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Translational Psychiatry

Igor Bazov, Daniil Sarkisyan, Olga Kononenko, Hiroyuki Watanabe, Victor M Karpyak, Tatiana Yakovleva, Georgy Bakalkin
Molecular changes in cortical areas of addicted brain may underlie cognitive impairment and loss of control over intake of addictive substances and alcohol. Prodynorphin (PDYN) gives rise to dynorphin (DYNs) opioid peptides which target kappa-opioid receptor (KOR). DYNs mediate alcohol-induced impairment of learning and memory, while KOR antagonists block excessive, compulsive-like drug and alcohol self-administration in animal models. In human brain, the DYN/KOR system may undergo adaptive changes, which along with neuronal loss, may contribute to alcohol-associated cognitive deficit...
June 20, 2018: Translational Psychiatry
Fabrice Jollant, Gerd Wagner, Stéphane Richard-Devantoy, Stefanie Köhler, Karl-Jürgen Bär, Gustavo Turecki, Fabricio Pereira
The identification of brain markers of suicidal risk is highly expected. However, neuroimaging studies have yielded mixed results, possibly due to phenotypic heterogeneity. In the present study, we addressed this issue using structural brain imaging. First, two independent samples of suicide attempters (n = 17 in Montreal, 32 in Jena), patient controls (n = 26/34), and healthy controls (n = 66/34) were scanned with magnetic resonance imaging. Groups were compared with FSL. We then reviewed the literature and run a GingerALE meta-analysis of 12 structural imaging studies comparing suicide attempters and patient controls with whole-brain analyses (n = 693)...
June 19, 2018: Translational Psychiatry
Paschalis Efstathopoulos, Filip Andersson, Philippe A Melas, Liu L Yang, J Carlos Villaescusa, Joëlle Rȕegg, Tomas J Ekström, Yvonne Forsell, Maria Rosaria Galanti, Catharina Lavebratt
The disruption of key epigenetic processes during critical periods of brain development can increase an individual's vulnerability to psychopathology later in life. For instance, DNA methylation in the glucocorticoid receptor gene (NR3C1) in adulthood is known to be associated with early-life adversities and has been suggested to mediate the development of stress-related disorders. However, the association between NR3C1 methylation and the emergence of internalizing symptoms in childhood and adolescence has not been studied extensively...
June 19, 2018: Translational Psychiatry
Sheng Zhang, Chiang-Shan R Li
Research of dopaminergic deficits has focused on the ventral striatum (VS) with many studies elucidating altered resting state functional connectivity (rsFC) in individuals with cocaine dependence (CD). The VS comprises functional subregions and delineation of subregional changes in rsFC requires careful consideration of the differences between addicted and healthy populations. In the current study, we parcellated the VS using whole-brain rsFC differences between CD and non-drug-using controls (HC). Voxels with similar rsFC changes formed functional clusters...
June 18, 2018: Translational Psychiatry
Pnina Rappel, Odeya Marmor, Atira S Bick, David Arkadir, Eduard Linetsky, Anna Castrioto, Idit Tamir, Sara A Freedman, Tomer Mevorach, Moran Gilad, Hagai Bergman, Zvi Israel, Renana Eitan
Obsessive-compulsive disorder (OCD) is a common and serious psychiatric disorder. Although subthalamic nucleus deep brain stimulation (DBS) has been studied as a treatment for OCD patients the underlying mechanism of this treatment and the optimal method of stimulation are unknown. To study the neural basis of subthalamic nucleus DBS in OCD patients we used a novel, implantable DBS system with long-term local field potential sensing capability. We focus our analysis on two patients with OCD who experienced severe treatment-resistant symptoms and were implanted with subthalamic nucleus DBS systems...
June 18, 2018: Translational Psychiatry
Brigitte Vanle, William Olcott, Jaime Jimenez, Luma Bashmi, Itai Danovitch, Waguih William IsHak
Among patients with Parkinson's disease (PD), depression is prevalent and disabling, impacting both health outcomes and quality of life. There is a critical need for alternative pharmacological methods to treat PD depression, as mainstream antidepressant drugs are largely ineffective in this population. Currently, there are no recommendations for the optimal treatment of PD neuropsychiatric symptoms. Given the dual antidepressant and anti-dyskinetic effects of ketamine and other N-methyl-D-aspartate (NMDA) antagonists for PD, this review aims to examine the current evidence of NMDA antagonists for treating neuropsychiatric symptoms, including memantine, amantadine, ketamine, dizoclopine, and d-cycloserine...
June 15, 2018: Translational Psychiatry
Meghan H Puglia, Jessica J Connelly, James P Morris
Aberrant attentional biases to social stimuli have been implicated in a number of disorders including autism and social anxiety disorder. Oxytocin, a naturally-occurring mammalian hormone and neuromodulator involved in regulating social behavior, has been proposed to impact basic biological systems that facilitate the detection of and orientation to social information. Here, we investigate a role for naturally-occurring variability in the endogenous oxytocinergic system in regulating neural response during attention to social information...
June 15, 2018: Translational Psychiatry
Chun Chieh Fan, Andrew J Schork, Timothy T Brown, Barbara E Spencer, Natacha Akshoomoff, Chi-Hua Chen, Joshua M Kuperman, Donald J Hagler, Vidar M Steen, Stephanie Le Hellard, Asta Kristine Håberg, Thomas Espeseth, Ole A Andreassen, Anders M Dale, Terry L Jernigan, Eric Halgren
Despite great interest in using magnetic resonance imaging (MRI) for studying the effects of genes on brain structure in humans, current approaches have focused almost entirely on predefined regions of interest and had limited success. Here, we used multivariate methods to define a single neuroanatomical score of how William's Syndrome (WS) brains deviate structurally from controls. The score is trained and validated on measures of T1 structural brain imaging in two WS cohorts (training, n = 38; validating, n = 60)...
June 8, 2018: Translational Psychiatry
Steven J Korzeniewski, Elizabeth N Allred, T Michael O'Shea, Alan Leviton, Karl C K Kuban
Among the 1 of 10 children who are born preterm annually in the United States, 6% are born before the third trimester. Among children who survive birth before the 28th week of gestation, the risks of autism spectrum disorder (ASD) and non-autistic social impairment are severalfold higher than in the general population. We examined the relationship between top quartile inflammation-related protein concentrations among children born extremely preterm and ASD or, separately, a high score on the Social Responsiveness Scale (SRS total score ≥65) among those who did not meet ASD criteria, using information only from the subset of children whose DAS-II verbal or non-verbal IQ was ≥70, who were assessed for ASD, and who had proteins measured in blood collected on ≥2 days (N = 763)...
June 8, 2018: Translational Psychiatry
Monica Sathyanesan, Michael J Watt, Jacob M Haiar, Jamie L Scholl, Shaydel R Davies, Riley T Paulsen, Jayme Wiederin, Pawel Ciborowski, Samuel S Newton
Cognitive deficits are widespread in psychiatric disorders and frequently as debilitating as the affective component. Widely prescribed antidepressants for treating depressive disorders have limited efficacy in normalizing cognitive function. Erythropoietin (Epo) has been shown to improve cognitive function in schizophrenia and treatment resistant depressed patients. However, the potent elevation of red blood cell counts by Epo can cause hematological complications in non-anemic patients. We investigated a chemically engineered, posttranslational modification of Epo, carbamoylation, which renders it non-erythropoietic...
June 8, 2018: Translational Psychiatry
Clark D Jeffries, Diana O Perkins, Margot Fournier, Kim Q Do, Michel Cuenod, Ines Khadimallah, Enrico Domenici, Jean Addington, Carrie E Bearden, Kristin S Cadenhead, Tyrone D Cannon, Barbara A Cornblatt, Daniel H Mathalon, Thomas H McGlashan, Larry J Seidman, Ming Tsuang, Elaine F Walker, Scott W Woods
Levels of certain circulating cytokines and related immune system molecules are consistently altered in schizophrenia and related disorders. In addition to absolute analyte levels, we sought analytes in correlation networks that could be prognostic. We analyzed baseline blood plasma samples with a Luminex platform from 72 subjects meeting criteria for a psychosis clinical high-risk syndrome; 32 subjects converted to a diagnosis of psychotic disorder within two years while 40 other subjects did not. Another comparison group included 35 unaffected subjects...
June 6, 2018: Translational Psychiatry
Albert J Fenoy, Paul E Schulz, Sudhakar Selvaraj, Christina L Burrows, Giovanna Zunta-Soares, Kathryn Durkin, Paolo Zanotti-Fregonara, Joao Quevedo, Jair C Soares
Deep brain stimulation (DBS) to the superolateral branch of the medial forebrain bundle (MFB) has been reported to lead to rapid antidepressant effects. In this longitudinal study, we expand upon the initial results we reported at 26 weeks (Fenoy et al., 2016), showing sustained antidepressant effects of MFB DBS on six patients with treatment-resistant depression (TRD) over 1 year. The Montgomery-Åsberg Depression Rating Scale (MADRS) was used as the primary assessment tool. Deterministic fiber tracking was used to individually map the target area; analysis was performed to compare modulated fiber tracts between patients...
June 4, 2018: Translational Psychiatry
Li Rebekah Feng, Juan Luis Fernández-Martínez, Kristien J M Zaal, Enrique J deAndrés-Galiana, Brian S Wolff, Leorey N Saligan
Cancer-related fatigue (CRF) is a common burden in cancer patients and little is known about its underlying mechanism. The primary aim of this study was to identify gene signatures predictive of post-radiotherapy fatigue in prostate cancer patients. We employed Fisher Linear Discriminant Analysis (LDA) to identify predictive genes using whole genome microarray data from 36 men with prostate cancer. Ingenuity Pathway Analysis was used to determine functional networks of the predictive genes. Functional validation was performed using a T lymphocyte cell line, Jurkat E6...
May 30, 2018: Translational Psychiatry
Vinod Jangir Kumar, Nicola M Grissom, Sarah E McKee, Hannah Schoch, Nicole Bowman, Robbert Havekes, Manoj Kumar, Stephen Pickup, Harish Poptani, Teresa M Reyes, Mike Hawrylycz, Ted Abel, Thomas Nickl-Jockschat
Neurodevelopmental disorders, such as ASD and ADHD, affect males about three to four times more often than females. 16p11.2 hemideletion is a copy number variation that is highly associated with neurodevelopmental disorders. Previous work from our lab has shown that a mouse model of 16p11.2 hemideletion (del/+) exhibits male-specific behavioral phenotypes. We, therefore, aimed to investigate with magnetic resonance imaging (MRI), whether del/+ animals also exhibited a sex-specific neuroanatomical endophenotype...
May 29, 2018: Translational Psychiatry
Gili Ezra-Nevo, Naama Volk, Assaf Ramot, Claudia Kuehne, Michael Tsoory, Jan Deussing, Alon Chen
A well-coordinated stress response is pivotal for an organisms' survival. Corticotropin-releasing factor (CRF) is an essential component of the emotional and neuroendocrine stress response, however its role in cerebellar functions is poorly understood. Here, we explore the role of CRF in the inferior olive (IO) nucleus, which is a major source of input to the cerebellum. Using a CRF reporter line, in situ hybridization and immunohistochemistry, we demonstrate very high levels of the CRF neuropeptide expression throughout the IO sub-regions...
May 25, 2018: Translational Psychiatry
Jamie Horder, Marija M Petrinovic, Maria A Mendez, Andreas Bruns, Toru Takumi, Will Spooren, Gareth J Barker, Basil Künnecke, Declan G Murphy
Autism spectrum disorder (ASD) is a pervasive neurodevelopmental syndrome with a high human and economic burden. The pathophysiology of ASD is largely unclear, thus hampering development of pharmacological treatments for the core symptoms of the disorder. Abnormalities in glutamate and GABA signaling have been hypothesized to underlie ASD symptoms, and may form a therapeutic target, but it is not known whether these abnormalities are recapitulated in humans with ASD, as well as in rodent models of the disorder...
May 25, 2018: Translational Psychiatry
D H Bergin, Y Jing, B G Mockett, H Zhang, W C Abraham, P Liu
While amyloid-beta (Aβ) peptides play a central role in the development of Alzheimer's disease (AD), recent evidence also implicates altered metabolism of L-arginine in the pathogenesis of AD. The present study systematically investigated how behavioural function and the brain and plasma arginine metabolic profiles changed in a chronic Aβ accumulation model using male APPswe/PS1ΔE9 transgenic (Tg) mice at 7 and 13 months of age. As compared to their wild-type (WT) littermates, Tg mice displayed age-related deficits in spatial water maze tasks and alterations in brain arginine metabolism...
May 25, 2018: Translational Psychiatry
Peilin Jia, Xiangning Chen, Ayman H Fanous, Zhongming Zhao
Genetic components susceptible to complex disease such as schizophrenia include a wide spectrum of variants, including common variants (CVs) and de novo mutations (DNMs). Although CVs and DNMs differ by origin, it remains elusive whether and how they interact at the gene, pathway, and network levels that leads to the disease. In this work, we characterized the genes harboring schizophrenia-associated CVs (CVgenes) and the genes harboring DNMs (DNMgenes) using measures from network, tissue-specific expression profile, and spatiotemporal brain expression profile...
May 24, 2018: Translational Psychiatry
Nathalia Zak, Torgeir Moberget, Erlend Bøen, Birgitte Boye, Trine R Waage, Espen Dietrichs, Nina Harkestad, Ulrik F Malt, Lars T Westlye, Ole A Andreassen, Stein Andersson, Torbjørn Elvsåshagen
Visual evoked potential (VEP) plasticity is a promising assay for noninvasive examination of long-term potentiation (LTP)-like synaptic processes in the cerebral cortex. We conducted longitudinal and cross-sectional investigations of VEP plasticity in controls and individuals with bipolar disorder (BD) type II. VEP plasticity was assessed at baseline, as described previously (Elvsåshagen et al. Biol Psychiatry 2012), and 2.2 years later, at follow-up. The longitudinal sample with VEP data from both time points comprised 29 controls and 16 patients...
May 24, 2018: Translational Psychiatry
Guido K W Frank, Megan E Shott, Marisa C DeGuzman, Andrew Smolen
The prediction error model is a widely used paradigm that is conceptually based on neuronal dopamine function. However, whether dopamine receptor gene alleles contribute to human neuroimaging prediction error results is uncertain. Recent research implicated the dopamine D2 receptor in behavior response during a prediction error paradigm and we expected that polymorphisms of that receptor would contribute to prediction error brain response. In this study, healthy female participants in the early follicular phase of the menstrual cycle underwent a taste prediction error paradigm during functional magnetic resonance imaging...
May 23, 2018: Translational Psychiatry
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