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Translational Psychiatry

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https://www.readbyqxmd.com/read/29681622/analysis-of-182-cerebral-palsy-transcriptomes-points-to-dysregulation-of-trophic-signalling-pathways-and-overlap-with-autism
#1
Clare L van Eyk, Mark A Corbett, Alison Gardner, Bregje W van Bon, Jessica L Broadbent, Kelly Harper, Alastair H MacLennan, Jozef Gecz
Cerebral palsy (CP) is the most common motor disability of childhood. It is characterised by permanent, non-progressive but not unchanging problems with movement, posture and motor function, with a highly heterogeneous clinical spectrum and frequent neurodevelopmental comorbidities. The aetiology of CP is poorly understood, despite recent reports of a genetic contribution in some cases. Here we demonstrate transcriptional dysregulation of trophic signalling pathways in patient-derived cell lines from an unselected cohort of 182 CP-affected individuals using both differential expression analysis and weighted gene co-expression network analysis (WGCNA)...
April 23, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29666432/genetic-validation-of-bipolar-disorder-identified-by-automated-phenotyping-using-electronic-health-records
#2
Chia-Yen Chen, Phil H Lee, Victor M Castro, Jessica Minnier, Alexander W Charney, Eli A Stahl, Douglas M Ruderfer, Shawn N Murphy, Vivian Gainer, Tianxi Cai, Ian Jones, Carlos N Pato, Michele T Pato, Mikael Landén, Pamela Sklar, Roy H Perlis, Jordan W Smoller
Bipolar disorder (BD) is a heritable mood disorder characterized by episodes of mania and depression. Although genomewide association studies (GWAS) have successfully identified genetic loci contributing to BD risk, sample size has become a rate-limiting obstacle to genetic discovery. Electronic health records (EHRs) represent a vast but relatively untapped resource for high-throughput phenotyping. As part of the International Cohort Collection for Bipolar Disorder (ICCBD), we previously validated automated EHR-based phenotyping algorithms for BD against in-person diagnostic interviews (Castro et al...
April 18, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29666375/association-and-cis-mqtl-analysis-of-variants-in-chrna3-a5-chrna7-chrnb2-and-chrnb4-in-relation-to-nicotine-dependence-in-a-chinese-han-population
#3
Qiang Liu, Haijun Han, Maiqiu Wang, Yinghao Yao, Li Wen, Keran Jiang, Yunlong Ma, Rongli Fan, Jiali Chen, Kunkai Su, Zhongli Yang, Wenyan Cui, Wenji Yuan, Xianzhong Jiang, Jingjing Li, Thomas J Payne, Jundong Wang, Ming D Li
Nicotine dependence (ND) is a worldwide health problem. Numerous genetic studies have demonstrated a significant association of variants in nicotinic acetylcholine receptors (nAChRs) with smoking behaviors. However, most of these studies enrolled only subjects of European or African ancestry. In addition, although an increasing body of evidence implies a causal connection of single-nucleotide polymorphisms (SNPs) and epigenetic regulation of gene expression, few studies of this issue have been reported. In this study, we performed both association and interaction analysis for 67 SNPs in CHRNA3-A5, CHRNA7, CHRNB2, and CHRNB4 with ND in a Chinese Han population (N = 5055)...
April 18, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29666372/brain-serotonin-synthesis-capacity-in-obsessive-compulsive-disorder-effects-of-cognitive-behavioral-therapy-and-sertraline
#4
Jennifer I Lissemore, Debbie Sookman, Paul Gravel, Alexandre Berney, Amir Barsoum, Mirko Diksic, Thomas E Nordahl, Gilbert Pinard, Igor Sibon, Jean Cottraux, Marco Leyton, Chawki Benkelfat
Cognitive behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) are both effective treatments for some patients with obsessive-compulsive disorder (OCD), yet little is known about the neurochemical changes related to these treatment modalities. Here, we used positron emission tomography and the α-[11 C]methyl-L-tryptophan tracer to examine the changes in brain regional serotonin synthesis capacity in OCD patients following treatment with CBT or SSRI treatment. Sixteen medication-free OCD patients were randomly assigned to 12 weeks of either CBT or sertraline treatment...
April 18, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29666369/lithium-associated-transcriptional-regulation-of-crmp1-in-patient-derived-olfactory-neurons-and-symptom-changes-in-bipolar-disorder
#5
Charlee K McLean, Soumya Narayan, Sandra Y Lin, Narayan Rai, Youjin Chung, MariaMananita S Hipolito, Nicola G Cascella, John I Nurnberger, Koko Ishizuka, Akira S Sawa, Evaristus A Nwulia
There is growing evidence that lithium used in the treatment of bipolar disorder (BD) affects molecular targets that are involved in neuronal growth, survival, and maturation, but it remains unclear if neuronal alterations in any of these molecules predict specific symptom changes in BD patients undergoing lithium monotherapy. The goals of this study were to (a) determine which molecular changes in the olfactory neurons of symptomatic patients receiving lithium are associated with antimanic or antidepressant response, and (b) uncover novel intraneuronal regulatory mechanisms of lithium therapy...
April 18, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29666363/altered-function-and-maturation-of-primary-cortical-neurons-from-a-22q11-2-deletion-mouse-model-of-schizophrenia
#6
Ziyi Sun, Damian J Williams, Bin Xu, Joseph A Gogos
Given its high penetrance, clearly delineated and evolutionary conserved genomic structure, mouse models of the 22q11.2 deletion provide an ideal organism-based and cell-based model of this well-established disease mutation for schizophrenia. In this study we examined the development of changes in intrinsic properties, action potential firing and synaptic transmission using whole-cell patch-clamp recordings of cultured embryonic cortical neurons from Df(16)A +/- and WT mice at DIV7 and DIV14, respectively. Compared to neurons from the WT littermates, significantly increased input resistance and decreased rising rate of action potential was observed in Df(16)A +/- mice at DIV7 but not at DIV14 indicative of delayed neuronal maturation...
April 18, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29666360/signaling-pathways-responsible-for-the-rapid-antidepressant-like-effects-of-a-glun2a-preferring-nmda-receptor-antagonist
#7
Marta Gordillo-Salas, Fuencisla Pilar-Cuéllar, Yves P Auberson, Albert Adell
In a previous study we found that the preferring GluN2A receptor antagonist, NVP-AAM077, elicited rapid antidepressant-like effects in the forced swim test that was related to the release of glutamate and serotonin in the medial prefrontal cortex. In the present work we sought to examine the duration of this behavioral effect as well as the molecular readouts involved. Our results showed that NVP-AAM077 reduced the immobility in the forced swim test 30 min and 24 h after its administration. However, this effect waned 7 days later...
April 18, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29643358/polygenic-risk-for-schizophrenia-and-measured-domains-of-cognition-in-individuals-with-psychosis-and-controls
#8
Rebecca Shafee, Pranav Nanda, Jaya L Padmanabhan, Neeraj Tandon, Ney Alliey-Rodriguez, Sreeja Kalapurakkel, Daniel J Weiner, Raquel E Gur, Richard S E Keefe, Scot K Hill, Jeffrey R Bishop, Brett A Clementz, Carol A Tamminga, Elliot S Gershon, Godfrey D Pearlson, Matcheri S Keshavan, John A Sweeney, Steven A McCarroll, Elise B Robinson
Psychotic disorders including schizophrenia are commonly accompanied by cognitive deficits. Recent studies have reported negative genetic correlations between schizophrenia and indicators of cognitive ability such as general intelligence and processing speed. Here we compare the effect of polygenetic risk for schizophrenia (PRSSCZ ) on measures that differ in their relationships with psychosis onset: a measure of current cognitive abilities (the Brief Assessment of Cognition in Schizophrenia, BACS) that is greatly reduced in psychotic disorder patients, a measure of premorbid intelligence that is minimally affected by psychosis onset (the Wide-Range Achievement Test, WRAT); and educational attainment (EY), which covaries with both BACS and WRAT...
April 12, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29643356/disc1-regulates-lactate-metabolism-in-astrocytes-implications-for-psychiatric-disorders
#9
Yan Jouroukhin, Yusuke Kageyama, Varvara Misheneva, Alexey Shevelkin, Shaida Andrabi, Emese Prandovszky, Robert H Yolken, Valina L Dawson, Ted M Dawson, Susan Aja, Hiromi Sesaki, Mikhail V Pletnikov
Our knowledge of how genetic risk variants contribute to psychiatric disease is mainly limited to neurons. However, the mechanisms whereby the same genetic risk factors could affect the physiology of glial cells remain poorly understood. We studied the role of a psychiatric genetic risk factor, Disrupted-In-Schizophrenia-1 (DISC1), in metabolic functions of astrocytes. We evaluated the effects of knockdown of mouse endogenous DISC1 (DISC1-KD) and expression of a dominant-negative, C-terminus truncated human DISC1 (DN-DISC1) on the markers of energy metabolism, including glucose uptake and lactate production, in primary astrocytes and in mice with selective expression of DN-DISC1 in astrocytes...
April 12, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29643355/reverse-translated-and-gold-standard-continuous-performance-tests-predict-global-cognitive-performance-in-schizophrenia
#10
Andrew W Bismark, Michael L Thomas, Melissa Tarasenko, Alexandra L Shiluk, Sonia Y Rackelmann, Jared W Young, Gregory A Light
Attentional dysfunction contributes to functional impairments in schizophrenia (SZ). Sustained attention is typically assessed via continuous performance tasks (CPTs), though many CPTs have limited cross-species translational validity and place demands on additional cognitive domains. A reverse-translated 5-Choice Continuous Performance Task (5C-CPT) for human testing-originally developed for use in rodents-was designed to minimize demands on perceptual, visual learning, processing speed, or working memory functions...
April 12, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29643339/desynchronization-of-diurnal-rhythms-in-bipolar-disorder-and-borderline-personality-disorder
#11
Oliver Carr, Kate E A Saunders, Amy C Bilderbeck, Athanasios Tsanas, Niclas Palmius, John R Geddes, Russell Foster, Maarten De Vos, Guy M Goodwin
It has long been proposed that diurnal rhythms are disturbed in bipolar disorder (BD). Such changes are obvious in episodes of mania or depression. However, detailed study of patients between episodes has been rare and comparison with other psychiatric disorders rarer still. Our hypothesis was that evidence for desynchronization of diurnal rhythms would be evident in BD and that we could test the specificity of any effect by studying borderline personality disorder (BPD). Individuals with BD (n = 36), BPD (n = 22) and healthy volunteers (HC, n = 25) wore a portable heart rate and actigraphy device and used a smart-phone to record self-assessed mood scores 10 times per day for 1 week...
April 12, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29643331/electroencephalographic-delta-alpha-frequency-activity-differentiates-psychotic-disorders-a-study-of-schizophrenia-bipolar-disorder-and-methamphetamine-induced-psychotic-disorder
#12
REVIEW
Fleur M Howells, Hendrik S Temmingh, Jennifer H Hsieh, Andrea V van Dijen, David S Baldwin, Dan J Stein
Electroencephalography (EEG) has been proposed as a neurophysiological biomarker to delineate psychotic disorders. It is known that increased delta and decreased alpha, which are apparent in psychosis, are indicative of inappropriate arousal state, which leads to reduced ability to attend to relevant information. On this premise, we investigated delta/alpha frequency activity, as this ratio of frequency activity may serve as an effective neurophysiological biomarker. The current study investigated differences in delta/alpha frequency activity, in schizophrenia (SCZ), bipolar I disorder with psychotic features and methamphetamine-induced psychosis...
April 12, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29643329/shared-effects-of-disc1-disruption-and-elevated-wnt-signaling-in-human-cerebral-organoids
#13
Priya Srikanth, Valentina N Lagomarsino, Christina R Muratore, Steven C Ryu, Amy He, Walter M Taylor, Constance Zhou, Marlise Arellano, Tracy L Young-Pearse
The development of three-dimensional culture methods has allowed for the study of developing cortical morphology in human cells. This provides a new tool to study the neurodevelopmental consequences of disease-associated mutations. Here, we study the effects of isogenic DISC1 mutation in cerebral organoids. DISC1 has been implicated in psychiatric disease based on genetic studies, including its interruption by a balanced translocation that increases the risk of major mental illness. Isogenic wild-type and DISC1-disrupted human-induced pluripotent stem cells were used to generate cerebral organoids, which were then examined for morphology and gene expression...
April 12, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29643360/ghrelin-is-a-persistent-biomarker-for-chronic-stress-exposure-in-adolescent-rats-and-humans
#14
Muhammad I Ul Akbar Yousufzai, Elia S Harmatz, Mohsin Shah, Muhammad O Malik, Ki A Goosens
Prolonged stressor exposure in adolescence enhances the risk of developing stress-sensitive mental illnesses, including posttraumatic stress disorder (PTSD), for many years following exposure cessation, but the biological underpinnings of this long-term vulnerability are unknown. We show that severe stressor exposure increased circulating levels of the hormone acyl-ghrelin in adolescent rats for at least 130 days and in adolescent humans for at least 4.5 years. Using a rodent model of longitudinal PTSD vulnerability in which rodents with a history of stressor exposure during adolescence display enhanced fear in response to fear conditioning administered weeks after stressor exposure ends, we show that systemic delivery of a ghrelin receptor antagonist for 4 weeks surrounding stressor exposure (2 weeks during and 2 weeks following) prevented stress-enhanced fear memory...
April 11, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29636460/cxcr4-involvement-in-neurodegenerative-diseases
#15
Luke W Bonham, Celeste M Karch, Chun C Fan, Chin Tan, Ethan G Geier, Yunpeng Wang, Natalie Wen, Iris J Broce, Yi Li, Matthew J Barkovich, Raffaele Ferrari, John Hardy, Parastoo Momeni, Günter Höglinger, Ulrich Müller, Christopher P Hess, Leo P Sugrue, William P Dillon, Gerard D Schellenberg, Bruce L Miller, Ole A Andreassen, Anders M Dale, A James Barkovich, Jennifer S Yokoyama, Rahul S Desikan
Neurodegenerative diseases likely share common underlying pathobiology. Although prior work has identified susceptibility loci associated with various dementias, few, if any, studies have systematically evaluated shared genetic risk across several neurodegenerative diseases. Using genome-wide association data from large studies (total n = 82,337 cases and controls), we utilized a previously validated approach to identify genetic overlap and reveal common pathways between progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), Parkinson's disease (PD) and Alzheimer's disease (AD)...
April 11, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29581432/maternal-deprivation-induces-alterations-in-cognitive-and-cortical-function-in-adulthood
#16
Sarine S Janetsian-Fritz, Nicholas M Timme, Aqilah M McCane, Anthony J Baucum Ii, Brian F O'Donnell, Christopher C Lapish
Early life trauma is a risk factor for a number of neuropsychiatric disorders, including schizophrenia (SZ). The current study assessed how an early life traumatic event, maternal deprivation (MD), alters cognition and brain function in rodents. Rats were maternally deprived in the early postnatal period and then recognition memory (RM) was tested in adulthood using the novel object recognition task. The expression of catechol-o-methyl transferase (COMT) and glutamic acid decarboxylase (GAD67) were quantified in the medial prefrontal cortex (mPFC), ventral striatum, and temporal cortex (TC)...
March 27, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29581423/effects-on-gene-expression-and-behavior-of-untagged-short-tandem-repeats-the-case-of-arginine-vasopressin-receptor-1a-avpr1a-and-externalizing-behaviors
#17
Clare C Landefeld, Colin A Hodgkinson, Primavera A Spagnolo, Cheryl A Marietta, Pei-Hong Shen, Hui Sun, Zhifeng Zhou, Barbara K Lipska, David Goldman
Genome-wide association studies (GWAS) of complex, heritable, behavioral phenotypes have yielded an incomplete accounting of the genetic influences. The identified loci explain only a portion of the observed heritability, and few of the loci have been shown to be functional. It is clear that current GWAS techniques overlook key components of phenotypically relevant genetic variation, either because of sample size, as is frequently asserted, or because of methodology. Here we use arginine vasopressin receptor 1a (AVPR1a) as an in-depth model of a methodologic limitation of GWAS: the functional genetic variation (in the form of short tandem repeats) of this key gene involved in affiliative behavior cannot be captured by current GWAS methodologies...
March 27, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29581422/low-frequency-and-rare-variants-may-contribute-to-elucidate-the-genetics-of-major-depressive-disorder
#18
Chenglong Yu, Mauricio Arcos-Burgos, Bernhard T Baune, Volker Arolt, Udo Dannlowski, Ma-Li Wong, Julio Licinio
Major depressive disorder (MDD) is a common but serious psychiatric disorder with significant levels of morbidity and mortality. Recent genome-wide association studies (GWAS) on common variants increase our understanding of MDD; however, the underlying genetic basis remains largely unknown. Many studies have been proposed to explore the genetics of complex diseases from a viewpoint of the "missing heritability" by considering low-frequency and rare variants, copy-number variations, and other types of genetic variants...
March 27, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29581421/lateral-habenula-perturbation-reduces-default-mode-network-connectivity-in-a-rat-model-of-depression
#19
Christian Clemm von Hohenberg, Wolfgang Weber-Fahr, Philipp Lebhardt, Namasivayam Ravi, Urs Braun, Natalia Gass, Robert Becker, Markus Sack, Alejandro Cosa Linan, Martin Fungisai Gerchen, Jonathan Rochus Reinwald, Lars-Lennart Oettl, Andreas Meyer-Lindenberg, Barbara Vollmayr, Wolfgang Kelsch, Alexander Sartorius
Hyperconnectivity of the default-mode network (DMN) is one of the most widely replicated neuroimaging findings in major depressive disorder (MDD). Further, there is growing evidence for a central role of the lateral habenula (LHb) in the pathophysiology of MDD. There is preliminary neuroimaging evidence linking LHb and the DMN, but no causal relationship has been shown to date. We combined optogenetics and functional magnetic resonance imaging (fMRI), to establish a causal relationship, using an animal model of treatment-resistant depression, namely Negative Cognitive State rats...
March 27, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29581420/aberrant-salience-network-functional-connectivity-in-auditory-verbal-hallucinations-a-first-episode-psychosis-sample
#20
Pavan Kumar Mallikarjun, Paris Alexandros Lalousis, Thomas Frederick Dunne, Kareen Heinze, Renate Lep Reniers, Matthew R Broome, Baldeep Farmah, Femi Oyebode, Stephen J Wood, Rachel Upthegrove
Auditory verbal hallucinations (AVH) often lead to distress and functional disability, and are frequently associated with psychotic illness. Previously both state and trait magnetic resonance imaging (MRI) studies of AVH have identified activity in brain regions involving auditory processing, language, memory and areas of default mode network (DMN) and salience network (SN). Current evidence is clouded by research mainly in participants on long-term medication, with chronic illness and by choice of seed regions made 'a priori'...
March 27, 2018: Translational Psychiatry
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