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Translational Psychiatry

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https://www.readbyqxmd.com/read/29217840/the-role-of-anxious-distress-in-immune-dysregulation-in-patients-with-major-depressive-disorder
#1
Roxanne Gaspersz, Femke Lamers, Gayle Wittenberg, Aartjan T F Beekman, Albert M van Hemert, Robert A Schoevers, Brenda W J H Penninx
Although depression with anxious distress appears to be a clinically relevant subtype of major depressive disorder (MDD), whether it involves specific pathophysiology remains unclear. Inflammation has been implicated, but not comprehensively studied. We examined within a large MDD sample whether anxious distress and related anxiety features are associated with differential basal inflammation and innate cytokine production capacity. Data are from 1078 MDD patients from the Netherlands Study of Depression and Anxiety...
December 8, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29217835/bayesian-prediction-intervals-for-assessing-p-value-variability-in-prospective-replication-studies
#2
Olga Vsevolozhskaya, Gabriel Ruiz, Dmitri Zaykin
Increased availability of data and accessibility of computational tools in recent years have created an unprecedented upsurge of scientific studies driven by statistical analysis. Limitations inherent to statistics impose constraints on the reliability of conclusions drawn from data, so misuse of statistical methods is a growing concern. Hypothesis and significance testing, and the accompanying P-values are being scrutinized as representing the most widely applied and abused practices. One line of critique is that P-values are inherently unfit to fulfill their ostensible role as measures of credibility for scientific hypotheses...
December 8, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29217834/gender-specific-alteration-of-energy-balance-and-circadian-locomotor-activity-in-the-crtc1-knockout-mouse-model-of-depression
#3
Clara Rossetti, Daniel Sciarra, Jean-Marie Petit, Chin B Eap, Olivier Halfon, Pierre J Magistretti, Benjamin Boutrel, Jean-René Cardinaux
Obesity and depression are major public health concerns, and there is increasing evidence that they share etiological mechanisms. CREB-regulated transcription coactivator 1 (CRTC1) participates in neurobiological pathways involved in both mood and energy balance regulation. Crtc1 -/- mice rapidly develop a depressive-like and obese phenotype in early adulthood, and are therefore a relevant animal model to explore possible common mechanisms underlying mood disorders and obesity. Here, the obese phenotype of male and female Crtc1 -/- mice was further characterized by investigating CRTC1's role in the homeostatic and hedonic regulation of food intake, as well as its influence on daily locomotor activity...
December 8, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29217832/inter-and-intra-hemispheric-structural-imaging-markers-predict-depression-relapse-after-electroconvulsive-therapy-a-multisite-study
#4
Benjamin S C Wade, Jing Sui, Gerhard Hellemann, Amber M Leaver, Randall T Espinoza, Roger P Woods, Christopher C Abbott, Shantanu H Joshi, Katherine L Narr
Relapse of depression following treatment is high. Biomarkers predictive of an individual's relapse risk could provide earlier opportunities for prevention. Since electroconvulsive therapy (ECT) elicits robust and rapidly acting antidepressant effects, but has a >50% relapse rate, ECT presents a valuable model for determining predictors of relapse-risk. Although previous studies have associated ECT-induced changes in brain morphometry with clinical response, longer-term outcomes have not been addressed. Using structural imaging data from 42 ECT-responsive patients obtained prior to and directly following an ECT treatment index series at two independent sites (UCLA: n = 17, age = 45...
December 8, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29217824/soluble-tau-has-devastating-effects-on-the-structural-plasticity-of-hippocampal-granule-neurons
#5
M Bolós, N Pallas-Bazarra, J Terreros-Roncal, J R Perea, J Jurado-Arjona, J Ávila, M Llorens-Martín
Tau is a neuronal microtubule-associated protein with countless physiological functions. Although the detrimental effects of insoluble aggregated Tau have been widely studied, recent evidence supports the notion that soluble Tau (composed mostly of monomers and dimers) is also toxic for neurons. Here we evaluated the long-term impact of a single stereotaxic injection of human soluble Tau on hippocampal granule neurons in mice. At the ultrastructural level, soluble Tau reduced the number of afferent synapses and caused a dramatic depletion of synaptic vesicles both in afferent and efferent synapses...
December 8, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29217819/association-between-serum-neuron-specific-enolase-age-overweight-and-structural-mri-patterns-in-901-subjects
#6
Johanna Hoffmann, Deborah Janowitz, Sandra Van der Auwera, Katharina Wittfeld, Matthias Nauck, Nele Friedrich, Mohamad Habes, Christos Davatzikos, Jan Terock, Martin Bahls, Annemarie Goltz, Angela Kuhla, Henry Völzke, Hans Jörgen Grabe
Serum neuron-specific enolase (sNSE) is considered a marker for neuronal damage, related to gray matter structures. Previous studies indicated its potential as marker for structural and functional damage in conditions with adverse effects to the brain like obesity and dementia. In the present study, we investigated the putative association between sNSE levels, body mass index (BMI), total gray matter volume (GMV), and magnetic resonance imaging-based indices of aging as well as Alzheimer's disease (AD)-like patterns...
December 8, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29213110/the-relationship-between-dlpfc-activity-during-unpredictable-threat-and-co2-induced-panic-symptoms
#7
Nicholas L Balderston, Jeffrey Liu, Roxann Roberson-Nay, Monique Ernst, Christian Grillon
Panic disorder is characterized by sudden, repeated, and unexpected attacks of intense fear and overwhelming anxiety about when another attack may strike. Patients with panic disorder and healthy individuals with a history of panic attacks show a hypersensitivity to unpredictable threats, suggesting a possible link between panic and sustained anxiety. The purpose of this study was to determine the degree to which induced symptoms of panic relate to fear and anxiety, as well as activity in the neural systems that mediate and regulate these affective states...
November 30, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29187755/a-mouse-model-of-the-schizophrenia-associated-1q21-1-microdeletion-syndrome-exhibits-altered-mesolimbic-dopamine-transmission
#8
Jacob Nielsen, Kim Fejgin, Florence Sotty, Vibeke Nielsen, Arne Mørk, Claus T Christoffersen, Leonid Yavich, Jes B Lauridsen, Dorte Clausen, Peter H Larsen, Jan Egebjerg, Thomas M Werge, Pekka Kallunki, Kenneth V Christensen, Michael Didriksen
1q21.1 hemizygous microdeletion is a copy number variant leading to eightfold increased risk of schizophrenia. In order to investigate biological alterations induced by this microdeletion, we generated a novel mouse model (Df(h1q21)/+) and characterized it in a broad test battery focusing on schizophrenia-related assays. Df(h1q21)/+ mice displayed increased hyperactivity in response to amphetamine challenge and increased sensitivity to the disruptive effects of amphetamine and phencyclidine hydrochloride (PCP) on prepulse inhibition...
November 30, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29187754/fluoxetine-treatment-is-effective-in-a-rat-model-of-childhood-induced-post-traumatic-stress-disorder
#9
Lior Ariel, Sapir Inbar, Schachaf Edut, Gal Richter-Levin
Although selective serotonin reuptake inhibitors (SSRIs) are first-line treatment for post-traumatic stress disorder (PTSD) patients, their therapeutic efficacy is limited. Childhood adversities are considered a risk factor for developing PTSD in adulthood but may trigger PTSD without additional trauma in some individuals. Nevertheless, just as childhood is considered a vulnerable period it may also be an effective period for preventive treatment. Using a rat model of childhood-induced PTSD, pre-pubertal stress (juvenile stress, JVS), we compared the therapeutic effects of fluoxetine and examined the effectiveness of 1 month of fluoxetine treatment following JVS and into adulthood compared to treatment in adulthood...
November 30, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29187753/subchronic-olanzapine-exposure-leads-to-increased-expression-of-myelination-related-genes-in-rat-fronto-medial-cortex
#10
Kari M Ersland, Silje Skrede, Christine Stansberg, Vidar M Steen
Schizophrenia is a psychotic disorder with severe and disabling symptoms, such as hallucinations, delusions, blunted affect and social withdrawal. The neuropathology remains elusive, but disturbances in immunity-related processes, neuronal connectivity and myelination have consistently been linked to schizophrenia. Antipsychotic drugs can be efficient in reducing symptoms, acting primarily on the dopamine system, but additional biological targets are likely to exist. Here we have screened for novel mechanisms of action in an animal model, using adult rats exposed to long-acting olanzapine, achieving stable and clinically relevant antipsychotic drug concentrations...
November 30, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29187748/genome-wide-association-study-of-subcortical-brain-volume-in-ptsd-cases-and-trauma-exposed-controls
#11
Rajendra A Morey, Sarah L Davis, Melanie E Garrett, Courtney C Haswell, Christine E Marx, Jean C Beckham, Gregory McCarthy, Michael A Hauser, Allison E Ashley-Koch
Depending on the traumatic event, a significant fraction of trauma survivors subsequently develop PTSD. The additional variability in PTSD risk is expected to arise from genetic susceptibility. Unfortunately, several genome-wide association studies (GWAS) have failed to identify a consistent genetic marker for PTSD. The heritability of intermediate phenotypes such as regional brain volumes is often 80% or higher. We conducted a GWAS of subcortical brain volumes in a sample of recent military veteran trauma survivors (n = 157), grouped into PTSD (n = 66) and non-PTSD controls (n = 91)...
November 30, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29187746/genome-wide-haplotype-based-association-analysis-of-major-depressive-disorder-in-generation-scotland-and-uk-biobank
#12
David M Howard, Lynsey S Hall, Jonathan D Hafferty, Yanni Zeng, Mark J Adams, Toni-Kim Clarke, David J Porteous, Reka Nagy, Caroline Hayward, Blair H Smith, Alison D Murray, Niamh M Ryan, Kathryn L Evans, Chris S Haley, Ian J Deary, Pippa A Thomson, Andrew M McIntosh
Genome-wide association studies using genotype data have had limited success in the identification of variants associated with major depressive disorder (MDD). Haplotype data provide an alternative method for detecting associations between variants in weak linkage disequilibrium with genotyped variants and a given trait of interest. A genome-wide haplotype association study for MDD was undertaken utilising a family-based population cohort, Generation Scotland: Scottish Family Health Study (n = 18,773), as a discovery cohort with UK Biobank used as a population-based replication cohort (n = 25,035)...
November 30, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29187730/genome-wide-analysis-in-uk-biobank-identifies-four-loci-associated-with-mood-instability-and-genetic-correlation-with-major-depressive-disorder-anxiety-disorder-and-schizophrenia
#13
Joey Ward, Rona J Strawbridge, Mark E S Bailey, Nicholas Graham, Amy Ferguson, Donald M Lyall, Breda Cullen, Laura M Pidgeon, Jonathan Cavanagh, Daniel F Mackay, Jill P Pell, Michael O'Donovan, Valentina Escott-Price, Daniel J Smith
Mood instability is a core clinical feature of affective and psychotic disorders. In keeping with the Research Domain Criteria approach, it may be a useful construct for identifying biology that cuts across psychiatric categories. We aimed to investigate the biological validity of a simple measure of mood instability and evaluate its genetic relationship with several psychiatric disorders, including major depressive disorder (MDD), bipolar disorder (BD), schizophrenia, attention deficit hyperactivity disorder (ADHD), anxiety disorder and post-traumatic stress disorder (PTSD)...
November 30, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29087373/deep-brain-stimulation-for-treatment-resistant-major-depressive-disorder-a-comparison-of-two-targets-and-long-term-follow-up
#14
S Raymaekers, L Luyten, C Bervoets, L Gabriëls, B Nuttin
We previously found that electrical stimulation in the anterior limb of the internal capsule/bed nucleus of the stria terminalis (IC/BST) alleviates depressive symptoms in severe treatment-resistant obsessive-compulsive disorder (OCD) patients. Here we tested the hypothesis that electrical stimulation in either IC/BST or in the inferior thalamic peduncle (ITP) effectively reduces depressive symptoms in treatment-resistant major depressive disorder (TRD). In a double-blind crossover design, the effects of electrical stimulation at both targets were compared in TRD patients...
October 31, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29087372/dementia-related-agitation-a-review-of-non-pharmacological-interventions-and-analysis-of-risks-and-benefits-of-pharmacotherapy
#15
REVIEW
E O Ijaopo
Unsurprisingly, the subject of dementia has been a rising matter of public health concerns as people now live longer. World Alzheimer Report 2015, estimate that about 46.8 million people worldwide have dementia. These numbers are projected to almost double every 20 years, reaching 74.7 million in 2030 and 131.5 million in 2050. The modality for treating agitation and other behavioral symptoms in dementia patients has been a challenge. Many years on, there has been no FDA-approved pharmacotherapy in treating dementia-related agitation...
October 31, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29064472/genome-wide-association-studies-of-smooth-pursuit-and-antisaccade-eye-movements-in-psychotic-disorders-findings-from-the-b-snip-study
#16
R Lencer, L J Mills, N Alliey-Rodriguez, R Shafee, A M Lee, J L Reilly, A Sprenger, J E McDowell, S A McCarroll, M S Keshavan, G D Pearlson, C A Tamminga, B A Clementz, E S Gershon, J A Sweeney, J R Bishop
Eye movement deviations, particularly deficits of initial sensorimotor processing and sustained pursuit maintenance, and antisaccade inhibition errors, are established intermediate phenotypes for psychotic disorders. We here studied eye movement measures of 849 participants from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study (schizophrenia N=230, schizoaffective disorder N=155, psychotic bipolar disorder N=206 and healthy controls N=258) as quantitative phenotypes in relation to genetic data, while controlling for genetically derived ancestry measures, age and sex...
October 24, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29039851/quantifying-person-level-brain-network-functioning-to-facilitate-clinical-translation
#17
T M Ball, A N Goldstein-Piekarski, J M Gatt, L M Williams
Although advances in neuroimaging have yielded insights into the intrinsic organization of human brain networks and their relevance to psychiatric and neurological disorders, there has been no translation of these insights into clinical practice. One necessary step toward clinical translation is identifying a summary metric of network function that is reproducible, reliable, and has known normative data, analogous to normed neuropsychological tests. Our aim was therefore to establish the proof of principle for such a metric, focusing on the default mode network (DMN)...
October 17, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28994820/sexual-dimorphism-of-ambra1-related-autistic-features-in-human-and-mouse
#18
M Mitjans, M Begemann, A Ju, E Dere, L Wüstefeld, S Hofer, I Hassouna, J Balkenhol, B Oliveira, S van der Auwera, R Tammer, K Hammerschmidt, H Völzke, G Homuth, F Cecconi, K Chowdhury, H Grabe, J Frahm, S Boretius, T Dandekar, H Ehrenreich
Ambra1 is linked to autophagy and neurodevelopment. Heterozygous Ambra1 deficiency induces autism-like behavior in a sexually dimorphic manner. Extraordinarily, autistic features are seen in female mice only, combined with stronger Ambra1 protein reduction in brain compared to males. However, significance of AMBRA1 for autistic phenotypes in humans and, apart from behavior, for other autism-typical features, namely early brain enlargement or increased seizure propensity, has remained unexplored. Here we show in two independent human samples that a single normal AMBRA1 genotype, the intronic SNP rs3802890-AA, is associated with autistic features in women, who also display lower AMBRA1 mRNA expression in peripheral blood mononuclear cells relative to female GG carriers...
October 10, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28972592/genetically-driven-brain-serotonin-deficiency-facilitates-panic-like-escape-behavior-in-mice
#19
J Waider, S Popp, M D Lange, R Kern, J F Kolter, J Kobler, N C Donner, K R Lowe, J H Malzbender, C J Brazell, M R Arnold, B Aboagye, A Schmitt-Böhrer, C A Lowry, H C Pape, K P Lesch
Multiple lines of evidence implicate brain serotonin (5-hydroxytryptamine; 5-HT) system dysfunction in the pathophysiology of stressor-related and anxiety disorders. Here we investigate the influence of constitutively deficient 5-HT synthesis on stressor-related anxiety-like behaviors using Tryptophan hydroxylase 2 (Tph2) mutant mice. Functional assessment of c-Fos after associated foot shock, electrophysiological recordings of GABAergic synaptic transmission, differential expression of the Slc6a4 gene in serotonergic neurons were combined with locomotor and anxiety-like measurements in different contextual settings...
October 3, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28972591/altered-activation-and-connectivity-in-a-hippocampal-basal-ganglia-midbrain-circuit-during-salience-processing-in-subjects-at-ultra-high-risk-for-psychosis
#20
T Winton-Brown, A Schmidt, J P Roiser, O D Howes, A Egerton, P Fusar-Poli, N Bunzeck, A A Grace, E Duzel, S Kapur, P McGuire
Animal models of psychosis propose that abnormal hippocampal activity drives increased subcortical dopamine function, which is thought to contribute to aberrant salience processing and psychotic symptoms. These effects appear to be mediated through connections between the hippocampus, ventral striatum/pallidum and the midbrain. The aim of the present study was to examine the activity and connectivity in this pathway in people at ultra high risk (UHR) for psychosis. Functional magnetic resonance imaging was used to compare neural responses in a hippocampal-basal ganglia-midbrain network during reward, novelty and aversion processing between 29 UHR subjects and 32 healthy controls...
October 3, 2017: Translational Psychiatry
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