala reactivity was positively correlated with depressive symptomatology and negatively correlated with dispositional mindfulness, an effect that was largely attributable to differences in resting activity. These findings indicate that mindfulness is associated with intrinsic neural activity and that changes in resting amygdala activity could be a potential mechanism by which mindfulness-based depression treatments elicit therapeutic improvement. PMID:20141298

A study on level of physical activity, depression, anxiety and stress symptoms among adolescents.

PubMed

Tajik, Esra; Abd Latiff, Latiffah; Adznam, Siti N; Awang, Hamidin; Yit Siew, Chin; Abu Bakar, Azrin S

2017-10-01

Inadequate physical activity has adverse health consequences among adolescents. Mental health problem can be developed by lack of physical activity however it is controversial. The current study aimed to examine the association between level of physical activity with depression, anxiety and stress symptoms among adolescents. A representative sample of 1747 adolescents (13-14 years) was randomly selected from 6 schools in a south part of Malaysia. Respondents were asked to fill consent form, and questionnaires including Depression Anxiety and Stress Scale-21 and Physical Activity Questionnaire for Adolescents. Majority of respondents (71.9%) was Malay and more than half of the adolescents had low physical activity. About 40% had depression symptoms, followed by anxiety symptoms (65.9%) and stress symptoms (38.5%). Level of physical activity was significantly associated with gender, anxiety and stress (P<0.001). There were no associations with race, religion and depression symptom. This study provides some evidence among school-going adolescents related to anxiety and stress symptoms and low physical activities. Further studies are needed to show the protection effects of higher physical activity for depression, anxiety and stress symptoms in adolescents.

Reduced striatal activation in females with major depression during the processing of affective stimuli.

PubMed

Connolly, Megan E; Gollan, Jackie K; Cobia, Derin; Wang, Xue

2015-09-01

The extent to which affective reactivity and associated neural underpinnings are altered by depression remains equivocal. This study assessed striatal activation in fifty-one unmedicated female participants meeting DSM-IV criteria for Major Depressive Disorder (MDD) and 61 age-matched healthy females (HC) aged 17-63 years. Participants completed an affective reactivity functional magnetic resonance imaging task. Data were preprocessed using SPM8, and region-of-interest analyses were completed using MarsBaR to extract caudate, putamen, and nucleus accumbens (NAcc) activation. General linear repeated measure ANOVAs were used to assess group differences and correlational analyses were used to measure the association between activation, depression severity, and anhedonia. Main effects of hemisphere, valence, and group status were observed, with MDD participants demonstrating decreased striatal activation compared with HC. Across groups and valence types, the left hemisphere demonstrated greater activation than the right hemisphere in the putamen and nucleus accumbens, whereas the right hemisphere demonstrated greater activation than the left in the caudate. Additionally, unpleasant stimuli elicited greater activation than pleasant and neutral stimuli in the caudate and putamen, and unpleasant stimuli elicited greater activation than neutral stimuli in the NAcc. There were no significant associations between activation, depression severity, and anhedonia. Overall, depression was characterized by reduced affective reactivity in the striatum, regardless of stimuli valence, supporting the emotion context insensitivity model of depression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Decreased activation and subsyndromal manic symptoms predict lower remission rates in bipolar depression.

PubMed

Caldieraro, Marco Antonio; Walsh, Samantha; Deckersbach, Thilo; Bobo, William V; Gao, Keming; Ketter, Terence A; Shelton, Richard C; Reilly-Harrington, Noreen A; Tohen, Mauricio; Calabrese, Joseph R; Thase, Michael E; Kocsis, James H; Sylvia, Louisa G; Nierenberg, Andrew A

2017-11-01

Activation encompasses energy and activity and is a central feature of bipolar disorder. However, the impact of activation on treatment response of bipolar depression requires further exploration. The aims of this study were to assess the association of decreased activation and sustained remission in bipolar depression and test for factors that could affect this association. We assessed participants with Diagnostic and Statistical Manual of Mental Disorders (4th ed) bipolar depression ( n = 303) included in a comparative effectiveness study of lithium- and quetiapine-based treatments (the Bipolar CHOICE study). Activation was evaluated using items from the Bipolar Inventory of Symptoms Scale. The selection of these items was based on a dimension of energy and interest symptoms associated with poorer treatment response in major depression. Decreased activation was associated with lower remission rates in the raw analyses and in a logistic regression model adjusted for baseline severity and subsyndromal manic symptoms (odds ratio = 0.899; p = 0.015). The manic features also predicted lower remission (odds ratio = 0.934; p < 0.001). Remission rates were similar in the two treatment groups. Decreased activation and subsyndromal manic symptoms predict lower remission rates in bipolar depression. Patients with these features may require specific treatment approaches, but new studies are necessary to identify treatments that could improve outcomes in this population.

Active aging is associated with low prevalence of depressive symptoms among Brazilian older adults.

PubMed

Galli, Rosangela; Moriguchi, Emílio Hideyuki; Bruscato, Neide Maria; Horta, Rogerio Lessa; Pattussi, Marcos Pascoal

2016-01-01

Active aging is the process of optimizing opportunities for health, participation and security, aiming to improve quality of life as people age. A series of studies had demonstrated that a lower prevalence of depression is found among more active elderly. To evaluate the association between indicators of active aging and depressive symptoms among the elderly (aged 60 years or more). A population-based cross-sectional study was conducted with 1,006 elderly people (aged 60 years or over) from a small-sized Brazilian municipality. Depressive symptoms were assessed using the Geriatric Depression Scale - 15, with cutoff point ≥ 6 symptoms. Active aging was evaluated using indicators such as: active occupational situation, manual work, reading and physical activities. Data analyses used modified Poisson regression to obtain crude and adjusted prevalence ratios (PR). Most of the elderly people were: white, women and aged between 60 and 74 years. All the indicators of active aging were associated with the outcome. After controlling for socioeconomic, demographic and health variables, elderly people who worked, participated in groups, did manual work and maintained interests such as reading and talking to friends had lower prevalence of depressive symptoms compared to those not doing these activities. Active aging approaches may serve as a valuable mental health promotion strategy aimed at the elderly.

Inhibition of allergen-induced basophil activation by ASM-024, a nicotinic receptor ligand.

PubMed

Watson, Brittany M; Oliveria, John Paul; Nusca, Graeme M; Smith, Steven G; Beaudin, Sue; Dua, Benny; Watson, Rick M; Assayag, Evelynne Israël; Cormier, Yvon F; Sehmi, Roma; Gauvreau, Gail M

2014-01-01

Nicotinic acetylcholine receptors (nAChRs) were identified on eosinophils and shown to regulate inflammatory responses, but nAChR expression on basophils has not been explored yet. We investigated surface receptor expression of nAChR α4, α7 and α1/α3/α5 subunits on basophils. Furthermore, we examined the effects of ASM-024, a synthetic nicotinic ligand, on in vitro anti-IgE and in vivo allergen-induced basophil activation. Basophils were enriched from the peripheral blood of allergic donors and the expression of nAChR subunits and muscarinic receptors was determined. Purified basophils were stimulated with anti-IgE in the presence of ASM-024 with or without muscarinic or nicotinic antagonists for the measurement of CD203c expression and histamine release. The effect of 9 days of treatment with 50 and 200 mg ASM-024 on basophil CD203c expression was examined in the blood of mild allergic asthmatics before and after allergen inhalation challenge. nAChR α4, α7 and α1/α3/α5 receptor subunit expression was detected on basophils. Stimulation of basophils with anti-IgE increased CD203c expression and histamine release, which was inhibited by ASM-024 (10(-5) to 10(-)(3) M, p < 0.05). The effect of ASM-024 was reversed in the presence of muscarinic and nicotinic antagonists. In subjects with mild asthma, ASM-024 inhalation significantly inhibited basophil CD203c expression measured 24 h after allergen challenge (p = 0.03). This study shows that ASM-024 inhibits IgE- and allergen-induced basophil activation through both nicotinic and muscarinic receptors, and suggests that ASM-024 may be an efficacious agent for modulating allergic asthma responses. © 2015 S. Karger AG, Basel.

Chamomile (Matricaria recutita) May Have Antidepressant Activity in Anxious Depressed Humans - An Exploratory Study

PubMed Central

Amsterdam, Jay D.; Shults, Justine; Soeller, Irene; Mao, Jun James; Rockwell, Kenneth; Newberg, Andrew B.

2013-01-01

Objective As part of a randomized, double-blind, placebo-controlled study, we examined the antidepressant action of oral chamomile (Matricaria recutita) extract in subjects with co-morbid anxiety and depression symptoms. We hypothesized that chamomile may demonstrate a clinically meaningful antidepressant activity versus placebo. Methods 57 subjects received either chamomile extract or placebo therapy. Nineteen subjects had anxiety with co-morbid depression, 16 had anxiety with past history of depression, and 22 had anxiety with no current or past depression. Generalized estimating equations analysis was used to identify clinically meaningful changes over time in Hamilton Depression Rating (HAM-D) rating outcome measures among treatment groups. Results We observed a significantly greater reduction in mean total HAM-D scores (p<0.05) and HAM-D core depression item score (p<0.05) for chamomile versus placebo in all subjects, and a non-significant trend for a greater reduction in HAM-D core depression score for chamomile versus placebo in subjects with anxiety with current co-morbid depression (p=0.062). Conclusion Chamomile may have clinically meaningful antidepressant activity that occurs in addition to its previously observed anxiolytic activity. PMID:22894890

Behavioral Activation for Moderately Depressed University Students: Randomized Controlled Trial

ERIC Educational Resources Information Center

Gawrysiak, Michael; Nicholas, Christopher; Hopko, Derek R.

2009-01-01

Although depression is prevalent among university students, limited and dated research has examined the efficacy of behavioral interventions in treating this population (C. Lee, 2005). On the basis of a modified version of the Behavioral Activation Treatment for Depression (BATD; D. R. Hopko & C. W. Lejuez, 2007; C. W. Lejuez, D. R. Hopko, & S. D.…

The chimeric gene CHRFAM7A, a partial duplication of the CHRNA7 gene, is a dominant negative regulator of α7*nAChR function.

PubMed

Araud, Tanguy; Graw, Sharon; Berger, Ralph; Lee, Michael; Neveu, Estele; Bertrand, Daniel; Leonard, Sherry

2011-10-15

The human α7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is a candidate gene for schizophrenia and an important drug target for cognitive deficits in the disorder. Activation of the α7*nAChR, results in opening of the channel and entry of mono- and divalent cations, including Ca(2+), that presynaptically participates to neurotransmitter release and postsynaptically to down-stream changes in gene expression. Schizophrenic patients have low levels of α7*nAChR, as measured by binding of the ligand [(125)I]-α-bungarotoxin (I-BTX). The structure of the gene, CHRNA7, is complex. During evolution, CHRNA7 was partially duplicated as a chimeric gene (CHRFAM7A), which is expressed in the human brain and elsewhere in the body. The association between a 2bp deletion in CHRFAM7A and schizophrenia suggested that this duplicate gene might contribute to cognitive impairment. To examine the putative contribution of CHRFAM7A on receptor function, co-expression of α7 and the duplicate genes was carried out in cell lines and Xenopus oocytes. Expression of the duplicate alone yielded protein expression but no functional receptor and co-expression with α7 caused a significant reduction of the amplitude of the ACh-evoked currents. Reduced current amplitude was not correlated with a reduction of I-BTX binding, suggesting the presence of non-functional (ACh-silent) receptors. This hypothesis is supported by a larger increase of the ACh-evoked current by the allosteric modulator 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl)-urea (PNU-120596) in cells expressing the duplicate than in the control. These results suggest that CHRFAM7A acts as a dominant negative modulator of CHRNA7 function and is critical for receptor regulation in humans. Copyright © 2011 Elsevier Inc. All rights reserved.

The chimeric gene CHRFAM7A, a partial duplication of the CHRNA7 gene, is a dominant negative regulator of α7*nAChR function

PubMed Central

Araud, Tanguy; Graw, Sharon; Berger, Ralph; Lee, Michael; Neveu, Estelle; Bertrand, Daniel; Leonard, Sherry

2011-01-01

The human α7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is a candidate gene for schizophrenia and an important drug target for cognitive deficits in the disorder. Activation of the α7*nAChR, results in opening of the channel and entry of mono- and divalent cations, including Ca++, that presynaptically participates to neurotransmitter release and postsynaptically to down-stream changes in gene expression. Schizophrenic patients have low levels of α7*nAChR, as measured by binding of the ligand [125I]-α-bungarotoxin (I-BTX). The structure of the gene, CHRNA7, is complex. During evolution, CHRNA7 was partially duplicated as a chimeric gene (CHRFAM7A), which is expressed in the human brain and elsewhere in the body. The association between a 2bp deletion in CHRFAM7A and schizophrenia suggested that this duplicate gene might contribute to cognitive impairment. To examine the putative contribution of CHRFAM7A on receptor function, co-expression of α7 and the duplicate genes was carried out in cell lines and Xenopus oocytes. Expression of the duplicate alone yielded protein expression but no functional receptor and co-expression with α7 caused a significant reduction of the amplitude of the ACh-evoked currents. Reduced current amplitude was not correlated with a reduction of I-BTX binding, suggesting the presence of non-functional (ACh-silent) receptors. This hypothesis is supported by a larger increase of the ACh-evoked current by the allosteric modulator 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl)-urea (PNU-120596) in cells expressing the duplicate than in the control. These results suggest that CHRFAM7A acts as a dominant negative modulator of CHRNA7 function and is critical for receptor regulation in humans. PMID:21718690

Reduced vasopressin receptors activation mediates the anti-depressant effects of fluoxetine and venlafaxine in bulbectomy model of depression.

PubMed

Poretti, María Belén; Sawant, Rahul S; Rask-Andersen, Mathias; de Cuneo, Marta Fiol; Schiöth, Helgi B; Perez, Mariela F; Carlini, Valeria Paola

2016-03-01

In response to stress, corticotropin releasing hormone (CRH) and vasopressin (AVP) are released from the hypothalamus, activate their receptors (CRHR1, CRHR2 or AVPr1b), and synergistically act to induce adrenocorticotropic hormone (ACTH) release from the anterior pituitary. Overstimulation of this system has been frequently associated with major depression states. The objective of the study is to assess the role of AVP and CRH receptors in fluoxetine and venlafaxine effects on the expression of depression-related behavior. In an animal model of depression (olfactory bulbectomy in mice, OB), we evaluated the effects of fluoxetine or venlafaxine (both 10 mg/kg/day) chronic administration on depression-related behavior in the tail suspension test. Plasma levels of AVP, CRH, and ACTH were determined as well as participation of their receptors in the expression of depression related-behavior and gene expression of AVP and CRH receptors (AVPr1b, CRHR1, and CRHR2) in the pituitary gland. The expression of depressive-like behavior in OB animals was reversed by treatment with both antidepressants. Surprisingly, OB-saline mice exhibited increased AVP and ACTH plasma levels, with no alterations in CRH levels when compared to sham mice. Chronic fluoxetine or venlafaxine reversed these effects. In addition, a significant increase only in AVPr1b gene expression was found in OB-saline. The antidepressant therapy used seems to be more likely related to a reduced activation of AVP rather than CRH receptors, since a positive correlation between AVP levels and depressive-like behavior was observed in OB animals. Furthermore, a full restoration of depressive behavior was observed in OB-fluoxetine- or venlafaxine-treated mice only when AVP was centrally administered but not CRH.

Dyadic Associations Between Physical Activity and Depressive Symptoms in Older Adults with Musculoskeletal Conditions and Their Spouses

PubMed Central

Monin, Joan K.; Chen, Baibing; Stahl, Sarah T.

2014-01-01

This study examined the association between physical activity of older individuals with musculoskeletal conditions (IMCs) and their spouses’ physical activity, how physical activity related to one’s own and one’s partner’s depressive symptoms, and whether the similarity of partners’ physical activity related to each partner’s depressive symptoms using the actor–partner interdependence model. Seventy-seven dyads completed self-report measures of physical activity, depressive symptoms and potential covariates (socio-demographics, physical health conditions and marital satisfaction; IMCs’ functional impairment and pain; and spouses’ support-related stress). As hypothesized, we found a positive association between the IMC’s and the spouse’s physical activity. Also, spouses had more depressive symptoms when IMCs engaged in less physical activity. However, for both partners, one’s own physical activity was not significantly associated with one’s own depressive symptoms. The spouse’s physical activity was also not significantly associated with the IMC’s depressive symptoms, and the similarity between partners’ physical activity did not significantly relate to either partner’s depressive symptoms. Our findings suggest that interventions that help increase the physical activity of both partners, but particularly IMCs, may benefit spouses’ well-being. PMID:25053173

A cry in the dark: depressed mothers show reduced neural activation to their own infant’s cry

PubMed Central

Ablow, Jennifer C.

2012-01-01

This study investigated depression-related differences in primiparous mothers’ neural response to their own infant’s distress cues. Mothers diagnosed with major depressive disorder (n = 11) and comparison mothers with no diagnosable psychopathology (n = 11) were exposed to their own 18-months-old infant’s cry sound, as well as unfamiliar infant’s cry and control sound, during functional neuroimaging. Depressed mothers’ response to own infant cry greater than other sounds was compared to non-depressed mothers’ response in the whole brain [false discovery rate (FDR) corrected]. A continuous measure of self-reported depressive symptoms (CESD) was also tested as a predictor of maternal response. Non-depressed mothers activated to their own infant’s cry greater than control sound in a distributed network of para/limbic and prefrontal regions, whereas depressed mothers as a group failed to show activation. Non-depressed compared to depressed mothers showed significantly greater striatal (caudate, nucleus accumbens) and medial thalamic activation. Additionally, mothers with lower depressive symptoms activated more strongly in left orbitofrontal, dorsal anterior cingulate and medial superior frontal regions. Non-depressed compared to depressed mothers activated uniquely to own infant greater than other infant cry in occipital fusiform areas. Disturbance of these neural networks involved in emotional response and regulation may help to explain parenting deficits in depressed mothers. PMID:21208990

Analgesic, antibacterial and central nervous system depressant activities of Albizia procera leaves

PubMed Central

Khatoon, Mst. Mahfuza; Khatun, Mst. Hajera; Islam, Md. Ekramul; Parvin, Mst. Shahnaj

2014-01-01

Objective To ascertain analgesic, antibacterial and central nervous system (CNS) depressant activities of ethyl acetate, dichloromethane and carbon tetrachloride fractions of methanol extract of Albizia procera (A. procera) leaves. Methods Leaves extracts of A. procera were tested for analgesic activity by acetic acid induced and formalin test method in mice. The in vitro antibacterial activity was performed by agar well diffusion method. CNS depressant activity was evaluated by hole cross and open field tests. Results All the extracts at 200 mg/kg exhibited significant (P<0.01) analgesic activity in acetic acid induced and formalin tests method in mice. Analgesic activity of the ethyl acetate fraction was almost same like as standard drug indomethacin in acetic acid induced method. The CNS depressant activity of the extracts at 500 mg/kg was comparable to the positive control diazepam as determined by hole cross and open field test method. The extracts exhibited moderate antimicrobial activity against all the tested microorganisms (Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, Esherichia coli, Shigella soneii, Shigella boydii) at concentration of 0.8 mg/disc. The measured diameter of zone of inhibition for the extracts was within the range of 7 to 12 mm which was less than the standard kanamycin (16-24 mm). Conclusions It is concluded that all the extracts possess potential analgesic and CNS depressants activity. This study also showed that different fractions of methanol extract could be potential sources of new antimicrobial agents. PMID:25182551

Analgesic, antibacterial and central nervous system depressant activities of Albizia procera leaves.

PubMed

Khatoon, Mst Mahfuza; Khatun, Mst Hajera; Islam, Md Ekramul; Parvin, Mst Shahnaj

2014-04-01

To ascertain analgesic, antibacterial and central nervous system (CNS) depressant activities of ethyl acetate, dichloromethane and carbon tetrachloride fractions of methanol extract of Albizia procera (A. procera) leaves. Leaves extracts of A. procera were tested for analgesic activity by acetic acid induced and formalin test method in mice. The in vitro antibacterial activity was performed by agar well diffusion method. CNS depressant activity was evaluated by hole cross and open field tests. All the extracts at 200 mg/kg exhibited significant (P<0.01) analgesic activity in acetic acid induced and formalin tests method in mice. Analgesic activity of the ethyl acetate fraction was almost same like as standard drug indomethacin in acetic acid induced method. The CNS depressant activity of the extracts at 500 mg/kg was comparable to the positive control diazepam as determined by hole cross and open field test method. The extracts exhibited moderate antimicrobial activity against all the tested microorganisms (Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, Esherichia coli, Shigella soneii, Shigella boydii) at concentration of 0.8 mg/disc. The measured diameter of zone of inhibition for the extracts was within the range of 7 to 12 mm which was less than the standard kanamycin (16-24 mm). It is concluded that all the extracts possess potential analgesic and CNS depressants activity. This study also showed that different fractions of methanol extract could be potential sources of new antimicrobial agents.

The association between immune activation and manic symptoms in patients with a depressive disorder.

PubMed

Becking, K; Boschloo, L; Vogelzangs, N; Haarman, B C M; Riemersma-van der Lek, R; Penninx, B W J H; Schoevers, R A

2013-10-22

Although recent studies have shown that immunological processes play an important role in the pathophysiology of mood disorders, immune activation may only be present in specific subgroups of patients. Our study aimed to examine whether immune activation was associated with (a) the presence of manic symptoms and (b) the onset of manic symptoms during 2 years of follow-up in depressed patients. Patients with a depressive disorder at baseline (N=957) and healthy controls (N=430) were selected from the Netherlands Study of Depression and Anxiety. Assessments included lifetime manic symptoms at baseline and two-year follow up, as well as C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) at baseline. Within depressed patients, immune activation was not related to the presence or absence of lifetime manic symptoms at baseline. However, CRP levels were strongly elevated in depressed men who developed manic symptoms compared with those who did not develop manic symptoms over 2 years (P<0.001, Cohen's d=0.89). IL-6 and TNF-α were also higher in depressed men with an onset of manic symptoms, but this association was not significant. However, we found that the onset of manic symptoms was particularly high in men with multiple elevated levels of inflammatory markers. Depressed men who developed manic symptoms during follow-up had increased immunological activity (especially CRP) compared with depressed men who did not develop manic symptoms. Further research should explore whether a treatment approach focusing on inflammatory processes may be more effective in this specific subgroup of depressed patients.

Depression and anxious apprehension distinguish frontocingulate cortical activity during top-down attentional control.

PubMed

Silton, Rebecca Levin; Heller, Wendy; Engels, Anna S; Towers, David N; Spielberg, Jeffrey M; Edgar, J Christopher; Sass, Sarah M; Stewart, Jennifer L; Sutton, Bradley P; Banich, Marie T; Miller, Gregory A

2011-05-01

A network consisting of left dorsolateral prefrontal cortex (LDLPFC) and dorsal anterior cingulate cortex (dACC) has been implicated in top-down attentional control. Few studies have systematically investigated how this network is altered in psychopathology, despite evidence that depression and anxiety are associated with attentional control impairments. Functional MRI and dense-array event-related brain potential (ERP) data were collected in separate sessions from 100 participants during a color-word Stroop task. Functional MRI results guided ERP source modeling to characterize the time course of activity in LDLPFC (300-440 ms) and dACC (520-680 ms). At low levels of depression, LDLPFC activity was indirectly related to Stroop interference and only via dACC activity. In contrast, at high levels of depression, dACC did not play an intervening role, and increased LDLPFC activity was directly related to decreased Stroop interference. Specific to high levels of anxious apprehension, higher dACC activity was related to more Stroop interference. Results indicate that depression and anxious apprehension modulate temporally and functionally distinct aspects of the frontocingulate network involved in top-down attention control.

Neighborhood Social Cohesion and Depressive Symptoms Among Latinos: Does Use of Community Resources for Physical Activity Matter?

PubMed

Perez, Lilian G; Arredondo, Elva M; McKenzie, Thomas L; Holguin, Margarita; Elder, John P; Ayala, Guadalupe X

2015-10-01

Greater neighborhood social cohesion is linked to fewer depressive symptoms and greater physical activity, but the role of physical activity on the relationship between neighborhood social cohesion and depression is poorly understood. The purpose of the study was to examine the effects of physical activity on the association between neighborhood social cohesion and depressive symptoms. Multivariate logistic regression tested the moderation of self-reported leisure-time moderate-to-vigorous physical activity (LTMVPA) and active use of parks or recreational facilities on the association between neighborhood social cohesion and depressive symptoms among 295 randomly selected Latino adults who completed a face-to-face interview. After adjusting for age, gender, and income, neighborhood social cohesion and depressive symptoms were inversely related (OR = 0.8; 95% CI: 0.5-1.2). Active use of parks or recreational facilities moderated the association between neighborhood social cohesion and depressive symptoms but meeting the recommendations for LTMVPA did not. Latinos who reported active use of parks or recreational facilities and higher levels of neighborhood social cohesion had fewer depressive symptoms than peers who did not use these spaces. Future studies are needed to test strategies for promoting active use of parks or recreational facilities to address depression in Latinos.

Neighborhood social cohesion and depressive symptoms among Latinos: Does use of community resources for physical activity matter?

PubMed Central

Perez, Lilian G.; Arredondo, Elva M.; McKenzie, Thomas L.; Holguin, Margarita; Elder, John P.; Ayala, Guadalupe X.

2017-01-01

Background Greater neighborhood social cohesion is linked to fewer depressive symptoms and greater physical activity, but the role of physical activity on the relationship between neighborhood social cohesion and depression is poorly understood. The purpose of the study was to examine the effects of physical activity on the association between neighborhood social cohesion and depressive symptoms. Methods Multivariate logistic regression tested the moderation of self-reported leisure time moderate-to vigorous-physical activity (LTMVPA) and active use of parks or recreational facilities on the association between neighborhood social cohesion and depressive symptoms among 295 randomly selected Latino adults who completed a face-to-face interview. Results After adjusting for age, gender, and income, neighborhood social cohesion and depressive symptoms were inversely related (OR=0.8; 95% CI: 0.5–1.2). Active use of parks or recreational facilities moderated the association between neighborhood social cohesion and depressive symptoms but meeting the recommendations for LTMVPA did not. Latinos who reported active use of parks or recreational facilities and higher levels of neighborhood social cohesion had fewer depressive symptoms than peers who did not use these spaces. Conclusions Future studies are needed to test strategies for promoting active use of parks or recreational facilities to address depression in Latinos. PMID:25599244

Integration of the brief behavioral activation treatment for depression (BATD) into a college orientation program: depression and alcohol outcomes.

PubMed

Reynolds, Elizabeth K; Macpherson, Laura; Tull, Matthew T; Baruch, David E; Lejuez, C W

2011-10-01

College freshmen face a variety of academic and social challenges as they adjust to college life that can place them at risk for a number of negative outcomes, including depression and alcohol-related problems. Orientation classes that focus on teaching incoming students how to better cope with college-oriented stress may provide an opportunity to prevent the development of these adjustment problems. This article outlines a program based on behavioral activation that can be integrated into college orientation programs to provide a more comprehensive orientation experience. Data are presented from an initial pilot study in which 71 first-semester freshman at the University of Maryland participated in a 15-week, 2 hr per week orientation class (n = 37 in the behavioral activation-enhanced orientation classes and n = 34 in the control orientation as usual classes). Students' depression and alcohol use were evaluated at the beginning, middle, and end of the course. Results indicated a Time × Group interaction such that problem drinking (but not consumption) was significantly reduced across assessments in the behavioral activation classes and largely unchanged in the standard classes. No difference was observed in depression scores; however, fairly low depression scores across the 3 time points may have limited the opportunity to observe any meaningful impact of the orientation classes on depression. The authors conclude with a discussion of the implications of their findings for preventing adjustment problems among incoming college students and future directions.

Effect of novel negative allosteric modulators of neuronal nicotinic receptors on cells expressing native and recombinant nicotinic receptors: implications for drug discovery.

PubMed

González-Cestari, Tatiana F; Henderson, Brandon J; Pavlovicz, Ryan E; McKay, Susan B; El-Hajj, Raed A; Pulipaka, Aravinda B; Orac, Crina M; Reed, Damon D; Boyd, R Thomas; Zhu, Michael X; Li, Chenglong; Bergmeier, Stephen C; McKay, Dennis B

2009-02-01

Allosteric modulation of nAChRs is considered to be one of the most promising approaches for drug design targeting nicotinic acetylcholine receptors (nAChRs). We have reported previously on the pharmacological activity of several compounds that seem to act noncompetitively to inhibit the activation of alpha3beta4(*) nAChRs. In this study, the effects of 51 structurally similar molecules on native and recombinant alpha3beta4 nAChRs are characterized. These 51 molecules inhibited adrenal neurosecretion activated via stimulation of native alpha3beta4(*) nAChR, with IC(50) values ranging from 0.4 to 13.0 microM. Using cells expressing recombinant alpha3beta4 nAChRs, these molecules inhibited calcium accumulation (a more direct assay to establish nAChR activity), with IC(50) values ranging from 0.7 to 38.2 microM. Radiolabeled nAChR binding studies to orthosteric sites showed no inhibitory activity on either native or recombinant nAChRs. Correlation analyses of the data from both functional assays suggested additional, non-nAChR activity of the molecules. To test this hypothesis, the effects of the drugs on neurosecretion stimulated through non-nAChR mechanisms were investigated; inhibitory effects ranged from no inhibition to 95% inhibition at concentrations of 10 microM. Correlation analyses of the functional data confirmed this hypothesis. Several of the molecules (24/51) increased agonist binding to native nAChRs, supporting allosteric interactions with nAChRs. Computational modeling and blind docking identified a binding site for our negative allosteric modulators near the orthosteric binding site of the receptor. In summary, this study identified several molecules for potential development as negative allosteric modulators and documented the importance of multiple screening assays for nAChR drug discovery.

Effect of Novel Negative Allosteric Modulators of Neuronal Nicotinic Receptors on Cells Expressing Native and Recombinant Nicotinic Receptors: Implications for Drug Discovery

PubMed Central

González-Cestari, Tatiana F.; Henderson, Brandon J.; Pavlovicz, Ryan E.; McKay, Susan B.; El-Hajj, Raed A.; Pulipaka, Aravinda B.; Orac, Crina M.; Reed, Damon D.; Boyd, R. Thomas; Zhu, Michael X.; Li, Chenglong; Bergmeier, Stephen C.; McKay, Dennis B.

2009-01-01

Allosteric modulation of nAChRs is considered to be one of the most promising approaches for drug design targeting nicotinic acetylcholine receptors (nAChRs). We have reported previously on the pharmacological activity of several compounds that seem to act noncompetitively to inhibit the activation of α3β4* nAChRs. In this study, the effects of 51 structurally similar molecules on native and recombinant α3β4 nAChRs are characterized. These 51 molecules inhibited adrenal neurosecretion activated via stimulation of native α3β4* nAChR, with IC50 values ranging from 0.4 to 13.0 μM. Using cells expressing recombinant α3β4 nAChRs, these molecules inhibited calcium accumulation (a more direct assay to establish nAChR activity), with IC50 values ranging from 0.7 to 38.2 μM. Radiolabeled nAChR binding studies to orthosteric sites showed no inhibitory activity on either native or recombinant nAChRs. Correlation analyses of the data from both functional assays suggested additional, non-nAChR activity of the molecules. To test this hypothesis, the effects of the drugs on neurosecretion stimulated through non-nAChR mechanisms were investigated; inhibitory effects ranged from no inhibition to 95% inhibition at concentrations of 10 μM. Correlation analyses of the functional data confirmed this hypothesis. Several of the molecules (24/51) increased agonist binding to native nAChRs, supporting allosteric interactions with nAChRs. Computational modeling and blind docking identified a binding site for our negative allosteric modulators near the orthosteric binding site of the receptor. In summary, this study identified several molecules for potential development as negative allosteric modulators and documented the importance of multiple screening assays for nAChR drug discovery. PMID:18984653

Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia.

PubMed

Segarra, Nuria; Metastasio, Antonio; Ziauddeen, Hisham; Spencer, Jennifer; Reinders, Niels R; Dudas, Robert B; Arrondo, Gonzalo; Robbins, Trevor W; Clark, Luke; Fletcher, Paul C; Murray, Graham K

2016-07-01

Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states.

Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia

PubMed Central

Segarra, Nuria; Metastasio, Antonio; Ziauddeen, Hisham; Spencer, Jennifer; Reinders, Niels R; Dudas, Robert B; Arrondo, Gonzalo; Robbins, Trevor W; Clark, Luke; Fletcher, Paul C; Murray, Graham K

2016-01-01

Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states. PMID:26708106

Active versus receptive group music therapy for major depressive disorder-A pilot study.

PubMed

Atiwannapat, Penchaya; Thaipisuttikul, Papan; Poopityastaporn, Patchawan; Katekaew, Wanwisa

2016-06-01

To compare the effects of 1) active group music therapy and 2) receptive group music therapy to group counseling in treatment of major depressive disorder (MDD). On top of standard care, 14 MDD outpatients were randomly assigned to receive 1) active group music therapy (n=5), 2) receptive group music therapy (n=5), or 3) group counseling (n=4). There were 12 one-hour weekly group sessions in each arm. Participants were assessed at baseline, 1 month (after 4 sessions), 3 months (end of interventions), and 6 months. Primary outcomes were depressive scores measured by Montgomery-Åsberg Depression Rating Scale (MADRS) Thai version. Secondary outcomes were self-rated depression score and quality of life. At 1 month, 3 months, and 6 months, both therapy groups showed statistically non-significant reduction in MADRS Thai scores when compared with the control group (group counseling). The reduction was slightly greater in the active group than the receptive group. Although there were trend toward better outcomes on self-report depression and quality of life, the differences were not statistically significant. Group music therapy, either active or receptive, is an interesting adjunctive treatment option for outpatients with MDD. The receptive group may reach peak therapeutic effect faster, but the active group may have higher peak effect. Group music therapy deserves further comprehensive studies. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Association between leisure time physical activity and depressive symptoms in men.

PubMed

Sieverdes, John C; Ray, Billy M; Sui, Xuemei; Lee, Duck-Chul; Hand, Gregory A; Baruth, Meghan; Blair, Steven N

2012-02-01

We examined the association between depressive symptoms and physical activity (PA) in a sample of men from the Aerobics Center Longitudinal Study. Secondary analysis included stratification by age and body mass index (BMI). Our cross-sectional analysis included 9580 men, age 20-87 yr, who completed the 10-item Center for Epidemiological Studies Depression Scale during 1996-2006. A score of 10 or higher defined depressive symptoms. Four PA categories based on the 2008 PA guidelines were created from a self-report leisure time PA questionnaire: inactive (0 MET·min·wk(-1)), low (1-499 MET·min·wk(-1)), medium (500-999 MET·min·wk(-1)), and high (≥1000 MET·min·wk(-1)). There were 727 men with depressive symptoms. Cross-sectional analyses showed a significant inverse relationship between PA categories and depressive symptoms (P for trend < 0.0001). This reduction in odds was shown across all types of measured leisure time activities (odds ratios = 0.36-0.58). Compared with the inactive group, the light, medium, and high PA categories were 24%, 51%, and 51% less likely to exhibit depressive symptoms, respectively. The inverse relationship was maintained for age and BMI groups except for those 60 yr or older, who exhibited fewer depressive symptoms than other ages. Men with a BMI of 30 kg·m(-2) or higher lowered their odds of depressive symptoms for all PA categories, whereas those with a BMI less than 30 kg·m(-2) needed at least 500 MET·min·wk(-1) to show a similar association. Overall, our analyses found an inverse association between PA and depressive symptoms. Most of this benefit was seen in the medium PA category, which seemed to plateau around 500 MET·min·wk(-1). This indicates that men meeting the 2008 PA Guidelines may not only experience physical health benefits but also reduce the likelihood of depressive symptoms.

Nicotine-induced activation of soluble adenylyl cyclase participates in ion transport regulation in mouse tracheal epithelium.

PubMed

Hollenhorst, Monika I; Lips, Katrin S; Kummer, Wolfgang; Fronius, Martin

2012-11-27

Functional nicotinic acetylcholine receptors (nAChR) have been identified in airway epithelia and their location in the apical and basolateral membrane makes them targets for acetylcholine released from neuronal and non-neuronal sources. One function of nAChR in airway epithelia is their involvement in the regulation of transepithelial ion transport by activation of chloride and potassium channels. However, the mechanisms underlying this nicotine-induced activation of ion transport are not fully elucidated. Thus, the aim of this study was to investigate the involvement of adenylyl cyclases in the nicotine-induced ion current in mouse tracheal epithelium. To evaluate the nicotine-mediated changes of transepithelial ion transport processes electrophysiological Ussing chamber measurements were applied and nicotine-induced ion currents were recorded in the absence and presence of adenylyl cyclase inhibitors. The ion current changes induced by nicotine (100 μM, apical) were not altered in the presence of high doses of atropine (25 μM, apical and basolateral), underlining the involvement of nAChR. Experiments with the transmembrane adenylyl cyclase inhibitor 2'5'-dideoxyadenosine (50 μM, apical and basolateral) and the soluble adenylyl cyclase inhibitor KH7 (10 μM, apical and basolateral) both reduced the nicotine-mediated ion current to a similar extent. Yet, a statistically significant reduction was obtained only in the experiments with KH7. This study indicates that nicotine binding to nAChR in mouse tracheal epithelium activates transepithelial ion transport involving adenylyl cyclase activity. This might be important for novel therapeutic strategies targeting epithelial ion transport mediated by the non-neuronal cholinergic system. Copyright © 2012 Elsevier Inc. All rights reserved.

Amygdala Activity During Autobiographical Memory Recall in Depressed and Vulnerable Individuals: Association With Symptom Severity and Autobiographical Overgenerality.

PubMed

Young, Kymberly D; Siegle, Greg J; Bodurka, Jerzy; Drevets, Wayne C

2016-01-01

In healthy individuals, autobiographical memory recall is biased toward positive and away from negative events, while the opposite is found in depressed individuals. This study examined amygdala activity during autobiographical memory recall as a putative mechanism underlying biased memory recall and depressive symptoms in currently depressed adults and two vulnerable populations: individuals remitted from depression and otherwise healthy individuals at high familial risk of developing depression. Identification of such vulnerability factors could enable interception strategies that prevent depression onset. Sixty healthy control subjects, 45 unmedicated currently depressed individuals, 25 unmedicated remitted depressed individuals, and 30 individuals at high familial risk of developing depression underwent functional MRI while recalling autobiographical memories in response to emotionally valenced cue words. Amygdala reactivity and connectivity with anatomically defined amygdala regions were examined. During positive recall, depressed participants exhibited significantly decreased left amygdala activity and decreased connectivity with regions of the salience network compared with the other groups. During negative recall, control subjects had significantly decreased left amygdala activity compared with the other groups, while depressed participants exhibited increased amygdala connectivity with the salience network. In depressed participants, left amygdala activity during positive recall correlated significantly with depression severity (r values >-0.38) and percent of positive specific memories recalled (r values >0.59). The results suggest that left amygdala hyperactivity during negative autobiographical recall is a trait-like marker of depression, as both vulnerable groups showed activity similar to the depressed group, while amygdala hypoactivity during positive autobiographical recall is a state marker of depression manifesting in active disease. Treatments

[Physical activity among pregnant women in relation to pregnancy-related complaints and symptoms of depression].

PubMed

Nordhagen, Ingjerd Haarstad; Sundgot-Borgen, Jorunn

2002-02-20

The possible association between physical activity and symptoms of depression during pregnancy and post partum has not been examined in Norway. The objectives of this study were to track levels of physical activity of pregnant women and to examine possible differences in symptoms of depression and prenatal complaints. 203 pregnant women in Oslo aged 18 to 40 completed the depression scale of the Hospital Anxiety and Depression Scale (HADS-D) and a self-developed questionnaire. Their average physical activity was two hours and 36 minutes per week; 70% were active during at least two trimesters. The most popular activities reported were walking, aerobics and swimming. Respondents who had high score on the HADS-D test during pregnancy and/or post partum had significantly more pre-natal complaints than those with a normal score. Pregnant women defined as moderately physically active during the third trimester had significantly lower scores on the HADS-D test six weeks after birth than the not-active. There was also a significant inverse correlation between test score and amount of physical activity. This study indicates that women who are physically active during pregnancy have lower scores on a test measuring depressive symptoms during pregnancy and post partum. However, randomised controlled prospective studies are necessary in order to confirm the possible association.

Physical activity patterns and risk of depression in young adulthood: a 20-year cohort study since childhood.

PubMed

McKercher, Charlotte; Sanderson, Kristy; Schmidt, Michael D; Otahal, Petr; Patton, George C; Dwyer, Terence; Venn, Alison J

2014-11-01

Little is known about how physical activity patterns during childhood and adolescence are associated with risk of subsequent depression. We examined prospective and retrospective associations between leisure physical activity patterns from childhood to adulthood and risk of clinical depression in young adulthood. Participants (759 males, 871 females) in a national survey, aged 9-15 years, were re-interviewed approximately 20 years later. Leisure physical activity was self-reported at baseline (1985) and follow-up (2004-2006). To bridge the interval between the two time-points, historical leisure activity from age 15 years to adulthood was self-reported retrospectively at follow-up. Physical activity was categorized into groups that, from a public health perspective, compared patterns that were least beneficial (persistently inactive) with those increasingly beneficial (decreasing, increasing and persistently active). Depression (major depressive or dysthymic disorder) was assessed using the Composite International Diagnostic Interview. Compared with those persistently inactive, males who were increasingly and persistently active had a 69 and 65 % reduced risk of depression in adulthood, respectively (all p < 0.05). In retrospective analyses, females who were persistently active had a 51 % reduced risk of depression in adulthood (p = 0.01). Similar but non-significant trends were observed for leisure physical activity in females and historical leisure activity in males. Results excluded those with childhood onset of depression and were adjusted for various sociodemographic and health covariates. Findings from both prospective and retrospective analyses indicate a beneficial effect of habitual discretionary physical activity since childhood on risk of depression in young adulthood.

Depressed mood, usual activity level, and continued employment after starting dialysis.

PubMed

Kutner, Nancy G; Zhang, Rebecca; Huang, Yijian; Johansen, Kirsten L

2010-11-01

When patients start dialysis, their employment rate declines and disability benefits are an option. With patient sociodemographic and clinical characteristics including disability income status controlled, we investigated the significance of depressed mood and usual activity level as predictors of patients' continued employment after dialysis start. Incident patients from 296 randomly selected dialysis clinics were surveyed in the Comprehensive Dialysis Study (CDS). Participants provided information about employment status, disability income status, education, depressive symptoms measured by the Patient Health Questionnaire-2 (PHQ-2), and usual activity level/energy expenditure measured by the Human Activity Profile. Age, gender, race, insurance, diabetes, inability to ambulate or transfer, chronic obstructive pulmonary disease, cardiovascular conditions, and hemoglobin and serum albumin values at treatment start were obtained from US Renal Data System files. Dialysis modality was defined at time of interview. Among 585 CDS participants who worked in the previous year, 191 (32.6%) continued working after dialysis start. On the basis of the PHQ-2 cutoff score ≥3, 12.1% of patients who remained employed had possible or probable depression, compared with 32.8% of patients who were no longer employed. In adjusted analyses, higher Human Activity Profile scores were associated with increased likelihood of continued employment, and there was a borderline association between lower PHQ-2 scores and continued employment. Screening and management of depressive symptoms and support for increased activity level may facilitate patients' opportunity for continued employment after dialysis start, along with generally improving their overall quality of life.

Physical activity, social support, and depression: possible independent and indirect associations in persons with multiple sclerosis.

PubMed

Suh, Yoojin; Weikert, Madeline; Dlugonski, Deirdre; Sandroff, Brian; Motl, Robert W

2012-01-01

The present study examined the pattern of associations among physical activity, social support, mobility disability, perceived stress, and depressive symptoms in relapsing-remitting MS (RRMS). Persons (N = 218) with RRMS completed a battery of questionnaires that was sent and returned through the United States Postal Service (USPS). Bivariate correlation analysis indicated that physical activity and social support were both inversely associated with depressive symptoms (r's = -0.288 and -0.386, p ≤ 0.05, respectively). Multiple linear regression analysis indicated that physical activity (β = -0.21, p = 0.002) and social support (β = -0.37, p = 0.0001) were independently associated with depressive symptoms. Path analysis confirmed that the associations between physical activity and social support with depressive symptoms were indirect via mobility disability and perceived stress. Collectively, the evidence indicates that physical activity and social support are independently and indirectly associated with depression via mobility disability and perceived stress in relapsing-remitting MS. This supports the design of interventions and programs that target physical activity and social support for reducing depressive symptoms among persons with MS.

Anxiolytic- and Antidepressant-like Effects of the Methadone Metabolite 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP)

PubMed Central

Lee, Bridgin G.; Olson, Thao T.; Xie, Teresa; Xiao, Yingxian; Blendy, Julie A.; Kellar, Kenneth J.

2015-01-01

The enhancement of GABAergic and monoaminergic neurotransmission has been the mainstay of pharmacotherapy and the focus of drug-discovery for anxiety and depressive disorders for several decades. However, the significant limitations of drugs used for these disorders underscores the need for novel therapeutic targets. Neuronal nicotinic acetylcholine receptors (nAChRs) may represent one such target. For example, mecamylamine, a non-competitive antagonist of nAChRs, displays positive effects in preclinical tests for anxiolytic and antidepressant activity in rodents. In addition, nicotine elicits similar effects in rodent models, possibly by receptor desensitization. Previous studies (Xiao et al., 2001) have identified two metabolites of methadone, EMDP (2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline) and EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine), which are considered to be inactive at opiate receptors, as relatively potent noncompetitive channel blockers of rat α3β4 nAChRs. Here, we show that these compounds are likewise highly effective blockers of human α3β4 and α4β2 nAChRs. Moreover, we show that they display relatively low affinity for opiate binding sites labeled by [3H]-naloxone. We then evaluated these compounds in rats and mice in preclinical behavioral models predictive of potential anxiolytic and antidepressant efficacy. We found that EMDP, but not EDDP, displayed robust effects predictive of anxiolytic and antidepressant efficacy without significant effects on locomotor activity. Moreover, EMDP at behaviorally active doses, unlike mecamylamine, did not produce eyelid ptosis, suggesting it may produce fewer autonomic side effects than mecamylamine. Thus, the methadone metabolite EMDP may represent a novel therapeutic avenue for the treatment of some affective disorders. PMID:26365569

Social cognitive correlates of physical activity among persons with multiple sclerosis: Influence of depressive symptoms.

PubMed

Ensari, Ipek; Kinnett-Hopkins, Dominique; Motl, Robert W

2017-10-01

Physical inactivity and elevated depressive symptoms are both highly prevalent and correlated among persons with multiple sclerosis (MS). Variables from Social Cognitive Theory (SCT) might be differentially correlated with physical activity in persons with MS who have elevated depressive symptoms. This study investigated the influence of elevated depressive symptoms on correlates of physical activity based on SCT in persons with MS. Participants (mean age = 50.3 years, 87% female, 69% Caucasian) completed questionnaires on physical activity, depressive symptoms, self-efficacy, social support, outcome expectations, functional limitations, and goal setting. The questionnaires were delivered and returned through the U.S. Postal Service. The sample (N = 551) was divided into 2 subgroups (i.e., elevated vs non-elevated levels of depressive symptoms) for statistical analyses. Bivariate correlations and stepwise multiple regressions were conducted using SPSS. Self-efficacy (r = 0.16), functional limitations (r = 0.22) and goal-setting (r = 0.42) were significantly (p < 0.05) associated with physical activity among the elevated depressive sample. The regression analysis indicated that self-efficacy predicted physical activity in Step 1 (β = 0.16, p < 0.05), but was no longer significant when goal-setting (β = 0.06, p > 0.05) entered the model. All social cognitive variables were significantly associated with physical activity levels (r = 0.16-0.40, p < 0.001) among the non-elevated depressive sample. Self-efficacy predicted physical activity in Step 1 (β = 0.24, p < 0.001), but it was no longer significant once goal-setting, functional limitations, and self-evaluative outcome expectations entered the model. Based on SCT, self-efficacy and goal-setting represent possible targets of behavior interventions for increasing physical activity among persons with MS who have elevated depressive symptoms. There is a larger set of targets among those

Fetal muscle-type nicotinic acetylcholine receptor activation in TE-671 cells and inhibition of fetal movement in a day 40 pregnant goat model by optical isomers of the piperidine alkaloid coniine.

PubMed

Green, Benedict T; Lee, Stephen T; Welch, Kevin D; Pfister, James A; Panter, Kip E

2013-01-01

Coniine is an optically active toxic piperidine alkaloid and nicotinic acetylcholine receptor (nAChR) agonist found in poison hemlock (Conium maculatum L.). Coniine teratogenicity is hypothesized to be attributable to the binding, activation, and prolonged desensitization of fetal muscle-type nAChR, which results in the complete inhibition of fetal movement. However, pharmacological evidence of coniine actions at fetal muscle-type nAChR is lacking. The present study compared (-)-coniine, (+)-coniine, and nicotine for the ability to inhibit fetal movement in a day 40 pregnant goat model and in TE-671 cells that express fetal muscle-type nAChR. Furthermore, α-conotoxins (CTx) EI and GI were used to antagonize the actions of (+)- and (-)-coniine in TE-671 cells. (-)-Coniine was more effective at eliciting electrical changes in TE-671 cells and inhibiting fetal movement than was (+)-coniine, suggesting stereoselectivity by the receptor. The pyridine alkaloid nicotine did not inhibit fetal movement in a day 40 pregnant goat model, suggesting agonist specificity for the inhibition of fetal movement. Low concentrations of both CTxs potentiated the TE-671 cell response and higher concentrations of CTx EI, and GI antagonized the actions of both coniine enantiomers demonstrating concentration-dependent coagonism and selective antagonism. These results provide pharmacological evidence that the piperidine alkaloid coniine is acting at fetal muscle-type nAChR in a concentration-dependent manner.

Outdoor activities and depressive symptoms in displaced older adults following natural disaster: community cohesion as mediator and moderator.

PubMed

Chao, Shiau-Fang

2016-09-01

This investigation examined whether community cohesion mediates or moderates the relationship between outdoor activities and depressive symptoms in older adults displaced by Typhoon Morakot in Taiwan. This cross-sectional study included 292 adults aged 65 years or older who were relocated to permanent houses after Typhoon Morakot damaged their homes on 8th August 2009. Multiple regression analysis was applied to test the role of community cohesion on the association between outdoor activities and depressive symptoms. The sample of displaced older adults displayed higher prevalence of depressive symptoms than the average for community dwelling older people in Taiwan. Community cohesion fully mediated the relationship between outdoor activities and depressive symptoms. Community cohesion also moderated the relationship between outdoor activities and depressive symptoms. Community cohesion occupies a key role on the link between outdoor activities and depressive symptoms. Participation in outdoor activities was associated positively with community cohesion, while high community cohesion was related negatively to depressive symptoms. Additionally, the benefit of outdoor activities to fewer depressive symptoms only manifested in older adults with high community cohesion. Programs and services should be designed to enhance community cohesion in order to maximize the benefit of outdoor activities to the mental health of displaced older adults after natural disasters.

The Relationship Between Reminiscence Functions, Optimism, Depressive Symptoms, Physical Activity, and Pain in Older Adults.

PubMed

McDonald, Deborah Dillon; Shellman, Juliette M; Graham, Lindsey; Harrison, Lisa

2016-09-01

The study purpose was to examine the association between reminiscence functions, optimism, depressive symptoms, physical activity, and pain in older adults with chronic lower extremity osteoarthritis pain. One hundred ninety-five community-dwelling adults were interviewed using the Modified Reminiscence Functions Scale, Brief Pain Inventory, Life Orientation Test-Revised, Center for Epidemiologic Studies Short Depression Scale, and Physical Activity Scale for the Elderly in random counterbalanced order. Structural equation modeling supported chronic pain as positively associated with depressive symptoms and comorbidities and unrelated to physical activity. Depressive symptoms were positively associated with self-negative reminiscence and negatively associated with optimism. Spontaneous reminiscence was not associated with increased physical activity or reduced pain. Individuals may require facilitated integrative reminiscence to assist them in reinterpreting negative memories in a more positive way. Facilitated integrative reminiscence about enjoyed past physical activity is a potential way to increase physical activity, but must be tested in future research. [Res Gerontol Nurs. 2016; 9(5):223-231.]. Copyright 2016, SLACK Incorporated.

Frequency of leisure activities and depressive symptomatology in elderly people: the moderating role of rumination.

PubMed

Fernández-Fernández, Virginia; Márquez-González, María; Losada-Baltar, Andrés; Romero-Moreno, Rosa

2014-02-01

The positive effects of leisure activities on depressive symptomatology are well known. However, the extent to which emotional regulation variables moderate that relationship has scarcely been studied, especially in older people. The aim of this study is to analyze the moderating role of rumination in the relation between leisure activities and depressive symptoms. Participants in this study were 311 people, aged 60 to 90 years (mean age: 71.27 years; SD: 6.99; 71.7% women). We evaluated depressive symptomatology, frequency of leisure activities, and rumination. We carried out a hierarchical regression analysis to confirm the moderating role of rumination. We obtained a model that explains 39.4% of the variance of depressive symptomatology. Main effects were found for the frequency of leisure activities (β = -0.397; p < 0.01) and for rumination (β = 0.497; p < 0.01). Moreover, we found a significant effect of the interaction between frequency of leisure activities and rumination (β = 0.110; p < 0.05), suggesting that rumination plays a moderating role in the relation between leisure activities and depressive symptomatology. A risk profile of elderly people may consist of those who engage in low levels of leisure activities but also use more frequently the dysfunctional emotional regulation strategy of rumination.

Changes in Leisure Activities and Dimensions of Depressive Symptoms in Later Life: A 12-Year Follow-Up.

PubMed

Chao, Shiau-Fang

2016-06-01

Although leisure activities benefit the mental health of the elderly population, the effect of changes in leisure activities on dimensions of depressive symptoms remains unclear. This investigation examined the influences of changes in intellectual, social, and physical activities between waves on four dimensions of depressive symptoms at follow-up. Random effects modeling was utilized with data from a nationwide longitudinal study conducted in Taiwan. The study data comprised 6,942 observations from 2,660 older adults over a 12-year period. The results suggested that changes in physical activities contributed to depressive symptoms which reflected positive affect in the later wave. Increased social activities between waves predicted higher positive affect and lower interpersonal difficulties scores at follow-up. Increased intellectual activities between waves did not substantially affect any domain of depressive symptoms. In contrast, declines in intellectual activities between waves predicted higher scores in three depressive symptoms domains, including depressed mood, somatic symptoms, and interpersonal difficulties. Engagement in a varied range of activities benefits mental health among elders more than participation in any single type of activity among elders. Reducing physical activities can lower positive affect, while the adverse effect may be balanced by increasing social activities. Also, the impact of decreasing intellectual activities on the interpersonal difficulties domain of depressive symptoms may be offset by increasing social activities. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A feasibility study of behavioural activation for depressive symptoms in adults with intellectual disabilities.

PubMed

Jahoda, A; Melville, C A; Pert, C; Cooper, S-A; Lynn, H; Williams, C; Davidson, C

2015-11-01

Important work has been carried out adapting cognitive behavioural therapy for people with intellectual disabilities. However, there is a lack of alternative psychological therapies available for people with intellectual disabilities and emotional difficulties. Behavioural activation for depression is less reliant on verbal communication and focuses on increasing purposeful activity and reducing avoidance. This feasibility study involved the development and piloting of an adapted manual of behavioural activation for people with intellectual disabilities. The intervention consisted of 10-12 sessions and a key adaptation was that the therapist worked with the clients alongside a significant other in their life, either a paid carer or family member. Baseline, post-intervention (3 months after entering the study) and 6-month quantitative follow-up data were obtained. Primary outcome data were gathered, concerning depressive symptoms, participants' levels of activity and general well-being. Twenty-three adults with intellectual disabilities with symptoms of depression were recruited from specialist health services. In terms of acceptability, the behavioural activation intervention was well received and only two individuals dropped out, with a further two lost to follow-up. The main measures of depression appeared to be sensitive to change. Pre- to post-intervention data showed a significant reduction in self-report of depressive symptoms with a strong effect size (r = 0.78), that was maintained at follow-up (r = 0.86). Positive change was also obtained for informant reports of depressive symptoms from pre- to post-intervention, with a strong effect size (r = 0.7). Once again, this positive change was maintained at follow-up (r = 0.72). The study suggested that behavioural activation may be a feasible and worthwhile approach to tackling depression in people with intellectual disabilities. However, a randomised controlled trial would be required to establish its

Habitual physical activity and the risk for depressive and anxiety disorders among older men and women.

PubMed

Pasco, Julie A; Williams, Lana J; Jacka, Felice N; Henry, Margaret J; Coulson, Carolyn E; Brennan, Sharon L; Leslie, Eva; Nicholson, Geoffrey C; Kotowicz, Mark A; Berk, Michael

2011-03-01

Regular physical activity is generally associated with psychological well-being, although there are relatively few prospective studies in older adults. We investigated habitual physical activity as a risk factor for de novo depressive and anxiety disorders in older men and women from the general population. In this nested case-control study, subjects aged 60 years or more were identified from randomly selected cohorts being followed prospectively in the Geelong Osteoporosis Study. Cases were individuals with incident depressive or anxiety disorders, diagnosed using the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP); controls had no history of these disorders. Habitual physical activity, measured using a validated questionnaire, and other exposures were documented at baseline, approximately four years prior to psychiatric interviews. Those with depressive or anxiety disorders that pre-dated baseline were excluded. Of 547 eligible subjects, 14 developed de novo depressive or anxiety disorders and were classified as cases; 533 controls remained free of disease. Physical activity was protective against the likelihood of depressive and anxiety disorders; OR = 0.55 (95% CI 0.32-0.94), p = 0.03; each standard deviation increase in the transformed physical activity score was associated with an approximate halving in the likelihood of developing depressive or anxiety disorders. Leisure-time physical activity contributed substantially to the overall physical activity score. Age, gender, smoking, alcohol consumption, weight and socioeconomic status did not substantially confound the association. This study provides evidence consistent with the notion that higher levels of habitual physical activity are protective against the subsequent risk of development of de novo depressive and anxiety disorders.

The effects of 3,4-methylenedioxymethamphetamine (MDMA) on nicotinic receptors: Intracellular calcium increase, calpain/caspase 3 activation, and functional upregulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garcia-Rates, Sara; Camarasa, Jordi; Sanchez-Garcia, Ana I.

2010-05-01

Previous work by our group demonstrated that homomeric alpha7 nicotinic acetylcholine receptors (nAChR) play a role in the neurotoxicity induced by 3,4-methylenedioxymethamphetamine (MDMA), as well as the binding affinity of this drug to these receptors. Here we studied the effect of MDMA on the activation of nAChR subtypes, the consequent calcium mobilization, and calpain/caspase 3 activation because prolonged Ca{sup 2+} increase could contribute to cytotoxicity. As techniques, we used fluorimetry in Fluo-4-loaded PC12 cells and electrophysiology in Xenopus oocytes. MDMA produced a rapid and sustained increase in calcium without reaching the maximum effect induced by ACh. It also concentration-dependently inhibitedmore » the response induced by ACh, nicotine, and the specific alpha7 agonist PNU 282987 with IC{sub 50} values in the low micromolar range. Similarly, MDMA induced inward currents in Xenopus oocytes transfected with human alpha7 but not with alpha4beta2 nAChR and inhibited ACh-induced currents in both receptors in a concentration-dependent manner. The calcium response was inhibited by methyllycaconitine (MLA) and alpha-bungarotoxin but not by dihydro-beta-erythroidine. These results therefore indicate that MDMA acts as a partial agonist on alpha7 nAChRs and as an antagonist on the heteromeric subtypes. Subsequently, calcium-induced Ca{sup 2+} release from the endoplasmic reticulum and entry through voltage-operated calcium channels are also implicated as proved using specific antagonists. In addition, treatment with MDMA for 24 h significantly increased basal Ca{sup 2+} levels and induced an increase in alpha-spectrin breakdown products, which indicates that calpain and caspase 3 were activated. These effects were inhibited by pretreatment with MLA. Moreover, pretreatment with MDMA induced functional upregulation of calcium responses to specific agonists of both heteromeric and alpha7 nAChR. Sustained calcium entry and calpain activation could favor

Fatigue, depression, sleep, and activity during chemotherapy: daily and intraday variation and relationships among symptom changes.

PubMed

Jim, Heather S L; Small, Brent; Faul, Leigh Anne; Franzen, Jamie; Apte, Sachin; Jacobsen, Paul B

2011-12-01

Previous research suggests that cancer patients frequently experience multiple symptoms during chemotherapy; however, relationships among symptom changes are largely unknown. The aim of the current study was to examine daily and intraday changes and interrelationships among fatigue, depression, and objectively measured disruptions in sleep and activity during chemotherapy. Participants were 78 women with gynecologic cancer. Fatigue, depression, sleep, and activity were assessed the week before and the week after the participants' first three infusions. Significant changes in fatigue, depression, sleep, and activity were observed over time. Before infusions, increases in fatigue were associated with increases in depression. After infusions, increases in fatigue were associated with increases in depression and minutes awake at night, as well as decreases in daytime activity and regularity of sleep/activity patterns (ps < .05). This study is among the first to track daily and intraday changes in symptoms and interrelationships during chemotherapy. Results indicate that symptoms are interrelated and return to baseline levels after infusions.

[Morita Therapy to Treat Depression: When and How to Encourage Patients to Join Activities].

PubMed

Nakamura, Kei

2015-01-01

The author discusses how Morita therapy is used to treat depression, illustrated with a clinical case, and makes comparisons between Morita therapy and behavioral activation (BA). The author further examines the issue of when and how to encourage patients to join activities in clinical practice in Japan. Both Morita therapy and BA share at least a common view that it is effective to activate patients' constructive behavior at a certain point in depression treatment. However, BA therapists, compared to Morita therapists, seem to pay less attention to the necessity of resting and the appropriate timing for introducing behavioral activation. There may be some contextual differences between depressive patients in Japan and those in North America. In the case of Japanese patients, exhaustion from overwork is often considered a factor triggering the development of depression. At the same time, the Morita-based pathogenic model of depression seems different from BA's model of the same disorder. BA's approach to understanding depression may be considered a psychological (behavioristic) model. In this model, the cause of depression lies in: (a) a lack of positive reinforcement, and (b) negative reinforcement resulting from avoidance of the experience of discomfort. Therefore, the basic strategy of BA is to release depressive patients from an avoidant lifestyle, which serves as a basis for negative reinforcement, and to redirect the patients toward activities which offer the experience of positive reinforcement BA is primarily practiced by clinical psychologists in the U. S. while psychiatrists prescribe medication as a medical service. On the other hand, the clinical practice of treating depression in Japan is based primarily on medical models of depression. This is also true of Morita therapy, but in a broad sense. While those who follow medical models in a narrow sense try to identify the cause of illness and then remove it, Morita therapists pay more attention to the

α6β2 nicotinic acetylcholine receptors influence locomotor activity and ethanol consumption.

PubMed

Kamens, Helen M; Peck, Colette; Garrity, Caitlin; Gechlik, Alex; Jenkins, Brenita C; Rajan, Akshat

2017-06-01

Nicotinic acetylcholine receptors (nAChRs) in the mesolimbic dopamine system have been implicated in ethanol behaviors. In particular, work in genetically engineered mice has demonstrated that α6-containing nAChRs are involved in ethanol consumption and sedation. A limitation of these studies is that the alteration in the receptor was present throughout development. The recently described α6β2 antagonist, N,N-decane-1,10-diyl-bis-3-picolinium diiodide (bPiDI), now makes it possible to test for the involvement of these receptors using a pharmacological approach. The aim of this study was to examine the role of α6β2 nAChRs in ethanol behaviors using a pharmacological approach. Adolescent C57BL/6J mice were treated with bPiDI 30 min prior to testing the mice for binge-like ethanol consumption in the drinking-in-the-dark (DID) test, ethanol-induced motor incoordination using the balance beam, and ethanol-induced sedation using the Loss of Righting Reflex (LORR) paradigm. Adolescent animals were chosen because they express a high amount of α6 mRNA relative to adult animals. Control studies were also performed to determine the effect of bPiDI on locomotor activity and ethanol metabolism. Female mice treated with 20 mg/kg bPiDI had reduced locomotor activity compared to saline-treated animals during the first 30 min following an acute injection. Pretreatment with the α6β2 antagonist reduced adolescent ethanol consumption but also reduced saccharin consumption. No significant effects were observed on ethanol-induced ataxia, sedation, or metabolism. This study provides evidence that α6β2 nAChRs are involved in locomotor activity as well as ethanol and saccharin consumption in adolescent animals. Copyright © 2017 Elsevier Inc. All rights reserved.

Does trans‐spinal and local DC polarization affect presynaptic inhibition and post‐activation depression?

PubMed Central

Kaczmarek, D.; Ristikankare, J.

2017-01-01

Key points Trans‐spinal polarization was recently introduced as a means to improve deficient spinal functions. However, only a few attempts have been made to examine the mechanisms underlying DC actions. We have now examined the effects of DC on two spinal modulatory systems, presynaptic inhibition and post‐activation depression, considering whether they might weaken exaggerated spinal reflexes and enhance excessively weakened ones.Direct current effects were evoked by using local intraspinal DC application (0.3–0.4 μA) in deeply anaesthetized rats and were compared with the effects of trans‐spinal polarization (0.8–1.0 mA).Effects of local intraspinal DC were found to be polarity dependent, as locally applied cathodal polarization enhanced presynaptic inhibition and post‐activation depression, whereas anodal polarization weakened them. In contrast, both cathodal and anodal trans‐spinal polarization facilitated them.The results suggest some common DC‐sensitive mechanisms of presynaptic inhibition and post‐activation depression, because both were facilitated or depressed by DC in parallel. Abstract Direct current (DC) polarization has been demonstrated to alleviate the effects of various deficits in the operation of the central nervous system. However, the effects of trans‐spinal DC stimulation (tsDCS) have been investigated less extensively than the effects of transcranial DC stimulation, and their cellular mechanisms have not been elucidated. The main objectives of this study were, therefore, to extend our previous analysis of DC effects on the excitability of primary afferents and synaptic transmission by examining the effects of DC on two spinal modulatory feedback systems, presynaptic inhibition and post‐activation depression, in an anaesthetized rat preparation. Other objectives were to compare the effects of locally and trans‐spinally applied DC (locDC and tsDCS). Local polarization at the sites of terminal branching of afferent

A Cross-Sectional Study of the Relationship of Physical Activity with Depression and Cognitive Deficit in Older Adults.

PubMed

Paulo T, R S; Tribess, Sheilla; Sasaki, Jeffer Eidi; Meneguci, Joilson; Martins, Cristiane A; Freitas, Ismael F; Romo-Perez, Vicente; Virtuoso, Jair S

2016-04-01

The aim of this study was to examine the association of physical activity with depression and cognition deficit, separately and combined, in Brazilian older adults. We analyzed data from 622 older adults. Physical activity was assessed using the International Physical Activity Questionnaire. Depressive symptoms were assessed using the Geriatric Depression Scale, while cognitive deficit was assessed using the Mini-Mental State Examination. Multinomial logistic regressions were used to assess associations of depression and cognitive deficit with sociodemographic, health, and behavioral variables. Prevalence of physical inactivity (< 150 min of moderate-to-vigorous physical activity/ week), depression, and cognitive deficit were 35.7%, 37.4%, and 16.7%. Physical inactivity was associated with depression (OR: 1.83, 95% CI: 1.14-2.94) and with depression and cognitive deficit combined (OR: 4.23, 95% CI: 2.01-8.91). Physically inactive participants were also more likely to present limitations in orientation and language functions. Physical inactivity was associated with depression and also with depression and cognitive deficit combined in older adults.

Depression, coronary artery disease, and physical activity: how much exercise is enough?

PubMed

Peterson, Janey C; Charlson, Mary E; Wells, Martin T; Altemus, Margaret

2014-11-01

The mechanisms by which depressive symptoms negatively affect clinical outcomes in patients with coronary artery disease (CAD) remain poorly understood. Previous interventions that have attempted to treat depressive symptoms in patients with CAD to improve their clinical outcomes have been disappointing. Our objectives were, among a cohort of CAD patients, to evaluate the impact of depressive symptoms over time, controlling for comorbidity, in determining both successful long-term lifestyle change (ie, increased physical activity), and cardiovascular morbidity and mortality outcomes. In addition, we examined the impact of physical activity changes over time on 2 known mediators of cardiovascular morbidity: parasympathetic tone and inflammation. Clinical data were previously collected (2004-2006) from 242 elective/urgent coronary angioplasty patients who participated in a prospective randomized controlled trial evaluating the efficacy of a behavioral intervention versus an educational control to motivate physical activity over 12 months. Exclusion criteria included: (1) inability to walk; (2) enrollment in other risk-reduction trials; (3) non-English speaking; and (4) lack of cardiologist's permission to increase physical activity. Participants were assessed every 2 months for interval clinical events and physical activity. In addition, biomarkers were collected at baseline and at 12 months in a subset of 54 participants; these biomarkers included low-frequency heart rate variability (lfHRV), high-frequency heart rate variability (hfHRV), serum C-reactive protein, interleukin-6, and salivary cortisol. The mean age of participants was 63 years and 30% were female. Overall, 37% had high depressive symptoms at baseline. Patients with high depressive symptoms who achieved an increase in physical activity of ≥336 kilocalories(kcal)/week by 12 months had significantly lower rates of cardiovascular morbidity/mortality (5.1% vs. 21.3%; odds ratio [OR], 0.20, [95% CI, 0

Physical activity, but not fitness level, is associated with depression in Australian adults.

PubMed

Forsyth, A; Williams, P; Deane, F P

2015-01-01

The objective of this study was to evaluate the fitness and physical activity levels of people referred to a nutrition and physical activity program for the management of mental health in general practice. General practitioners referred 109 patients being treated for depression and/or anxiety to a lifestyle intervention program. All participants completed anthropometric measurements and questionnaires including the Depression, Anxiety and Stress Scale (DASS) and the Active Australia Survey. Aerobic fitness was measured with the YMCA step test and muscular fitness was measured with repeated chair stands and arm curls. Fitness scores were compared to population norms, and physical activity levels were compared to population norms and national recommendations. Eighty percent of participants were overweight or obese. A greater proportion of study participants (51%) than the general Australian population (38%) met the recommended 150 minutes per week spent in moderate physical activity. However, participants demonstrated lower than average levels of fitness and participated in low levels of vigorous physical activity. Levels of physical activity, but not fitness, were inversely correlated with DASS scores. Patients presenting with depression and/or anxiety should be screened for physical activity behaviours and encouraged to meet the National Physical Activity Guidelines.

Relapse Prevention in Major Depressive Disorder: Mindfulness-Based Cognitive Therapy Versus an Active Control Condition

PubMed Central

Shallcross, Amanda J.; Gross, James J.; Visvanathan, Pallavi D.; Kumar, Niketa; Palfrey, Amy; Ford, Brett Q.; Dimidjian, Sona; Shirk, Stephen; Holm-Denoma, Jill; Goode, Kari M.; Cox, Erica; Chaplin, William; Mauss, Iris B.

2015-01-01

Objective We evaluated the comparative effectiveness of Mindfulness-based cognitive therapy (MBCT) versus an active control condition (ACC) for depression relapse prevention, depressive symptom reduction, and improvement in life satisfaction. Method Ninety-two participants in remission from Major Depressive Disorder with residual depressive symptoms were randomized to either an 8-week MBCT or a validated ACC that is structurally equivalent to MBCT and controls for non-specific effects (e.g., interaction with a facilitator, perceived social support, treatment outcome expectations). Both interventions were delivered according to their published manuals. Results Intention-to-treat analyses indicated no differences between MBCT and ACC in depression relapse rates or time to relapse over a 60-week follow-up. Both groups experienced significant and equal reductions in depressive symptoms and improvements in life satisfaction. A significant quadratic interaction (group x time) indicated that the pattern of depressive symptom reduction differed between groups. The ACC experienced immediate symptom reduction post-intervention and then a gradual increase over the 60-week follow-up. The MBCT group experienced a gradual linear symptom reduction. The pattern for life satisfaction was identical but only marginally significant. Conclusions MBCT did not differ from an ACC on rates of depression relapse, symptom reduction, or life satisfaction, suggesting that MBCT is no more effective for preventing depression relapse and reducing depressive symptoms than the active components of the ACC. Differences in trajectory of depressive symptom improvement suggest that the intervention-specific skills acquired may be associated with differential rates of therapeutic benefit. This study demonstrates the importance of comparing psychotherapeutic interventions to active control conditions. PMID:26371618

Rest-activity rhythm and sleep characteristics associated with depression symptom severity in strained dementia caregivers.

PubMed

Smagula, Stephen F; Krafty, Robert T; Taylor, Briana J; Martire, Lynn M; Schulz, Richard; Hall, Martica H

2017-12-01

Depression is associated with disturbances to sleep and the 24-h sleep-wake pattern (known as the rest-activity rhythm: RAR). However, there remains a need to identify the specific sleep/RAR correlates of depression symptom severity in population subgroups, such as strained dementia caregivers, who are at elevated risk for major depressive disorder. We assessed the cross-sectional associations of sleep/RARs with non-sleep depression symptom severity among 57 (mean age: 74 years, standard deviation: 7.4) strained dementia caregivers who were currently without clinical depression. We derived sleep measures from polysomnography and actigraphy, modelled RARs using a sigmoidally transformed cosine curve and measured non-sleep depression symptom severity using the Hamilton Depression Rating Scale (HRDS) with sleep items removed. The following sleep-wake measures were associated with greater depression symptom severity (absolute Spearman's correlations ranged from 0.23 to 0.32): more time awake after sleep onset (WASO), higher RAR middle level (mesor), relatively shorter active periods (alpha), earlier evening settling time (down-mesor) and less steep RARs (beta). In multivariable analysis, high WASO and low RAR beta were associated independently with depression symptom severity. Predicted non-sleep HDRS means (95% confidence intervals) in caregivers with and without these characteristics were: normal WASO/beta = 3.7 (2.3-5.0), high WASO/normal beta = 5.5 (3.5-7.6), normal WASO/low beta = 6.3 (3.6-8.9) and high WASO/low beta = 8.1 (5.3-10.9). Thus, in our sample of strained caregivers, greater sleep fragmentation (WASO) and less sustained/sharply segregated resting and active periods (low RAR beta) correlate uniquely with depression symptom severity. Longitudinal studies are needed to establish whether these independent sleep-wake correlates of depression symptoms explain heightened depression risk in dementia caregivers. © 2017 European Sleep Research Society.

Physical activity inversely associated with the presence of depression among urban adolescents in regional China

PubMed Central

Hong, Xin; Li, JieQuan; Xu, Fei; Tse, Lap Ah; Liang, YaQiong; Wang, ZhiYong; Yu, Ignatius Tak-sun; Griffiths, Sian

2009-01-01

Background An inverse relationship between physical activity (PA) and depression among adolescents has been reported in developed communities without consideration of sedentary behaviors (SB, including sitting for course study, viewing TV, and sleeping). We explored the association between recreational PA time (hr/wk) and depression after adjustment with SB and other possible confounders among Chinese adolescents. Methods A population-based cross-sectional study was conducted in Nanjing municipality of China in 2004 using a multi-stage cluster sampling approach. A total of 72 classes were randomly selected from 24 urban junior high schools and all students completed the structured questionnaire. Adolescent depression was examined by the Children's Depression Inventory (CDI) of Chinese version with cutoff point value of 20 or above as the presence of depression. Recreational PA time was measured by a question on weekly hours of PA outside of school. Descriptive statistics, multivariate logistic and linear regression models were used in analysis. Results The overall prevalence of depression was 15.7% (95%CI: 14.3%, 17.1%) among 2,444 eligible participants. It was found that physical activity was negatively associated with depression. After adjustment for sedentary behaviors and other potential confounders, participants who spent 1–7 hr/wk, 8–14 hr/wk and 15+ hr/wk for recreational PA, respectively, had odds ratios of 0.70 (95% CI = 0.57, 0.86), 0.68 (95% CI = 0.53, 0.88) and 0.66 (95% CI = 0.50, 0.87) for likelihood of being depressive, compared to their counterparts who spent 0–0.9 hr/wk for PA. This inverse relationship between PA time and depression remained statistically significant by gender and grade. Conclusion This study, conducted among Chinese adolescents, strengthened the evidence that physical activity was inversely associated with depression. Our study has important implications for health officers and public health professionals to pay much

Hippocampal Morphology in a Rat Model of Depression: The Effects of Physical Activity

PubMed Central

Sierakowiak, Adam; Mattsson, Anna; Gómez-Galán, Marta; Feminía, Teresa; Graae, Lisette; Aski, Sahar Nikkhou; Damberg, Peter; Lindskog, Mia; Brené, Stefan; Åberg, Elin

2015-01-01

Accumulating in vivo and ex vivo evidences show that humans suffering from depression have decreased hippocampal volume and altered spine density. Moreover, physical activity has an antidepressant effect in humans and in animal models, but to what extent physical activity can affect hippocampal volume and spine numbers in a model for depression is not known. In this study we analyzed whether physical activity affects hippocampal volume and spine density by analyzing a rodent genetic model of depression, Flinders Sensitive Line Rats (FSL), with Magnetic Resonance Imaging (MRI) and ex vivo Golgi staining. We found that physical activity in the form of voluntary wheel running during 5 weeks increased hippocampal volume. Moreover, runners also had larger numbers of thin spines in the dentate gyrus. Our findings support that voluntary wheel running, which is antidepressive in FSL rats, is associated with increased hippocampal volume and spine numbers. PMID:25674191

Hippocampal morphology in a rat model of depression: the effects of physical activity.

PubMed

Sierakowiak, Adam; Mattsson, Anna; Gómez-Galán, Marta; Feminía, Teresa; Graae, Lisette; Aski, Sahar Nikkhou; Damberg, Peter; Lindskog, Mia; Brené, Stefan; Åberg, Elin

2014-01-01

Accumulating in vivo and ex vivo evidences show that humans suffering from depression have decreased hippocampal volume and altered spine density. Moreover, physical activity has an antidepressant effect in humans and in animal models, but to what extent physical activity can affect hippocampal volume and spine numbers in a model for depression is not known. In this study we analyzed whether physical activity affects hippocampal volume and spine density by analyzing a rodent genetic model of depression, Flinders Sensitive Line Rats (FSL), with Magnetic Resonance Imaging (MRI) and ex vivo Golgi staining. We found that physical activity in the form of voluntary wheel running during 5 weeks increased hippocampal volume. Moreover, runners also had larger numbers of thin spines in the dentate gyrus. Our findings support that voluntary wheel running, which is antidepressive in FSL rats, is associated with increased hippocampal volume and spine numbers.

Depressive Symptoms and Inductive Reasoning Performance: Findings from the ACTIVE Reasoning Training Intervention

PubMed Central

Parisi, Jeanine M.; Franchetti, Mary Kathryn; Rebok, George W.; Spira, Adam P.; Carlson, Michelle C.; Willis, Sherry L.; Gross, Alden L.

2015-01-01

Within the context of the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study, we examined the longitudinal association of baseline depressive symptoms on inductive reasoning performance over a ten-year period between the reasoning training and control conditions (N = 1,375). At baseline, 322 participants (23%) reported elevated depressive symptoms, defined by a score ≥ 9 on the Center for Epidemiological Studies Depression scale (12-item). Differences in baseline depressive status were not associated with immediate post-training gains or with subsequent annual change in reasoning performance, suggesting that the presence of elevated baseline depressive symptoms does not impact the ability to benefit from reasoning training. PMID:25244465

Therapeutic horticulture in clinical depression: a prospective study of active components.

PubMed

Gonzalez, Marianne Thorsen; Hartig, Terry; Patil, Grete Grindal; Martinsen, Egil W; Kirkevold, Marit

2010-09-01

This paper is a report of a study conducted to assess change in depression severity, perceived attentional capacity and rumination (brooding) in individuals with clinical depression during a therapeutic horticulture programme and to investigate if the changes were mediated by experiences of being away and fascination. Individuals with clinical depression suffer from distortion of attention and rumination. Interventions can help to disrupt maladaptive rumination and promote restoration of depleted attentional capacity. A single-group study was conducted with a convenience sample of 28 people with clinical depression in 2009. Data were collected before, twice during, and immediately after a 12-week therapeutic horticulture programme, and at 3-month follow-up. Assessment instruments were the Beck Depression Inventory, Attentional Function Index, Brooding Scale, and Being Away and Fascination subscales from the Perceived Restorativeness Scale. Mean Beck Depression Inventory scores declined by 4.5 points during the intervention (F = 5.49, P = 0.002). The decline was clinically relevant for 50% of participants. Attentional Function Index scores increased (F = 4.14, P = 0.009), while Brooding scores decreased (F = 4.51, P = 0.015). The changes in Beck Depression Inventory and Attentional Function Index scores were mediated by increases in Being Away and Fascination, and decline in Beck Depression Inventory scores was also mediated by decline in Brooding. Participants maintained their improvements in Beck Depression Inventory scores at 3-month follow-up. Being away and fascination appear to work as active components in a therapeutic horticulture intervention for clinical depression.

Physical activity in the prevention and treatment of anxiety and depression.

PubMed

Martinsen, Egil W

2008-01-01

Anxiety and depressive disorders are major public health problems, and desirable changes in lifestyle, such as physical exercise, can have great potential in prevention and treatment. There is growing evidence that physically active people are at a reduced risk of developing depression, and that exercise interventions are associated with significant benefits for patients with mild to moderate forms of depression as well as in reducing anxiety. These findings have led to the proposal that exercise may serve as an alternative or a supplement to traditional forms of therapy. This paper will present a broad overview of research involving the efficacy of exercise as means to prevent and treat depression and anxiety, and related issues regarding dosage and compliance. Finally, exercise will be discussed in the frame of cognitive-behavioural theory.

A school-level analysis of adolescent extracurricular activity, delinquency, and depression: the importance of situational context.

PubMed

Guest, Andrew M; McRee, Nick

2009-01-01

In this article we investigate the extent to which the relationship between extracurricular activities and youth development depends on situational contexts. Using a national sample including 13,466 youths in grades 7-12 across 120 schools, we conduct school-level analyses of the association between extracurricular activities, delinquency, and depression. Three main findings are reported. First, we observe near-normal distributions across schools in the proportions of delinquent or depressed youths involved in extracurricular activities, illustrating that extracurricular activities can be positive, neutral, or negative settings for youth development. Second, within individual schools we fail to uncover consistent associations in the propensity of delinquent or depressed youth to be involved with different types of extracurricular activities. Third, standard macro-level context variables do not explain the observed variations within or between schools. The results suggest that the relationships between extracurricular activities, delinquent conduct and depressive symptoms among youth ultimately depend more upon micro-level contextual factors than the type or content of the activities themselves.

Physical activity and depression symptoms among pregnant women from the National Health and Nutrition Examination Survey 2005-2006.

PubMed

Loprinzi, Paul D; Fitzgerald, Elizabeth M; Cardinal, Bradley J

2012-03-01

To examine the association between objectively measured physical activity and depression symptoms among a nationally representative sample of pregnant women to provide a more accurate understanding of the relationship between physical activity and depression symptoms. We employed a cross-sectional study design. Data from the National Health and Nutrition Examination Survey 2005-2006 were used for this study. One-hundred and forty-one pregnant women wore an ActiGraph accelerometer for 7 days and completed the Patient Health Questionnaire-9 to assess depression status. More than 19% of the participants experienced some depression symptoms, and compared to their counterparts not having depression symptoms, they were less physically active. An inverse association was found between physical activity and depression symptoms among pregnant women. When feasible, nurses are encouraged to help facilitate physical activity among pregnant women, assuming an uncomplicated pregnancy. © 2012 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

Elevated amygdala activity to sad facial expressions: a state marker of bipolar but not unipolar depression.

PubMed

Almeida, Jorge R C; Versace, Amelia; Hassel, Stefanie; Kupfer, David J; Phillips, Mary L

2010-03-01

Difficulties in emotion processing and poor social function are common to bipolar disorder (BD) and major depressive disorder (MDD) depression, resulting in many BD depressed individuals being misdiagnosed with MDD. The amygdala is a key region implicated in processing emotionally salient stimuli, including emotional facial expressions. It is unclear, however, whether abnormal amygdala activity during positive and negative emotion processing represents a persistent marker of BD regardless of illness phase or a state marker of depression common or specific to BD and MDD depression. Sixty adults were recruited: 15 depressed with BD type 1 (BDd), 15 depressed with recurrent MDD, 15 with BD in remission (BDr), diagnosed with DSM-IV and Structured Clinical Interview for DSM-IV Research Version criteria; and 15 healthy control subjects (HC). Groups were age- and gender ratio-matched; patient groups were matched for age of illness onset and illness duration; depressed groups were matched for depression severity. The BDd were taking more psychotropic medication than other patient groups. All individuals participated in three separate 3T neuroimaging event-related experiments, where they viewed mild and intense emotional and neutral faces of fear, happiness, or sadness from a standardized series. The BDd-relative to HC, BDr, and MDD-showed elevated left amygdala activity to mild and neutral facial expressions in the sad (p < .009) but not other emotion experiments that was not associated with medication. There were no other significant between-group differences in amygdala activity. Abnormally elevated left amygdala activity to mild sad and neutral faces might be a depression-specific marker in BD but not MDD, suggesting different pathophysiologic processes for BD versus MDD depression. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Enhanced platelet/endothelial activation in depressed patients with acute coronary syndromes: evidence from recent clinical trials.

PubMed

Serebruany, Victor L; Glassman, Alexander H; Malinin, Alex I; Sane, David C; Finkel, Mitchell S; Krishnan, Ranga R; Atar, Dan; Lekht, Vladimir; O'Connor, Christopher M

2003-09-01

Platelets play a key role in the progression of acute coronary syndromes (ACS). Clinical depression alone is also associated with enhanced platelet activation. The purpose of this study was to compare concentrations of established biomarkers of enhanced platelet/endothelial activation in clinically depressed versus non-depressed patients enrolled in recent clinical trials for ACS. Two hundred and eighty-one baseline plasma samples from patients with acute myocardial infarction (ASSENT-2; n = 41), with ACS (PRONTO; n = 126) and with clinical depression plus previous acute coronary syndrome within 6 months (SADHART; n = 64), and from normal healthy controls (n = 50) were analyzed. Blood was drawn before applying any therapeutic strategies including interventions, thrombolytics, infusions, and selective serotonin re-uptake inhibitors. Platelet factor 4, beta-thromboglobulin, platelet/endothelial cell adhesion molecule-1, P-selectin, thromboxane, prostacyclin, vascular cell adhesion molecule-1, and E-selectin were measured by enzyme-linked immunosorbent assay by a single core laboratory. Patients with ACS exhibited a higher degree of platelet activation than controls independently of the presence of depression. Plasma levels of P-selectin, thromboxane, prostacyclin, and vascular cell adhesion molecule-1 were the highest in the acute myocardial infarction group when compared with ACS despite the presence or absence of clinical depression. Surprisingly, patients with ACS and depression exhibited the highest levels of platelet factor 4, beta-thromboglobulin, and platelet/endothelial cell adhesion molecule-1 when compared with myocardial infarction or angina patients without clinical depression. E-selectin plasma level was constantly elevated compared with controls but did not differ among the groups dependent on the incidence of depression. The depressed plus ACS group had higher plasma levels of all biomarkers compared with the non-depressed patients. Retrospective

Physical activity, quality of life and symptoms of depression in community-dwelling and institutionalized older adults.

PubMed

Salguero, Alfonso; Martínez-García, Raquel; Molinero, Olga; Márquez, Sara

2011-01-01

This study was aimed to investigate in a sample of Spanish elderly whether measures of physical activity are related to health-related quality of life (HRQoL) and symptoms of depression in community dwelling and institutionalized elderly. The sample was a cohort of 436 elderly (234 women and 202 men, aged 60-98 years) from the North of Spain. 58% were community-dwellers and 42% were institutionalized in senior residences. Participants completed measures of physical activity (Yale Physical Activity Survey, YPAS), HRQoL (Medical Outcomes Study 36-item Short Form Health Survey, SF-36) and symptoms of depression (Geriatric Depression Scale, GDS). All SF-36 domains, except role-emotional, were significantly correlated with the YPAS activity dimension summary index. Physical function, role-physical, general health and vitality correlated with total time activity, and correlations were observed between weekly energy expenditure and physical function, role physical, vitality and mental health. Depressive symptom scores correlated significantly with the YPAS activity dimension summary index and the weekly energy expenditure. Scores for various domains of the SF-36 and for depressive symptoms significantly differed among less and more active individuals of the same sex and institutionalization category. Differences generally reached a higher extent in institutionalized subjects in comparison to community dwellers. In conclusion, physical activity was related to different domains of both the physical and mental components of HRQoL and to decreased depressive symptoms. Results emphasize the positive effects of physical activity in both community-dwelling and institutionalized older adults. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Depression (Major Depressive Disorder)

MedlinePlus

... of interest in normal activities, and avoidance of social interaction. Depression symptoms in older adults Depression is not a normal part of growing older, and it should never be taken lightly. ... social phobia Family conflicts, relationship difficulties, and work or ...

The role of fast and slow EEG activity during sleep in males and females with Major Depressive Disorder

PubMed Central

Cheng, Philip; Goldschmied, Jennifer; Deldin, Patricia; Hoffmann, Robert; Armitage, Roseanne

2015-01-01

Sleep difficulties are highly prevalent in depression, and appears to be a contributing factor in the development and maintenance of symptoms. However, despite the generally acknowledged relationship between sleep and depression, the neurophysiological substrates underlying this relationship still remain unclear. Two main hypotheses were tested in this study. The first hypothesis states that sleep in depression is characterized by inadequate generation of restorative sleep, as indexed by reduced amounts of slow-wave activity. Conversely, the second hypothesis states that poor sleep in depression is due to intrusions of fast-frequency activity that may be reflective of a hyperaroused central nervous system. This study aimed to test both hypotheses in a large sample of individuals with clinically validated depression, as well as examine sex as a moderator. Results suggest that depression is better characterized by an overall decrease in slow-wave activity, which is related to elevated anxious and depressed mood the following morning. Results also suggest that females may be more likely to experience fast frequency activity related to depression symptom severity. PMID:26175101

Depression symptoms reduce physical activity in COPD patients: a prospective multicenter study.

PubMed

Dueñas-Espín, Iván; Demeyer, Heleen; Gimeno-Santos, Elena; Polkey, Michael I; Hopkinson, Nicholas S; Rabinovich, Roberto A; Dobbels, Fabienne; Karlsson, Niklas; Troosters, Thierry; Garcia-Aymerich, Judith

2016-01-01

The role of anxiety and depression in the physical activity (PA) of patients with COPD is controversial. We prospectively assessed the effect of symptoms of anxiety and depression on PA in COPD patients. We evaluated anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), PA (Dynaport(®) accelerometer), and other relevant characteristics in 220 COPD patients from five European countries at baseline and at 6 and 12 months of follow-up. HADS score was categorized as: no symptoms (score 0-7), suggested (8-10), and probable (>11) anxiety or depression. We estimated the association between anxiety and depression at t (baseline and 6 months) and PA at t+1 (6 and 12 months) using regression models with a repeated measures approach. Patients had a mean (standard deviation) age of 67 (8) years, forced expiratory volume in 1 second 57 (20)% predicted. At baseline, the prevalence of probable anxiety and depression was 10% and 5%, respectively. In multivariable models adjusted by confounders and previous PA, patients performed 81 fewer steps/day (95% confidence interval, -149 to -12, P=0.02) per extra point in HADS-depression score. HADS-anxiety symptoms were not associated with PA. In COPD patients, symptoms of depression are prospectively associated with a measurable reduction in PA 6 months later.

Association between obesity and depressive symptoms among U.S. Military active duty service personnel, 2002.

PubMed

Kress, Amii M; Peterson, Michael R; Hartzell, Michael C

2006-03-01

The association between obesity and depression remains equivocal. The purpose of this study was to describe the prevalence and association of obesity and depressive symptoms among military personnel. A cross-sectional analysis was performed using data (N=10,040) from the U.S. Department of Defense (DoD) Survey of Health-Related Behaviors. Prevalence odds ratios were calculated to describe the association between obesity and depressive symptoms. Approximately 10% of active duty men and 4% of active duty women were obese. The prevalence of depressive symptoms ranged from approximately 16% of overweight men to 49% of obese women. Obese men and women and underweight men had increased odds of depressive symptoms as compared with normal-weight individuals. The DoD should emphasize prevention and regular screening for obesity and depressive symptoms to improve readiness and reduce health care costs and disease burden in this cohort.

A new chronobiological approach to discriminate between acute and chronic depression using peripheral temperature, rest-activity, and light exposure parameters

PubMed Central

2013-01-01

Background Circadian theories for major depressive disorder have suggested that the rhythm of the circadian pacemaker is misaligned. Stable phase relationships between internal rhythms, such as temperature and rest/activity, and the external day-night cycle, are considered to be crucial for adapting to life in the external environmental. Therefore, the relationship and possible alterations among (i) light exposure, (ii) activity rhythm, and (iii) temperature rhythm could be important factors in clinical depression. This study aimed to investigate the rhythmic alterations in depression and evaluate the ability of chronobiological parameters to discriminate between healthy subjects and depressed patients. Methods Thirty female subjects, including healthy subjects, depressed patients in the first episode, and major recurrent depression patients. Symptoms were assessed using Hamilton Depression Scale, Beck Depression Inventory and Montgomery-Äsberg Scale. Motor activity, temperature, and light values were determined for 7 days by actigraph, and circadian rhythms were calculated. Results Depressed groups showed a lower amplitude in the circadian rhythm of activity and light exposure, but a higher amplitude in the rhythm of peripheral temperature. The correlation between temperature and activity values was different in the day and night among the control and depressed groups. For the same level of activity, depressed patients had lowest temperature values during the day. The amplitudes of temperature and activity were the highest discriminant parameters. Conclusions These results indicate that the study of rhythms is useful for diagnosis and therapy for depressive mood disorders. PMID:23510455

Physical activity in European adolescents and associations with anxiety, depression and well-being.

PubMed

McMahon, Elaine M; Corcoran, Paul; O'Regan, Grace; Keeley, Helen; Cannon, Mary; Carli, Vladimir; Wasserman, Camilla; Hadlaczky, Gergö; Sarchiapone, Marco; Apter, Alan; Balazs, Judit; Balint, Maria; Bobes, Julio; Brunner, Romuald; Cozman, Doina; Haring, Christian; Iosue, Miriam; Kaess, Michael; Kahn, Jean-Pierre; Nemes, Bogdan; Podlogar, Tina; Poštuvan, Vita; Sáiz, Pilar; Sisask, Merike; Tubiana, Alexandra; Värnik, Peeter; Hoven, Christina W; Wasserman, Danuta

2017-01-01

In this cross-sectional study, physical activity, sport participation and associations with well-being, anxiety and depressive symptoms were examined in a large representative sample of European adolescents. A school-based survey was completed by 11,110 adolescents from ten European countries who took part in the SEYLE (Saving and Empowering Young Lives in Europe) study. The questionnaire included items assessing physical activity, sport participation and validated instruments assessing well-being (WHO-5), depressive symptoms (BDI-II) and anxiety (SAS). Multi-level mixed effects linear regression was used to examine associations between physical activity/sport participation and mental health measures. A minority of the sample (17.9 % of boys and 10.7 % of girls; p < 0.0005) reported sufficient activity based on WHO guidelines (60 min + daily). The mean number of days of at least 60 min of moderate-to-vigorous activity in the past 2 weeks was 7.5 ± 4.4 among boys and 5.9 days ± 4.3 among girls. Frequency of activity was positively correlated with well-being and negatively correlated with both anxiety and depressive symptoms, up to a threshold of moderate frequency of activity. In a multi-level mixed effects model more frequent physical activity and participation in sport were both found to independently contribute to greater well-being and lower levels of anxiety and depressive symptoms in both sexes. Increasing activity levels and sports participation among the least active young people should be a target of community and school-based interventions to promote well-being. There does not appear to be an additional benefit to mental health associated with meeting the WHO-recommended levels of activity.

Improving fatigue and depression in individuals with multiple sclerosis using telephone-administered physical activity counseling.

PubMed

Turner, Aaron P; Hartoonian, Narineh; Sloan, Alicia P; Benich, Marisa; Kivlahan, Daniel R; Hughes, Christina; Hughes, Abbey J; Haselkorn, Jodie K

2016-04-01

To evaluate the impact of a physical activity intervention consisting of telephone counseling with home-based monitoring to improve fatigue and depression in individuals with multiple sclerosis (MS). Single-blind randomized controlled trial. Sixty-four individuals with MS received either telephone counseling (N = 31), or self-directed physical activity education (N = 33). The education condition (EC) consisted of advice to increase physical activity and a DVD with examples of in-home exercises for multiple physical ability levels. The telephone counseling condition (TC) included EC as well as mailed graphic feedback, 6 telephone counseling sessions using principles of motivational interviewing, and telehealth home monitoring to track progress on physical activity goals. Booster sessions were provided when participants indicated they did not meet their goals. Assessment was conducted at baseline, 3-month, and 6-month follow-up. TC participants reported significantly reduced fatigue (d = -.70), reduced depression (d = -.72) and increased physical activity (d = .92) relative to EC participants. Of individuals receiving TC, 33.3% experienced clinically significant improvement in fatigue (vs. 18.2% in EC) and 53.3% experienced clinically significant improvement in depression (vs. 9.1% in EC). Improvements in physical activity mediated improvements in fatigue with a similar trend for depression. TC was highly feasible (participants completed 99.5% of schedule telephone sessions) and well tolerated (100% rated it highly successful). Telephone-based counseling with home monitoring is a promising modality to improve physical activity and treat fatigue and depression. (c) 2016 APA, all rights reserved).

Emotion processing biases and resting EEG activity in depressed adolescents

PubMed Central

Auerbach, Randy P.; Stewart, Jeremy G.; Stanton, Colin H.; Mueller, Erik M.; Pizzagalli, Diego A.

2015-01-01

Background While theorists have posited that adolescent depression is characterized by emotion processing biases (greater propensity to identify sad than happy facial expressions), findings have been mixed. Additionally, the neural correlates associated with putative emotion processing biases remain largely unknown. Our aim was to identify emotion processing biases in depressed adolescents and examine neural abnormalities related to these biases using high-density resting EEG and source localization. Methods Healthy (n = 36) and depressed (n = 23) female adolescents, aged 13–18 years, completed a facial recognition task in which they identified happy, sad, fear, and angry expressions across intensities from 10% (low) to 100% (high). Additionally, 128-channel resting (i.e., task-free) EEG was recorded and analyzed using a distributed source localization technique (LORETA). Given research implicating the dorsolateral prefrontal cortex (DLPFC) in depression and emotion processing, analyses focused on this region. Results Relative to healthy youth, depressed adolescents were more accurate for sad and less accurate for happy, particularly low-intensity happy faces. No differences emerged for fearful or angry facial expressions. Further, LORETA analyses revealed greater theta and alpha current density (i.e., reduced brain activity) in depressed versus healthy adolescents, particularly in the left DLPFC (BA9/BA46). Theta and alpha current density were positively correlated, and greater current density predicted reduced accuracy for happy faces. Conclusion Depressed female adolescents were characterized by emotion processing biases in favor of sad emotions and reduced recognition of happiness, especially when cues of happiness were subtle. Blunted recognition of happy was associated with left DLPFC resting hypoactivity. PMID:26032684

Pharmacological evaluation of Pachyrrhizus erosus (L) seeds for central nervous system depressant activity.

PubMed

Abid, Mohd; Hrishikeshavan, H J; Asad, Mohammed

2006-01-01

The research work deals with the screening of ethanol and chloroform extracts of Pachyrrhizus erosus seeds for central nervous system (CNS) depressant activity. The Pachyrrhizus erosus seed is known to contain rotinoids, flavonoids and phenylfuranocoumarin derivatives as chemical components and is reported to have antifungal, antisecretory, insecticides, antibacterial and spasmolytic activity. Since seeds of Pachyrrhizus erosus is used as folk medicine in treatment of insomnia, we made an attempt to study its CNS depressant effect. The different activities studied were potentiation of pentobarbitone-induced sleep, test for locomotor activity, effect on muscle co-ordination, antiaggressive and antianxiety activities. The result of the study reflected that ethanol extract of the seeds (150 mg/kg, p.o) decreased locomotor activity, produced muscle relaxation and showed antianxiety and antiaggressive activity.

Altered Brain Activity in Unipolar Depression Revisited: Meta-analyses of Neuroimaging Studies.

PubMed

Müller, Veronika I; Cieslik, Edna C; Serbanescu, Ilinca; Laird, Angela R; Fox, Peter T; Eickhoff, Simon B

2017-01-01

During the past 20 years, numerous neuroimaging experiments have investigated aberrant brain activation during cognitive and emotional processing in patients with unipolar depression (UD). The results of those investigations, however, vary considerably; moreover, previous meta-analyses also yielded inconsistent findings. To readdress aberrant brain activation in UD as evidenced by neuroimaging experiments on cognitive and/or emotional processing. Neuroimaging experiments published from January 1, 1997, to October 1, 2015, were identified by a literature search of PubMed, Web of Science, and Google Scholar using different combinations of the terms fMRI (functional magnetic resonance imaging), PET (positron emission tomography), neural, major depression, depression, major depressive disorder, unipolar depression, dysthymia, emotion, emotional, affective, cognitive, task, memory, working memory, inhibition, control, n-back, and Stroop. Neuroimaging experiments (using fMRI or PET) reporting whole-brain results of group comparisons between adults with UD and healthy control individuals as coordinates in a standard anatomic reference space and using an emotional or/and cognitive challenging task were selected. Coordinates reported to show significant activation differences between UD and healthy controls during emotional or cognitive processing were extracted. By using the revised activation likelihood estimation algorithm, different meta-analyses were calculated. Meta-analyses tested for brain regions consistently found to show aberrant brain activation in UD compared with controls. Analyses were calculated across all emotional processing experiments, all cognitive processing experiments, positive emotion processing, negative emotion processing, experiments using emotional face stimuli, experiments with a sex discrimination task, and memory processing. All meta-analyses were calculated across experiments independent of reporting an increase or decrease of activity in

The BDNF Val66Met polymorphism does not moderate the effect of self-reported physical activity on depressive symptoms in midlife

PubMed Central

Gujral, Swathi; Manuck, Stephen B.; Ferrell, Robert E.; Flory, Janine D.; Erickson, Kirk I.

2014-01-01

Background The brain-derived neurotrophic factor (BDNF) Val66Met single nucleotide polymorphism may be associated with clinical and subsyndromal depression, but physical activity improves mood and increases BDNF expression. Aims To examine whether the BDNF polymorphism moderates an effect of physical activity on depressive symptoms. Methods BDNF genotype, physical activity measured by the Paffenbarger Questionnaire, and depressive symptoms using the Center for Epidemiology Depression Scale (CES-D) were collected on 1072 participants (Mean Age=44). Multiple linear regression was used to examine the association between BDNF genotype, physical activity, and depressive symptoms. Results After adjusting for family income, age, and education, depressive symptoms were higher in Met carriers compared to Val homozygotes (p=0.03), but this was only significant in men. Physical activity was associated with fewer depressive symptoms, but only in women (p=0.01). BDNF genotype did not moderate the effect of physical activity on depressive symptoms (p= 0.94). Conclusions In midlife, the BDNF Val66Met polymorphism neither attenuates nor magnifies the effect of physical activity on depressive symptoms. PMID:24745471

A novel training approach to activate alternative behaviors for smoking in depressed smokers.

PubMed

Kopetz, Catalina; MacPherson, Laura; Mitchell, Avery D; Houston-Ludlam, Alexandra N; Wiers, Reinout W

2017-02-01

The current research developed and tested a novel training strategy to alter the implicit associations between alternative behaviors to smoking and negative affect, and explored its effects on depressive symptoms and on smoking behavior as part of a quit attempt. Using a joystick, participants identified as smokers with depressive symptoms were trained to approach alternative behaviors to smoking in the context of negative affect. Specifically, in the experimental condition, participants were trained to avoid smoking-related targets and to approach alternative activities. In the control condition, participants pushed and pulled an equal amount of smoking and alternative activity-related targets. Compared with the participants in the control condition, those in the experimental condition showed an increase in the accessibility of the alternative activity relative to smoking and a decrease in depressive symptoms. Smoking outcomes did not differ significantly across the 2 conditions. Taken together these results indicate that the value of alternative behaviors to smoking can be modified in the lab without participants' conscious intentions with implications for depressive symptomatology. Future research is required to explore the impact of such training on smoking outcomes. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Mechanisms underlying the comorbidity between depressive and addictive disorders in adolescents: interactions between stress and HPA activity.

PubMed

Rao, Uma; Hammen, Constance L; Poland, Russell E

2009-03-01

Depression may be a precursor to substance use disorder in some youngsters, and substance abuse might complicate the subsequent course of depression. This study examined whether hypothalamic-pituitary-adrenal (HPA) activity and stressful life experiences are related to the development of substance use disorder in depressed and nondepressed adolescents, and whether substance use disorder predicts a worsening course of depression. Urinary-free cortisol was measured for 3 nights in 151 adolescents with no prior history of substance use disorder (55 depressed, 48 at high risk for depression, and 48 normal subjects). Information was obtained on recent stressful life experiences. The participants were followed for up to 5 years to assess the onset of substance use disorder, course of depression, and stressful experiences. The relationships among depression, cortisol as a measure of HPA activity, stressful experiences, and substance use disorder were examined. Elevated cortisol was associated with onset of substance use disorder. Stressful life experiences moderated this relationship. Cortisol and stress accounted for the effects of a history or risk of depression on the development of substance use disorder. Substance use disorder was associated with higher frequency of subsequent depressive episodes. Higher cortisol prior to the onset of substance use disorder may indicate vulnerability to substance use disorder. Stressful experiences increase the risk for substance use disorder in such vulnerable youth. The high prevalence of substance use disorders in depressed individuals may be explained, in part, by high levels of stress and increased HPA activity.

Depression-Related Increases and Decreases in Appetite: Dissociable Patterns of Aberrant Activity in Reward and Interoceptive Neurocircuitry.

PubMed

Simmons, W Kyle; Burrows, Kaiping; Avery, Jason A; Kerr, Kara L; Bodurka, Jerzy; Savage, Cary R; Drevets, Wayne C

2016-04-01

Appetite and weight changes are common but variable diagnostic markers in major depressive disorder: some depressed individuals manifest increased appetite, while others lose their appetite. Many of the brain regions implicated in appetitive responses to food have also been implicated in depression. It is thus remarkable that there exists no published research comparing the neural responses to food stimuli of depressed patients with increased versus decreased appetites. Using functional MRI, brain activity was compared in unmedicated depressed patients with increased or decreased appetite and healthy control subjects while viewing photographs of food and nonfood objects. The authors also measured how resting-state functional connectivity related to subjects' food pleasantness ratings. Within putative reward regions, depressed participants with increased appetites exhibited greater hemodynamic activity to food stimuli than both those reporting appetite decreases and healthy control subjects. In contrast, depressed subjects experiencing appetite loss exhibited hypoactivation within a region of the mid-insula implicated in interoception, with no difference observed in this region between healthy subjects and those with depression-related appetite increases. Mid-insula activity was negatively correlated with food pleasantness ratings of depressed participants with increased appetites, and its functional connectivity to reward circuitry was positively correlated with food pleasantness ratings. Depression-related increases in appetite are associated with hyperactivation of putative mesocorticolimbic reward circuitry, while depression-related appetite loss is associated with hypoactivation of insular regions that support monitoring the body's physiological state. Importantly, the interactions among these regions also contribute to individual differences in the depression-related appetite changes.

[Regular physical activity and mental health. The role of exercise in the prevention of, and intervention in depressive disorders].

PubMed

Takács, Johanna

2014-01-01

In our review we examine the relationship between physical activity and mental health; especially we determine the effectiveness of exercise in the prevention and treatment of depression. Over the past two decades the literature in the area of physical activity and mental health has been growing. However it seems that the findings and evidences not being utilized by mental health agencies and health practitioners. Depression is the most common disorder in the world, generally has a higher prevalence among women. In our study we overview and demonstrate that the exercise is a powerful intervention for prevention and treatment not only in non-clinical but also in clinical levels of depression. In sub-clinical levels of depression the meta-analytic findings and population surveys suggest that the exercise is associated with a significant moderate reduction of depression in different groups by gender and age; as well as a physically active lifestyle associates with lower levels of depression. In clinical levels of depression the physical activity is an effective tool in the prevention, studies support an association between higher levels of physical activity and lower levels of depression. In the treatment of clinical depression the randomized-controlled trials suggest the clear positive effects of exercise. This effect is similar to psychotherapeutic interventions and it was appeared under relatively short time (4-8 weeks). The exercise is one of the most important preventive health-related behaviors. Our review suggests a protective effect from activity on the development of clinical levels of depression and depressive symptoms. In addition the randomized controlled trials support a causal connection between exercise and reduction of depression. In sum the reviewed studies clearly support the antidepressant effect of exercise.

Depressed mood in breast cancer survivors: associations with physical activity, cancer-related fatigue, quality of life, and fitness level.

PubMed

Galiano-Castillo, Noelia; Ariza-García, Angelica; Cantarero-Villanueva, Irene; Fernández-Lao, Carolina; Díaz-Rodríguez, Lourdes; Arroyo-Morales, Manuel

2014-04-01

One out of five cancer survivors suffer from depression after oncology treatment. The aim of this study was to examine the relationship between depression and quality of life (QoL), cancer-related symptoms, physical activity level, health-related fitness, and salivary flow rate in breast cancer survivors. 108 breast cancer survivors in the year after the conclusion of treatment were included in this cross-sectional study. Demographic and clinically relevant information, cancer-related fatigue (Piper Fatigue Scale), QoL (QLQ-Br23 module), pain intensity VAS scale, salivary flow rate, physical activity level (Minnesota Leisure Time Physical Activity Questionnaire), and health-related fitness were assessed in all participants. Depressed mood was measured with the Profile of Mood States (POMS) Depression subscale. Significant positive correlations between depressed mood and fatigue, systemic side effects, perceived shoulder pain, and breast-arms symptoms (r ranged between .57 and .28, P < .01) were found. In addition, significant negative correlations between depressed mood and body image, future perspective, force handgrip, and physical activity level (r ranged between -.41 and -.19; p < .05) were found. Regression analyses revealed that cancer-related fatigue, physical activity level, systemic side effects, and body image were significant predictors of depressed mood, and when combined, they explained 39.6% of the variance in depressed mood. Cancer-related fatigue, physical activity level, and QoL partially explain the variability of depressed mood in breast cancer survivors. This paper facilitates a better understanding of the relationship between depressed mood and possible factors associated with it. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Novel α2/α4 Subtype-selective Positive Allosteric Modulator of Nicotinic Acetylcholine Receptors Acting from the C-tail of an α Subunit*

PubMed Central

Wang, Jingyi; Kuryatov, Alexander; Jin, Zhuang; Norleans, Jack; Kamenecka, Theodore M.; Kenny, Paul J.; Lindstrom, Jon

2015-01-01

Positive allosteric modulators (PAMs) of nicotinic acetylcholine receptors (nAChR) are important therapeutic candidates as well as valuable research tools. We identified a novel type II PAM, (R)-7-bromo-N-(piperidin-3-yl)benzo[b]thiophene-2-carboxamide (Br-PBTC), which both increases activation and reactivates desensitized nAChRs. This compound increases acetylcholine-evoked responses of α2* and α4* nAChRs but is without effect on α3* or α6* nAChRs (* indicates the presence of other nAChR subunits). Br-BPTC acts from the C-terminal extracellular sequences of α4 subunits, which is also a PAM site for steroid hormone estrogens such as 17β-estradiol. Br-PBTC is much more potent than estrogens. Like 17β-estradiol, the non-steroid Br-PBTC only requires one α4 subunit to potentiate nAChR function, and its potentiation is stronger with more α4 subunits. This feature enables Br-BPTC to potentiate activation of (α4β2)(α6β2)β3 but not (α6β2)2β3 nAChRs. Therefore, this compound is potentially useful in vivo for determining functions of different α6* nAChR subtypes. Besides activation, Br-BPTC affects desensitization of nAChRs induced by sustained exposure to agonists. After minutes of exposure to agonists, Br-PBTC reactivated short term desensitized nAChRs that have at least two α4 subunits but not those with only one. Three α4 subunits were required for Br-BPTC to reactivate long term desensitized nAChRs. These data suggest that higher PAM occupancy promotes channel opening more efficiently and overcomes short and long term desensitization. This C-terminal extracellular domain could be a target for developing subtype or state-selective drugs for nAChRs. PMID:26432642

Functional analysis of Torpedo californica nicotinic acetylcholine receptors in multiple activation states by SSM-based electrophysiology.

PubMed

Niessen, K V; Muschik, S; Langguth, F; Rappenglück, S; Seeger, T; Thiermann, H; Worek, F

2016-04-15

Organophosphorus compounds (OPC), i.e. nerve agents or pesticides, are highly toxic due to their strong inhibition potency against acetylcholinesterase (AChE). Inhibited AChE results in accumulation of acetylcholine in the synaptic cleft and thus the desensitisation of the nicotinic acetylcholine receptor (nAChR) in the postsynaptic membrane is provoked. Direct targeting of nAChR to reduce receptor desensitisation might be an alternative therapeutic approach. For drug discovery, functional properties of potent therapeutic candidates need to be investigated in addition to affinity properties. Solid supported membrane (SSM)-based electrophysiology is useful for functional characterisation of ligand-gated ion channels like nAChRs, as charge translocations via capacitive coupling of the supporting membrane can be measured. By varying the agonist (carbamoylcholine) concentration, different functional states of the nAChR were initiated. Using plasma membrane preparations obtained from Torpedo californica electric organ, functional properties of selected nAChR ligands and non-oxime bispyridinium compounds were investigated. Depending on overall-size, the bispyridinium compounds enhanced or inhibited cholinergic signals induced by 100 μM carbamoylcholine. Applying excessive concentrations of the agonist carbamoylcholine provoked desensitisation of the nAChRs, whereas addition of bispyridinium compounds bearing short alkyl linkers exhibited functional recovery of previously desensitised nAChRs. The results suggest that these non-oxime bispyridinium compounds possibly interacted with nAChR subtypes in a manner of a positive allosteric modulator (PAM). The described newly developed functional assay is a valuable tool for the assessment of functional properties of potential compounds such as nAChR modulating ligands, which might be a promising approach in the therapeutically treatment of OPC-poisonings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A meta-meta-analysis of the effect of physical activity on depression and anxiety in non-clinical adult populations.

PubMed

Rebar, Amanda L; Stanton, Robert; Geard, David; Short, Camille; Duncan, Mitch J; Vandelanotte, Corneel

2015-01-01

Amidst strong efforts to promote the therapeutic benefits of physical activity for reducing depression and anxiety in clinical populations, little focus has been directed towards the mental health benefits of activity for non-clinical populations. The objective of this meta-meta-analysis was to systematically aggregate and quantify high-quality meta-analytic findings of the effects of physical activity on depression and anxiety for non-clinical populations. A systematic search identified eight meta-analytic outcomes of randomised trials that investigated the effects of physical activity on depression or anxiety. The subsequent meta-meta-analyses were based on a total of 92 studies with 4310 participants for the effect of physical activity on depression and 306 study effects with 10,755 participants for the effect of physical activity on anxiety. Physical activity reduced depression by a medium effect [standardised mean difference (SMD) = -0.50; 95% CI: -0.93 to -0.06] and anxiety by a small effect (SMD = -0.38; 95% CI: -0.66 to -0.11). Neither effect showed significant heterogeneity across meta-analyses. These findings represent a comprehensive body of high-quality evidence that physical activity reduces depression and anxiety in non-clinical populations.

Physical activity and calorie intake mediate the relationship from depression to body fat mass among female Mexican health workers.

PubMed

Quezada, Amado D; Macías-Waldman, Nayeli; Salmerón, Jorge; Swigart, Tessa; Gallegos-Carrillo, Katia

2017-11-17

Depression is a foremost cause of morbidity throughout the world and the prevalence of depression in women is about twice as high as men. Additionally, overweight and obesity are major global health concerns. We explored the relationship between depression and body fat, and the role of physical activity and diet as mediators of this relationship in a sample of 456 adult female Mexican health workers. Longitudinal and cross-sectional analyses using data from adult women of the Health Workers Cohort Study (HWCS) Measures of body fat mass (kg from DEXA), dietary intake (kcal from FFQ), leisure time activity (METs/wk) and depression (CES-D) were determined in two waves (2004-2006 and 2010-2011). We explored the interrelation between body fat, diet, leisure time, physical activity, and depression using a cross-lagged effects model fitted to longitudinal data. We also fitted a structural equations model to cross-sectional data with body fat as the main outcome, and dietary intake and physical activity from leisure time as mediators between depression and body fat. Baseline depression was significantly related to higher depression, higher calorie intake, and lower leisure time physical activity at follow-up. From our cross-sectional model, each standard deviation increase in the depression score was associated with an average increase of 751 ± 259 g (± standard error) in body fat through the mediating effects of calorie intake and physical activity. The results of this study show how depression may influence energy imbalance between calories consumed and calories expended, resulting in higher body fat among those with a greater depression score. Evaluating the role of mental conditions like depression in dietary and physical activity behaviors should be positioned as a key research goal for better designed and targeted public health interventions. The HealthWorkers Cohort Study (HWCS) has been approved by the Institutional IRB. Number: 2005-785-012.

Undergraduate Physical Activity and Depressive Symptoms: A National Study

ERIC Educational Resources Information Center

Elliot, Catherine A.; Kennedy, Catherine; Morgan, George; Anderson, Sharon K.; Morris, Debra

2012-01-01

Objective: To study the effects of college students' physical activity and gender on depressive and suicidal symptoms. Method: The National College Health Assessment survey was administered to college students nationwide. Data were analyzed with 4x2 ANOVAs and Games-Howell post hoc tests when appropriate. Results: More frequent physical activity…

Altered Brain Activity in Unipolar Depression Revisited Meta-analyses of Neuroimaging Studies

PubMed Central

Müller, Veronika I.; Cieslik, Edna C.; Serbanescu, Ilinca; Laird, Angela R.; Fox, Peter T.; Eickhoff, Simon B.

2017-01-01

IMPORTANCE During the past 20 years, numerous neuroimaging experiments have investigated aberrant brain activation during cognitive and emotional processing in patients with unipolar depression (UD). The results of those investigations, however, vary considerably; moreover, previous meta-analyses also yielded inconsistent findings. OBJECTIVE To readdress aberrant brain activation in UD as evidenced by neuroimaging experiments on cognitive and/or emotional processing. DATA SOURCES Neuroimaging experiments published from January 1, 1997, to October 1, 2015, were identified by a literature search of PubMed, Web of Science, and Google Scholar using different combinations of the terms fMRI (functional magnetic resonance imaging), PET (positron emission tomography), neural, major depression, depression, major depressive disorder, unipolar depression, dysthymia, emotion, emotional, affective, cognitive, task, memory, working memory, inhibition, control, n-back, and Stroop. STUDY SELECTION Neuroimaging experiments (using fMRI or PET) reporting whole-brain results of group comparisons between adults with UD and healthy control individuals as coordinates in a standard anatomic reference space and using an emotional or/and cognitive challenging task were selected. DATA EXTRACTION AND SYNTHESIS Coordinates reported to show significant activation differences between UD and healthy controls during emotional or cognitive processing were extracted. By using the revised activation likelihood estimation algorithm, different meta-analyses were calculated. MAIN OUTCOMES AND MEASURES Meta-analyses tested for brain regions consistently found to show aberrant brain activation in UD compared with controls. Analyses were calculated across all emotional processing experiments, all cognitive processing experiments, positive emotion processing, negative emotion processing, experiments using emotional face stimuli, experiments with a sex discrimination task, and memory processing. All meta

Physical Activity of Depressed Patients and Their Motivation to Exercise: Nordic Walking in Family Practice

ERIC Educational Resources Information Center

Suija, Kadri; Pechter, Ulle; Kalda, Ruth; Tahepold, Heli; Maaroos, Jaak; Maaroos, Heidi-Ingrid

2009-01-01

The objectives of this study were to find out how motivated depressed patients are to exercise regularly, to measure the physical activity of depressed patients and to find out how regular Nordic Walking affects the mood and physical fitness of depressed patients. A cross-sectional study was carried out. Three years after the Prediction of Primary…

Associations of Leisure-Time and Occupational Physical Activity and Cardiorespiratory Fitness With Incident and Recurrent Major Depressive Disorder, Depressive Symptoms, and Incident Anxiety in a General Population.

PubMed

Baumeister, Sebastian E; Leitzmann, Michael F; Bahls, Martin; Dörr, Marcus; Schmid, Daniela; Schomerus, Georg; Appel, Katja; Markus, Marcello R P; Völzke, Henry; Gläser, Sven; Grabe, Hans-Jörgen

2017-01-01

Physical activity and cardiorespiratory fitness may help prevent depression and anxiety. Previous studies have been limited by error-prone measurements. We examined whether self-reported physical activity domains and peak exercise capacity (peakVO₂) are associated with incident and recurrent major depressive disorder (MDD), depressive symptoms, and anxiety disorders. This was a prospective population-based study of 1,080 adult men and women (25-83 years) with a median follow-up of 4.5 years and measures of physical activity during leisure time, sports, and work (Baecke questionnaire); a measure of depressive symptoms (Beck Depression Inventory II); symptom-limited cycle ergometer testing (peakVO₂, oxygen uptake at anaerobic threshold [VO₂@AT], maximum power output at peak exertion); and a structured psychiatric interview (Munich Composite International Diagnostic Interview). Baseline data were collected between 2002 and 2006, and follow-up data, between 2007 and 2010. After adjustment for age, sex, education, smoking, alcohol consumption, and waist circumference, the relative risks for incident MDD per standard deviation (SD) increase in leisure-time physical activity, physical activity during sport, physical activity at work, peakVO₂, VO₂@AT, and maximum power output were 1.002 (95% confidence interval, 0.90 to 1.12), 1.02 (0.90 to 1.15), 0.94 (0.80 to 1.10), 0.71 (0.52 to 0.98), 0.83 (0.66 to 1.04), and 0.71 (0.52 to 0.96), respectively. PeakVO₂, VO₂@AT, and maximum power output were associated with recurrent MDD, depressive symptoms, and anxiety. PeakVO₂ was more strongly related to the co-occurrence of MDD and anxiety (adjusted odds ratio [OR] = 0.45 [0.24 to 0.84]) than depression or anxiety alone (OR = 0.71 [0.53 to 0.94]). Greater cardiorespiratory fitness but not domain-specific physical activity was associated with a lower incidence of MDD and clinical anxiety. © Copyright 2017 Physicians Postgraduate Press, Inc.

Music therapy modulates fronto-temporal activity in rest-EEG in depressed clients.

PubMed

Fachner, Jörg; Gold, Christian; Erkkilä, Jaakko

2013-04-01

Fronto-temporal areas process shared elements of speech and music. Improvisational psychodynamic music therapy (MT) utilizes verbal and musical reflection on emotions and images arising from clinical improvisation. Music listening is shifting frontal alpha asymmetries (FAA) in depression, and increases frontal midline theta (FMT). In a two-armed randomized controlled trial (RCT) with 79 depressed clients (with comorbid anxiety), we compared standard care (SC) versus MT added to SC at intake and after 3 months. We found that MT significantly reduced depression and anxiety symptoms. The purpose of this study is to test whether or not MT has an impact on anterior fronto-temporal resting state alpha and theta oscillations. Correlations between anterior EEG, Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hospital Anxiety and Depression Scale-Anxiety Subscale (HADS-A), power spectral analysis (topography, means, asymmetry) and normative EEG database comparisons were explored. After 3 month of MT, lasting changes in resting EEG were observed, i.e., significant absolute power increases at left fronto-temporal alpha, but most distinct for theta (also at left fronto-central and right temporoparietal leads). MT differed to SC at F7-F8 (z scored FAA, p < .03) and T3-T4 (theta, p < .005) asymmetry scores, pointing towards decreased relative left-sided brain activity after MT; pre/post increased FMT and decreased HADS-A scores (r = .42, p < .05) indicate reduced anxiety after MT. Verbal reflection and improvising on emotions in MT may induce neural reorganization in fronto-temporal areas. Alpha and theta changes in fronto-temporal and temporoparietal areas indicate MT action and treatment effects on cortical activity in depression, suggesting an impact of MT on anxiety reduction.

An active inference theory of allostasis and interoception in depression

PubMed Central

Quigley, Karen S.; Hamilton, Paul

2016-01-01

In this paper, we integrate recent theoretical and empirical developments in predictive coding and active inference accounts of interoception (including the Embodied Predictive Interoception Coding model) with working hypotheses from the theory of constructed emotion to propose a biologically plausible unified theory of the mind that places metabolism and energy regulation (i.e. allostasis), as well as the sensory consequences of that regulation (i.e. interoception), at its core. We then consider the implications of this approach for understanding depression. We speculate that depression is a disorder of allostasis, whose myriad symptoms result from a ‘locked in’ brain that is relatively insensitive to its sensory context. We conclude with a brief discussion of the ways our approach might reveal new insights for the treatment of depression. This article is part of the themed issue ‘Interoception beyond homeostasis: affect, cognition and mental health’. PMID:28080969

Physical activity correlates among 24,230 people with depression across 46 low- and middle-income countries.

PubMed

Vancampfort, Davy; Stubbs, Brendon; Firth, Joseph; Hallgren, Mats; Schuch, Felipe; Lahti, Jouni; Rosenbaum, Simon; Ward, Philip B; Mugisha, James; Carvalho, André F; Koyanagi, Ai

2017-10-15

There is a paucity of nationally representative data available on the correlates of physical activity (PA) among people with depression, especially in low- and middle-income countries (LMICs). Thus, we investigated PA correlates among community-dwelling adults with depression in this setting. World Health Survey data included 24,230 adults (43.1 ± 16.1 years; 36.1% male) with ICD-10 diagnoses of depression including brief depressive episode and subsyndromal depression aged ≥ 18 years from 46 LMICs. PA was assessed by the International Physical Activity Questionnaire. Participants were dichotomised into low and moderate-to-high physically active groups. Associations between PA and a range of sociodemographic, health behaviour and mental and physical health variables were examined using multivariable logistic regressions. 34.8% of participants with depression were physically inactive. In the multivariate analyses, inactivity was associated with male sex, older age, not being married/cohabiting, high socio-economic status, unemployment, living in an urban setting, less vegetable consumption, and poor sleep/ low energy. In addition, mobility difficulties and some somatic co-morbidity were associated with not complying with the 150min per week moderate-to-vigorous PA recommendations. The current data provide guidance for future population level interventions across LMICs to help people with depression engage in regular PA. Copyright © 2017 Elsevier B.V. All rights reserved.

Depressive symptoms and inductive reasoning performance: findings from the ACTIVE reasoning training intervention.

PubMed

Parisi, Jeanine M; Franchetti, Mary Kathryn; Rebok, George W; Spira, Adam P; Carlson, Michelle C; Willis, Sherry L; Gross, Alden L

2014-12-01

Within the context of the Advanced Cognitive Training for Independent and Vital Elderly study (ACTIVE; Ball et al., 2002; Jobe et al., 2001; Willis et al., 2006), we examined the longitudinal association of baseline depressive symptoms on inductive reasoning performance over a 10-year period between the reasoning training and control conditions (N = 1,375). At baseline, 322 participants (23%) reported elevated depressive symptoms, defined by a score ≥9 on the 12-item version of the Center for Epidemiological Studies Depression Scale (CES-D; Mirowsky & Ross, 2003; Radloff, 1977). Differences in baseline depressive status were not associated with immediate posttraining gains or with subsequent annual change in reasoning performance, suggesting that the presence of elevated baseline depressive symptoms does not impact the ability to benefit from reasoning training. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

The Mediating and Moderating Effect of Volunteering on Pain and Depression, Life Purpose, Well-Being, and Physical Activity.

PubMed

Salt, Elizabeth; Crofford, Leslie J; Segerstrom, Suzanne

2017-08-01

To improve function and quality of life in patients with chronic pain, a prevalent and costly condition, an understanding of the relationships among well-being, physical activity, depression, and life purpose with pain is needed. Because of the role loss experienced by people with chronic pain, activities such as volunteering could have an important role in improving health and well-being. In one study, chronic pain patients who participated in volunteer activities reported both decreased pain and "a sense of purpose." The aim of this study is to test the relationships among pain and well-being, physical activity, depression, and life purpose and then to determine if volunteering activities mediated or moderated these relationships. This observational study was conducted in a large university setting in Kentucky and used a sample of 200 women older than age 50. We found that people with higher pain were more depressed and had lower life purpose and well-being. People who volunteered less had more pain, lower perceived life purpose, more depressive symptoms, and decreased physical activity. Volunteer activities did have a significant mediating effect on the relationship between pain and depression; approximately 9% of the relationship between pain and depression can be accounted for by volunteering. Moderation by volunteering was found between pain and life purpose. We identified important relationships among pain, volunteering, and health outcomes and found that volunteering has a role in improving depressive symptoms and life purpose in women with pain. Copyright © 2017 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Symptoms of anxiety and depression are related to cardiovascular responses to active, but not passive, coping tasks.

PubMed

Yuenyongchaiwat, Kornanong; Baker, Ian S; Sheffield, David

2017-01-01

Anxiety and depression have been linked to blunted blood pressure (BP) and heart rate (HR) reactions to mental stress tests; however, most studies have not included indices of underlying hemodynamics nor multiple stress tasks. This study sought to examine the relationships of anxiety and depression with hemodynamic responses to acute active and passive coping tasks. A total of 104 participants completed the Hospital Anxiety and Depression Scales and mental arithmetic, speech, and cold pressor tasks while BP, HR, total peripheral resistance, and cardiac output (CO) were assessed. After adjustment for traditional risk factors and baseline cardiovascular activity, depression scores were negatively associated with systolic BP, HR, and CO responses to the mental arithmetic task, while anxiety scores were inversely related to the systolic BP response to mental arithmetic. High anxiety or depression scores appear to be associated with blunted cardiac reactions to mental arithmetic (an active coping task), but not to the cold pressor test or speech tasks. Future research should further examine potential mechanisms and longitudinal pathways relating depression and anxiety to cardiovascular reactivity. TCTR20160208004.

Relationships between discretionary time activities, emotional experiences, delinquency and depressive symptoms among urban African American adolescents.

PubMed

Bohnert, Amy M; Richards, Maryse; Kohl, Krista; Randall, Edin

2009-04-01

Using the Experience Sampling Method (ESM), this cross-sectional study examined mediated and moderated associations between different types of discretionary time activities and depressive symptoms and delinquency among a sample of 246 (107 boys, 139 girls) fifth through eighth grade urban African American adolescents. More time spent in passive unstructured activities was associated with higher levels of depressive symptoms only for adolescents residing in less dangerous neighborhoods, whereas more time spent in active unstructured activities was associated with higher levels of delinquency only if adolescents resided in more dangerous neighborhoods. Alienation was positively associated with depressive symptoms and delinquency, but neither alienation nor positive affect mediated the relationship between activities and adjustment. These findings suggest the importance of considering neighborhood environment issues when determining what types of discretionary time activities are most beneficial for urban African American young adolescents.

Depression and Unmet Needs for Assistance With Daily Activities Among Community-Dwelling Older Adults.

PubMed

Xiang, Xiaoling; An, Ruopeng; Heinemann, Allen

2018-05-08

This study aims to investigate the impact of depressive symptoms on adverse consequences of unmet needs for assistance with daily activities among community-dwelling older adults. Data came from round 1 to 5 of the National Health and Aging Trends Study. Study sample consisted of 3,400 Medicare beneficiaries needing assistance with activities of daily living (ADL), instrumental activities of daily living (IADL), or mobility for any two consecutive years between 2011 and 2015. Study outcome was the number of self-reported adverse consequences of unmet needs for assistance with daily activities (e.g., went without eating, wet or soiled clothes). Mixed-effects negative binomial regression was used to estimate the association of lagged depressive symptoms and covariates in period t-1 and the number of adverse consequences of unmet needs in period t. The prevalence rates of adverse consequences of unmet needs were twice as high among older adults with elevated depressive symptoms as those without depression. After adjusting for covariates, prior wave depressive symptoms were associated with 1.24 times the rate of adverse consequences of unmet needs for assistance with ADL (Incidence Rate Ratio [IRR] = 1.24, 95% confidence interval [CI] = 1.09-1.41, p < .01) and IADL (IRR = 1.24, 95% CI = 1.06-1.44, p < .01), and 1.14 times the rate of adverse consequences of unmet needs for assistance with mobility (IRR = 1.14, 95% CI = 1.03-1.27, p < .05). Caring for older adults with mental health and long-term care needs calls for an integrated social and health services system.

Abnormal activation of the occipital lobes during emotion picture processing in major depressive disorder patients

PubMed Central

Li, Jianying; Xu, Cheng; Cao, Xiaohua; Gao, Qiang; Wang, Yan; Wang, Yanfang; Peng, Juyi; Zhang, Kerang

2013-01-01

A large number of studies have demonstrated that depression patients have cognitive dysfunction. With recently developed brain functional imaging, studies have focused on changes in brain function to investigate cognitive changes. However, there is still controversy regarding abnormalities in brain functions or correlation between cognitive impairment and brain function changes. Thus, it is important to design an emotion-related task for research into brain function changes. We selected positive, neutral, and negative pictures from the International Affective Picture System. Patients with major depressive disorder were asked to judge emotion pictures. In addition, functional MRI was performed to synchronously record behavior data and imaging data. Results showed that the total correct rate for recognizing pictures was lower in patients compared with normal controls. Moreover, the consistency for recognizing pictures for depressed patients was worse than normal controls, and they frequently recognized positive pictures as negative pictures. The consistency for recognizing pictures was negatively correlated with the Hamilton Depression Rating Scale. Functional MRI suggested that the activation of some areas in the frontal lobe, temporal lobe, parietal lobe, limbic lobe, and cerebellum was enhanced, but that the activation of some areas in the frontal lobe, parietal lobe and occipital lobe was weakened while the patients were watching positive and neutral pictures compared with normal controls. The activation of some areas in the frontal lobe, temporal lobe, parietal lobe, and limbic lobe was enhanced, but the activation of some areas in the occipital lobe were weakened while the patients were watching the negative pictures compared with normal controls. These findings indicate that patients with major depressive disorder have negative cognitive disorder and extensive brain dysfunction. Thus, reduced activation of the occipital lobe may be an initiating factor for

The association between dietary intake of folate and physical activity with psychological dimensions of depressive symptoms among students from Iran.

PubMed

Yary, Teymoor

2013-01-01

Depression in students is a major public health problem. Although several risk factors associated with depression have been identified, the cause of depression is still not clear. Several studies have demonstrated that physical activity and nutrient intake, such as increased levels of B vitamins in serum, decrease symptoms of depression. The aim of this study was to investigate the association between physical activity and dietary intake of vitamins B₆, B₉, and B₁₂ and symptoms of depression among postgraduate students. The results of this study suggest that intake of vitamin B9 may modulate the total score of Center for Epidemiological Studies Depression Scale (CES-D) and two subscales of the CES-D including depressive affect and interpersonal difficulties. This study also showed that moderate/high levels of physical activity were inversely and significantly associated with symptoms of depression (total scores) and three subscales of the CES-D including depressive affect, positive affect, and somatic complaints.

Age Dependency of Inhibition of α7 Nicotinic Receptors and Tonically Active N-Methyl-d-aspartate Receptors by Endogenously Produced Kynurenic Acid in the Brain

PubMed Central

Alkondon, Manickavasagom; Pereira, Edna F. R.; Eisenberg, Howard M.; Kajii, Yasushi; Schwarcz, Robert

2011-01-01

In the mouse hippocampus normal levels of kynurenic acid (KYNA), a neuroactive metabolite synthesized in astrocytes primarily by kynurenine aminotransferase II (KAT II)-catalyzed transamination of l-kynurenine, maintain a degree of tonic inhibition of α7 nicotinic acetylcholine receptors (nAChRs). The present in vitro study was designed to test the hypothesis that α7 nAChR activity decreases when endogenous production of KYNA increases. Incubation (2–7 h) of rat hippocampal slices with kynurenine (200 μM) resulted in continuous de novo synthesis of KYNA. Kynurenine conversion to KYNA was significantly decreased by the KAT II inhibitor (S)-(−)-9-(4-aminopiperazine-1-yl)-8-fluoro-3-methyl-6-oxo-2,3,5,6-tetrahydro-4H-1-oxa-3a-azaphenalene-5carboxylic acid (BFF122) (100 μM) and was more effective in slices from postweaned than preweaned rats. Incubation of slices from postweaned rats with kynurenine inhibited α7 nAChRs and extrasynaptic N-methyl-d-aspartate receptors (NMDARs) on CA1 stratum radiatum interneurons. These effects were attenuated by BFF122 and mimicked by exogenously applied KYNA (200 μM). Exposure of human cerebral cortical slices to kynurenine also inhibited α7 nAChRs. The α7 nAChR sensitivity to KYNA is age-dependent, because neither endogenously produced nor exogenously applied KYNA inhibited α7 nAChRs in slices from preweaned rats. In these slices, kynurenine-derived KYNA also failed to inhibit extrasynaptic NMDARs, which could, however, be inhibited by exogenously applied KYNA. In slices from preweaned and postweaned rats, glutamatergic synaptic currents were not affected by endogenously produced KYNA, but were inhibited by exogenously applied KYNA. These results suggest that in the mature brain α7 nAChRs and extrasynaptic NMDARs are in close apposition to KYNA release sites and, thereby, readily accessible to inhibition by endogenously produced KYNA. PMID:21270133

Activation and Self-Efficacy in a Randomized Trial of a Depression Self-Care Intervention

ERIC Educational Resources Information Center

McCusker, Jane; Lambert, Sylvie D.; Cole, Martin G.; Ciampi, Antonio; Strumpf, Erin; Freeman, Ellen E.; Belzile, Eric

2016-01-01

Objectives: In a sample of primary care participants with chronic physical conditions and comorbid depressive symptoms: to describe the cross-sectional and longitudinal associations of activation and self-efficacy with demographic, physical and mental health status, health behaviors, depression self-care, health care utilization, and use of…

Depression-related increases and decreases in appetite reveal dissociable patterns of aberrant activity in reward and interoceptive neurocircuitry

PubMed Central

Simmons, W. Kyle; Burrows, Kaiping; Avery, Jason A.; Kerr, Kara L.; Bodurka, Jerzy; Savage, Cary R.; Drevets, Wayne C.

2016-01-01

Objective Appetite and weight changes are common but variable diagnostic markers in major depressive disorder: some depressed individuals manifest increased appetite, while others lose their appetite. Many of the brain regions implicated in appetitive responses to food have also been implicated in depression. It is thus remarkable that there exists no published research comparing the neural responses to food stimuli of depressed patients with increased versus decreased appetites. Method Using functional magnetic resonance imaging we compared brain activity in unmedicated depressed patients with increased or decreased appetite, and healthy control subjects, while viewing photographs of food and non-food objects. We also measured how resting-state functional connectivity related to subjects’ food pleasantness ratings. Results Within putative reward regions, depressed participants with increased appetites exhibited greater hemodynamic activity to food stimuli than both those reporting appetite decreases and healthy control subjects. In contrast, depressed subjects experiencing appetite loss exhibited hypoactivation within a region of the mid-insula implicated in interoception, with no difference observed in this region between healthy subjects and those with depression-related appetite increases. Mid-insula activity was negatively correlated with food pleasantness ratings of depressed participants with increased appetites, and its functional connectivity to reward circuitry was positively correlated with food pleasantness ratings. Conclusions Depression-related increases in appetite are associated with hyperactivation of putative mesocorticolimbic reward circuitry, while depression-related appetite loss is associated with hypoactivation of insular regions that support monitoring the body’s physiological state. Importantly, the interactions among these regions also contribute to individual differences in the depression-related appetite changes. PMID:26806872

Altered striatal activation predicting real-world positive affect in adolescent major depressive disorder.

PubMed

Forbes, Erika E; Hariri, Ahmad R; Martin, Samantha L; Silk, Jennifer S; Moyles, Donna L; Fisher, Patrick M; Brown, Sarah M; Ryan, Neal D; Birmaher, Boris; Axelson, David A; Dahl, Ronald E

2009-01-01

Alterations in reward-related brain function and phenomenological aspects of positive affect are increasingly examined in the development of major depressive disorder. The authors tested differences in reward-related brain function in healthy and depressed adolescents, and the authors examined direct links between reward-related brain function and positive mood that occurred in real-world contexts. Fifteen adolescents with major depressive disorder and 28 adolescents with no history of psychiatric disorder, ages 8-17 years, completed a functional magnetic resonance imaging guessing task involving monetary reward. Participants also reported their subjective positive affect in natural environments during a 4-day cell-phone-based ecological momentary assessment. Adolescents with major depressive disorder exhibited less striatal response than healthy comparison adolescents during reward anticipation and reward outcome, but more response in dorsolateral and medial prefrontal cortex. Diminished activation in a caudate region associated with this depression group difference was correlated with lower subjective positive affect in natural environments, particularly within the depressed group. Results support models of altered reward processing and related positive affect in young people with major depressive disorder and indicate that depressed adolescents' brain response to monetary reward is related to their affective experience in natural environments. Additionally, these results suggest that reward-processing paradigms capture brain function relevant to real-world positive affect.

Emamectin is a non-selective allosteric activator of nicotinic acetylcholine receptors and GABAA/C receptors

PubMed Central

Xu, Xiaojun; Sepich, Caraline; Lukas, Ronald J; Zhu, Guonian; Chang, Yongchang

2016-01-01

Avermectins are a group of compounds isolated from a soil-dwelling bacterium. They have been widely used as parasiticides and insecticides, acting by relatively irreversible activation of invertebrate chloride channels. Emamectin is a soluble derivative of an avermectin. It is an insecticide, which persistently activates glutamate-gated chloride channels. However, its effects on mammalian ligand-gated ion channels are unknown. To this end, we tested the effect of emamectin on two cation selective nicotinic receptors and two GABA-gated chloride channels expressed in Xenopus oocytes using two-electrode voltage clamp. Our results demonstrate that emamectin could directly activate α7 nAChR, α4β2 nAChR, α1β2γ2 GABAA receptor and ρ1 GABAC receptor concentration dependently, with similar potencies for each channel. However, the potencies for it to activate these channels were at least two orders of magnitude lower than its potency of activating invertebrate glutamate-gated chloride channel. In contrast, ivermectin only activated the α1β2γ2 GABAA receptor. PMID:27049309

Emamectin is a non-selective allosteric activator of nicotinic acetylcholine receptors and GABAA/C receptors.

PubMed

Xu, Xiaojun; Sepich, Caraline; Lukas, Ronald J; Zhu, Guonian; Chang, Yongchang

2016-05-13

Avermectins are a group of compounds isolated from a soil-dwelling bacterium. They have been widely used as parasiticides and insecticides, acting by relatively irreversible activation of invertebrate chloride channels. Emamectin is a soluble derivative of an avermectin. It is an insecticide, which persistently activates glutamate-gated chloride channels. However, its effects on mammalian ligand-gated ion channels are unknown. To this end, we tested the effect of emamectin on two cation selective nicotinic receptors and two GABA-gated chloride channels expressed in Xenopus oocytes using two-electrode voltage clamp. Our results demonstrate that emamectin could directly activate α7 nAChR, α4β2 nAChR, α1β2γ2 GABAA receptor and ρ1 GABAC receptor concentration dependently, with similar potencies for each channel. However, the potencies for it to activate these channels were at least two orders of magnitude lower than its potency of activating invertebrate glutamate-gated chloride channel. In contrast, ivermectin only activated the α1β2γ2 GABAA receptor. Copyright © 2016 Elsevier Inc. All rights reserved.

Participation in productive activities and depression among older Europeans: survey of Health, Ageing and Retirement in Europe (SHARE).

PubMed

Choi, Kyeong-Sook; Stewart, Robert; Dewey, Michael

2013-11-01

Although engagement in productive activities is associated with favourable outcomes with respect to the health and well-being of older individuals, the association between such activities and depression in older populations remains relatively unexplored. The purpose of this study was to evaluate the association among five productive activities (paid work, formal volunteering, caregiving, informal helping and caring for grandchildren) with depression in older adults in 14 European countries. This cross-sectional study used the first two waves of data collected by the Survey of Health, Ageing and Retirement in Europe and analysed a total sample of 7238 relatively healthy community residents aged 60 years and older from 14 European countries. The Survey of Health, Ageing and Retirement in Europe excluded potential participants with a past history of depression, cognitive impairment and physical limitations. Depression was categorised using the EURO-D instrument, and associations with participating in productive activities were investigated. Depression was less prevalent among those individuals who were employed or self-employed and those who participated in formal volunteering or informal helping, whereas caregiving was associated with a higher risk of depression. Caring for grandchildren was not associated positively or negatively with depression. Formal volunteering and caregiving remained associated with depression after adjustment for age, sex, marital status, education, economic status, country and presence of long-term illness. Availability of formal volunteering may be important in reducing depression risk, whereas caregiving is associated with a higher risk of depression in older European adults. Further research is required to clarify the direction of causation and evaluate interventions. Copyright © 2013 John Wiley & Sons, Ltd.

Hypothalamic damage in multiple sclerosis correlates with disease activity, disability, depression, and fatigue.

PubMed

Kantorová, E; Poláček, H; Bittšanský, M; Baranovičová, E; Hnilicová, P; Čierny, D; Sivák, Š; Nosáľ, V; Zeleňák, K; Kurča, E

2017-04-01

Disturbances in the hypothalamo-pituitary axis are supposed to modulate activity of multiple sclerosis (MS). We hypothesised that the extent of HYP damage may determine severity of MS and may be associated with the disease evolution. We suggested fatigue and depression may depend on the degree of damage of the area. 33 MS patients with relapsing-remitting and secondary progressive disease, and 24 age and sex-related healthy individuals (CON) underwent 1H-MR spectroscopy (1H-MRS) of the hypothalamus. Concentrations of glutamate + glutamin (Glx), cholin (Cho), myoinositol (mIns), N-acetyl aspartate (NAA) expressed as ratio with creatine (Cr) and NAA were correlated with markers of disease activity (RIO score), Multiple Sclerosis Severity Scale (MSSS), Depressive-Severity Status Scale and Simple Numerical Fatigue Scale. Cho/Cr and NAA/Cr ratios were decreased and Glx/NAA ratio increased in MS patients vs CON. Glx/NAA, Glx/Cr, and mIns/NAA were significantly higher in active (RIO 1-2) vs non-active MS patients (RIO 0). Glx/NAA and Glx/Cr correlated with MSSS and fatigue score, and Glx/Cr with depressive score of MS patients. In CON, relationships between Glx/Cr and age, and Glx/NAA and fatigue score were inverse. Our study provides the first evidence about significant hypothalamic alterations correlating with clinical outcomes of MS, using 1H-MRS. The combination of increased Glu or mIns with reduced NAA in HYP reflects whole-brain activity of MS. In addition, excess of Glu is linked to severe disease course, depressive mood and fatigue in MS patients, suggesting superiority of Glu over other metabolites in determining MS burden.

Activation of α7 nicotinic acetylcholine receptors protects potentiated synapses from depotentiation during theta pattern stimulation in the hippocampal CA1 region of rats

PubMed Central

Galvez, Bryan; Gross, Noah; Sumikawa, Katumi

2016-01-01

Long-term potentiation (LTP) shows memory-like consolidation and thus becomes increasingly resistant to disruption by low-frequency stimulation (LFS). However, it is known that nicotine application during LFS uniquely depotentiates consolidated LTP. Here, we investigated how nicotine contributes to the disruption of stabilized LTP in the hippocampal CA1 region. We found that nicotine-induced depotentiation is not due to masking LTP by inducing long-term depression and requires the activation of GluN2A-containing NMDARs. We further examined whether nicotine-induced depotentiation involves the reversal of LTP mechanisms. LTP causes phosphorylation of Ser-831 on GluA1 subunits of AMPARs that increases the single-channel conductance of AMPARs. This phosphorylation remained unchanged after depotentiation. LTP involves the insertion of new AMPARs into the synapse and the internalization of AMPARs is associated with dephosphorylation of Ser-845 on GluA1 and caspase-3 activity. Nicotine-induced depotentiation occurred without dephosphorylation of the Ser-845 and in the presence of a caspase-3 inhibitor. LTP is also accompanied by increased filamentous actin (F-actin), which controls spine size. Nicotine-induced depotentiation was prevented by jasplakinolide, which stabilizes F-actin, suggesting that nicotine depotentiates consolidated LTP by destabilizing F-actin. α7 nicotinic acetylcholine receptor (nAChR) antagonists mimicked the effect of nicotine and selective removal of hippocampal cholinergic input caused depotentiation in the absence of nicotine, suggesting that nicotine depotentiates consolidated LTP by inducing α7 nAChR desensitization. Our results demonstrate a new role for nicotinic cholinergic systems in protecting potentiated synapses from depotentiation by preventing GluN2A-NMDAR-mediated signaling for actin destabilization. PMID:26867505

Chamomile (Matricaria recutita) may provide antidepressant activity in anxious, depressed humans: an exploratory study.

PubMed

Amsterdam, Jay D; Shults, Justine; Soeller, Irene; Mao, Jun James; Rockwell, Kenneth; Newberg, Andrew B

2012-01-01

Anxiety and depression are the most commonly reported psychiatric conditions and frequently occur as comorbid disorders. While the advent of conventional drug therapies has simplified treatment, a large segment of the population goes untreated or declines conventional therapy for financial, cultural, or personal reasons. Therefore, the identification of inexpensive and effective alternative therapies for anxiety and depression is of relevance to public health. The current study explores data from a 2009 clinical chamomile trial in humans to determine if chamomile provides clinically meaningful antidepressant activity versus a placebo. In the 2009 randomized, double-blind, placebo-controlled study, the research team examined the antianxiety and antidepressant action of oral chamomile (Matricaria recutita) extract in participants with symptoms of comorbid anxiety and depression. In the 2009 study, all of participants' evaluations took place at the Depression Research Unit at the University of Pennsylvania. The study drew participants from patients at the Department of Family Medicine and Community Health's primary care clinic at the University of Pennsylvania, Philadelphia. Of the 57 participants in the 2009 trial, 19 had anxiety with comorbid depression; 16 had anxiety with a past history of depression; and 22 had anxiety with no current or past depression. The intervention and placebo groups in the 2009 trial received identically appearing 220-mg capsules containing either pharmaceutical-grade chamomile extract standardized to a content of 1.2% apigenin or a placebo (ie, lactose monohydrate NF), respectively. In the current study, the research team used generalized estimating equations analysis to identify clinically meaningful changes over time in scores from the Hamilton Depression Rating (HAM-D) questionnaire among treatment groups. In the current study, the research team observed a significantly greater reduction over time in total HAM-D scores for chamomile vs

Attention bias in older women with remitted depression is associated with enhanced amygdala activity and functional connectivity.

PubMed

Albert, Kimberly; Gau, Violet; Taylor, Warren D; Newhouse, Paul A

2017-03-01

Cognitive bias is a common characteristic of major depressive disorder (MDD) and is posited to remain during remission and contribute to recurrence risk. Attention bias may be related to enhanced amygdala activity or altered amygdala functional connectivity in depression. The current study examined attention bias, brain activity for emotional images, and functional connectivity in post-menopausal women with and without a history of major depression. Attention bias for emotionally valenced images was examined in 33 postmenopausal women with (n=12) and without (n=21) a history of major depression using an emotion dot probe task during fMRI. Group differences in amygdala activity and functional connectivity were assessed using fMRI and examined for correlations to attention performance. Women with a history of MDD showed greater attentional bias for negative images and greater activity in brain areas including the amygdala for both positive and negative images (pcorr <0.001) than women without a history of MDD. In all participants, amygdala activity for negative images was correlated with attention facilitation for emotional images. Women with a history of MDD had significantly greater functional connectivity between the amygdala and hippocampal complex. In all participants amygdala-hippocampal connectivity was positively correlated with attention facilitation for negative images. Small sample with unbalanced groups. These findings provide evidence for negative attentional bias in euthymic, remitted depressed individuals. Activity and functional connectivity in limbic and attention networks may provide a neurobiological basis for continued cognitive bias in remitted depression. Copyright © 2016 Elsevier B.V. All rights reserved.

Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection

PubMed Central

2017-01-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is vital to the survival, growth, and maintenance of neurons in key brain circuits involved in emotional and cognitive function. Convergent evidence indicates that neuroplastic mechanisms involving BDNF are deleteriously altered in major depressive disorder (MDD) and animal models of stress. Herein, clinical and preclinical evidence provided that stress-induced depressive pathology contributes to altered BDNF level and function in persons with MDD and, thereby, disruptions in neuroplasticity at the regional and circuit level. Conversely, effective therapeutics that mitigate depressive-related symptoms (e.g., antidepressants and physical activity) optimize BDNF in key brain regions, promote neuronal health and recovery of function in MDD-related circuits, and enhance pharmacotherapeutic response. A greater knowledge of the interrelationship between BDNF, depression, therapeutic mechanisms of action, and neuroplasticity is important as it necessarily precedes the derivation and deployment of more efficacious treatments. PMID:28928987

Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection.

PubMed

Phillips, Cristy

2017-01-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is vital to the survival, growth, and maintenance of neurons in key brain circuits involved in emotional and cognitive function. Convergent evidence indicates that neuroplastic mechanisms involving BDNF are deleteriously altered in major depressive disorder (MDD) and animal models of stress. Herein, clinical and preclinical evidence provided that stress-induced depressive pathology contributes to altered BDNF level and function in persons with MDD and, thereby, disruptions in neuroplasticity at the regional and circuit level. Conversely, effective therapeutics that mitigate depressive-related symptoms (e.g., antidepressants and physical activity) optimize BDNF in key brain regions, promote neuronal health and recovery of function in MDD-related circuits, and enhance pharmacotherapeutic response. A greater knowledge of the interrelationship between BDNF, depression, therapeutic mechanisms of action, and neuroplasticity is important as it necessarily precedes the derivation and deployment of more efficacious treatments.

Neural activity in relation to empirically derived personality syndromes in depression using a psychodynamic fMRI paradigm

PubMed Central

Taubner, Svenja; Wiswede, Daniel; Kessler, Henrik

2013-01-01

Objective: The heterogeneity between patients with depression cannot be captured adequately with existing descriptive systems of diagnosis and neurobiological models of depression. Furthermore, considering the highly individual nature of depression, the application of general stimuli in past research efforts may not capture the essence of the disorder. This study aims to identify subtypes of depression by using empirically derived personality syndromes, and to explore neural correlates of the derived personality syndromes. Materials and Methods: In the present exploratory study, an individually tailored and psychodynamically based functional magnetic resonance imaging paradigm using dysfunctional relationship patterns was presented to 20 chronically depressed patients. Results from the Shedler–Westen Assessment Procedure (SWAP-200) were analyzed by Q-factor analysis to identify clinically relevant subgroups of depression and related brain activation. Results: The principle component analysis of SWAP-200 items from all 20 patients lead to a two-factor solution: “Depressive Personality” and “Emotional-Hostile-Externalizing Personality.” Both factors were used in a whole-brain correlational analysis but only the second factor yielded significant positive correlations in four regions: a large cluster in the right orbitofrontal cortex (OFC), the left ventral striatum, a small cluster in the left temporal pole, and another small cluster in the right middle frontal gyrus. Discussion: The degree to which patients with depression score high on the factor “Emotional-Hostile-Externalizing Personality” correlated with relatively higher activity in three key areas involved in emotion processing, evaluation of reward/punishment, negative cognitions, depressive pathology, and social knowledge (OFC, ventral striatum, temporal pole). Results may contribute to an alternative description of neural correlates of depression showing differential brain activation dependent

Understanding temporal relationships between depression, falls, and physical activity in a cohort of post-hospitalized older adults - a breakthrough or a conundrum?

PubMed

Lee, Den-Ching A; Lalor, Aislinn F; Russell, Grant; Stolwyk, Rene; Brown, Ted; McDermott, Fiona; Haines, Terry P

2017-10-01

Clinical depression affects approximately 15% of community-dwelling older adults, of which half of these cases present in later life. Falls and depressive symptoms are thought to co-exist, while physical activity may protect an older adult from developing depressive symptoms. This study investigates the temporal relationships between depressive symptoms, falls, and participation in physical activities amongst older adults recently discharged following extended hospitalization. A prospective cohort study in which 311 older adults surveyed prior to hospital discharge were assessed monthly post-discharge for six months. N = 218 completed the six-month follow-up. Participants were recruited from hospitals in Melbourne, Australia. The survey instrument used was designed based on Fiske's behavioral model depicting onset and maintenance of depression. The baseline survey collected data on self-reported falls, physical activity levels, and depressive symptoms. The monthly follow-up surveys repeated measurement of these outcomes. At any assessment point, falls were positively associated with depressive symptoms; depressive symptoms were negatively associated with physical activity levels; and, physical activity levels were negatively associated with falls. When compared with data in the subsequent assessment point, depressive symptoms were positively associated with falls reported over the next month (unadjusted OR: 1.20 (1.12, 1.28)), and physical activity levels were negatively associated with falls reported over the next month (unadjusted OR: 0.97 (0.96, 0.99) household and recreational), both indicating a temporal relationship. Falls, physical activity, and depressive symptoms were inter-associated, and depressive symptoms and low physical activity levels preceded falls. Clear strategies for management of these interconnected problems remain elusive.

Prenatal maternal immune activation increases anxiety- and depressive-like behaviors in offspring with experimental autoimmune encephalomyelitis.

PubMed

Majidi-Zolbanin, J; Doosti, M-H; Kosari-Nasab, M; Salari, A-A

2015-05-21

Multiple sclerosis (MS) is thought to result from a combination of genetics and environmental factors. Several lines of evidence indicate that significant prevalence of anxiety and depression-related disorders in MS patients can influence the progression of the disease. Although we and others have already reported the consequences of prenatal maternal immune activation on anxiety and depression, less is known about the interplay between maternal inflammation, MS and gender. We here investigated the effects of maternal immune activation with Poly I:C during mid-gestation on the progression of clinical symptoms of experimental autoimmune encephalomyelitis (EAE; a mouse model of MS), and then anxiety- and depressive-like behaviors in non-EAE and EAE-induced offspring were evaluated. Stress-induced corticosterone and tumor necrosis factor-alpha (TNF-α) levels in EAE-induced offspring were also measured. Maternal immune activation increased anxiety and depression in male offspring, but not in females. This immune challenge also resulted in an earlier onset of the EAE clinical signs in male offspring and enhanced the severity of the disease in both male and female offspring. Interestingly, the severity of the disease was associated with increased anxiety/depressive-like behaviors and elevated corticosterone or TNF-α levels in both sexes. Overall, these data suggest that maternal immune activation with Poly I:C during mid-pregnancy increases anxiety- and depressive-like behaviors, and the clinical symptoms of EAE in a sex-dependent manner in non-EAE or EAE-induced offspring. Finally, the progression of EAE in offspring seems to be linked to maternal immune activation-induced dysregulation in neuro-immune-endocrine system. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Dopamine D2-receptor activation elicits akinesia, rigidity, catalepsy, and tremor in mice expressing hypersensitive α4 nicotinic receptors via a cholinergic-dependent mechanism

PubMed Central

Zhao-Shea, Rubing; Cohen, Bruce N.; Just, Herwig; McClure-Begley, Tristan; Whiteaker, Paul; Grady, Sharon R.; Salminen, Outi; Gardner, Paul D.; Lester, Henry A.; Tapper, Andrew R.

2010-01-01

Recent studies suggest that high-affinity neuronal nicotinic acetylcholine receptors (nAChRs) containing α4 and β2 subunits (α4β2*) functionally interact with G-protein-coupled dopamine (DA) D2 receptors in basal ganglia. We hypothesized that if a functional interaction between these receptors exists, then mice expressing an M2 point mutation (Leu9′Ala) rendering α4 nAChRs hypersensitive to ACh may exhibit altered sensitivity to a D2-receptor agonist. When challenged with the D2R agonist, quinpirole (0.5–10 mg/kg), Leu9′Ala mice, but not wild-type (WT) littermates, developed severe, reversible motor impairment characterized by rigidity, catalepsy, akinesia, and tremor. While striatal DA tissue content, baseline release, and quinpirole-induced DA depletion did not differ between Leu9′Ala and WT mice, quinpirole dramatically increased activity of cholinergic striatal interneurons only in mutant animals, as measured by increased c-Fos expression in choline acetyltransferase (ChAT)-positive interneurons. Highlighting the importance of the cholinergic system in this mouse model, inhibiting the effects of ACh by blocking muscarinic receptors, or by selectively activating hypersensitive nAChRs with nicotine, rescued motor symptoms. This novel mouse model mimics the imbalance between striatal DA/ACh function associated with severe motor impairment in disorders such as Parkinson’s disease, and the data suggest that a D2R–α4*-nAChR functional interaction regulates cholinergic interneuron activity.—Zhao-Shea, R., Cohen, B. N., Just, H., McClure-Begley, T., Whiteaker, P., Grady, S. R., Salminen, O., Gardner, P. D., Lester, H. A., Tapper, A. R. Dopamine D2-receptor activation elicits akinesia, rigidity, catalepsy, and tremor in mice expressing hypersensitive α4 nicotinic receptors via a cholinergic-dependent mechanism. PMID:19720621

The efficacy of behavioural activation treatment for co-occurring depression and substance use disorder (the activate study): a randomized controlled trial.

PubMed

Ross, Joanne; Teesson, Maree; Lejuez, Carl; Mills, Katherine; Kaye, Sharlene; Brady, Kathleen; Dore, Glenys; Prior, Katrina; Larkin, Xanthe; Cassar, Joanne; Ewer, Philippa; Memedovic, Sonja; Kihas, Ivana; Masters, Sarah Louise

2016-07-08

Epidemiological studies suggest that compared with the general population, mood disorders are up to 4.7 times more prevalent in substance dependent samples. Comorbid substance use disorder (SUD) and depression has been associated with a more severe and protracted illness course and poorer treatment outcomes. Despite this, the development and assessment of behavioural interventions for treating depression among individuals with SUDs have received little empirical attention. Behavioural Activation Treatment for Depression (BATD-R) is an empirically supported treatment for depression that has shown some efficacy among substance users. This paper describes the study protocol of a parallel, single blind, randomised controlled trial to determine the efficacy and feasibility of a modified version of the BATD-R (Activate) in reducing symptoms of depression and substance dependence among individuals in residential rehabilitation (RR) and opioid substitution therapy (OST). A sample of approximately 200 individuals with depressive symptomatology in treatment for SUD will be recruited from RR and OST services in New South Wales, Australia. Dynamic random allocation following minimisation methodology will be used to assign participants to one of two groups. The control group will receive treatment as usual (TAU), which will be the model of care provided in accordance with standard practice at participating RR and OST services. The intervention group will receive Activate, comprising 10 individual 60-min therapy sessions with a psychologist employed on the research team, in addition to TAU. Data collection will occur at baseline (pre-intervention), and 3-months and 12-months post baseline. The association between depression and substance dependence has been well documented, yet practical and effective treatments are scarce. The findings of the present study will contribute significantly to understanding the types of programs that are effective in treating this comorbidity. This

Amygdala and whole-brain activity to emotional faces distinguishes major depressive disorder and bipolar disorder.

PubMed

Fournier, Jay C; Keener, Matthew T; Almeida, Jorge; Kronhaus, Dina M; Phillips, Mary L

2013-11-01

It can be clinically difficult to distinguish depressed individuals with bipolar disorder (BD) and major depressive disorder (MDD). To examine potential biomarkers of difference between the two disorders, the current study examined differences in the functioning of emotion-processing neural regions during a dynamic emotional faces task. During functional magnetic resonance imaging, healthy control adults (HC) (n = 29) and depressed adults with MDD (n = 30) and BD (n = 22) performed an implicit emotional-faces task in which they identified a color label superimposed on neutral faces that dynamically morphed into one of four emotional faces (angry, fearful, sad, happy). We compared neural activation between the groups in an amygdala region-of-interest and at the whole-brain level. Adults with MDD showed significantly greater activity than adults with BD in the left amygdala to the anger condition (p = 0.01). Results of whole-brain analyses (at p < 0.005, k ≥ 20) revealed that adults with BD showed greater activity to sad faces in temporoparietal regions, primarily in the left hemisphere, whereas individuals with MDD demonstrated greater activity than those with BD to displays of anger, fear, and happiness. Many of the observed BD-MDD differences represented abnormalities in functioning compared to HC. We observed a dissociation between depressed adults with BD and MDD in the processing of emerging emotional faces. Those with BD showed greater activity during mood-congruent (i.e., sad) faces, whereas those with MDD showed greater activity for mood-incongruent (i.e., fear, anger, and happy) faces. Such findings may reflect markers of differences between BD and MDD depression in underlying pathophysiological processes. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Physical activity patterns of people affected by depressive and anxiety disorders as measured by accelerometers: a cross-sectional study.

PubMed

Helgadóttir, Björg; Forsell, Yvonne; Ekblom, Örjan

2015-01-01

Exercise can relieve both depressive and anxiety disorders and it is therefore of importance to establish movement patterns of mildly to moderately affected sufferers to estimate the treatment potential. The aim is to describe the physical activity patterns of people affected by mild to moderate depressive and/or anxiety symptoms using objective measures of physical activity. The design of the study was cross-sectional using data from 165 people aged 18-65 years, with mild to moderate depressive and/or anxiety disorder symptoms (scoring ≥ 10 on the PHQ-9). Diagnoses were made using Mini International Neuropsychiatric Interview (MINI) and symptom severity was measured with the Montgomery-Åsberg Depression Rating Scale (MADRS). The participants wore accelerometers for a week to evaluate physical activity patterns. No statistically significant differences were detected between different diagnoses, though depressed participants tended to be less active and more sedentary. Only one-fifth of the sample followed public health guidelines regarding physical activity. Each one point increase in MADRS was associated with a 2.4 minute reduction in light physical activity, independent of moderate-to-vigorous physical activity and sedentary time. MADRS was positively associated with number of sedentary bouts. The physical activity pattern of people with depressive and/or anxiety disorders was characterized by large amounts of sedentary time and low fulfillment of physical activity guidelines. There is therefore a large treatment potential for this group by increasing exercise. The results suggest that instead of focusing exclusively on high intensity exercise for treating depressive and anxiety disorders, health care providers might encourage patients to reduce sedentary time by increasing light physical activity and decreasing the number of sedentary bouts, though further studies are needed that can determine directionality.

Cognitive Behavioral Therapy Is Associated With Enhanced Cognitive Control Network Activity in Major Depression and Posttraumatic Stress Disorder

PubMed Central

Yang, Zhen; Oathes, Desmond J.; Linn, Kristin A.; Bruce, Steven E.; Satterthwaite, Theodore D.; Cook, Philip A.; Satchell, Emma K.; Shou, Haochang; Sheline, Yvette I.

2018-01-01

BACKGROUND Both major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are characterized by depressive symptoms, abnormalities in brain regions important for cognitive control, and response to cognitive behavioral therapy (CBT). However, whether a common neural mechanism underlies CBT response across diagnoses is unknown. METHODS Brain activity during a cognitive control task was measured using functional magnetic resonance imaging in 104 participants: 28 patients with MDD, 53 patients with PTSD, and 23 healthy control subjects; depression and anxiety symptoms were determined on the same day. A patient subset (n = 31) entered manualized CBT and, along with controls (n = 19), was rescanned at 12 weeks. Linear mixed effects models assessed the relationship between depression and anxiety symptoms and brain activity before and after CBT. RESULTS At baseline, activation of the left dorsolateral prefrontal cortex was negatively correlated with Montgomery–Åsberg Depression Rating Scale scores across all participants; this brain–symptom association did not differ between MDD and PTSD. Following CBT treatment of patients, regions within the cognitive control network, including ventrolateral prefrontal cortex and dorsolateral prefrontal cortex, showed a significant increase in activity. CONCLUSIONS Our results suggest that dimensional abnormalities in the activation of cognitive control regions were associated primarily with symptoms of depression (with or without controlling for anxious arousal). Furthermore, following treatment with CBT, activation of cognitive control regions was similarly increased in both MDD and PTSD. These results accord with the Research Domain Criteria conceptualization of mental disorders and implicate improved cognitive control activation as a transdiagnostic mechanism for CBT treatment outcome. PMID:29628063

Autonomic nervous system activity and anxiety and depressive symptoms in mothers up to 2 years postpartum.

PubMed

Izumi, Mie; Manabe, Emiko; Uematsu, Sayo; Watanabe, Ayako; Moritani, Toshio

2016-01-01

We investigated the association between autonomic nervous system (ANS) activity and symptoms of anxiety and depression for the first 2 years postpartum. A total of 108 participants within 2 years postpartum underwent physiological measurements of ANS activity using the heart rate variability (HRV) power spectrum and self-reported questionnaires (14-item Hospital Anxiety and Depression Score). The cutoff points for anxiety and depressive symptom scores in this questionnaire were as follows: 7 or less, non-cases; 8-10, doubtful cases; 11 or more, definite cases. This study was conducted from 2012 to 2014 at University Hospital in Kyoto Prefectural University of Medicine and a nearby obstetrics and gynecology department clinic in Japan. Anxiety and depression non-cases accounted for 67.6% (n = 73) of subjects, anxiety non-cases and depression doubtful and definite cases 7.4% (n = 8), anxiety doubtful and definite cases and depression non-cases 8.3% (n = 9), and anxiety and depression doubtful and definite cases 16.7% (n = 18). Findings were similar for women with anxiety or depression, with total power (TP), low-frequency (LF) and high-frequency (HF) components of HRV among doubtful and definite cases significantly lower than among non-cases for both anxiety (p = 0.006, 0.034, 0.029, respectively) and depression (p = 0.001, 0.004, 0.007). Significant correlations were observed between TP, LF and HF and anxiety and depression scores (respective values for anxiety: rs = -0.331, p <0.001; rs = -0.286, p = 0.003; rs = -0.269, p = 0.005; and depression: rs = -0.389, rs = -0.353, rs = -0.337, all p <0.001). The present study demonstrated that mothers with anxiety or depressive symptoms had significantly lower HRV (HF, LF and TP) than those without.

Depression and Anxiety are Common in Acute HIV Infection and Associate with Plasma Immune Activation.

PubMed

Hellmuth, Joanna; Colby, Donn; Valcour, Victor; Suttichom, Duanghathai; Spudich, Serena; Ananworanich, Jintanat; Prueksakaew, Peeriya; Sailasuta, Napapon; Allen, Isabel; Jagodzinski, Linda L; Slike, Bonnie; Ochi, Derek; Paul, Robert

2017-11-01

This observational study of 123 Thai participants sought to determine the rate and severity of affective symptoms during acute HIV infection (AHI) and possible associations to disease mechanisms. At diagnosis, just prior to starting combination antiretroviral therapy (cART), AHI participants completed assessments of depression and anxiety symptoms that were repeated at 4, 12, and 24 weeks. Blood markers of HIV infection and immune activation were measured at study entry, with optional cerebrospinal fluid measures. A high frequency of participants reported symptoms that exceeded published thresholds supportive of depression (55.0%) and anxiety (65.8%) at diagnosis, with significant reductions after starting cART. Meeting a threshold for clinically relevant depressive symptoms at study entry was associated with higher baseline plasma HIV RNA (5.98 vs. 5.50, t = 2.46, p = 0.015), lower CD4 counts (328 vs. 436 cells/mm 3 , t = 3.46, p = 0.001), and higher plasma neopterin, a marker of macrophage activation (2694 vs. 1730 pg/mL, Mann-Whitney U = 152.5, p = 0.011). Controlling for plasma HIV RNA and CD4 count, higher baseline plasma neopterin correlated with worse initial depression and anxiety scores. Depression and anxiety symptoms are frequent in acute HIV infection, associate with plasma immune activation, and can improve concurrent with cART.

The association between physical activity and depression among individuals residing in Brazil.

PubMed

de Oliveira, Gisele Dias; Oancea, S Cristina; Nucci, Luciana B; Vogeltanz-Holm, Nancy

2018-04-01

There is very limited literature investigating the association between physical activity (PA) and depression in South American countries such as Brazil. The purpose of the current study was to evaluate the prevalence of depression and its association with PA in a very large, representative sample of young adults (ages 18-39 years) (YA), middle-aged adults (ages 40-59 years) (MAA) and older adults (ages ≥ 60 years) (OA) residing in Brazil. The sample for this cross-sectional study was based on the Brazilian National Health Survey conducted in 2013. The Personal Health Questionnaire depression scale (PHQ-8) was applied to measure current (past 2 weeks) depression as the outcome of interest, and the exposure was self-reported PA for leisure. Multivariable weighted logistic regression models were conducted to investigate the association between PA and depression while adjusting for socio-demographic characteristics and number of health comorbidities among YA, MAA and OA. The final study sample size was 59,399 (33,480 females; 25,919 males). After adjusting for the covariates of interest, the lack of PA for leisure was associated with a significant increase in depression only among males (YA: OR 1.45, 95% CI 1.02-2.06; MAA: OR 2.38, 95% CI 1.40-4.03; OA: OR 5.35, 95% CI 2.14-13.37). There was no significant association between PA for leisure and depression among females of all age groups. Although PA for leisure is not associated with depression among Brazilian females, the obtained results suggest that this association is significant among Brazilian males, who may be able to benefit from PA for leisure to reduce their symptoms of depression.

Randomized Controlled Trial of Behavioral Activation Smoking Cessation Treatment for Smokers with Elevated Depressive Symptoms

ERIC Educational Resources Information Center

MacPherson, Laura; Tull, Matthew T.; Matusiewicz, Alexis K.; Rodman, Samantha; Strong, David R.; Kahler, Christopher W.; Hopko, Derek R.; Zvolensky, Michael J.; Brown, Richard A.; Lejuez, C. W.

2010-01-01

Objective: Depressive symptoms are associated with poor smoking cessation outcomes, and there remains continued interest in behavioral interventions that simultaneously target smoking and depressive symptomatology. In this pilot study, we examined whether a behavioral activation treatment for smoking (BATS) can enhance cessation outcomes. Method:…

αConotoxin ArIB[V11L,V16D] is a potent and selective antagonist at rat and human native α7 nicotinic acetylcholine receptors

PubMed Central

Innocent, Neal; Livingstone, Phil D.; Hone, Arik; Kimura, Atsuko; Young, Tracey; Whiteaker, Paul; McIntosh, J. Michael; Wonnacott, Susan

2008-01-01

A recently developed α-conotoxin, α-CtxArIB[V11L,V16D] is a potent and selective competitive antagonist at rat recombinant α7 nicotinic acetylcholine receptors (nAChRs), making it an attractive probe for this receptor subtype. α7 nAChRs are potential therapeutic targets that are widely expressed in both neuronal and non-neuronal tissues where they are implicated in a variety of functions. Here we evaluate this toxin at rat and human native nAChRs. Functional α7 nAChR responses were evoked by choline plus the allosteric potentiator PNU-120596 in rat PC12 cells and human SHSY5Y cells loaded with calcium indicators. α-CtxArIB[V11L,V16D] specifically inhibited α7 nAChR-mediated increases in Ca2+ in PC12 cells. Responses to other stimuli (5-iodo-A-85380, nicotine or KCl) that did not activate α7 nAChRs were unaffected. Human α7 nAChRs were also sensitive to α-CtxArIB[V11L,V16D]: ACh-evoked currents in X. laevis oocytes expressing human α7 nAChRs were inhibited by α-CtxArIB[V11L,V16D] (IC50 3.4 nM) in a slowly reversible manner, with full recovery taking 15 min. This is consistent with the timecourse of recovery from blockade of rat α7 nAChRs in PC12 cells. α-CtxArIB[V11L,V16D] inhibited human native α7 nAChRs in SHSY5Y cells, activated by either choline or AR-R17779 plus PNU-120596. Rat brain α7 nAChRs contribute to dopamine release from striatal minces: α-CtxArIB[V11L,V16D] (300 nM) selectively inhibited choline-evoked dopamine release without affecting responses evoked by nicotine that activates heteromeric nAChRs. This study establishes that α-CtxArIB[V11L,V16D] selectively inhibits human and rat native α7 nAChRs with comparable potency, making this a potentially useful antagonist for investigating α7 nAChR functions. PMID:18664588

Bidirectional Regulation of Aggression in Mice by Hippocampal Alpha-7 Nicotinic Acetylcholine Receptors.

PubMed

Lewis, Alan S; Pittenger, Steven T; Mineur, Yann S; Stout, Dawson; Smith, Philip H; Picciotto, Marina R

2018-05-01

Humans with 15q13.3 microdeletion syndrome (15q13.3DS) are typically hemizygous for CHRNA7, the gene coding for the α7 nicotinic acetylcholine receptor (nAChR), and manifest a variable neuropsychiatric phenotype that frequently includes persistent aggression. In mice, nAChR activation by nicotine is anti-aggressive, or 'serenic,' an effect which requires α7 nAChRs and is recapitulated by GTS-21, an α7 nAChR partial agonist. Pharmacotherapies potentiating α7 nAChR signaling have also been shown to reduce aggression in human 15q13.3DS. These findings identify the α7 nAChR as an important regulator of aggressive behavior, but the underlying neurobiological substrates remain to be determined. We therefore investigated the brain regions and potential neural circuits in which α7 nAChRs regulate aggressive behavior in male mice. As in 15q13.3DS, mice heterozygous for Chrna7 were significantly more aggressive compared to wild-type controls in the resident-intruder test. We subsequently examined the hippocampus, where α7 nAChRs are highly expressed, particularly in GABAergic interneurons. Resident-intruder interactions strongly activated granule cells in the dentate gyrus (DG). In contrast, GTS-21, which reduces aggression in mice, reduced DG granule cell activity during resident-intruder interactions. Short hairpin RNA knockdown of Chrna7 in the DG enhanced baseline aggression and eliminated the serenic effects of both nicotine and GTS-21 on attack latency. These data further implicate α7 nAChRs in regulation of aggression, and demonstrate that hippocampal α7 nAChR signaling is necessary and sufficient to limit aggression. These findings suggest that nAChR-mediated regulation of hippocampal excitatory-inhibitory balance could be a promising therapeutic intervention for aggression arising in certain forms of neuropsychiatric disease.

The interaction between maternal immune activation and alpha 7 nicotinic acetylcholine receptor in regulating behaviors in the offspring

PubMed Central

Wu, Wei-Li; Adams, Catherine E.; Stevens, Karen E.; Chow, Ke-Huan; Freedman, Robert; Patterson, Paul H.

2015-01-01

Mutation of human chromosome 15q13.3 increases the risk for autism and schizophrenia. One of the noteworthy genes in 15q13.3 is CHRNA7, which encodes the nicotinic acetylcholine receptor alpha 7 subunit (α7nAChR) associated with schizophrenia in clinical studies and rodent models. This study investigates the role of α7nAChR in maternal immune activation (MIA) mice model, a murine model of environmental risk factor for autism and schizophrenia. We provided choline, a selective α7nAChR agonist among its several developmental roles, in the diet of C57BL/6N wild-type dams throughout the gestation and lactation period and induced MIA at mid-gestation. The adult offspring behavior and gene expression profile in the maternal spleen-placenta-fetal brain axis at mid-gestation were investigated. We found that choline supplementation prevented several MIA-induced behavioral abnormalities in the wild-type offspring. Pro-inflammatory cytokine interleukin-6 (IL-6) and Chrna7 gene expression in the wild-type fetal brain were elevated by poly(I:C) injection and were suppressed by gestational choline supplementation. We further investigated the gene expression level of IL-6 in Chrna7 mutant mice. We found that the basal level of IL-6 was higher in Chrna7 mutant fetal brain, which suggests that α7nAChR may serve an anti-inflammatory role in the fetal brain during development. Lastly, we induced MIA in Chrna7+/− offspring. The Chrna7+/− offspring were more vulnerable to MIA, with increased behavioral abnormalities. Our study shows that α7nAChR modulates inflammatory response affecting the fetal brain and demonstrates its effects on offspring behavior development after MIA. PMID:25683697

The interaction between maternal immune activation and alpha 7 nicotinic acetylcholine receptor in regulating behaviors in the offspring.

PubMed

Wu, Wei-Li; Adams, Catherine E; Stevens, Karen E; Chow, Ke-Huan; Freedman, Robert; Patterson, Paul H

2015-05-01

Mutation of human chromosome 15q13.3 increases the risk for autism and schizophrenia. One of the noteworthy genes in 15q13.3 is CHRNA7, which encodes the nicotinic acetylcholine receptor alpha 7 subunit (α7nAChR) associated with schizophrenia in clinical studies and rodent models. This study investigates the role of α7nAChR in maternal immune activation (MIA) mice model, a murine model of environmental risk factor for autism and schizophrenia. We provided choline, a selective α7nAChR agonist among its several developmental roles, in the diet of C57BL/6N wild-type dams throughout the gestation and lactation period and induced MIA at mid-gestation. The adult offspring behavior and gene expression profile in the maternal-placental-fetal axis at mid-gestation were investigated. We found that choline supplementation prevented several MIA-induced behavioral abnormalities in the wild-type offspring. Pro-inflammatory cytokine interleukin-6 (Il6) and Chrna7 gene expression in the wild-type fetal brain were elevated by poly(I:C) injection and were suppressed by gestational choline supplementation. We further investigated the gene expression level of Il6 in Chrna7 mutant mice. We found that the basal level of Il6 was higher in Chrna7 mutant fetal brain, which suggests that α7nAChR may serve an anti-inflammatory role in the fetal brain during development. Lastly, we induced MIA in Chrna7(+/-) offspring. The Chrna7(+/-) offspring were more vulnerable to MIA, with increased behavioral abnormalities. Our study shows that α7nAChR modulates inflammatory response affecting the fetal brain and demonstrates its effects on offspring behavior development after MIA. Copyright © 2015 Elsevier Inc. All rights reserved.

The efficacy of a behavioral activation intervention among depressed US Latinos with limited English language proficiency: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Major depressive disorder is highly prevalent among Latinos with limited English language proficiency in the United States. Although major depressive disorder is highly treatable, barriers to depression treatment have historically prevented Latinos with limited English language proficiency from accessing effective interventions. The project seeks to evaluate the efficacy of behavioral activation treatment for depression, an empirically supported treatment for depression, as an intervention that may address some of the disparities surrounding the receipt of efficacious mental health care for this population. Methods/design Following a pilot study of behavioral activation treatment for depression with 10 participants which yielded very promising results, the current study is a randomized control trial testing behavioral activation treatment for depression versus a supportive counseling treatment for depression. We are in the process of recruiting 60 Latinos with limited English language proficiency meeting criteria for major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders 4th and 5th Edition for participation in a single-center efficacy trial. Participants are randomized to receive 10 sessions of behavioral activation treatment for depression (n = 30) or 10 sessions of supportive counseling (n = 30). Assessments occur prior to each session and at 1 month after completing treatment. Intervention targets include depressive symptomatology and the proposed mechanisms of behavioral activation treatment for depression: activity level and environmental reward. We will also examine other factors related to treatment outcome such as treatment adherence, treatment satisfaction, and therapeutic alliance. Discussion This randomized controlled trial will allow us to determine the efficacy of behavioral activation treatment for depression in a fast-growing, yet highly underserved population in US mental health services

The efficacy of a behavioral activation intervention among depressed US Latinos with limited English language proficiency: study protocol for a randomized controlled trial.

PubMed

Collado, Anahi; Long, Katherine E; MacPherson, Laura; Lejuez, Carl W

2014-06-18

Major depressive disorder is highly prevalent among Latinos with limited English language proficiency in the United States. Although major depressive disorder is highly treatable, barriers to depression treatment have historically prevented Latinos with limited English language proficiency from accessing effective interventions. The project seeks to evaluate the efficacy of behavioral activation treatment for depression, an empirically supported treatment for depression, as an intervention that may address some of the disparities surrounding the receipt of efficacious mental health care for this population. Following a pilot study of behavioral activation treatment for depression with 10 participants which yielded very promising results, the current study is a randomized control trial testing behavioral activation treatment for depression versus a supportive counseling treatment for depression. We are in the process of recruiting 60 Latinos with limited English language proficiency meeting criteria for major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders 4th and 5th Edition for participation in a single-center efficacy trial. Participants are randomized to receive 10 sessions of behavioral activation treatment for depression (n = 30) or 10 sessions of supportive counseling (n = 30). Assessments occur prior to each session and at 1 month after completing treatment. Intervention targets include depressive symptomatology and the proposed mechanisms of behavioral activation treatment for depression: activity level and environmental reward. We will also examine other factors related to treatment outcome such as treatment adherence, treatment satisfaction, and therapeutic alliance. This randomized controlled trial will allow us to determine the efficacy of behavioral activation treatment for depression in a fast-growing, yet highly underserved population in US mental health services. The study is also among the first to

Isolation and characterization of α-conotoxin LsIA with potent activity at nicotinic acetylcholine receptors.

PubMed

Inserra, Marco C; Kompella, Shiva N; Vetter, Irina; Brust, Andreas; Daly, Norelle L; Cuny, Hartmut; Craik, David J; Alewood, Paul F; Adams, David J; Lewis, Richard J

2013-09-15

A new α-conotoxin LsIA was isolated from the crude venom of Conus limpusi using assay-guided RP-HPLC fractionation. Synthetic LsIA was a potent antagonist of α3β2, α3α5β2 and α7 nAChRs, with half-maximal inhibitory concentrations of 10, 31 and 10 nM, respectively. The structure of LsIA determined by NMR spectroscopy comprised a characteristic disulfide bond-stabilized α-helical structure and disordered N-terminal region. Potency reductions of up to 9-fold were observed for N-terminally truncated analogues of LsIA at α7 and α3β2 nAChRs, whereas C-terminal carboxylation enhanced potency 3-fold at α3β2 nAChRs but reduced potency 3-fold at α7 nAChRs. This study gives further insight into α-conotoxin pharmacology and the molecular basis of nAChR selectivity, highlighting the influence of N-terminal residues and C-terminal amidation on conotoxin pharmacology. Copyright © 2013. Published by Elsevier Inc.

Association between physical activity and major depressive disorder among current or former smokers with pulmonary disease.

PubMed

Loprinzi, Paul D; Kane, Christy; Walker, Jerome F

2013-11-01

To examine the association between physical activity and major depressive disorder (MDD) in a nationally representative sample of current or former smokers with pulmonary impairments. The analyzed sample from the National Health and Nutrition Examination Survey (NHANES) 2007-2010 included 536 adults who indicated that they were current or former smokers, had at least mild pulmonary impairment (FEV1/FVC<0.70), and provided depression and physical activity data. After controlling for asthma status, pulmonary impairment, age, poverty-to-income ratio (PIR), education, gender, marital status, body mass index (BMI), cotinine, comorbidity index, race-ethnicity, and smoking status, those who met physical activity guidelines had a 59% (odds ratio (OR)=0.41; 95% confidence interval (CI): 0.18-0.94) lower odds of having MDD. Using multivariate linear regression with depression symptoms as the outcome variable, and after adjustments, physical activity was inversely associated with depression symptoms in a dose-response manner; lowest tertile was the referent group, middle tertile coefficient: -1.06 (95% CI: -1.98 to -0.14), and highest tertile coefficient: -1.10 (95% CI: -1.84 to -0.34). Physical activity inversely associates with MDD in adults with pulmonary impairments, and does so in a dose-response manner. This suggests that individuals with pulmonary impairments should be encouraged to engage in enjoyable, safe forms of physical activity in a progressive manner. © 2013.

Trajectory of change in pain, depression, and physical functioning after physical activity adoption in fibromyalgia.

PubMed

Steiner, Jennifer L; Bigatti, Silvia M; Ang, Dennis C

2015-07-01

Fibromyalgia is associated with widespread pain, depression, and declines in physical functioning. The purpose of this study was to examine the trajectory of these symptoms over time related to physical activity adoption and maintenance via motivational interviewing versus education, to increase physical activity. There were no treatment group differences; we divided the sample (n = 184) based on changes in physical activity. Repeated measures analyses demonstrated differential patterns in depression, pain, and physical functioning at 24 and 36 weeks. Findings suggest increased physical activity may serve as a multiple-target intervention that provides moderate to large, long-lasting benefits for individuals with fibromyalgia. © The Author(s) 2013.

Graph theory applied to the analysis of motor activity in patients with schizophrenia and depression

PubMed Central

Fasmer, Erlend Eindride; Berle, Jan Øystein; Oedegaard, Ketil J.; Hauge, Erik R.

2018-01-01

Depression and schizophrenia are defined only by their clinical features, and diagnostic separation between them can be difficult. Disturbances in motor activity pattern are central features of both types of disorders. We introduce a new method to analyze time series, called the similarity graph algorithm. Time series of motor activity, obtained from actigraph registrations over 12 days in depressed and schizophrenic patients, were mapped into a graph and we then applied techniques from graph theory to characterize these time series, primarily looking for changes in complexity. The most marked finding was that depressed patients were found to be significantly different from both controls and schizophrenic patients, with evidence of less regularity of the time series, when analyzing the recordings with one hour intervals. These findings support the contention that there are important differences in control systems regulating motor behavior in patients with depression and schizophrenia. The similarity graph algorithm we have described can easily be applied to the study of other types of time series. PMID:29668743

Graph theory applied to the analysis of motor activity in patients with schizophrenia and depression.

PubMed

Fasmer, Erlend Eindride; Fasmer, Ole Bernt; Berle, Jan Øystein; Oedegaard, Ketil J; Hauge, Erik R

2018-01-01

Depression and schizophrenia are defined only by their clinical features, and diagnostic separation between them can be difficult. Disturbances in motor activity pattern are central features of both types of disorders. We introduce a new method to analyze time series, called the similarity graph algorithm. Time series of motor activity, obtained from actigraph registrations over 12 days in depressed and schizophrenic patients, were mapped into a graph and we then applied techniques from graph theory to characterize these time series, primarily looking for changes in complexity. The most marked finding was that depressed patients were found to be significantly different from both controls and schizophrenic patients, with evidence of less regularity of the time series, when analyzing the recordings with one hour intervals. These findings support the contention that there are important differences in control systems regulating motor behavior in patients with depression and schizophrenia. The similarity graph algorithm we have described can easily be applied to the study of other types of time series.

Attentional bias modification (ABM) training induces spontaneous brain activity changes in young women with subthreshold depression: a randomized controlled trial.

PubMed

Li, H; Wei, D; Browning, M; Du, X; Zhang, Q; Qiu, J

2016-04-01

Attention bias modification (ABM) training has been suggested to effectively reduce depressive symptoms, and may be useful in the prevention of the illness in individuals with subthreshold symptoms, yet little is known about the spontaneous brain activity changes associated with ABM training. Resting-state functional MRI was used to explore the effects of ABM training on subthreshold depression (SubD) and corresponding spontaneous brain activity changes. Participants were 41 young women with SubD and 26 matched non-depressed controls. Participants with SubD were randomized to receive either ABM or placebo training during 28 sessions across 4 weeks. Non-depressed controls were assessed before training only. Attentional bias, depressive severity, and spontaneous brain activity before and after training were assessed in both training groups. Findings revealed that compared to active control training, ABM training significantly decreased depression symptoms, and increased attention for positive stimuli. Resting-state data found that ABM training significantly reduced amplitude of low-frequency fluctuations (ALFF) of the right anterior insula (AI) and right middle frontal gyrus which showed greater ALFF than non-depressed controls before training; Functional connectivity strength between right AI and the right frontoinsular and right supramarginal gyrus were significantly decreased after training within the ABM group; moreover, the improvement of depression symptoms following ABM significantly correlated with the connectivity strength reductions between right AI and right frontoinsular and right supramarginal gyrus. These results suggest that ABM has the potential to reshape the abnormal patterns of spontaneous brain activity in relevant neural circuits associated with depression.

Longitudinal associations between changes in physical activity and depressive symptoms in adulthood: the young Finns study.

PubMed

Yang, Xiaolin; Hirvensalo, Mirja; Hintsanen, Mirka; Hintsa, Taina; Pulkki-Råback, Laura; Jokela, Markus; Telama, Risto; Tammelin, Tuija; Hutri-Kähönen, Nina; Viikari, Jorma S A; Raitakari, Olli T

2014-12-01

Although previous studies have associated physical activity (PA) with lower depressive symptoms, the combined effects of the (1) frequency, (2) intensity, and (3) duration of long-term PA have not been examined in detail. We examined the dose-response association between changes in frequency, intensity, and duration of PA and depressive symptoms in men and women over 6 years. Participants comprised 1,959 healthy adults (833 men and 1,126 women), aged 24-39 years in 2001, drawn from the ongoing Young Finns Study. PA was assessed using a self-report questionnaire completed in connection with a medical examination in 2001 and 2007. Depressive symptoms were simultaneously assessed using a modified version of Beck's Depression Inventory in both phases. High doses of PA at baseline were prospectively associated with fewer depressive symptoms in men, while moderate doses of PA at baseline were inversely associated with the prevalence of depressive symptoms in women. Associations between baseline PA and depressive symptom changes were mediated by social and health-related factors which differed between men and women. Long-term participation in regular PA in all dimensions remained remarkably stable (all p < 0.001). Compared to those who remained inactive, the persistently active participants in all dimensions, with the exception of women's intensity group, were more likely to show decreases in depressive symptoms independent of the included confounders. An increase in PA in certain groups was also independently associated with fewer depressive symptoms, particularly in women. Regular and persistent participation in different doses of PA may provide short-term and long-term beneficial effects on depressive symptom changes. The results imply that the moderate to high doses of PA may serve as a buffer against depression in early midlife.

Strain-dependent effects of prenatal maternal immune activation on anxiety- and depression-like behaviors in offspring.

PubMed

Babri, Shirin; Doosti, Mohammad-Hossein; Salari, Ali-Akbar

2014-03-01

There is converging evidence that prenatal maternal infection can increase the risk of occurrence of neuropsychiatric disorders like schizophrenia, autism, anxiety and depression in later life. Experimental studies have shown conflicting effects of prenatal maternal immune activation on anxiety-like behavior and hypothalamic-pituitary-adrenal (HPA) axis development in offspring. We investigated the effects of maternal immune activation during pregnancy on anxiety- and depression-like behaviors in pregnant mice and their offspring to determine whether these effects are dependent on strain. NMRI and C57BL/6 pregnant mice were treated with either saline or lipopolysaccharide on gestational day 17 and then interleukin (IL)-6 and corticosterone (COR) levels; anxiety or depression in the pregnant mice and their offspring were evaluated. The results indicate that maternal inflammation increased the levels of COR and anxiety-like behavior in NMRI pregnant mice, but not in C57BL/6 dams. Our data also demonstrate that maternal inflammation elevated the levels of anxiety-and depression-like behaviors in NMRI offspring on the elevated plus-maze, elevated zero-maze, tail suspension test and forced swimming test respectively, but not in the open field and light-dark box. In addition, we did not find any significant change in anxiety- and depression-like behaviors of adult C57BL/6 offspring. Our findings suggest that prenatal maternal immune activation can alter the HPA axis activity, anxiety- and depression-like behaviors in a strain- and task-dependent manner in offspring and further comprehensive studies are needed to prove the causal relationship between the findings found here and to validate their relevance to neuropsychiatric disorders in humans. Copyright © 2013 Elsevier Inc. All rights reserved.

IDO chronic immune activation and tryptophan metabolic pathway: A potential pathophysiological link between depression and obesity.

PubMed

Chaves Filho, Adriano José Maia; Lima, Camila Nayane Carvalho; Vasconcelos, Silvânia Maria Mendes; de Lucena, David Freitas; Maes, Michael; Macedo, Danielle

2018-01-03

Obesity and depression are among the most pressing health problems in the contemporary world. Obesity and depression share a bidirectional relationship, whereby each condition increases the risk of the other. By inference, shared pathways may underpin the comorbidity between obesity and depression. Activation of cell-mediated immunity (CMI) is a key factor in the pathophysiology of depression. CMI cytokines, including IFN-γ, TNFα and IL-1β, induce the catabolism of tryptophan (TRY) by stimulating indoleamine 2,3-dioxygenase (IDO) resulting in the synthesis of kynurenine (KYN) and other tryptophan catabolites (TRYCATs). In the CNS, TRYCATs have been related to oxidative damage, inflammation, mitochondrial dysfunction, cytotoxicity, excitotoxicity, neurotoxicity and lowered neuroplasticity. The pathophysiology of obesity is also associated with a state of aberrant inflammation that activates aryl hydrocarbon receptor (AHR), a pathway involved in the detection of intracellular or environmental changes as well as with increases in the production of TRYCATs, being KYN an agonists of AHR. Both AHR and TRYCATS are involved in obesity and related metabolic disorders. These changes in the TRYCAT pathway may contribute to the onset of neuropsychiatric symptoms in obesity. This paper reviews the role of immune activation, IDO stimulation and increased TRYCAT production in the pathophysiology of depression and obesity. Here we suggest that increased synthesis of detrimental TRYCATs is implicated in comorbid obesity and depression and is a new drug target to treat both diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Individuals with more severe depression fail to sustain nucleus accumbens activity to preferred music over time.

PubMed

Jenkins, Lisanne M; Skerrett, Kristy A; DelDonno, Sophie R; Patrón, Víctor G; Meyers, Kortni K; Peltier, Scott; Zubieta, Jon-Kar; Langenecker, Scott A; Starkman, Monica N

2018-05-30

We investigated the ability of preferred classical music to activate the nucleus accumbens in patients with Major depressive disorder (MDD). Twelve males with MDD and 10 never mentally ill male healthy controls (HC) completed measures of anhedonia and depression severity, and listened to 90-second segments of preferred classical music during fMRI. Compared to HCs, individuals with MDD showed less activation of the left nucleus accumbens (NAcc). Individuals with MDD showed attenuation of the left NAcc response in later compared to earlier parts of the experiment, supporting theories that MDD involves an inability to sustain reward network activation. Counter intuitively, we found that NAcc activity during early music listening was associated with greater depression severity. In whole-brain analyses, anhedonia scores predicted activity in regions within the default mode network, supporting previous findings. Our results support theories that MDD involves an inability to sustain reward network activation. It also highlights that pleasant classical music can engage critical neural reward circuitry in MDD. Copyright © 2018 Elsevier B.V. All rights reserved.

Depression, diet and exercise.

PubMed

Jacka, Felice N; Berk, Michael

2013-09-16

Unhealthy lifestyle behaviour is driving an increase in the burden of chronic non-communicable diseases worldwide. Recent evidence suggests that poor diet and a lack of exercise contribute to the genesis and course of depression. While studies examining dietary improvement as a treatment strategy in depression are lacking, epidemiological evidence clearly points to diet quality being of importance to the risk of depression. Exercise has been shown to be an effective treatment strategy for depression, but this is not reflected in treatment guidelines, and increased physical activity is not routinely encouraged when managing depression in clinical practice. Recommendations regarding dietary improvement, increases in physical activity and smoking cessation should be routinely given to patients with depression. Specialised and detailed advice may not be necessary. Recommendations should focus on following national guidelines for healthy eating and physical activity.

Sleep quality in fibromyalgia and rheumatoid arthritis: associations with pain, fatigue, depression, and disease activity.

PubMed

Ulus, Y; Akyol, Y; Tander, B; Durmus, D; Bilgici, A; Kuru, O

2011-01-01

The aim of this study was to compare the sleep quality in patients with rheumatoid arthritis (RA) and fibromyalgia syndrome (FMS); and to evaluate the relationship between sleep quality and pain, fatigue, depression, and disease activity in patients with RA and FMS. Forty RA, 40 FMS and 40 healthy controls were enrolled in the study. Disease activity and disease duration were reported in patients. Pain by visual analogue scale (VAS), fatigue by Multidimensional Assesment of Fatigue (MAF), depression by Beck Depression Index (BDI), and sleep quality by Pittsburgh Sleep Quality Index (PSQI) were gathered in all participants. All participants were aged between 20 and 65 years, with a mean age of 42.97±10.75 years. There was no significant difference with respect to demographic characteristics among the three study groups. Patients reported more depression than controls, but BDI scores were similar in FMS and RA patients. VAS pain scores and MAF scores were significantly different in the three groups (p<0.001). FMS and RA patients had poor sleep quality (p<0.001). FMS patients had daytime dysfunction due to sleep disorder and had worse habitual sleep efficiency than RA patients (p<0.05). In patients, positive correlations were found between PSQI and clinic assessment variables except disease duration. FMS and RA may have poor sleep quality when compared to subjects without rheumatologic disorders. The quality of sleep can be impaired by pain, fatigue, depression, and disease activity in such patients.

Sustained anterior cingulate cortex activation during reward processing predicts response to psychotherapy in major depressive disorder.

PubMed

Carl, Hannah; Walsh, Erin; Eisenlohr-Moul, Tory; Minkel, Jared; Crowther, Andrew; Moore, Tyler; Gibbs, Devin; Petty, Chris; Bizzell, Josh; Dichter, Gabriel S; Smoski, Moria J

2016-10-01

The purpose of the present investigation was to evaluate whether pre-treatment neural activation in response to rewards is a predictor of clinical response to Behavioral Activation Therapy for Depression (BATD), an empirically validated psychotherapy that decreases depressive symptoms by increasing engagement with rewarding stimuli and reducing avoidance behaviors. Participants were 33 outpatients with major depressive disorder (MDD) and 20 matched controls. We examined group differences in activation, and the capacity to sustain activation, across task runs using functional magnetic resonance imaging (fMRI) and the monetary incentive delay (MID) task. Hierarchical linear modeling was used to investigate whether pre-treatment neural responses predicted change in depressive symptoms over the course of BATD treatment. MDD and Control groups differed in sustained activation during reward outcomes in the right nucleus accumbens, such that the MDD group experienced a significant decrease in activation in this region from the first to second task run relative to controls. Pretreatment anhedonia severity and pretreatment task-related reaction times were predictive of response to treatment. Furthermore, sustained activation in the anterior cingulate cortex during reward outcomes predicted response to psychotherapy; patients with greater sustained activation in this region were more responsive to BATD treatment. The current study only included a single treatment condition, thus it unknown whether these predictors of treatment response are specific to BATD or psychotherapy in general. Findings add to the growing body of literature suggesting that the capacity to sustain neural responses to rewards may be a critical endophenotype of MDD. Copyright © 2016 Elsevier B.V. All rights reserved.

Divergent Relationship of Depression Severity to Social Reward Responses Among Patients with Bipolar Versus Unipolar Depression

PubMed Central

Sharma, Anup; Satterthwaite, Theodore D.; Vandekar, Lillie; Katchmar, Natalie; Daldal, Aylin; Ruparel, Kosha; A.Elliott, Mark; Baldassano, Claudia; Thase, Michael E.; Gur, Raquel E.; Kable, Joseph W.; Wolf, Daniel H.

2016-01-01

Neuroimaging studies of mood disorders demonstrate abnormalities in brain regions implicated in reward processing. However, there is a paucity of research investigating how social rewards affect reward circuit activity in these disorders. Here, we evaluated the relationship of both diagnostic category and dimensional depression severity to reward system function in bipolar and unipolar depression. In total, 86 adults were included, including 24 patients with bipolar depression, 24 patients with unipolar depression, and 38 healthy comparison subjects. Participants completed a social reward task during 3T BOLD fMRI. On average, diagnostic groups did not differ in activation to social reward. However, greater depression severity significantly correlated with reduced bilateral ventral striatum activation to social reward in the bipolar depressed group, but not the unipolar depressed group. In addition, decreased left orbitofrontal cortical activation correlated with more severe symptoms in bipolar depression, but not unipolar depression. These differential dimensional effects resulted in a significant voxelwise group by depression severity interaction. Taken together, these results provide initial evidence that deficits in social reward processing are differentially related to depression severity in the two disorders. PMID:27295401

Canonical and Novel Non-Canonical Cholinergic Agonists Inhibit ATP-Induced Release of Monocytic Interleukin-1β via Different Combinations of Nicotinic Acetylcholine Receptor Subunits α7, α9 and α10

PubMed Central

Zakrzewicz, Anna; Richter, Katrin; Agné, Alisa; Wilker, Sigrid; Siebers, Kathrin; Fink, Bijan; Krasteva-Christ, Gabriela; Althaus, Mike; Padberg, Winfried; Hone, Arik J.; McIntosh, J. Michael; Grau, Veronika

2017-01-01

Recently, we discovered a cholinergic mechanism that inhibits the adenosine triphosphate (ATP)-dependent release of interleukin-1β (IL-1β) by human monocytes via nicotinic acetylcholine receptors (nAChRs) composed of α7, α9 and/or α10 subunits. Furthermore, we identified phosphocholine (PC) and dipalmitoylphosphatidylcholine (DPPC) as novel nicotinic agonists that elicit metabotropic activity at monocytic nAChR. Interestingly, PC does not provoke ion channel responses at conventional nAChRs composed of subunits α9 and α10. The purpose of this study is to determine the composition of nAChRs necessary for nicotinic signaling in monocytic cells and to test the hypothesis that common metabolites of phosphatidylcholines, lysophosphatidylcholine (LPC) and glycerophosphocholine (G-PC), function as nAChR agonists. In peripheral blood mononuclear cells from nAChR gene-deficient mice, we demonstrated that inhibition of ATP-dependent release of IL-1β by acetylcholine (ACh), nicotine and PC depends on subunits α7, α9 and α10. Using a panel of nAChR antagonists and siRNA technology, we confirmed the involvement of these subunits in the control of IL-1β release in the human monocytic cell line U937. Furthermore, we showed that LPC (C16:0) and G-PC efficiently inhibit ATP-dependent release of IL-1β. Of note, the inhibitory effects mediated by LPC and G-PC depend on nAChR subunits α9 and α10, but only to a small degree on α7. In Xenopus laevis oocytes heterologously expressing different combinations of human α7, α9 or α10 subunits, ACh induced canonical ion channel activity, whereas LPC, G-PC and PC did not. In conclusion, we demonstrate that canonical nicotinic agonists and PC elicit metabotropic nAChR activity in monocytes via interaction of nAChR subunits α7, α9 and α10. For the metabotropic signaling of LPC and G-PC, nAChR subunits α9 and α10 are needed, whereas α7 is virtually dispensable. Furthermore, molecules bearing a PC group in general seem to

Lower Odds of Poststroke Symptoms of Depression When Physical Activity Guidelines Met: National Health and Nutrition Examination Survey 2011-2012.

PubMed

Aaron, Stacey E; Gregory, Chris M; Simpson, Annie N

2016-08-01

One-third of individuals with stroke report symptoms of depression, which has a negative impact on recovery. Physical activity (PA) is a potentially effective therapy. Our objective was to examine the associations of subjectively assessed PA levels and symptoms of depression in a nationally representative stroke sample. We conducted a cross-sectional study of 175 adults in the National Health and Nutrition Examination Survey 2011-2012 cycle. Moderate, vigorous, and combination equivalent PA metabolic equivalent (MET)-minutes per week averages were derived from the Global Physical Activity Questionnaire, and .the 2008 Physical Activity Guidelines/American College of Sports Medicine recommendations of ≥500 MET-minutes per week of moderate, vigorous, or combination equivalent PA were used as cut points. Depression symptoms were measured using the Patient Health Questionnaire-9. Meeting moderate PA guidelines resulted in 74% lower odds of having depression symptoms (P < .0001) and 89% lower odds of major symptoms of depression (P = .0003). Meeting vigorous guidelines showed a 91% lower odds of having mild symptoms of depression (P = .04). Participating in some moderate, vigorous, or combination equivalent PA revealed the odds of depression symptoms 13 times greater compared with meeting guidelines (P = .005); odds of mild symptoms of depression were 9 times greater (P = .01); and odds of major symptoms of depression were 15 times greater (P = .006). There is a lower risk of developing mild symptoms of depression when vigorous guidelines for PA are met and developing major symptoms of depression when moderate guidelines met. Participating in some PA is not enough to reduce the risk of depression symptoms.

Lifestyle factors and adolescent depressive symptomatology: Associations and effect sizes of diet, physical activity and sedentary behaviour.

PubMed

Hayward, Joshua; Jacka, Felice N; Skouteris, Helen; Millar, Lynne; Strugnell, Claudia; Swinburn, Boyd A; Allender, Steven

2016-11-01

Depression affects many Australian adolescents. Research points to the potential of lifestyle improvement for the population-level prevention of mental disorders. However, most studies examine single relationships without considering the combined contribution of lifestyle factors to variance in depression. This study examined associations between adolescent diet, physical activity and screen time behaviours and depressive symptomatology. A cross-sectional sample of year 8 and 10 students was recruited from 23 participating schools in 18 Victorian communities. Students were recruited using opt-out consent, resulting in 3295 participants from 4680 registered school enrolments (Participation Rate: 70.4%). Participants completed a supervised self-report questionnaire comprising Moods and Feelings Questionnaire-Short Form, an assessment of physical activity and sedentary behaviours during and outside school, and weekly food intake. Surveyed covariates included hours of sleep per night, age, socio-economic status and measured anthropometry. A hierarchical regression stratified by gender was conducted, with dichotomised Moods and Feelings Questionnaire-Short Form score as the outcome, and screen time, physical activity and dietary patterns as predictors. Nested regression analyses were then conducted to ascertain the variance in Moods and Feelings Questionnaire-Short Form score attributable to each significant predictor from the initial regression. Increased scores on an unhealthy dietary pattern (odds ratio = 1.18; 95% confidence interval = [1.07, 1.32]) and physical activity guideline attainment (0.91; [0.85, 0.97]) were associated with depressive symptomatology in males, while screen time guideline attainment (0.95; [0.91, 0.98]) was associated with depression in females. No association was observed between healthy diet pattern and Moods and Feelings Questionnaire-Short Form. Overall, effect sizes were generally small, and the regression model accounted for 5.22% of

The role of daily mobility in mental health inequalities: the interactive influence of activity space and neighbourhood of residence on depression.

PubMed

Vallée, Julie; Cadot, Emmanuelle; Roustit, Christelle; Parizot, Isabelle; Chauvin, Pierre

2011-10-01

The literature reports an association between neighbourhood deprivation and individual depression after adjustment for individual factors. The present paper investigates whether vulnerability to neighbourhood features is influenced by individual "activity space" (i.e., the space within which people move about or travel in the course of their daily activities). It can be assumed that a deprived residential environment can exert a stronger influence on the mental health of people whose activity space is limited to their neighbourhood of residence, since their exposure to their neighbourhood would be greater. Moreover, we studied the relationship between activity space size and depression. A limited activity space could indeed reflect spatial and social confinement and thus be associated with a higher risk of being depressed, or, conversely, it could be linked to a deep attachment to the neighbourhood of residence and thus be associated with a lower risk of being depressed. Multilevel logistic regression analyses of a representative sample consisting of 3011 inhabitants surveyed in 2005 in the Paris, France metropolitan area and nested within 50 census blocks showed, after adjusting for individual-level variables, that people living in deprived neighbourhoods were significantly more depressed that those living in more advantaged neighbourhoods. We also observed a statistically significant cross-level interaction between activity space and neighbourhood deprivation, as they relate to depression. Living in a deprived neighbourhood had a stronger and statistically significant effect on depression in people whose activity space was limited to their neighbourhood than in those whose daily travels extended beyond it. In addition, a limited activity space appeared to be a protective factor with regard to depression for people living in advantaged neighbourhoods and a risk factor for those living in deprived neighbourhoods. It could therefore be useful to take activity space

Reactive oxygen species inactivate neuronal nicotinic acetylcholine receptors through a highly conserved cysteine near the intracellular mouth of the channel: implications for diseases that involve oxidative stress

PubMed Central

Krishnaswamy, Arjun; Cooper, Ellis

2012-01-01

Abstract An intriguing feature of several nicotinic acetylcholine receptors (nAChRs) on neurons is that their subunits contain a highly conserved cysteine residue located near the intracellular mouth of the receptor pore. The work summarized in this review indicates that α3β4-containing and α4β2-containing neuronal nAChRs, and possibly other subtypes, are inactivated by elevations in intracellular reactive oxygen species (ROS). This review discusses a model for the molecular mechanisms that underlie this inactivation. In addition, we explore the implications of this mechanism in the context of complications that arise from diabetes. We review the evidence that diabetes elevates cytosolic ROS in sympathetic neurons and inactivates postsynaptic α3β4-containing nAChRs shortly after the onset of diabetes, leading to a depression of synaptic transmission in sympathetic ganglia, an impairment of sympathetic reflexes. These effects of ROS on nAChR function are due to the highly conserved Cys residues in the receptors: replacing the cysteine residues in α3 allow ganglionic transmission and sympathetic reflexes to function normally in diabetes. This example from diabetes suggests that other diseases involving oxidative stress, such as Parkinson's disease, could lead to the inactivation of nAChRs on neurons and disrupt cholinergic nicotinic signalling. PMID:21969449

Activation of α7 nicotinic acetylcholine receptors protects potentiated synapses from depotentiation during theta pattern stimulation in the hippocampal CA1 region of rats.

PubMed

Galvez, Bryan; Gross, Noah; Sumikawa, Katumi

2016-06-01

Long-term potentiation (LTP) shows memory-like consolidation and thus becomes increasingly resistant to disruption by low-frequency stimulation (LFS). However, it is known that nicotine application during LFS uniquely depotentiates consolidated LTP. Here, we investigated how nicotine contributes to the disruption of stabilized LTP in the hippocampal CA1 region. We found that nicotine-induced depotentiation is not due to masking LTP by inducing long-term depression and requires the activation of GluN2A-containing NMDARs. We further examined whether nicotine-induced depotentiation involves the reversal of LTP mechanisms. LTP causes phosphorylation of Ser-831 on GluA1 subunits of AMPARs that increases the single-channel conductance of AMPARs. This phosphorylation remained unchanged after depotentiation. LTP involves the insertion of new AMPARs into the synapse and the internalization of AMPARs is associated with dephosphorylation of Ser-845 on GluA1 and caspase-3 activity. Nicotine-induced depotentiation occurred without dephosphorylation of the Ser-845 and in the presence of a caspase-3 inhibitor. LTP is also accompanied by increased filamentous actin (F-actin), which controls spine size. Nicotine-induced depotentiation was prevented by jasplakinolide, which stabilizes F-actin, suggesting that nicotine depotentiates consolidated LTP by destabilizing F-actin. α7 nicotinic acetylcholine receptor (nAChR) antagonists mimicked the effect of nicotine and selective removal of hippocampal cholinergic input caused depotentiation in the absence of nicotine, suggesting that nicotine depotentiates consolidated LTP by inducing α7 nAChR desensitization. Our results demonstrate a new role for nicotinic cholinergic systems in protecting potentiated synapses from depotentiation by preventing GluN2A-NMDAR-mediated signaling for actin destabilization. Copyright © 2016 Elsevier Ltd. All rights reserved.

Are There Gender-Specific Risk Factors for Suicidal Activity among Patients with Schizophrenia and Depression?

ERIC Educational Resources Information Center

Kaplan, Kalman J.; Harrow, Martin; Faull, Robert N.

2012-01-01

Are there gender-specific risk factors for suicidal activity among patients with schizophrenia and depression? A total of 74 schizophrenia patients (51 men, 23 women) and 77 unipolar nonpsychotic depressed patients (26 men, 51 women) from the Chicago Follow-up Study were studied prospectively at 2 years posthospitalization and again at 7.5 years.…

Nicotinic Acetylcholine Receptors in Sensory Cortex

ERIC Educational Resources Information Center

Metherate, Raju

2004-01-01

Acetylcholine release in sensory neocortex contributes to higher-order sensory function, in part by activating nicotinic acetylcholine receptors (nAChRs). Molecular studies have revealed a bewildering array of nAChR subtypes and cellular actions; however, there is some consensus emerging about the major nAChR subtypes and their functions in…

Neural activity to intense positive versus negative stimuli can help differentiate bipolar disorder from unipolar major depressive disorder in depressed adolescents: a pilot fMRI study.

PubMed

Diler, Rasim Somer; de Almeida, Jorge Renner Cardoso; Ladouceur, Cecile; Birmaher, Boris; Axelson, David; Phillips, Mary

2013-12-30

Failure to distinguish bipolar depression (BDd) from the unipolar depression of major depressive disorder (UDd) in adolescents has significant clinical consequences. We aimed to identify differential patterns of functional neural activity in BDd versus UDd and employed two (fearful and happy) facial expression/ gender labeling functional magnetic resonance imaging (fMRI) experiments to study emotion processing in 10 BDd (8 females, mean age=15.1 ± 1.1) compared to age- and gender-matched 10 UDd and 10 healthy control (HC) adolescents who were age- and gender-matched to the BDd group. BDd adolescents, relative to UDd, showed significantly lower activity to both intense happy (e.g., insula and temporal cortex) and intense fearful faces (e.g., frontal precentral cortex). Although the neural regions recruited in each group were not the same, both BDd and UDd adolescents, relative to HC, showed significantly lower neural activity to intense happy and mild happy faces, but elevated neural activity to mild fearful faces. Our results indicated that patterns of neural activity to intense positive and negative emotional stimuli can help differentiate BDd from UDd in adolescents. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Active faults of the Baikal depression

USGS Publications Warehouse

Levi, K.G.; Miroshnichenko, A.I.; San'kov, V. A.; Babushkin, S.M.; Larkin, G.V.; Badardinov, A.A.; Wong, H.K.; Colman, S.; Delvaux, D.

1997-01-01

The Baikal depression occupies a central position in the system of the basins of the Baikal Rift Zone and corresponds to the nucleus from which the continental lithosphere began to open. For different reasons, the internal structure of the Lake Baikal basin remained unknown for a long time. In this article, we present for the first time a synthesis of the data concerning the structure of the sedimentary section beneath Lake Baikal, which were obtained by complex seismic and structural investigations, conducted mainly from 1989 to 1992. We make a brief description of the most interesting seismic profiles which provide a rough idea of a sedimentary unit structure, present a detailed structural interpretation and show the relationship between active faults in the lake, heat flow anomalies and recent hydrothermalism.

Evidence of successful modulation of brain activation and subjective experience during reappraisal of negative emotion in unmedicated depression.

PubMed

Dillon, Daniel Gerard; Pizzagalli, Diego Andrea

2013-05-30

Functional magnetic resonance imaging (fMRI) was used to examine cognitive regulation of negative emotion in 12 unmedicated patients with major depressive disorder (MDD) and 24 controls. The participants used reappraisal to increase (real condition) and reduce (photo condition) the personal relevance of negative and neutral pictures during fMRI as valence ratings were collected; passive viewing (look condition) served as a baseline. Reappraisal was not strongly affected by MDD. Ratings indicated that both groups successfully reappraised negative emotional experience. Both groups also showed better memory for negative vs. neutral pictures 2 weeks later. Across groups, increased brain activation was observed on negative/real vs. negative/look and negative/photo trials in left dorsolateral prefrontal cortex (DLPFC), rostral anterior cingulate, left parietal cortex, caudate, and right amygdala. Depressive severity was inversely correlated with activation modulation in the left DLPFC, right amygdala, and right cerebellum during negative reappraisal. The lack of group differences suggests that depressed adults can modulate the brain activation and subjective experience elicited by negative pictures when given clear instructions. However, the negative relationship between depression severity and effects of reappraisal on brain activation indicates that group differences may be detectable in larger samples of more severely depressed participants. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Mild Depressive Symptoms Among Americans in Relation to Physical Activity, Current Overweight/Obesity, and Self-Reported History of Overweight/Obesity.

PubMed

Dankel, Scott J; Loenneke, Jeremy P; Loprinzi, Paul D

2016-10-01

Overweight/obese individuals are at an increased risk for depression with some evidence of a bidirectional association. The preventative effects of physical activity among overweight/obese individuals have been well documented; however, less is known on how the duration of overweight/obesity alters the association with negative health outcomes. Therefore, the purpose of this investigation was to determine how the classification, and more specifically duration, of overweight/obesity alters the association between physical activity and depressive symptoms. The 2005-2006 National Health and Nutrition Examination Survey (NHANES) data were used (n = 764), and individuals were divided into six mutually exclusive groups based on physical activity status, weight classification (measured BMI), and duration of weight classification (assessed via recall). Multivariable linear and logistic regression analyses were computed to examine odds of depressive symptoms (patient health questionnaire (PHQ)-9) among groups. After adjusting for covariates, only individuals who were inactive and overweight/obese at the examination and 10 years prior were at an increased odds of depressive symptoms in comparison to those who were active and normal weight (odds ratio (OR) = 2.40; 95 % confidence interval (CI) 1.03, 5.61; p = 0.04). Physical activity appeared to ameliorate the association with depressive symptoms independent of overweight/obesity classification or duration. The cyclic nature of overweight/obesity and depression (i.e., bidirectional association) appears to increase the odds of depression as the length of overweight/obesity is increased. These results provide support for clinicians to assess not only their clients' current BMI but also the duration in which they have been at a certain weight classification and to further promote physical activity as a preventative measure against depressive symptoms.

Familial aggregation of anxiety and depression in the community: the role of adolescents' self-esteem and physical activity level (the HUNT Study).

PubMed

Ranøyen, Ingunn; Stenseng, Frode; Klöckner, Christian A; Wallander, Jan; Jozefiak, Thomas

2015-02-04

Symptoms of anxiety and depression are significantly associated in parents and children, but few studies have examined associations between recurrent parental problems and offspring symptoms, and fathers have rarely been included in these studies. Additionally, few have investigated factors that may protect against familial aggregation of anxiety and depression. The aims of the present study are to examine the associations between recurrent parental anxiety/depression over a ten-year time span and offspring anxiety/depression in adolescence and to test whether two factors proposed to be inversely related to anxiety and depression, namely, adolescent self-esteem and physical activity, may moderate and mediate the transmission of anxiety/depression. This study used data from two waves of a Norwegian community study (the HUNT study) consisting of 5,732 adolescents, ages 13-18, (mean age = 15.8, 50.3% girls) who had one (N = 1,761 mothers; N = 742 fathers) or both parents (N = 3,229) participating in the second wave. In the first wave, 78% of the parents also participated. The adolescents completed self-reported questionnaires on self-esteem, physical activity, and symptoms of anxiety/depression, whereas parents reported on their own anxiety/depressive symptoms. The data were analysed with structural equation modeling. The presence of parental anxiety/depression when offspring were of a preschool age predicted offspring anxiety/depression when they reached adolescence, but these associations were entirely mediated by current parental symptoms. Self-esteem partly mediated the associations between anxiety/depression in parents and offspring. No sex differences were found. Physical activity moderated the direct associations between anxiety/depression in mothers and offspring, whereas no moderating effect was evident with regard to paternal anxiety/depression. These findings suggest that children of parents with anxiety/depression problems are at a sustained risk for

Evaluation of the Nicotinic Acetylcholine Receptor-Associated Proteome at Baseline and Following Nicotine Exposure in Human and Mouse Cortex.

PubMed

McClure-Begley, Tristan D; Esterlis, Irina; Stone, Kathryn L; Lam, TuKiet T; Grady, Sharon R; Colangelo, Christopher M; Lindstrom, Jon M; Marks, Michael J; Picciotto, Marina R

2016-01-01

Nicotinic acetylcholine receptors (nAChRs) support the initiation and maintenance of smoking, but the long-term changes occurring in the protein complex as a result of smoking and the nicotine in tobacco are not known. Human studies and animal models have also demonstrated that increasing cholinergic tone increases behaviors related to depression, suggesting that the nAChR-associated proteome could be altered in individuals with mood disorders. We therefore immunopurified nAChRs and associated proteins for quantitative proteomic assessment of changes in protein-protein interactions of high-affinity nAChRs containing the β2 subunit (β2*-nAChRs) from either cortex of mice treated with saline or nicotine, or postmortem human temporal cortex tissue from tobacco-exposed and nonexposed individuals, with a further comparison of diagnosed mood disorder to control subjects. We observed significant effects of nicotine exposure on the β2*-nAChR-associated proteome in human and mouse cortex, particularly in the abundance of the nAChR subunits themselves, as well as putative interacting proteins that make up core components of neuronal excitability (Na/K ATPase subunits), presynaptic neurotransmitter release (syntaxins, SNAP25, synaptotagmin), and a member of a known nAChR protein chaperone family (14-3-3ζ). These findings identify candidate-signaling proteins that could mediate changes in cholinergic signaling via nicotine or tobacco use. Further analysis of identified proteins will determine whether these interactions are essential for primary function of nAChRs at presynaptic terminals. The identification of differences in the nAChR-associated proteome and downstream signaling in subjects with various mood disorders may also identify novel etiological mechanisms and reveal new treatment targets.

Insect nicotinic receptor interactions in vivo with neonicotinoid, organophosphorus, and methylcarbamate insecticides and a synergist

PubMed Central

Shao, Xusheng; Xia, Shanshan; Durkin, Kathleen A.; Casida, John E.

2013-01-01

The nicotinic acetylcholine (ACh) receptor (nAChR) is the principal insecticide target. Nearly half of the insecticides by number and world market value are neonicotinoids acting as nAChR agonists or organophosphorus (OP) and methylcarbamate (MC) acetylcholinesterase (AChE) inhibitors. There was no previous evidence for in vivo interactions of the nAChR agonists and AChE inhibitors. The nitromethyleneimidazole (NMI) analog of imidacloprid, a highly potent neonicotinoid, was used here as a radioligand, uniquely allowing for direct measurements of house fly (Musca domestica) head nAChR in vivo interactions with various nicotinic agents. Nine neonicotinoids inhibited house fly brain nAChR [3H]NMI binding in vivo, corresponding to their in vitro potency and the poisoning signs or toxicity they produced in intrathoracically treated house flies. Interestingly, nine topically applied OP or MC insecticides or analogs also gave similar results relative to in vivo nAChR binding inhibition and toxicity, but now also correlating with in vivo brain AChE inhibition, indicating that ACh is the ultimate OP- or MC-induced nAChR active agent. These findings on [3H]NMI binding in house fly brain membranes validate the nAChR in vivo target for the neonicotinoids, OPs and MCs. As an exception, the remarkably potent OP neonicotinoid synergist, O-propyl O-(2-propynyl) phenylphosphonate, inhibited nAChR in vivo without the corresponding AChE inhibition, possibly via a reactive ketene metabolite reacting with a critical nucleophile in the cytochrome P450 active site and the nAChR NMI binding site. PMID:24108354

Associations of immunometabolic risk factors with symptoms of depression and anxiety: The role of cardiac vagal activity.

PubMed

Hu, Mandy X; Penninx, Brenda W J H; de Geus, Eco J C; Lamers, Femke; Kuan, Dora C-H; Wright, Aidan G C; Marsland, Anna L; Muldoon, Matthew F; Manuck, Stephen B; Gianaros, Peter J

2018-06-18

This study examined 1) the cross-sectional relationships between symptoms of depression/anxiety and immunometabolic risk factors, and 2) whether these relationships might be explained in part by cardiac vagal activity. Data were drawn from the Adult Health and Behavior registries (n = 1785), comprised of community dwelling adults (52.8% women, aged 30-54). Depressive symptoms were measured with the Center for Epidemiological Studies Depression Scale (CES-D) and the Beck Depression Inventory-II (BDI-II), and anxious symptoms with the Trait Anxiety scale of the State-Trait Anxiety Inventory (STAI-T). Immunometabolic risk factors included fasting levels of triglycerides, high-density lipoproteins, glucose, and insulin, as well as blood pressure, waist circumference, body mass index, C-reactive protein, and interleukin-6. Measures of cardiac autonomic activity were high- and low-frequency indicators of heart rate variability (HRV), standard deviation of normal-to-normal R-R intervals, and the mean of absolute and successive differences in R-R intervals. Higher BDI-II scores, in contrast to CES-D and STAI-T scores, were associated with increased immunometabolic risk and decreased HRV, especially HRV likely reflecting cardiac vagal activity. Decreased HRV was also associated with increased immunometabolic risk. Structural equation models indicated that BDI-II scores may relate to immunometabolic risk via cardiac vagal activity (indirect effect: β = .012, p = .046) or to vagal activity via immunometabolic risk (indirect effect: β = -.015, p = .021). Depressive symptoms, as measured by the BDI-II, but not anxious symptoms, were related to elevated levels of immunometabolic risk factors and low cardiac vagal activity. The latter may exhibit bidirectional influences on one another in a meditational framework. Future longitudinal, intervention, an nonhuman animal work is needed to elucidate the precise and mechanistic pathways linking depressive symptoms

Combining behavioural activation with physical activity promotion for adults with depression: findings of a parallel-group pilot randomised controlled trial (BAcPAc).

PubMed

Pentecost, Claire; Farrand, Paul; Greaves, Colin J; Taylor, Rod S; Warren, Fiona C; Hillsdon, Melvyn; Green, Colin; Welsman, Jo R; Rayson, Kat; Evans, Philip H; Taylor, Adrian H

2015-08-20

Depression is associated with physical inactivity, which may mediate the relationship between depression and a range of chronic physical health conditions. However, few interventions have combined a psychological intervention for depression with behaviour change techniques, such as behavioural activation (BA), to promote increased physical activity. To determine procedural and clinical uncertainties to inform a definitive randomised controlled trial (RCT), a pilot parallel-group RCT was undertaken within two Improving Access to Psychological Therapies (IAPT) services in South West England. We aimed to recruit 80 adults with depression and randomise them to a supported, written self-help programme based on either BA or BA plus physical activity promotion (BAcPAc). Data were collected at baseline and 4 months post-randomisation to evaluate trial retention, intervention uptake and variance in outcomes to inform a sample size calculation. Qualitative data were collected from participants and psychological wellbeing practitioners (PWPs) to assess the acceptability and feasibility of the trial methods and the intervention. Routine data were collected to evaluate resource use and cost. Sixty people with depression were recruited, and a 73 % follow-up rate was achieved. Accelerometer physical activity data were collected for 64 % of those followed. Twenty participants (33 %) attended at least one treatment appointment. Interview data were analysed for 15 participants and 9 study PWPs. The study highlighted the challenges of conducting an RCT within existing IAPT services with high staff turnover and absences, participant scheduling issues, PWP and participant preferences for cognitive focussed treatment, and deviations from BA delivery protocols. The BAcPAc intervention was generally acceptable to patients and PWPs. Although recruitment procedures and data collection were challenging, participants generally engaged with the BAcPAc self-help booklets and reported

Leisure time physical activity, risk of depressive symptoms, and inflammatory mediators: the English Longitudinal Study of Ageing.

PubMed

Hamer, Mark; Molloy, Gerard J; de Oliveira, Cesar; Demakakos, Panayotes

2009-08-01

To examine if inflammatory markers (CRP, fibrinogen) might partly explain the association between physical activity (PA) and risk of depression. The English Longitudinal Study of Ageing, a prospective study of community dwelling older adults. 4323 men and women (aged 63.4+/-9.7 yrs) free from depression at baseline. Self reported leisure time PA levels and depressive symptoms (a score of > or = 4 using the 8-item CES-D scale) were assessed at baseline and 4 yrs follow up. The inflammatory markers, CRP and fibrinogen, were assessed at a 2 yrs intermediate time point between baseline and follow up. At follow up 8% of the sample reported depressive symptomatology. In comparison with participants reporting none or light PA, the odds of depressive symptomatology for those reporting moderate or vigorous PA were 0.71 (95% CI, 0.54-0.95) and 0.58 (0.41-0.81), respectively, after adjustments for baseline CES-D score, age, gender, social-occupational class, smoking, alcohol, and chronic illness. Each standard unit increase in log CRP was associated with higher odds of depressive symptomatology at follow up (1.32, 1.13-1.55) and CRP was inversely associated with physical activity. The association between PA and depressive symptomatology was not, however, substantially modified by further adjustment for CRP (odds for none vs. vigorous PA=0.60, 0.43-0.84). These data suggest that low grade systemic inflammation, as indexed by CRP, is a risk marker for depressive symptomatology, although this mechanism explains only a modest (approximately 5%) amount of the association between PA and risk of depression.

Modulation of intrinsic brain activity by electroconvulsive therapy in major depression

PubMed Central

Leaver, Amber M.; Espinoza, Randall; Pirnia, Tara; Joshi, Shantanu H.; Woods, Roger P.; Narr, Katherine L.

2015-01-01

Introduction One of the most effective interventions for intractable major depressive episodes is electroconvulsive therapy (ECT). Because ECT is also relatively fast-acting, longitudinal study of its neurobiological effects offers critical insight into the mechanisms underlying depression and antidepressant response. Here we assessed modulation of intrinsic brain activity in corticolimbic networks associated with ECT and clinical response. Methods We measured resting-state functional connectivity (RSFC) in patients with treatment-resistant depression (n=30), using functional magnetic resonance imaging (fMRI) acquired before and after completing a treatment series with right-unilateral ECT. Using independent component analysis, we assessed changes in RSFC with 1) symptom improvement and 2) ECT regardless of treatment outcome in patients, with reference to healthy controls (n=33, also scanned twice). Results After ECT, consistent changes in RSFC within targeted depression-relevant functional networks were observed in the dorsal anterior cingulate (ACC), mediodorsal thalamus (mdTh), hippocampus, and right anterior temporal, medial parietal, and posterior cingulate cortex in all patients. In a separate analysis, changes in depressive symptoms were associated with RSFC changes in the dorsal ACC, mdTh, putamen, medial prefrontal, and lateral parietal cortex. RSFC of these regions did not change in healthy controls. Conclusions Neuroplasticity underlying clinical change was in part separable from changes associated with the effects of ECT observed in all patients. However, both ECT and clinical change were associated with RSFC modulation in dorsal ACC, mdTh and hippocampus, which may indicate that these regions underlie the mechanisms of clinical outcome in ECT and may be effective targets for future neurostimulation therapies. PMID:26878070

Linking depression symptom trajectories in adolescence to physical activity and team sports participation in young adults.

PubMed

Sabiston, Catherine M; O'Loughlin, Erin; Brunet, Jennifer; Chaiton, Michael; Low, Nancy C; Barnett, Tracie; O'Loughlin, Jennifer

2013-02-01

The objective of this study is to examine depressive symptom trajectories during adolescence as predictors of physical activity (PA) in young adulthood. Adolescents residing in Montreal, Canada (n=860) reported their depressive symptoms every 3-4 months during high school in 20 data collections. Three years later, participants reported engaging in moderate and vigorous intensity PA and team sports participation. Trajectories of depressive symptoms were estimated using latent growth modeling and examined as predictors of PA outcomes. Three depression symptom trajectory groups were identified during adolescence: low and declining depressive symptom scores (group 1; 37.8%); moderate and stable depressive symptom scores (group 2; 41.6%); and high increasing depressive symptom scores (group 3; 20.6%). In multivariable analyses, group 2 and group 3 participated in less moderate-intensity PA and were less likely to participate in team sports compared to group 1. The importance of examining intensity and type of PA as outcomes of depressive symptoms is highlighted. Targeted approaches are needed to encourage adolescents with moderate to high depression symptoms to engage in PA and team sports to improve their health and well-being. Copyright © 2012 Elsevier Inc. All rights reserved.

Telephone-Based Physical Activity Counseling for Major Depression in People with Multiple Sclerosis

ERIC Educational Resources Information Center

Bombardier, Charles H.; Ehde, Dawn M.; Gibbons, Laura E.; Wadhwani, Roini; Sullivan, Mark D.; Rosenberg, Dori E.; Kraft, George H.

2013-01-01

Objective: Physical activity represents a promising treatment for major depressive disorder (MDD) in people with multiple sclerosis (MS). We conducted a single-blind, two-arm randomized controlled trial comparing a 12-week physical activity counseling intervention delivered primarily by telephone (n = 44) to a wait-list control group (N = 48).…

Negative allosteric modulators that target human alpha4beta2 neuronal nicotinic receptors.

PubMed

Henderson, Brandon J; Pavlovicz, Ryan E; Allen, Jerad D; González-Cestari, Tatiana F; Orac, Crina M; Bonnell, Andrew B; Zhu, Michael X; Boyd, R Thomas; Li, Chenglong; Bergmeier, Stephen C; McKay, Dennis B

2010-09-01

Allosteric modulation of neuronal nicotinic acetylcholine receptors (nAChRs) is considered to be one of the most promising approaches for therapeutics. We have previously reported on the pharmacological activity of several compounds that act as negative allosteric modulators (NAMs) of nAChRs. In the following studies, the effects of 30 NAMs from our small chemical library on both human alpha4beta2 (Halpha4beta2) and human alpha3beta4 (Halpha3beta4) nAChRs expressed in human embryonic kidney ts201 cells were investigated. During calcium accumulation assays, these NAMs inhibited nAChR activation with IC(50) values ranging from 2.4 microM to more than 100 microM. Several NAMs showed relative selectivity for Halpha4beta2 nAChRs with IC(50) values in the low micromolar range. A lead molecule, KAB-18, was identified that shows relative selectivity for Halpha4beta2 nAChRs. This molecule contains three phenyl rings, one piperidine ring, and one ester bond linkage. Structure-activity relationship (SAR) analyses of our data revealed three regions of KAB-18 that contribute to its relative selectivity. Predictive three-dimensional quantitative SAR (comparative molecular field analysis and comparative molecular similarity indices analysis) models were generated from these data, and a pharmacophore model was constructed to determine the chemical features that are important for biological activity. Using docking approaches and molecular dynamics on a Halpha4beta2 nAChR homology model, a binding mode for KAB-18 at the alpha/beta subunit interface that corresponds to the predicted pharmacophore is described. This binding mode was supported by mutagenesis studies. In summary, these studies highlight the importance of SAR, computational, and molecular biology approaches for the design and synthesis of potent and selective antagonists targeting specific nAChR subtypes.

Negative Allosteric Modulators That Target Human α4β2 Neuronal Nicotinic Receptors

PubMed Central

Henderson, Brandon J.; Pavlovicz, Ryan E.; Allen, Jerad D.; González-Cestari, Tatiana F.; Orac, Crina M.; Bonnell, Andrew B.; Zhu, Michael X.; Boyd, R. Thomas; Li, Chenglong; Bergmeier, Stephen C.

2010-01-01

Allosteric modulation of neuronal nicotinic acetylcholine receptors (nAChRs) is considered to be one of the most promising approaches for therapeutics. We have previously reported on the pharmacological activity of several compounds that act as negative allosteric modulators (NAMs) of nAChRs. In the following studies, the effects of 30 NAMs from our small chemical library on both human α4β2 (Hα4β2) and human α3β4 (Hα3β4) nAChRs expressed in human embryonic kidney ts201 cells were investigated. During calcium accumulation assays, these NAMs inhibited nAChR activation with IC50 values ranging from 2.4 μM to more than 100 μM. Several NAMs showed relative selectivity for Hα4β2 nAChRs with IC50 values in the low micromolar range. A lead molecule, KAB-18, was identified that shows relative selectivity for Hα4β2 nAChRs. This molecule contains three phenyl rings, one piperidine ring, and one ester bond linkage. Structure–activity relationship (SAR) analyses of our data revealed three regions of KAB-18 that contribute to its relative selectivity. Predictive three-dimensional quantitative SAR (comparative molecular field analysis and comparative molecular similarity indices analysis) models were generated from these data, and a pharmacophore model was constructed to determine the chemical features that are important for biological activity. Using docking approaches and molecular dynamics on a Hα4β2 nAChR homology model, a binding mode for KAB-18 at the α/β subunit interface that corresponds to the predicted pharmacophore is described. This binding mode was supported by mutagenesis studies. In summary, these studies highlight the importance of SAR, computational, and molecular biology approaches for the design and synthesis of potent and selective antagonists targeting specific nAChR subtypes. PMID:20551292

Initial Open Trial of a Computerized Behavioral Activation Treatment for Depression

ERIC Educational Resources Information Center

Spates, C. Richard; Kalata, Alyssa H.; Ozeki, Satoshi; Stanton, Cory E.; Peters, Sofia

2013-01-01

This article presents preliminary findings from use of a novel computer program that implements an evidence-based psychological intervention to treat depression based on behavioral activation (BA) therapy. The program is titled “Building a Meaningful Life Through Behavioral Activation”. The findings derive from an open trial with moderate to…

Receptor protection studies comparing recombinant and native nicotinic receptors: Evidence for a subpopulation of mecamylamine-sensitive native alpha3beta4* nicotinic receptors.

PubMed

Free, R Benjamin; Kaser, Daniel J; Boyd, R Thomas; McKay, Dennis B

2006-01-09

Studies involving receptor protection have been used to define the functional involvement of specific receptor subtypes in tissues expressing multiple receptor subtypes. Previous functional studies from our laboratory demonstrate the feasibility of this approach when applied to neuronal tissues expressing multiple nicotinic acetylcholine receptors (nAChRs). In the current studies, the ability of a variety of nAChR agonists and antagonists to protect native and recombinant alpha3beta4 nAChRs from alkylation were investigated using nAChR binding techniques. Alkylation of native alpha3beta4* nAChRs from membrane preparations of bovine adrenal chromaffin cells resulted in a complete loss of specific [(3)H]epibatidine binding. This loss of binding to native nAChRs was preventable by pretreatment with the agonists, carbachol or nicotine. The partial agonist, cytisine, produced partial protection. Several nAChR antagonists were also tested for their ability to protect. Hexamethonium and decamethonium were without protective activity while mecamylamine and tubocurarine were partially effective. Addition protection studies were performed on recombinant alpha3beta4 nAChRs. As with native alpha3beta4* nAChRs, alkylation produced a complete loss of specific [(3)H]epibatidine binding to recombinant alpha3beta4 nAChRs which was preventable by pretreatment with nicotine. However, unlike native alpha3beta4* nAChRs, cytisine and mecamylamine, provide no protection for alkylation. These results highlight the differences between native alpha3beta4* nAChRs and recombinant alpha3beta4 nAChRs and support the use of protection assays to characterize native nAChR subpopulations.

Activation of α4β2*/α6β2* nicotinic receptors alleviates anxiety during nicotine withdrawal without upregulating nicotinic receptors.

PubMed

Yohn, Nicole L; Turner, Jill R; Blendy, Julie A

2014-05-01

Although nicotine mediates its effects through several nicotinic acetylcholine receptor (nAChR) subtypes, it remains to be determined which nAChR subtypes directly mediate heightened anxiety during withdrawal. Relative success in abstinence has been found with the nAChR partial agonist varenicline (Chantix; Pfizer, Groton, CT); however, treatment with this drug fails to alleviate anxiety in individuals during nicotine withdrawal. Therefore, it is hypothesized that success can be found by the repurposing of other nAChR partial agonists for cessation therapies that target anxiety. It is noteworthy that the selective partial agonists for α4β2, ABT-089 [2-methyl-3-[2(S)-pyrrolidinylmethoxy]pyridine], and α7, ABT-107 [5-(6-[(3R)-1-azabicyclo[2.2.2]oct-3-yloxy] pyridazin-3-yl)-1H-indole] (AbbVie, North Chicago, IL), have not been evaluated as possible therapeutics for nicotine cessation. Therefore, we examined the effect of ABT-089 and ABT-107 on anxiety during withdrawal from nicotine in the novelty-induced hypophagia (NIH) paradigm. We found that short-term administration of ABT-089 and ABT-107 alleviate anxiety-like behavior during withdrawal from nicotine while long-term administration of ABT-089 but not ABT-107 reduces anxiety-like behavior during withdrawal. After behavioral testing, brains were harvested and β2-containing nAChRs were measured using [(3)H]epibaditine. ABT-089 and ABT-107 do not upregulate nAChRs, which is in contrast to the upregulation of nAChRs observed after nicotine. Furthermore, ABT-089 is anxiogenic in nicotine naive animals, suggesting that the effects on anxiety are specifically related to the nicotine-dependent state. Together, these studies identify additional nAChR partial agonists that may aid in the rational development of smoking cessation aids.

Brief report: Associations of physical activity with anxiety and depression symptoms and status among adolescents.

PubMed

McDowell, Cillian P; MacDonncha, Ciaran; Herring, Matthew P

2017-02-01

The purpose of this study is to investigate associations between physical activity (PA), depression, and anxiety among adolescents in Ireland. Adolescents (N = 481; 281 male, 200 female) aged 15.1 ± 1.7y self-reported PA level, depression, and anxiety. Approximately 21% of adolescents were high trait anxious, and ∼37% reported scores indicating probable depression. Anxiety and depressive symptoms were higher for low PA (60 min/d, 0-2 d/wk) compared to moderate (60 min/d, 3-4 d/wk) and high (60 min/d, 5-7 d/wk) PA. After adjustment for relevant covariates, reduced odds of depression were 30% and 56% for moderate and high PA, respectively; reduced odds of high trait anxiety were 46% and 47% for moderate and high PA, respectively. These findings support the need for adolescents to engage in moderate PA, with potential for increased benefits with increased PA. To conclude, moderate and high PA are inversely associated with anxiety and depressive symptoms, and risk of depression and high trait anxiety in adolescents. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Immune and hormonal activity in adults suffering from depression.

PubMed

Nunes, S O V; Reiche, E M V; Morimoto, H K; Matsuo, T; Itano, E N; Xavier, E C D; Yamashita, C M; Vieira, V R; Menoli, A V; Silva, S S; Costa, F B; Reiche, F V; Silva, F L V; Kaminami, M S

2002-05-01

An association between depression and altered immune and hormonal systems has been suggested by the results of many studies. In the present study we carried out immune and hormonal measurements in 40 non-medicated, ambulatory adult patients with depression determined by CID-10 criteria and compared with 34 healthy nondepressed subjects. The severity of the condition was determined with the Hamilton Depression Rating Scale. Of 40 depressed patients, 31 had very severe and 9 severe or moderate depression, 29 (72.5%) were females and 11 (27.5%) were males (2.6:1 ratio). The results revealed a significant reduction of albumin and elevation of alpha-1, alpha-2 and beta-globulins, and soluble IL-2 receptor in patients with depression compared to the values obtained for nondepressed subjects (P<0.05). The decrease lymphocyte proliferation in response to a mitogen was significantly lower in severely or moderately depressed patients when compared to control (P<0.05). These data confirm the immunological disturbance of acute phase proteins and cellular immune response in patients with depression. Other results may be explained by a variety of interacting factors such as number of patients, age, sex, and the nature, severity and/or duration of depression. Thus, the data obtained should be interpreted with caution and the precise clinical relevance of these findings requires further investigation.

Antidepressant activity of standardized extract of Bacopa monniera in experimental models of depression in rats.

PubMed

Sairam, K; Dorababu, M; Goel, R K; Bhattacharya, S K

2002-04-01

Bacopa monniera Wettst. (syn. Herpestis monniera L.; Scrophulariaceae) is a commonly used Ayurvedic drug for mental disorders. The standardized extract was reported earlier to have significant anti-oxidant effect, anxiolytic activity and improve memory retention in Alzheimer's disease. Presently, the standardized methanolic extract of Bacopa monniera (bacoside A - 38.0+/-0.9) was investigated for potential antidepressant activity in rodent models of depression. The effect was compared with the standard antidepressant drug imipramine (15 mg/kg, ip). The extract when given in the dose of 20 and 40 mg/kg, orally once daily for 5 days was found to have significant antidepressant activity in forced swim and learned helplessness models of depression and was comparable to that of imipramine.

Structural Relationships between Social Activities and Longitudinal Trajectories of Depression among Older Adults

ERIC Educational Resources Information Center

Hong, Song-Iee; Hasche, Leslie; Bowland, Sharon

2009-01-01

Purpose: This study examines the structural relationships between social activities and trajectories of late-life depression. Design and Methods: Latent class analysis was used with a nationally representative sample of older adults (N = 5,294) from the Longitudinal Study on Aging II to classify patterns of social activities. A latent growth curve…

Distinguishing Bipolar Depression from Unipolar Depression in Youth: Preliminary Findings

PubMed Central

Goldstein, Tina R.; Hafeman, Danella; Merranko, John; Liao, Fangzi; Goldstein, Benjamin I.; Hower, Heather; Gill, Mary Kay; Hunt, Jeffrey; Yen, Shirley; Keller, Martin B.; Axelson, David; Strober, Michael; Iyengar, Satish; Ryan, Neal D.; Birmaher, Boris

2017-01-01

Abstract Objectives: To identify mood symptoms that distinguishes bipolar disorder (BP) depression versus unipolar depression in youth during an acute depressive episode. Methods: Youth with BP (N = 30) were compared with youth with unipolar depression (N = 59) during an acute depressive episode using the depression and mania items derived from the Schedule for Affective Disorders and Schizophrenia for Children (K-SADS)-Present Version. The results were adjusted for multiple comparisons, and any significant between-group differences in demographic, nonmood comorbid disorders, and psychiatric family history. Results: In comparison with unipolar depressed youth, BP depressed youth had significantly higher scores in several depressive symptoms and all subsyndromal manic symptoms, with the exception of increased goal-directed activity. Among the depressive symptoms, higher ratings of nonsuicidal physical self-injurious acts and mood reactivity, and lower ratings of aches/pains, were the symptoms that best discriminated BP from unipolar depressed youth. Subsyndromal manic symptoms, particularly motor hyperactivity, distractibility, and pressured speech, were higher in BP depressed youth and discriminated BP depressed from unipolar depressed youth. Conclusions: The results of this study suggest that it is possible to differentiate BP depression from unipolar depression based on depressive symptoms, and in particular subsyndromal manic symptoms. If replicated, these results have important clinical and research implications. PMID:28398819

Relationships of leisure-time and non-leisure-time physical activity with depressive symptoms: a population-based study of Taiwanese older adults.

PubMed

Chen, Li-Jung; Stevinson, Clare; Ku, Po-Wen; Chang, Yu-Kai; Chu, Da-Chen

2012-03-14

Limited research has explored the relationship between non-leisure-time physical activity (NLTPA), including domestic and work-related physical activities, with depressive symptoms. This study was designed to elucidate independent associations between leisure-time physical activity (LTPA), NLTPA, and specific parameters of physical activity (frequency, duration and intensity) with depressive symptoms in older adults. A total of 2,727 persons aged ≥ 65 years participating in the 2005 Taiwan National Health Interview Survey were studied. Depressive symptoms were measured by the Center for Epidemiological Studies Depression Scale. Information regarding energy parameters for each type of LTPA and NLTPA during the past 2-week period was analyzed. After adjusting for socio-demographic variables, lifestyle behaviors and health status, multivariate logistic regression models were used to compute adjusted odds ratios (AOR) for LTPA and NLTPA for predicting depressive symptoms. LTPA but not NLTPA was significantly associated with depressive symptoms. Compared with participants expending 2000+ kcal/week through LTPA, the risk of experiencing depressive symptoms was significantly higher for those expending 1-999 kcal/week (AOR = 2.06, 95% CI: 1.25-3.39), and those who expending 0 kcal/week (AOR = 3.72, 95%CI: 2.28-6.06). Among the three parameters of LTPA (intensity, duration and frequency) examined, only intensity was independently associated with depressive symptoms. These findings imply that exercise recommendations for older adults should emphasize the importance of higher intensity activity, rather than frequency or duration, for improved mental well-being. However, well-designed prospective cohort studies or intervention trials are needed to confirm these findings.

Hair cortisol as a marker of hypothalamic-pituitary-adrenal Axis activity in female patients with major depressive disorder.

PubMed

Pochigaeva, Ksenia; Druzhkova, Tatiana; Yakovlev, Alexander; Onufriev, Mikhail; Grishkina, Maria; Chepelev, Aleksey; Guekht, Alla; Gulyaeva, Natalia

2017-04-01

Hair cortisol is regarded as a promising marker of hypothalamic-pituitary-adrenal axis (HPAA) activity alterations due to stress, somatic and mental health conditions. Hair cortisol was previously reported to be elevated in patients with depression, however the data related to remission and recurrent depressive episodes are different. In this study, levels of hair cortisol were assessed in female patients with major depressive disorder (MDD) and the validity of hair cortisol as a marker of HPAA activity in this condition was evaluated. Hair cortisol was measured in 1 cm hair segments of 21 female patients with MDD and 22 female age-matched controls using enzyme-immunoassay analysis. Concurrently, serum cortisol was assessed and psychological status was evaluated using 17-item Hamilton Depression Rating Scale (HAMD-17), Beck Depression Inventory (BDI) and the Spielberger state trait anxiety inventory (STAI). The levels of hair cortisol were significantly lower in the MDD group, while serum cortisol levels were significantly higher in patients, as compared with controls. A significant negative correlation was found between HAMD-17 scores and hair cortisol. Decreased hair cortisol found in female patients with MDD as compared to controls suggests downregulation of HPAA activity during the preceding month. Further studies are needed to investigate the profiles of hair cortisol at different stages of depressive disorder to establish this parameter as a handy clinical tool.

The association of fatigue, pain, depression and anxiety with work and activity impairment in immune mediated inflammatory diseases.

PubMed

Enns, Murray W; Bernstein, Charles N; Kroeker, Kristine; Graff, Lesley; Walker, John R; Lix, Lisa M; Hitchon, Carol A; El-Gabalawy, Renée; Fisk, John D; Marrie, Ruth Ann

2018-01-01

Impairment in work function is a frequent outcome in patients with chronic conditions such as immune-mediated inflammatory diseases (IMID), depression and anxiety disorders. The personal and economic costs of work impairment in these disorders are immense. Symptoms of pain, fatigue, depression and anxiety are potentially remediable forms of distress that may contribute to work impairment in chronic health conditions such as IMID. The present study evaluated the association between pain [Medical Outcomes Study Pain Effects Scale], fatigue [Daily Fatigue Impact Scale], depression and anxiety [Hospital Anxiety and Depression Scale] and work impairment [Work Productivity and Activity Impairment Scale] in four patient populations: multiple sclerosis (n = 255), inflammatory bowel disease (n = 248, rheumatoid arthritis (n = 154) and a depression and anxiety group (n = 307), using quantile regression, controlling for the effects of sociodemographic factors, physical disability, and cognitive deficits. Each of pain, depression symptoms, anxiety symptoms, and fatigue individually showed significant associations with work absenteeism, presenteeism, and general activity impairment (quantile regression standardized estimates ranging from 0.3 to 1.0). When the distress variables were entered concurrently into the regression models, fatigue was a significant predictor of work and activity impairment in all models (quantile regression standardized estimates ranging from 0.2 to 0.5). These findings have important clinical implications for understanding the determinants of work impairment and for improving work-related outcomes in chronic disease.

Subjective memory complaints, depressive symptoms and instrumental activities of daily living in mild cognitive impairment.

PubMed

Ryu, Seon Young; Lee, Sang Bong; Kim, Tae Woo; Lee, Taek Jun

2016-03-01

The diagnostic relevance of subjective memory complaints (SMCs) in mild cognitive impairment (MCI) remains to be unresolved. The aim of this study is to determine clinical correlates of SMCs in MCI. Furthermore, we examined whether there are the differences due to different aspects of complaints (i.e. prospective memory (PM) versus retrospective memory (RM) complaints). We examined the cross-sectional associations between SMCs and depressive symptoms, instrumental activities of daily living (IADL), and cognitive measures in sixty-six individuals with MCI (mean age: 65.7 ± 8.01 years). The criteria for MCI included SMCs, objective cognitive impairment, normal general cognitive function, largely intact functional activities, and absence of dementia. SMCs were assessed using the Prospective and Retrospective Memory Questionnaire (PRMQ), which contains 16 items describing everyday memory failure of both PM and RM. SMC severity (i.e. PRMQ total score) was associated with stronger depressive symptoms and worse IADL performance. SMCs were not related to cognitive measures. For PM and RM subscores, both depressive symptoms and IADL were related to the PRMQ-PM and -RM scores. The main contributors to these PM and RM scores were depressive symptoms and IADL impairment, respectively. This study suggests that SMCs are more associated with depressive symptoms and IADL problems than with cognitive performance in individuals with MCI. Furthermore, while PM and RM complaints are related to both depressive symptoms and IADL, the differences between these main contributors suggest that RM complaints based on IADL could be more associated with the organically driven pathological features of MCI.

Behavioral Activation and Therapeutic Exposure: An Investigation of Relative Symptom Changes in PTSD and Depression During the Course of Integrated Behavioral Activation, Situational Exposure, and Imaginal Exposure Techniques

PubMed Central

Gros, Daniel F.; Price, Matthew; Strachan, Martha; Yuen, Erica K.; Milanak, Melissa E.; Acierno, Ron

2012-01-01

Effectiveness of exposure therapy for posttraumatic stress disorder (PTSD) may be adversely influenced by comorbid disorders. The present study investigated behavioral activation and therapeutic exposure (BA-TE), a new integrated treatment designed specifically for comorbid symptoms of PTSD and depression. Combat veterans with PTSD (N = 117) completed eight sessions of BA-TE that included two phases of treatment: (a) behavioral activation (BA) in which some activities involved situational exposures and (b) BA and situational exposures with imaginal exposures. Findings supported improvements in symptoms of PTSD, and overlapping symptoms of PTSD and depression, but not in nonoverlapping symptoms of depression. The findings also demonstrated a relatively consistent rate of change in PTSD and depression symptoms during BA-TE, despite the addition of imaginal exposures midway through the treatment. Together, these findings provide preliminary support for BA-TE as a treatment for PTSD and depression, and highlight the utility of transdiagnostic treatments in addressing comorbidity and symptom overlap. PMID:22679240

Relationship of activities outside work to sleep and depression/anxiety disorders in Korean workers: the 4th Korean working condition survey.

PubMed

Lee, Kyung-Jae; Jung, Sung Won; Lee, Hee Sung; Kim, Guang Hwi; Lee, Jae Gwang; Lee, June-Hee; Kim, Joo Ja

2017-01-01

Sleep disorders and depression/anxiety disorders are long-standing and significant problem for mental health. Also there are already known so many negative health effect of these disorders. But there were few studies to examine the association between activities outside work and forementioned disorders. So this study aimed the association of those things by using the Republic of Korean data. Data from 32,232 wage workers were used in the 4th Korean Working Condition Survey. General and occupational characteristics, sleep disorders, depression/anxiety disorders and activities outside work are included in questionnaire. To find the relationship between activities outside work and sleep, depression/anxiety disorders, multivariate logistic regression analysis was used after adjusting for general and occupational characteristics. We observed that volunteer activities increased the odds ratio of both sleep disorders and depression/anxiety disorders(Odds ratio[OR] = 1.35, 95% confidence interval[CI]: 1.03-1.78 and OR = 1.54, 95% CI: 1.29-1.84, respectively). And self-development activities increase the odds ratio of sleep disorders(OR = 1.35, 95% CI: 1.17-1.57). Gardening activities lowered the odds ratio of depression/anxiety disorders(OR = 0.74, 95% CI: 0.59-0.94). Some of activities outside work were related to sleep disorders and depression/anxiety disorders among Korean wage workers. Our results showed negative health effect of some kinds of activities outside work such as volunteering and self-devlopment compared to other studies that emphasized positive effect of those activities for health.

Decreased phosphorylation of δ and ε subunits of the acetylcholine receptor coincides with delayed postsynaptic maturation in PKC θ deficient mouse.

PubMed

Lanuza, Maria A; Besalduch, Núria; González, Carmen; Santafé, Manel M; Garcia, Neus; Tomàs, Marta; Nelson, Phillip G; Tomàs, Josep

2010-09-01

Protein kinase C (PKC) activity is involved in the nicotinic acetylcholine receptor (nAChR) redistribution at the neuromuscular junction in vivo during postnatal maturation. Here we studied, in PKC theta (PKCtheta) deficient mice (KO), how the theta isoform of PKC is involved in the nAChR cluster maturation that is accompanied by the developmental activity-dependent neuromuscular synapse elimination process. We found that axonal elimination and dispersion of nAChR from the postsynaptic plaques and its redistribution to form the mature postsynaptic apparatus were delayed but not totally suppressed in PKCtheta deficient mice. Moreover, the delay in the maturation of the morphology of the nAChR clusters during the early postnatal synapse elimination period in the PKCtheta deficient mice coincides with a reduction in the PKCtheta-mediated phosphorylation on the delta subunit of the nAChR. In addition, we show evidence for PKCtheta regulation of PKA in normally phosphorylating the epsilon subunit of nAChR. We have also found that the theta isoform of PKC is located on the postsynaptic component of the neuromuscular junction but is also expressed by motoneurons in the spinal cord and in the motor nerve terminals. The results allow us to hypothesize that a spatially specific and opposing action of PKCtheta and PKA may result in activity-dependent alterations to synaptic connectivity at both the nerve inputs and the postsynaptic nAChR clusters. Copyright 2010 Elsevier Inc. All rights reserved.

Implicit depression and hopelessness in remitted depressed individuals.

PubMed

Meites, Tiffany M; Deveney, Christen M; Steele, Katherine T; Holmes, Avram J; Pizzagalli, Diego A

2008-09-01

Cognitive theories of depression posit that automatically activated cognitive schemas, including negative thoughts about the self and the future, predispose individuals to develop depressive disorders. However, prior research has largely examined these constructs using explicit tests in currently depressed individuals. Using the Implicit Association Test (IAT), the present study examined automatic associations between the self and mood state ("depression IAT") and between the future and mood state ("hopelessness IAT") before and after a negative mood induction in 19 remitted depressed individuals and 23 healthy controls. In the depression IAT, remitted depressed participants exhibited an overall lower tendency to associate themselves with happiness relative to the healthy controls before the mood induction. Control, but not remitted depressed, participants' automatic associations between the self and happiness diminished following the mood induction. Contrary to our hypotheses, no significant findings emerged when considering the hopelessness IAT. Consistent with prior studies, no significant correlations emerged between implicit and explicit biases, suggesting that these measures probe different processes. Results extend prior IAT research by documenting the presence of a reduced tendency to associate the self with happiness in a sample at increased risk for depression.

Implicit Depression and Hopelessness in Remitted Depressed Individuals

PubMed Central

Meites, Tiffany M.; Deveney, Christen M.; Steele, Katherine T.; Holmes, Avram J.; Pizzagalli, Diego A.

2008-01-01

Cognitive theories of depression posit that automatically activated cognitive schemas, including negative thoughts about the self and the future, predispose individuals to develop depressive disorders. However, prior research has largely examined these constructs using explicit tests in currently depressed individuals. Using the Implicit Association Test (IAT), the present study examined automatic associations between the self and mood state (“depression IAT”) and between the future and mood state (“hopelessness IAT”) before and after a negative mood induction in 19 remitted depressed individuals and 23 healthy controls. In the depression IAT, remitted depressed participants exhibited an overall lower tendency to associate themselves with happiness relative to the healthy controls before the mood induction. Control, but not remitted depressed, participants’ automatic associations between the self and happiness diminished following the mood induction. Contrary to our hypotheses, no significant findings emerged when considering the hopelessness IAT. Consistent with prior studies, no significant correlations emerged between implicit and explicit biases, suggesting that these measures probe different processes. Results extend prior IAT research by documenting the presence of a reduced tendency to associate the self with happiness in a sample at increased risk for depression. PMID:18692169

Elevated Hippocampal Cholinergic Neurostimulating Peptide precursor protein (HCNP-pp) mRNA in the amygdala in major depression.

PubMed

Bassi, Sabrina; Seney, Marianne L; Argibay, Pablo; Sibille, Etienne

2015-04-01

The amygdala is innervated by the cholinergic system and is involved in major depressive disorder (MDD). Evidence suggests a hyper-activate cholinergic system in MDD. Hippocampal Cholinergic Neurostimulating Peptide (HCNP) regulates acetylcholine synthesis. The aim of the present work was to investigate expression levels of HCNP-precursor protein (HCNP-pp) mRNA and other cholinergic-related genes in the postmortem amygdala of MDD patients and matched controls (females: N = 16 pairs; males: N = 12 pairs), and in the mouse unpredictable chronic mild stress (UCMS) model that induced elevated anxiety-/depressive-like behaviors (females: N = 6 pairs; males: N = 6 pairs). Results indicate an up-regulation of HCNP-pp mRNA in the amygdala of women with MDD (p < 0.0001), but not males, and of UCMS-exposed mice (males and females; p = 0.037). HCNP-pp protein levels were investigated in the human female cohort, but no difference was found. There were no differences in gene expression of acetylcholinesterase (AChE), muscarinic (mAChRs) or nicotinic receptors (nAChRs) between MDD subjects and controls or UCMS and control mice, except for an up-regulation of AChE in UCMS-exposed mice (males and females; p = 0.044). Exploratory analyses revealed a baseline expression difference of cholinergic signaling-related genes between women and men (p < 0.0001). In conclusion, elevated amygdala HCNP-pp expression may contribute to mechanisms of MDD in women, potentially independently from regulating the cholinergic system. The differential expression of genes between women and men could also contribute to the increased vulnerability of females to develop MDD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Actigraphically assessed activity in unipolar depression: a comparison of inpatients with and without motor retardation.

PubMed

Krane-Gartiser, Karoline; Henriksen, Tone E G; Vaaler, Arne E; Fasmer, Ole Bernt; Morken, Gunnar

2015-09-01

To compare the activity patterns of inpatients with unipolar depression, who had been divided into groups with and without motor retardation prior to actigraphy monitoring. Twenty-four-hour actigraphy recordings from 52 consecutively, acutely admitted inpatients with unipolar depression (ICD-10) were compared to recordings from 28 healthy controls. The patients, admitted between September 2011 and April 2012, were separated into 2 groups: 25 with motor retardation and 27 without motor retardation. Twenty-eight healthy controls were also included. Twenty-four-hour recordings, 9-hour daytime sequences, and 64-minute periods of continuous motor activity in the morning and evening were analyzed for mean activity, variability, and complexity. Patients with motor retardation had a reduced mean activity level (P = .04) and higher intraindividual variability, as shown by increased standard deviation (SD) (P = .003) and root mean square successive difference (RMSSD) (P = .025), during 24 hours compared to the patients without motor retardation. Both patient groups demonstrated significantly lower mean activity compared to healthy controls (P < .001) as well as higher SD (P < .02) and RMSSD (P < .001) and a higher RMSSD/SD ratio (P = .04). In the active morning period, the patients without motor retardation displayed significantly increased complexity compared to motor-retarded patients (P = .006). The patients with and without motor retardation differ in activity patterns. Findings in depressed inpatients without motor retardation closely resemble those of inpatients with mania. © Copyright 2015 Physicians Postgraduate Press, Inc.

The Effects of Unilateral Adaptation of Hearing Aids on Symptoms of Depression and Social Activity Constraints of Elderly

PubMed Central

Santos, Fernanda Dutra dos; Teixeira, Adriane Ribeiro

2014-01-01

Introduction Hearing loss is one of the most common problems in the elderly population. Besides compromising oral communication, it directly affects social relations and prevents elderly patients from living actively in society, possibly leading to the onset of depression or other conditions. Objective To analyze the effects of unilateral adaptation of hearing aids on symptoms of depression and the social activity constraints of elderly subjects with hearing impairment. Methods The sample consisted of elderly subjects with hearing loss who did not use hearing aids. Data were collected in two phases. Initially, all participants underwent an audiological assessment and answered the Hearing Handicap Inventory for Elderly (summarized version) and the Geriatric Depression Scale. All subjects participated in the selection and hearing aid adaptation processes and became monaural hearing aid users. After 30 days of hearing aid use, they were assessed with the same instruments. The results of the questionnaires before and after hearing aid adaptation were compared. Results The sample consisted of 13 individuals, between 60 and 90 years old (mean 72.85 ± 11.05 years). Data analysis showed that there was significant improvement in social activity constraints (p < 0.001) and in symptoms of depression (p = 0.031). Conclusion Results show that, in the sample studied, unilateral hearing aid adaptation reduced social activity constraints and depression symptoms. PMID:26157497