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Translational Psychiatry

M Peciña, J Heffernan, J Wilson, J K Zubieta, A Y Dombrovski
Placebo responses in depression exemplify how expectancies and appraisals impact mood. Cognitive and neural mechanisms underlying these responses are still poorly understood, partly due to the difficulty of simulating antidepressant effects and manipulating mood experimentally. To address these challenges, we developed an acute antidepressant placebo experiment involving the intravenous administration of a "fast-acting antidepressant" and a trial-by-trial sham fMRI "neurofeedback" manipulation, purporting to reveal mood-relevant neural responses...
October 15, 2018: Translational Psychiatry
Tatsushi Okayama, Yasuyuki Hashiguchi, Hiroki Kikuyama, Hiroshi Yoneda, Tetsufumi Kanazawa
Atypical psychosis (similar to acute and transient psychotic disorder, brief psychotic disorder) is highly heritable, but the causal genes remain unidentified. We conducted whole-genome sequencing on multiplex Japanese families with atypical psychosis. The patient group of interest shows acute psychotic features including hallucinations, delusions, and catatonic symptoms while they often show good prognosis after the onset. In addition to the next-generation analysis, HLA typing has been conveyed to check the similarity with autoimmune disease, such as systemic lupus erythematosus (SLE)...
October 15, 2018: Translational Psychiatry
Jinxu Liu, Pauravi J Gandhi, Ratnamala Pavuluri, Gajanan P Shelkar, Shashank M Dravid
Cocaine exposure induces plasticity of glutamatergic synapses of medium spiny neurons (MSNs) in the nucleus accumbens (NAc), which has been proposed to contribute to its addictive behavior. The mechanisms underlying cocaine-induced plasticity are not fully understood. The orphan glutamate delta-1 (GluD1) receptor is a member of the ionotropic glutamate receptor family but does not function as a typical ligand-gated ion channel. Instead it serves a synaptogenic function by interacting with presynaptic Neurexin protein...
October 12, 2018: Translational Psychiatry
Gitalee Sarker, Rebecca Berrens, Judith von Arx, Pawel Pelczar, Wolf Reik, Christian Wolfrum, Daria Peleg-Raibstein
Maternal overnutrition has been associated with increased susceptibility to develop obesity and neurological disorders later in life. Most epidemiological as well as experimental studies have focused on the metabolic consequences across generations following an early developmental nutritional insult. Recently, it has been shown that maternal high-fat diet (HFD) affects third-generation female body mass via the paternal lineage. We showed here that the offspring born to HFD ancestors displayed addictive-like behaviors as well as obesity and insulin resistance up to the third generation in the absence of any further exposure to HFD...
October 12, 2018: Translational Psychiatry
Rachel L Kember, Liping Hou, Xiao Ji, Lars H Andersen, Arpita Ghorai, Lisa N Estrella, Laura Almasy, Francis J McMahon, Christopher Brown, Maja Bućan
Bipolar disorder (BD) is a mental disorder characterized by alternating periods of depression and mania. Individuals with BD have higher levels of early mortality than the general population, and a substantial proportion of this is due to increased risk for comorbid diseases. To identify the molecular events that underlie BD and related medical comorbidities, we generated imputed whole-genome sequence data using a population-specific reference panel for an extended multigenerational Old Order Amish pedigree (n = 394), segregating BD and related disorders...
October 12, 2018: Translational Psychiatry
Paul Klauser, Lijing Xin, Margot Fournier, Alessandra Griffa, Martine Cleusix, Raoul Jenni, Michel Cuenod, Rolf Gruetter, Patric Hagmann, Philippe Conus, Philipp S Baumann, Kim Q Do
Mechanism-based treatments for schizophrenia are needed, and increasing evidence suggests that oxidative stress may be a target. Previous research has shown that N-acetylcysteine (NAC), an antioxidant and glutathione (GSH) precursor almost devoid of side effects, improved negative symptoms, decreased the side effects of antipsychotics, and improved mismatch negativity and local neural synchronization in chronic schizophrenia. In a recent double-blind randomized placebo-controlled trial by Conus et al., early psychosis patients received NAC add-on therapy (2700 mg/day) for 6 months...
October 12, 2018: Translational Psychiatry
Becky Inkster, Gwyneth Zai, Gemma Lewis, Kamilla W Miskowiak
Mood disorders are associated with significant psychosocial and occupational disability. It is estimated that major depressive disorder (MDD) will become the second leading cause of disability worldwide by 2020. Existing pharmacological and psychological treatments are limited for targeting cognitive dysfunctions in mood disorders. However, growing evidence from human and animal studies has shown that treatment with erythropoietin (EPO) can improve cognitive function. A recent study involving EPO-treated patients with mood disorders showed that the neural basis for their cognitive improvements appeared to involve an increase in hippocampal volume...
October 11, 2018: Translational Psychiatry
Rubai Zhou, Fan Wang, Guoqing Zhao, Weiping Xia, Daihui Peng, Ruizhi Mao, Jingjing Xu, Zuowei Wang, Wu Hong, Chen Zhang, Yong Wang, Yousong Su, Jia Huang, Tao Yang, Jijun Wang, Jun Chen, Lena Palaniyappan, Yiru Fang
Single Nucleotide Polymorphic (SNP) variations of proinflammatory cytokines such as Tumor Necrosis Factor-α (TNF-α) have been reported to be closely associated with the major depressive disorder (MDD). However, it is unclear if proinflammatory genetic burden adversely affects the regional gray matter volume in patients with MDD. The aim of this study was to test whether rs1799724, an SNP of TNF-α, contributes to the neuroanatomical changes in MDD. In this cross-sectional study, a total of 144 MDD patients and 111 healthy controls (HC) well matched for age, sex and education were recruited from Shanghai Mental Health Center...
October 11, 2018: Translational Psychiatry
Paulo Lizano, Olivia Lutz, George Ling, Jaya Padmanabhan, Neeraj Tandon, John Sweeney, Carol Tamminga, Godfrey Pearlson, Gualberto Ruaño, Mohan Kocherla, Andreas Windemuth, Brett Clementz, Elliot Gershon, Matcheri Keshavan
Vascular endothelial growth factor A (VEGFA) dysfunction may contribute to a number of pathological processes that characterize psychotic disorders. However, the influence of VEGFA gene variants on clinical and neuroimaging phenotypes in psychotic disorders has yet to be shown. In the present study, we examined whether different VEGFA gene variants influence psychosis risk, symptom severity, cognition, and brain volume. The study group included 480 probands (Bipolar I disorder with psychosis, n = 205; Schizoaffective disorder, n = 112; Schizophrenia, n = 163) and 126 healthy controls that were recruited across six sites in the B-SNIP consortium...
October 11, 2018: Translational Psychiatry
Le Shi, Jiahui Deng, Sijing Chen, Jianyu Que, Yekun Sun, Zhong Wang, Xiaojie Guo, Ying Han, Yuxin Zhou, Xiujun Zhang, Wen Xie, Xiao Lin, Jie Shi, Lin Lu
Fear is prone to return following extinction that is the basis of exposure therapy for fear-related disorders. Manipulations that enhance the extinction process can be beneficial for treatment. Animal studies have shown that fasting or caloric restriction can enhance extinction and inhibit the return of fear. The present study examined the effects of fasting on fear acquisition, extinction, and the return of fear in humans. One hundred and twenty-five male participants were randomized into a fasting group and food group and exposed to a Pavlovian fear conditioning paradigm...
October 9, 2018: Translational Psychiatry
Christina M Grimm, Sonat Aksamaz, Stefanie Schulz, Jasper Teutsch, Piotr Sicinski, Birgit Liss, Dennis Kätzel
Elevated activity at the output stage of the anterior hippocampus has been described as a physiological endophenotype of schizophrenia, and its development maps onto the transition from the prodromal to the psychotic state. Interventions that halt the spreading glutamatergic over-activity in this region and thereby the development of overt schizophrenia could be promising therapies. However, animal models with high construct validity to support such pre-clinical development are scarce. The Cyclin-D2 knockout (CD2-KO) mouse model shows a hippocampal parvalbumin-interneuron dysfunction, and its pattern of hippocampal over-activity shares similarities with that seen in prodromal patients...
October 9, 2018: Translational Psychiatry
Rébecca Robillard, Joanne S Carpenter, Naomi L Rogers, Sarah Fares, Ashlee B Grierson, Daniel F Hermens, Sharon L Naismith, Sharon J Mullin, Kristy-Lee Feilds, Nick Glozier, Elizabeth M Scott, Ian B Hickie
Abnormalities in circadian rhythms have been reported in people with mood disorders, but these abnormalities are marked by considerable inter-individual variability. This study aimed to identify pathophysiological subgroups on the basis of circadian markers and evaluate how these subgroups relate to psychiatric profiles. Thirty-five young adults (18-31 years old) receiving clinical care for unipolar depressive disorders and 15 healthy controls took part to this study. The Hamilton Rating Scale for Depression and the Young Mania rating scale were used to evaluate the severity of mood symptoms in participants with depressive disorders...
October 9, 2018: Translational Psychiatry
Daisuke Koshiyama, Kenji Kirihara, Mariko Tada, Tatsuya Nagai, Mao Fujioka, Eriko Ichikawa, Kazusa Ohta, Motoko Tani, Maiko Tsuchiya, Akiko Kanehara, Kentaro Morita, Kingo Sawada, Jun Matsuoka, Yoshihiro Satomura, Shinsuke Koike, Motomu Suga, Tsuyoshi Araki, Kiyoto Kasai
Previous studies have shown glutamatergic dysfunction and γ-aminobutyric acid (GABA)-ergic dysfunction in schizophrenia. Animal studies suggest that N-methyl-D-aspartate receptor (NMDAR) dysfunction and GABA-ergic dysfunction interact with each other and lead to alterations in excitatory/inhibitory balance. The NMDAR and GABAergic-interneuron functions may be indexed by mismatch negativity (MMN) and auditory steady-state gamma-band response (ASSR), respectively. However, no previous studies have tested the hypothesis of an abnormal association between MMN and gamma-band ASSR in the same patients to identify the in vivo evidence of NMDAR-GABA association during the early stages of psychosis...
October 8, 2018: Translational Psychiatry
Timothy Hughes, Ida E Sønderby, Tatiana Polushina, Lars Hansson, Asbjørn Holmgren, Lavinia Athanasiu, Christian Melbø-Jørgensen, Sahar Hassani, Louise K Hoeffding, Stefan Herms, Sarah E Bergen, Robert Karlsson, Jie Song, Marcella Rietschel, Markus M Nöthen, Andreas J Forstner, Per Hoffmann, Christina M Hultman, Mikael Landén, Sven Cichon, Thomas Werge, Ole A Andreassen, Stephanie Le Hellard, Srdjan Djurovic
Ankyrin-3 (ANK3) is one of the few genes that have been consistently identified as associated with bipolar disorder by multiple genome-wide association studies. However, the exact molecular basis of the association remains unknown. A rare loss-of-function splice-site SNP (rs41283526*G) in a minor isoform of ANK3 (incorporating exon ENSE00001786716) was recently identified as protective of bipolar disorder and schizophrenia. This suggests that an elevated expression of this isoform may be involved in the etiology of the disorders...
October 8, 2018: Translational Psychiatry
Marek Schwendt, John Shallcross, Natalie A Hadad, Mark D Namba, Helmut Hiller, Lizhen Wu, Eric G Krause, Lori A Knackstedt
PTSD is highly comorbid with cocaine use disorder (CUD), and cocaine users with PTSD + CUD are more resistant to treatment. Here we sought to develop a rat model of PTSD + CUD in order to identify the neurobiological changes underlying such comorbidity and screen potential medications for reducing cocaine seeking in the PTSD population. We utilized a predator scent stress model of PTSD, wherein rats received a single exposure to the fox pheromone 2,5-dihydro-2,4,5-trimethylthiazoline (TMT). One week after TMT exposure, stress-susceptible (susceptible), intermediate, and resilient phenotypes were detected and were consistent with behavioral, corticosterone, and gene expression profiles 3 weeks post TMT...
October 5, 2018: Translational Psychiatry
Ari Pinar, Ziarih Hawi, Tarrant Cummins, Beth Johnson, Marc Pauper, Janette Tong, Jeggan Tiego, Amy Finlay, Marieke Klein, Barbara Franke, Alex Fornito, Mark A Bellgrove
Intra-individual response time variability (IIRTV) is proposed as a viable endophenotype for many psychiatric disorders, particularly attention-deficit hyperactivity disorder (ADHD). Here we assessed whether IIRTV was associated with common DNA variation genome-wide and whether IIRTV mediated the relationship between any associated loci and self-reported ADHD symptoms. A final data set from 857 Australian young adults (489 females and 368 males; Mage  = 22.14 years, SDage  = 4.82 years) who completed five response time tasks and self-reported symptoms of ADHD using the Conners' Adult ADHD Rating Scale was used...
October 4, 2018: Translational Psychiatry
Inbal Reuveni, Allison C Nugent, Jessica Gill, Meena Vythilingam, Paul J Carlson, Alicja Lerner, Alexander Neumeister, Dennis S Charney, Wayne C Drevets, Omer Bonne
Agonists of the γ-aminobutyric acid (GABA) type A benzodiazepine (BZD) receptor exert anxiolytic effects in anxiety disorders, raising the possibility that altered GABA-ergic function may play a role in the pathophysiology of anxiety disorders, such as post-traumatic stress disorder (PTSD). However, few neuroimaging studies have assessed the function or binding potential of the central GABAA BZD receptor system in PTSD. Therefore, our aim was to compare the BZD receptor binding potential between PTSD patients and healthy controls...
October 4, 2018: Translational Psychiatry
Hang Zhou, Zhongshan Cheng, Nicholas Bass, John H Krystal, Lindsay A Farrer, Henry R Kranzler, Joel Gelernter
Smoking and major depression frequently co-occur, at least in part due to shared genetic risk. However, the nature of the shared genetic basis is poorly understood. To detect genetic risk variants for comorbid nicotine dependence (ND) and major depression (MD), we conducted genome-wide association study (GWAS) in two samples of African-American participants (Yale-Penn 1 and 2) using linear mixed model, followed by meta-analysis. 3724 nicotine-exposed subjects were analyzed: 2596 from Yale-Penn-1 and 1128 from Yale-Penn-2...
October 4, 2018: Translational Psychiatry
Andrea L Roberts, Nicole Gladish, Evan Gatev, Meaghan J Jones, Ying Chen, Julia L MacIsaac, Shelley S Tworoger, S Bryn Austin, Cigdem Tanrikut, Jorge E Chavarro, Andrea A Baccarelli, Michael S Kobor
Offspring of persons exposed to childhood abuse are at higher risk of neurodevelopmental and physical health disparities across the life course. Animal experiments have indicated that paternal environmental stressors can affect sperm DNA methylation and gene expression in an offspring. Childhood abuse has been associated with epigenetic marks in human blood, saliva, and brain tissue, with statistically significant methylation differences ranging widely. However, no studies have examined the association of childhood abuse with DNA methylation in gametes...
October 2, 2018: Translational Psychiatry
Saskia Selzam, Jonathan R I Coleman, Avshalom Caspi, Terrie E Moffitt, Robert Plomin
It has recently been proposed that a single dimension, called the p factor, can capture a person's liability to mental disorder. Relevant to the p hypothesis, recent genetic research has found surprisingly high genetic correlations between pairs of psychiatric disorders. Here, for the first time, we compare genetic correlations from different methods and examine their support for a genetic p factor. We tested the hypothesis of a genetic p factor by applying principal component analysis to matrices of genetic correlations between major psychiatric disorders estimated by three methods-family study, genome-wide complex trait analysis, and linkage-disequilibrium score regression-and on a matrix of polygenic score correlations constructed for each individual in a UK-representative sample of 7 026 unrelated individuals...
October 2, 2018: Translational Psychiatry
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