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Translational Psychiatry

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https://www.readbyqxmd.com/read/27922641/ip3-accumulation-and-or-inositol-depletion-two-downstream-lithium-s-effects-that-may-mediate-its-behavioral-and-cellular-changes
#1
Y Sade, L Toker, N Z Kara, H Einat, S Rapoport, D Moechars, G T Berry, Y Bersudsky, G Agam
Lithium is the prototype mood stabilizer but its mechanism is still unresolved. Two hypotheses dominate-the consequences of lithium's inhibition of inositol monophosphatase at therapeutically relevant concentrations (the 'inositol depletion' hypothesis), and of glycogen-synthase kinase-3. To further elaborate the inositol depletion hypothesis that did not decisively determine whether inositol depletion per se, or phosphoinositols accumulation induces the beneficial effects, we utilized knockout mice of either of two inositol metabolism-related genes-IMPA1 or SMIT1, both mimic several lithium's behavioral and biochemical effects...
December 6, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27922640/brain-network-reorganization-differs-in-response-to-stress-in-rats-genetically-predisposed-to-depression-and-stress-resilient-rats
#2
N Gass, R Becker, A J Schwarz, W Weber-Fahr, C Clemm von Hohenberg, B Vollmayr, A Sartorius
Treatment-resistant depression (TRD) remains a pressing clinical problem. Optimizing treatment requires better definition of the specificity of the involved brain circuits. The rat strain bred for negative cognitive state (NC) represents a genetic animal model of TRD with high face, construct and predictive validity. Vice versa, the positive cognitive state (PC) strain represents a stress-resilient phenotype. Although NC rats show depressive-like behavior, some symptoms such as anhedonia require an external trigger, i...
December 6, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27922639/mesolimbic-leptin-signaling-negatively-regulates-cocaine-conditioned-reward
#3
M Shen, C Jiang, P Liu, F Wang, L Ma
The regulatory mechanisms underlying the response to addictive drugs are complex, and increasing evidence indicates that there is a role for appetite-regulating pathways in substance abuse. Leptin, an important adipose hormone that regulates energy balance and appetite, exerts its physiological functions via leptin receptors. However, the role of leptin signaling in regulating the response to cocaine remains unclear. Here we examined the potential role of leptin signaling in cocaine reward using a conditioned place preference (CPP) procedure...
December 6, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27922638/enhancing-dopaminergic-signaling-and-histone-acetylation-promotes-long-term-rescue-of-deficient-fear-extinction
#4
N Whittle, V Maurer, C Murphy, J Rainer, D Bindreither, M Hauschild, A Scharinger, M Oberhauser, T Keil, C Brehm, T Valovka, J Striessnig, N Singewald
Extinction-based exposure therapy is used to treat anxiety- and trauma-related disorders; however, there is the need to improve its limited efficacy in individuals with impaired fear extinction learning and to promote greater protection against return-of-fear phenomena. Here, using 129S1/SvImJ mice, which display impaired fear extinction acquisition and extinction consolidation, we revealed that persistent and context-independent rescue of deficient fear extinction in these mice was associated with enhanced expression of dopamine-related genes, such as dopamine D1 (Drd1a) and -D2 (Drd2) receptor genes in the medial prefrontal cortex (mPFC) and amygdala, but not hippocampus...
December 6, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27922637/a-human-carboxypeptidase-e-nf-%C3%AE-1-gene-mutation-in-an-alzheimer-s-disease-patient-leads-to-dementia-and-depression-in-mice
#5
Y Cheng, N X Cawley, T Yanik, S R K Murthy, C Liu, F Kasikci, D Abebe, Y P Loh
Patients with Alzheimer's disease (AD), a common dementia among the aging population, often also suffer from depression. This comorbidity is poorly understood. Although most forms of AD are not genetically inherited, we have identified a new human mutation in the carboxypeptidase E (CPE)/neurotrophic factor-α1 (NF-α1) gene from an AD patient that caused memory deficit and depressive-like behavior in transgenic mice. This mutation consists of three adenosine inserts, introducing nine amino acids, including two glutamines into the mutant protein, herein called CPE-QQ...
December 6, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27922636/dna-methylation-and-substance-use-risk-a-prospective-genome-wide-study-spanning-gestation-to-adolescence
#6
C A M Cecil, E Walton, R G Smith, E Viding, E J McCrory, C L Relton, M Suderman, J-B Pingault, W McArdle, T R Gaunt, J Mill, E D Barker
Epigenetic processes have been implicated in addiction; yet, it remains unclear whether these represent a risk factor and/or a consequence of substance use. Here, we believe we conducted the first genome-wide, longitudinal study to investigate whether DNA methylation patterns in early life prospectively associate with substance use in adolescence. The sample comprised of 244 youth (51% female) from the Avon Longitudinal Study of Parents and Children (ALSPAC), with repeated assessments of DNA methylation (Illumina 450k array; cord blood at birth, whole blood at age 7) and substance use (tobacco, alcohol and cannabis use; age 14-18)...
December 6, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27922635/increased-plasma-levels-of-circulating-cell-free-mitochondrial-dna-in-suicide-attempters-associations-with-hpa-axis-hyperactivity
#7
D Lindqvist, J Fernström, C Grudet, L Ljunggren, L Träskman-Bendz, L Ohlsson, Å Westrin
Preclinical data suggest that chronic stress may cause cellular damage and mitochondrial dysfunction, potentially leading to the release of mitochondrial DNA (mtDNA) into the bloodstream. Major depressive disorder has been associated with an increased amount of mtDNA in leukocytes from saliva samples and blood; however, no previous studies have measured plasma levels of free-circulating mtDNA in a clinical psychiatric sample. In this study, free circulating mtDNA was quantified in plasma samples from 37 suicide attempters, who had undergone a dexamethasone suppression test (DST), and 37 healthy controls...
December 6, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27922634/the-efficacy-of-fish-oil-supplements-in-the-treatment-of-depression-food-for-thought
#8
J A Bastiaansen, M R Munafò, K M Appleton, A J Oldehinkel
No abstract text is available yet for this article.
December 6, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27922633/variable-telomere-length-across-post-mortem-human-brain-regions-and-specific-reduction-in-the-hippocampus-of-major-depressive-disorder
#9
F Mamdani, B Rollins, L Morgan, R M Myers, J D Barchas, A F Schatzberg, S J Watson, H Akil, S G Potkin, W E Bunney, M P Vawter, P A Sequeira
No abstract text is available yet for this article.
December 6, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27898076/growth-hormone-biases-amygdala-network-activation-after-fear-learning
#10
B Gisabella, S Farah, X Peng, A Burgos-Robles, S H Lim, K A Goosens
Prolonged stress exposure is a risk factor for developing posttraumatic stress disorder, a disorder characterized by the 'over-encoding' of a traumatic experience. A potential mechanism by which this occurs is through upregulation of growth hormone (GH) in the amygdala. Here we test the hypotheses that GH promotes the over-encoding of fearful memories by increasing the number of neurons activated during memory encoding and biasing the allocation of neuronal activation, one aspect of the process by which neurons compete to encode memories, to favor neurons that have stronger inputs...
November 29, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27898075/maternal-high-fat-diet-prevents-developmental-programming-by-early-life-stress
#11
M Rincel, A L Lépinay, P Delage, J Fioramonti, V S Théodorou, S Layé, M Darnaudéry
Anxiety disorders and depression are well-documented in subjects exposed to adverse childhood events. Recently, maternal obesity and/or maternal consumption of high-fat diets (HFD) have been also proposed as risk factors for offspring mental health. Here using an animal model in rats, we explored the combinatorial effects of a maternal HFD (40% of energy from fat without impact on maternal weight; during gestation and lactation) and maternal separation (MS) in offspring. In the prefrontal cortex (PFC) of pups, MS led to changes in the expression of several genes such as Bdnf (brain derived neurotrophic factor), 5HT-r1a (serotonin receptor 1a) and Rest4 (neuron-restrictive silencer element, repressor element 1, silencing transcription factor (Rest), splicing variant 4)...
November 29, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27898074/transcriptome-sequencing-of-the-choroid-plexus-in-schizophrenia
#12
S Kim, Y Hwang, D Lee, M J Webster
The choroid plexus (CP) has a key role in maintaining brain homeostasis by producing cerebrospinal fluid (CSF), by mediating transport of nutrients and removing metabolic products from the central nervous system and by responding to peripheral inflammatory signals. Although abnormal markers of immune response and inflammation are apparent in individuals with schizophrenia, the CP of these individuals has not been characterized. We therefore sequenced mRNA from the CP from two independent collections of individuals with schizophrenia and unaffected controls...
November 29, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27898073/proteomic-analysis-of-the-postsynaptic-density-implicates-synaptic-function-and-energy-pathways-in-bipolar-disorder
#13
M Föcking, P Dicker, L M Lopez, M Hryniewiecka, K Wynne, J A English, G Cagney, D R Cotter
The postsynaptic density (PSD) contains a complex set of proteins of known relevance to neuropsychiatric disorders such as schizophrenia and bipolar disorder. We enriched for this anatomical structure in the anterior cingulate cortex of 16 bipolar disorder samples and 20 controls from the Stanley Medical Research Institute. Unbiased shotgun proteomics incorporating label-free quantitation was used to identify differentially expressed proteins. Quantitative investigation of the PSD identified 2033 proteins, among which 288 were found to be differentially expressed...
November 29, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27898072/elevated-brain-lactate-in-schizophrenia-a-7%C3%A2-t-magnetic-resonance-spectroscopy-study
#14
L M Rowland, S Pradhan, S Korenic, S A Wijtenburg, L E Hong, R A Edden, P B Barker
Various lines of evidence suggest that brain bioenergetics and mitochondrial function may be altered in schizophrenia. On the basis of prior phosphorus-31 ((31)P)-magnetic resonance spectroscopy (MRS), post-mortem and preclinical studies, this study was designed to test the hypothesis that abnormal glycolysis leads to elevated lactate concentrations in subjects with schizophrenia. The high sensitivity of 7 Tesla proton ((1)H)-MRS was used to measure brain lactate levels in vivo. Twenty-nine controls and 27 participants with schizophrenia completed the study...
November 29, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27898071/are-adolescents-more-vulnerable-to-the-harmful-effects-of-cannabis-than-adults-a-placebo-controlled-study-in-human-males
#15
C Mokrysz, T P Freeman, S Korkki, K Griffiths, H V Curran
Preclinical research demonstrates that cannabinoids have differing effects in adolescent and adult animals. Whether these findings translate to humans has not yet been investigated. Here we believe we conducted the first study to compare the acute effects of cannabis in human adolescent (n=20; 16-17 years old) and adult (n=20; 24-28 years old) male cannabis users, in a placebo-controlled, double-blind cross-over design. After inhaling vaporized active or placebo cannabis, participants completed tasks assessing spatial working memory, episodic memory and response inhibition, alongside measures of blood pressure and heart rate, psychotomimetic symptoms and subjective drug effects (for example, 'stoned', 'want to have cannabis')...
November 29, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27898070/lipids-lipoprotein-distribution-and-depressive-symptoms-the-multi-ethnic-study-of-atherosclerosis
#16
K L Ong, M J Morris, R L McClelland, J Maniam, M A Allison, K-A Rye
Previous studies suggest lower concentrations of total and high-density lipoprotein (HDL) cholesterol to be predictive of depression. We therefore investigated the relationship of lipids and lipoprotein distribution with elevated depressive symptoms (EDS) in healthy men and women from the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were followed up over a 9.5-year period. EDS were defined as a Center for Epidemiological Studies Depression (CES-D) score ⩾16 and/or use of antidepressant drugs...
November 29, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27898069/clozapine-modifies-the-differentiation-program-of-human-adipocytes-inducing-browning
#17
E Kristóf, Q-M Doan-Xuan, A K Sárvári, Á Klusóczki, P Fischer-Posovszky, M Wabitsch, Z Bacso, P Bai, Z Balajthy, L Fésüs
Administration of second-generation antipsychotic drugs (SGAs) often leads to weight gain and consequent cardio-metabolic side effects. We observed that clozapine but not six other antipsychotic drugs reprogrammed the gene expression pattern of differentiating human adipocytes ex vivo, leading to an elevated expression of the browning marker gene UCP1, more and smaller lipid droplets and more mitochondrial DNA than in the untreated white adipocytes. Laser scanning cytometry showed that up to 40% of the differentiating single primary and Simpson-Golabi-Behmel syndrome (SGBS) adipocytes had the characteristic morphological features of browning cells...
November 29, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27898068/preliminary-indications-of-the-effect-of-a-brief-yoga-intervention-on-markers-of-inflammation-and-dna-methylation-in-chronically-stressed-women
#18
K N Harkess, J Ryan, P H Delfabbro, S Cohen-Woods
Yoga is associated with reduced stress and increased well-being, although the molecular basis for these benefits is not clear. Mounting evidence implicates the immune response, with current studies focused on protein immune markers (such as cytokines) in clinical populations. To explore the molecular impact, this pilot study uses a subsample (n=28) from a randomised waitlist control trial investigating the impact of an 8-week yoga intervention in a community population of women reporting psychological distress (N=116)...
November 29, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27874848/the-human-bdnf-gene-peripheral-gene-expression-and-protein-levels-as-biomarkers-for-psychiatric-disorders
#19
REVIEW
A Cattaneo, N Cattane, V Begni, C M Pariante, M A Riva
Brain-derived neurotrophic factor (BDNF) regulates the survival and growth of neurons, and influences synaptic efficiency and plasticity. The human BDNF gene consists of 11 exons, and distinct BDNF transcripts are produced through the use of alternative promoters and splicing events. The majority of the BDNF transcripts can be detected not only in the brain but also in the blood cells, although no study has yet investigated the differential expression of BDNF transcripts at the peripheral level. This review provides a description of the human BDNF gene structure as well as a summary of clinical and preclinical evidence supporting the role of BDNF in the pathogenesis of psychiatric disorders...
November 22, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27874847/early-changes-in-emotional-processing-as-a-marker-of-clinical-response-to-ssri-treatment-in-depression
#20
B R Godlewska, M Browning, R Norbury, P J Cowen, C J Harmer
Antidepressant treatment reduces behavioural and neural markers of negative emotional bias early in treatment and has been proposed as a mechanism of antidepressant drug action. Here, we provide a critical test of this hypothesis by assessing whether neural markers of early emotional processing changes predict later clinical response in depression. Thirty-five unmedicated patients with major depression took the selective serotonin re-uptake inhibitor (SSRI), escitalopram (10 mg), over 6 weeks, and were classified as responders (22 patients) versus non-responders (13 patients), based on at least a 50% reduction in symptoms by the end of treatment...
November 22, 2016: Translational Psychiatry
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