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Translational Psychiatry

Linyan Wang, Jun Li, Mei Shuang, Tianlan Lu, Ziqi Wang, Tian Zhang, Weihua Yue, Meixiang Jia, Yanyan Ruan, Jing Liu, Zhiliu Wu, Dai Zhang, Lifang Wang
Cytogenetic studies suggested that chromosome 15q11-q13 might be a candidate region that increases the risk of autism. Previous association studies in Caucasian populations identified the risk variants of genes in this region. However, the association of these genes with autism in Chinese Han population remains unclear. Herein, 512 autism trios were utilized for a family-based association study of 41 tag single nucleotide polymorphisms (SNPs) in this region to explore the association between protein-coding genes on chromosome 15q11-q13 and autism in Chinese Han population...
August 14, 2018: Translational Psychiatry
Masahir Okamoto, Jason D Gray, Chloe S Larson, Syed Faraz Kazim, Hideaki Soya, Bruce S McEwen, Ana C Pereira
Alzheimer's disease (AD) represents a major healthcare burden with no effective treatment. The glutamate modulator, riluzole, was shown to reverse many AD-related gene expression changes and improve cognition in aged rats. However, riluzole's effect on amyloid beta (Aβ) pathology, a major histopathological hallmark of AD, remains unclear. 5XFAD transgenic mice, which harbor amyloid β precursor protein (APP) and presenilin mutations and exhibit early Aβ accumulation, were treated with riluzole from 1 to 6 months of age...
August 14, 2018: Translational Psychiatry
Gauri Ang, Laura E McKillop, Ross Purple, Cristina Blanco-Duque, Stuart N Peirson, Russell G Foster, Paul J Harrison, Rolf Sprengel, Kay E Davies, Peter L Oliver, David M Bannerman, Vladyslav V Vyazovskiy
Sleep EEG spindles have been implicated in attention, sensory processing, synaptic plasticity and memory consolidation. In humans, deficits in sleep spindles have been reported in a wide range of neurological and psychiatric disorders, including schizophrenia. Genome-wide association studies have suggested a link between schizophrenia and genes associated with synaptic plasticity, including the Gria1 gene which codes for the GluA1 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor...
August 14, 2018: Translational Psychiatry
L- P Li, E T Dustrude, M M Haulcomb, A R Abreu, S D Fitz, P L Johnson, G A Thakur, A I Molosh, Y Lai, A Shekhar
Stimulation of N-methyl-D-aspartic acid receptors (NMDARs) and the resulting increase of nitric oxide (NO) production are critical for fear memory formation. Following NMDAR activation, efficient production of NO requires linking the 95 kDa postsynaptic density protein (PSD95), a scaffolding protein to neuronal nitric oxide synthase (nNOS). A variety of previously studied NMDAR antagonists and NOS inhibitors can disrupt fear conditioning, but they also affect many other CNS functions such as motor activity, anxiety, and learning...
August 14, 2018: Translational Psychiatry
Thomas A Wehr
In bipolar disorder, episodes of depression and mania are associated with dramatic disturbances in sleep, which experiments show are likely to contribute to the pathogenesis of the episodes. A recent finding that 18 patients' manic-depressive cycles oscillated in synchrony with biweekly surges in amplitude of the moon's tides provided a clue to the cause of the sleep-disturbances. Analyses of one of the patients' sleep-wake cycles suggest that his mood cycles arose when a circadian rhythm that normally is entrained to dawn and controls the daily onset of wakefulness became entrained instead to 24...
August 13, 2018: Translational Psychiatry
Hongyan Ren, Chiara Fabbri, Rudolf Uher, Marcella Rietschel, Ole Mors, Neven Henigsberg, Joanna Hauser, Astrid Zobel, Wolfgang Maier, Mojca Z Dernovsek, Daniel Souery, Annamaria Cattaneo, Gerome Breen, Ian W Craig, Anne E Farmer, Peter McGuffin, Cathryn M Lewis, Katherine J Aitchison
A key feature of major depressive disorder (MDD) is anhedonia, which is a predictor of response to antidepressant treatment. In order to shed light on its genetic underpinnings, we conducted a genome-wide association study (GWAS) followed by investigation of biological pathway enrichment using an anhedonia dimension for 759 patients with MDD in the GENDEP study. The GWAS identified 18 SNPs associated at genome-wide significance with the top one being an intronic SNP (rs9392549) in PRPF4B (pre-mRNA processing factor 4B) located on chromosome 6 (P = 2...
August 13, 2018: Translational Psychiatry
Xing Qian, Beatrice Rui Yi Loo, Francisco Xavier Castellanos, Siwei Liu, Hui Li Koh, Xue Wei Wendy Poh, Ranga Krishnan, Daniel Fung, Michael Wl Chee, Cuntai Guan, Tih-Shih Lee, Choon Guan Lim, Juan Zhou
A brain-computer-interface (BCI)-based attention training game system has shown promise for treating attention deficit/hyperactivity disorder (ADHD) children with inattentive symptoms. However, little is known about brain network organizational changes underlying behavior improvement following BCI-based training. To cover this gap, we aimed to examine the topological alterations of large-scale brain functional networks induced by the 8-week BCI-based attention intervention in ADHD boys using resting-state functional magnetic resonance imaging method...
August 10, 2018: Translational Psychiatry
Kathleen Connery, Marie Tippett, Leanna M Delhey, Shannon Rose, John C Slattery, Stephen G Kahler, Juergen Hahn, Uwe Kruger, Madeleine W Cunningham, Craig Shimasaki, Richard E Frye
The identification of brain-targeted autoantibodies in children with autism spectrum disorder (ASD) raises the possibility of autoimmune encephalopathy (AIE). Intravenous immunoglobulin (IVIG) is effective for AIE and for some children with ASD. Here, we present the largest case series of children with ASD treated with IVIG. Through an ASD clinic, we screened 82 children for AIE, 80 of them with ASD. IVIG was recommended for 49 (60%) with 31 (38%) receiving the treatment under our care team. The majority of parents (90%) reported some improvement with 71% reporting improvements in two or more symptoms...
August 10, 2018: Translational Psychiatry
Elmira Ismaylova, Melissa L Lévesque, Florence B Pomares, Moshe Szyf, Zsofia Nemoda, Cherine Fahim, Frank Vitaro, Mara Brendgen, Ginette Dionne, Michel Boivin, Richard E Tremblay, Linda Booij
Several studies have examined associations between peripheral DNA methylation patterns of the serotonin transporter gene (SLC6A4) promoter and symptoms of depression and anxiety. The SLC6A4 promoter methylation has also been associated with frontal-limbic brain responses to negative stimuli. However, it is unclear how much of this association is confounded by DNA sequence variations. We utilized a monozygotic-twin within-pair discordance design, to test whether DNA methylation at specific CpG sites in the SLC6A4 promoter of peripheral cells is associated with greater frontal-limbic brain responses to negative stimuli (sadness and fear), independently of DNA sequence effects...
August 8, 2018: Translational Psychiatry
Hannah J Jones, Jon Heron, Gemma Hammerton, Jan Stochl, Peter B Jones, Mary Cannon, George Davey Smith, Peter Holmans, Glyn Lewis, David E J Linden, Michael C O'Donovan, Michael J Owen, James Walters, Stanley Zammit
Whilst associations between polygenic risk scores (PRSs) for schizophrenia and various phenotypic outcomes have been reported, an understanding of developmental pathways can only be gained by modelling comorbidity across psychopathology. We examine how genetic risk for schizophrenia relates to adolescent psychosis-related and internalizing psychopathology using a latent modelling approach, and compare this to genetic risk for other psychiatric disorders, to gain a more comprehensive understanding of the developmental pathways at this age...
August 8, 2018: Translational Psychiatry
Ponson Laura, Gomot Marie, Blanc Romuald, Barthelemy Catherine, Roux Sylvie, Munnich Arnold, Romana Serge, Aguillon-Hernandez Nadia, Malan Valérie, Bonnet-Brilhault Frédérique
Phelan-McDermid syndrome is related to terminal 22q13 deletions of various sizes affecting the SHANK3 gene. In this neurodevelopmental disorder, behavioural symptoms of autism spectrum disorder (ASD) are reported in half of cases. Extensive clinical and neurophysiological characterization is lacking to understand the genotype-phenotype correlation. Eighteen patients (8 males, mean age 12.7 years, SD = 9.2) with known 22q13 deletions were fully explored with determination of deletion size, along with behavioural, language and cognitive standardized assessments...
August 8, 2018: Translational Psychiatry
Yongfeng Yang, Lu Wang, Lingyi Li, Wenqiang Li, Yan Zhang, Hong Chang, Xiao Xiao, Ming Li, Luxian Lv
Previous genome-wide association studies (GWAS) suggest that rs10489202 in the intron of MPC2 (mitochondrial pyruvate carrier 2) is a risk locus for schizophrenia in Han Chinese populations. To validate this discovery, we conducted a replication analysis in an independent case-control sample of Han Chinese ancestry (437 cases and 2031 controls), followed by a meta-analytic investigation in multiple East Asian samples. In the replication analysis, rs10489202 showed marginal association with schizophrenia (two-tailed P = 0...
August 7, 2018: Translational Psychiatry
Marius Hienert, Gregor Gryglewski, Mara Stamenkovic, Siegfried Kasper, Rupert Lanzenberger
Despite intense research, the underlying mechanisms and the etiology of Tourette's syndrome (TS) remain unknown. Data from molecular imaging studies targeting the dopamine system in Tourette patients are inconclusive. For a better understanding of the striatal dopamine function in adult dopamine-antagonist-free patients we performed a systematic review in August 2017 identifying 49 PET and SPECT studies on the topic of TS. A total of 8 studies appraised the dopamine transporter (DAT) with 111 Tourette patients and 93 healthy controls, and could be included in a meta-analytic approach...
August 2, 2018: Translational Psychiatry
Koichiro Sugimoto, Shingo Kakeda, Keita Watanabe, Asuka Katsuki, Issei Ueda, Natsuki Igata, Ryohei Igata, Osamu Abe, Reiji Yoshimura, Yukunori Korogi
Recently, accumulated evidence has indicated a role of inflammation in the pathogenesis of major depressive disorder (MDD). Therefore, we evaluated the relationship between white matter integrity and serum cytokine levels during the first depressive episode in drug-naive MDD patients, using a tract-based spatial statistics (TBSS) method. A total of 35 drug-naive MDD patients with a first depressive episode and 35 healthy subjects (HS) underwent diffusion tensor imaging, and an analysis was conducted using TBSS...
August 1, 2018: Translational Psychiatry
Junfang Chen, Han Cao, Andreas Meyer-Lindenberg, Emanuel Schwarz
Schizophrenia shows substantial sex differences in age of onset, course, and treatment response, but the biological basis of these effects is incompletely understood. Here we show that during human development, males show a regionally specific decrease in brain expression similarity compared to females. The genes modulating this effect were significantly co-expressed with schizophrenia risk genes during prefrontal cortex brain development in the fetal period as well as during early adolescence. This suggests a genetic contribution to a mechanism through which developmental abnormalities manifest with psychosis during adolescence...
August 1, 2018: Translational Psychiatry
A Santi, M Bot, A Aleman, B W J H Penninx, I Torres Aleman
Individual susceptibility to anxiety disorders after maladaptive responses to stress is not well understood. We now report that while exploring stress responses in mice after traumatic brain injury (TBI), a condition associated to stress susceptibility, we observed that the anxiogenic effects of either TBI or exposure to life-threatening experiences (predator) were blocked when both stressors were combined. Because TBI increases the entrance into the brain of serum insulin-like growth factor I (IGF-I), a known modulator of anxiety with a wide range of concentrations in the human population, we then determined whether circulating IGF-I is related to anxiety measures...
August 1, 2018: Translational Psychiatry
Adriana Cherskov, Alexa Pohl, Carrie Allison, Heping Zhang, Rupert A Payne, Simon Baron-Cohen
Elevated levels of prenatal testosterone may increase the risk for autism spectrum conditions (autism). Given that polycystic ovary syndrome (PCOS) is also associated with elevated prenatal testosterone and its precursor sex steroids, a hypothesis from the prenatal sex steroid theory is that women with PCOS should have elevated autistic traits and a higher rate of autism among their children. Using electronic health records obtained from the Clinical Practice Research Datalink (CPRD) in the UK between 1990 and 2014, we conducted three matched case-control studies...
August 1, 2018: Translational Psychiatry
Matthew Lander, Tarun Bastiampillai, Jitender Sareen
Withdrawal symptoms are common upon discontinuation of psychiatric medications. Catatonia, a neuropsychiatric condition proposed to be associated with gamma-aminobutyric acid (GABA) hypoactivity due to its robust response to benzodiazepines, has been described as a withdrawal syndrome in case reports but is not a well-recognized phenomenon. The authors undertook a review of withdrawal catatonia with an aim to understand its presentation as well as the medications and psychoactive substances it is associated with...
July 31, 2018: Translational Psychiatry
Sarine S Janetsian-Fritz, Nicholas M Timme, Maureen M Timm, Aqilah M McCane, Anthony J Baucum, Brian F O'Donnell, Christopher C Lapish
The original version of this Article omitted the author Maureen M. Timm from the Department of Psychology, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA.
July 31, 2018: Translational Psychiatry
Yan Sun, Yang Zhang, Dai Zhang, Suhua Chang, Rixing Jing, Weihua Yue, Lin Lu, Dong Chen, Yankun Sun, Yong Fan, Jie Shi
The reward system plays a vital role in drug addiction. The purpose of this study is to investigate the structural connectivity characteristics and driving-control subnetwork patterns of reward circuits in heroin abusers and assess the genetic modulation on the reward network. We first defined the reward network based on systematic literature review, and built the reward network based on diffusion tensor imaging data of 78 heroin abusers (HAs) and 79 healthy controls (HCs) using structural connectomics. Then we assessed genetic factors that might modulate changes in the reward network by performing imaging-genetic screening for 22 addiction-related polymorphisms...
July 30, 2018: Translational Psychiatry
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