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Translational Psychiatry

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https://www.readbyqxmd.com/read/29467462/hipsc-derived-neural-stem-cells-from-patients-with-schizophrenia-induce-an-impaired-angiogenesis
#1
Bárbara S Casas, Gabriela Vitória, Marcelo N do Costa, Rodrigo Madeiro da Costa, Pablo Trindade, Renata Maciel, Nelson Navarrete, Stevens K Rehen, Verónica Palma
Schizophrenia is a neurodevelopmental disease characterized by cerebral connectivity impairment and loss of gray matter. It was described in adult schizophrenia patients (SZP) that concentration of VEGFA, a master angiogenic factor, is decreased. Recent evidence suggests cerebral hypoperfusion related to a dysfunctional Blood Brain Barrier (BBB) in SZP. Since neurogenesis and blood-vessel formation occur in a coincident and coordinated fashion, a defect in neurovascular development could result in increased vascular permeability and, therefore, in poor functionality of the SZP's neurons...
February 22, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29463821/amygdala-hyper-connectivity-in-a-mouse-model-of-unpredictable-early-life-stress
#2
REVIEW
Frances K Johnson, Jean-Christophe Delpech, Garth J Thompson, Lan Wei, Jin Hao, Peter Herman, Fahmeed Hyder, Arie Kaffman
Childhood maltreatment is associated with a wide range of psychopathologies including anxiety that emerge in childhood and in many cases persist in adulthood. Increased amygdala activation in response to threat and abnormal amygdala connectivity with frontolimbic brain regions, such as the hippocampus and the prefrontal cortex, are some of the most consistent findings seen in individuals exposed to childhood maltreatment. The underlying mechanisms responsible for these changes are difficult to study in humans but can be elucidated using animal models of early-life stress...
February 21, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29430009/real-time-fmri-neurofeedback-to-down-regulate-superior-temporal-gyrus-activity-in-patients-with-schizophrenia-and-auditory-hallucinations-a-proof-of-concept-study
#3
Natasza D Orlov, Vincent Giampietro, Owen O'Daly, Sheut-Ling Lam, Gareth J Barker, Katya Rubia, Philip McGuire, Sukhwinder S Shergill, Paul Allen
Neurocognitive models and previous neuroimaging work posit that auditory verbal hallucinations (AVH) arise due to increased activity in speech-sensitive regions of the left posterior superior temporal gyrus (STG). Here, we examined if patients with schizophrenia (SCZ) and AVH could be trained to down-regulate STG activity using real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF). We also examined the effects of rtfMRI-NF training on functional connectivity between the STG and other speech and language regions...
February 12, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29391400/whole-exome-sequencing-and-gene-based-rare-variant-association-tests-suggest-that-pla2g4e-might-be-a-risk-gene-for-panic-disorder
#4
Yoshiro Morimoto, Mihoko Shimada-Sugimoto, Takeshi Otowa, Shintaro Yoshida, Akira Kinoshita, Hiroyuki Mishima, Naohiro Yamaguchi, Takatoshi Mori, Akira Imamura, Hiroki Ozawa, Naohiro Kurotaki, Christiane Ziegler, Katharina Domschke, Jürgen Deckert, Tadashi Umekage, Mamoru Tochigi, Hisanobu Kaiya, Yuji Okazaki, Katsushi Tokunaga, Tsukasa Sasaki, Koh-Ichiro Yoshiura, Shinji Ono
Panic disorder (PD) is characterized by recurrent and unexpected panic attacks, subsequent anticipatory anxiety, and phobic avoidance. Recent epidemiological and genetic studies have revealed that genetic factors contribute to the pathogenesis of PD. We performed whole-exome sequencing on one Japanese family, including multiple patients with panic disorder, which identified seven rare protein-altering variants. We then screened these genes in a Japanese PD case-control group (384 sporadic PD patients and 571 controls), resulting in the detection of three novel single nucleotide variants as potential candidates for PD (chr15: 42631993, T>C in GANC; chr15: 42342861, G>T in PLA2G4E; chr20: 3641457, G>C in GFRA4)...
February 2, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29391399/stress-hormone-response-to-the-dex-crh-test-and-its-relation-to-psychotherapy-outcome-in-panic-disorder-patients-with-and-without-agoraphobia
#5
Susann Wichmann, Stefan R Bornstein, Thomas Lorenz, Katja Petrowski
This study tested whether the hormonal stress response to the DEX-CRH test may be predictive of the psychotherapy success for panic disorder (PD). Thirty-four patients diagnosed either with agoraphobia with PD or PD without agoraphobia were subjected to cognitive behavioural therapy (CBT). Patients (pre-therapy) and healthy volunteers were exposed to the DEX-CRH test. Blood samples were taken for cortisol and adrenocorticotropic hormone (ACTH) assessment. Established panic-specific questionnaires were handed out for the pre-therapy and post-therapy evaluation of disease severity (with reference to panic beliefs and agoraphobic cognitions, fear of bodily sensations, agoraphobic avoidance behaviour)...
February 2, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29391398/non-coding-rna-dysregulation-in-the-amygdala-region-of-schizophrenia-patients-contributes-to-the-pathogenesis-of-the-disease
#6
Yichuan Liu, Xiao Chang, Chang-Gyu Hahn, Raquel E Gur, Patrick A M Sleiman, Hakon Hakonarson
Schizophrenia (SCZ) is a neuropsychiatric disorder with a complex genetic etiology. The redundancy of the gene networks underlying SCZ indicates that many gene combinations have the potential to cause a system dysfunction that can manifest as SCZ or a related neurodevelopmental disorder. Recent studies show that small non-coding microRNA (miRNA) and long non-coding RNA (lncRNA) are important factors in shaping these networks and are dynamically regulated by neuronal activation. We investigated the genome-wide transcription profiles of 46 human amygdala samples obtained from 22 SCZ patients and 24 healthy controls...
February 2, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29391397/butyrate-enhances-mitochondrial-function-during-oxidative-stress-in-cell-lines-from-boys-with-autism
#7
Shannon Rose, Sirish C Bennuri, Jakeira E Davis, Rebecca Wynne, John C Slattery, Marie Tippett, Leanna Delhey, Stephan Melnyk, Stephen G Kahler, Derrick F MacFabe, Richard E Frye
Butyrate (BT) is a ubiquitous short-chain fatty acid (SCFA) principally derived from the enteric microbiome. BT positively modulates mitochondrial function, including enhancing oxidative phosphorylation and beta-oxidation and has been proposed as a neuroprotectant. BT and other SCFAs have also been associated with autism spectrum disorders (ASD), a condition associated with mitochondrial dysfunction. We have developed a lymphoblastoid cell line (LCL) model of ASD, with a subset of LCLs demonstrating mitochondrial dysfunction (AD-A) and another subset of LCLs demonstrating normal mitochondrial function (AD-N)...
February 2, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29391396/bipolar-disorder-with-binge-eating-behavior-a-genome-wide-association-study-implicates-prr5-arhgap8
#8
Susan L McElroy, Stacey J Winham, Alfredo B Cuellar-Barboza, Colin L Colby, Ada Man-Choi Ho, Hugues Sicotte, Beth R Larrabee, Scott Crow, Mark A Frye, Joanna M Biernacka
Bipolar disorder (BD) is associated with binge eating behavior (BE), and both conditions are heritable. Previously, using data from the Genetic Association Information Network (GAIN) study of BD, we performed genome-wide association (GWA) analyses of BD with BE comorbidity. Here, utilizing data from the Mayo Clinic BD Biobank (969 BD cases, 777 controls), we performed a GWA analysis of a BD subtype defined by BE, and case-only analysis comparing BD subjects with and without BE. We then performed a meta-analysis of the Mayo and GAIN results...
February 2, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29391395/genome-wide-analysis-of-self-reported-risk-taking-behaviour-and-cross-disorder-genetic-correlations-in-the-uk-biobank-cohort
#9
Rona J Strawbridge, Joey Ward, Breda Cullen, Elizabeth M Tunbridge, Sarah Hartz, Laura Bierut, Amy Horton, Mark E S Bailey, Nicholas Graham, Amy Ferguson, Donald M Lyall, Daniel Mackay, Laura M Pidgeon, Jonathan Cavanagh, Jill P Pell, Michael O'Donovan, Valentina Escott-Price, Paul J Harrison, Daniel J Smith
Risk-taking behaviour is a key component of several psychiatric disorders and could influence lifestyle choices such as smoking, alcohol use, and diet. As a phenotype, risk-taking behaviour therefore fits within a Research Domain Criteria (RDoC) approach, whereby identifying genetic determinants of this trait has the potential to improve our understanding across different psychiatric disorders. Here we report a genome-wide association study in 116,255 UK Biobank participants who responded yes/no to the question "Would you consider yourself a risk taker?" Risk takers (compared with controls) were more likely to be men, smokers, and have a history of psychiatric disorder...
February 2, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29391394/testing-frameworks-for-personalizing-bipolar-disorder
#10
Amy L Cochran, André Schultz, Melvin G McInnis, Daniel B Forger
The hallmark of bipolar disorder is a clinical course of recurrent manic and depressive symptoms of varying severity and duration. Mathematical modeling of bipolar disorder holds the promise of an ability to personalize diagnoses, to predict future mood episodes, to directly compare diverse datasets, and to link basic mechanisms to behavioral data. Several modeling frameworks have been proposed for bipolar disorder, which represent competing hypothesis about the basic framework of the disorder. Here, we test these hypotheses with self-report assessments of mania and depression symptoms from 178 bipolar patients followed prospectively for 4 or more years...
February 2, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29391391/a-systematic-review-of-the-role-of-the-nociceptin-receptor-system-in-stress-cognition-and-reward-relevance-to-schizophrenia
#11
REVIEW
Muhammad Saad Khan, Isabelle Boileau, Nathan Kolla, Romina Mizrahi
Schizophrenia is a debilitating neuropsychiatric illness that is characterized by positive, negative, and cognitive symptoms. Research over the past two decades suggests that the nociceptin receptor system may be involved in domains affected in schizophrenia, based on evidence aligning it with hallmark features of the disorder. First, aberrant glutamatergic and striatal dopaminergic function are associated with psychotic symptoms, and the nociceptin receptor system has been shown to regulate dopamine and glutamate transmission...
February 2, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29391390/ulk4-regulates-gabaergic-signaling-and-anxiety-related-behavior
#12
Min Liu, Marie Fitzgibbon, Yanqin Wang, Jamie Reilly, Xiaohong Qian, Timothy O'Brien, Steve Clapcote, Sanbing Shen, Michelle Roche
Excitation/inhibition imbalance has been proposed as a fundamental mechanism in the pathogenesis of neuropsychiatric and neurodevelopmental disorders, in which copy number variations of the Unc-51 like kinase 4 (ULK4) gene encoding a putative Serine/Threonine kinase have been reported in approximately 1/1000 of patients suffering pleiotropic clinical conditions of schizophrenia, depression, autistic spectrum disorder (ASD), developmental delay, language delay, intellectual disability, or behavioral disorder...
February 2, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29382834/metabolite-identification-in-fecal-microbiota-transplantation-mouse-livers-and-combined-proteomics-with-chronic-unpredictive-mild-stress-mouse-livers
#13
Bo Li, Kenan Guo, Li Zeng, Benhua Zeng, Ran Huo, Yuanyuan Luo, Haiyang Wang, Meixue Dong, Peng Zheng, Chanjuan Zhou, Jianjun Chen, Yiyun Liu, Zhao Liu, Liang Fang, Hong Wei, Peng Xie
Major depressive disorder (MDD) is a common mood disorder. Gut microbiota may be involved in the pathogenesis of depression via the microbe-gut-brain axis. Liver is vulnerable to exposure of bacterial products translocated from the gut via the portal vein and may be involved in the axis. In this study, germ-free mice underwent fecal microbiota transplantation from MDD patients and healthy controls. Behavioral tests verified the depression model. Metabolomics using gas chromatography-mass spectrometry, nuclear magnetic resonance, and liquid chromatography-mass spectrometry determined the influence of microbes on liver metabolism...
January 31, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29382825/ultramicronized-palmitoylethanolamide-rescues-learning-and-memory-impairments-in-a-triple-transgenic-mouse-model-of-alzheimer-s-disease-by-exerting-anti-inflammatory-and-neuroprotective-effects
#14
Caterina Scuderi, Maria Rosanna Bronzuoli, Roberta Facchinetti, Lorenzo Pace, Luca Ferraro, Kevin Donald Broad, Gaetano Serviddio, Francesco Bellanti, Gianmauro Palombelli, Giulia Carpinelli, Rossella Canese, Silvana Gaetani, Luca Steardo, Luca Steardo, Tommaso Cassano
In an aging society, Alzheimer's disease (AD) exerts an increasingly serious health and economic burden. Current treatments provide inadequate symptomatic relief as several distinct pathological processes are thought to underlie the decline of cognitive and neural function seen in AD. This suggests that the efficacy of treatment requires a multitargeted approach. In this context, palmitoylethanolamide (PEA) provides a novel potential adjunct therapy that can be incorporated into a multitargeted treatment strategy...
January 31, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29382824/genetic-estimators-of-dna-methylation-provide-insights-into-the-molecular-basis-of-polygenic-traits
#15
Virginie Freytag, Vanja Vukojevic, Holger Wagner-Thelen, Annette Milnik, Christian Vogler, Markus Leber, Leonie Weinhold, Anne C Böhmer, Steffi Riedel-Heller, Wolfgang Maier, Dominique J-F de Quervain, Alfredo Ramirez, Andreas Papassotiropoulos
The large biological distance between genetic risk loci and their mechanistic consequences in the tissue of interest limits the ability to establish functionality of susceptibility variants for genetically complex traits. Such a biological gap may be reduced through the systematic study of molecular mediators of genomic action, such as epigenetic modification. Here, we report the identification of robust genetic estimators of whole-blood CpG methylation, which can serve as intermediate molecular traits amenable to association testing with other genetically complex traits...
January 31, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29382821/dopamine-psychosis-and-schizophrenia-the-widening-gap-between-basic-and-clinical-neuroscience
#16
REVIEW
J P Kesby, D W Eyles, J J McGrath, J G Scott
The stagnation in drug development for schizophrenia highlights the need for better translation between basic and clinical research. Understanding the neurobiology of schizophrenia presents substantial challenges but a key feature continues to be the involvement of subcortical dopaminergic dysfunction in those with psychotic symptoms. Our contemporary knowledge regarding dopamine dysfunction has clarified where and when dopaminergic alterations may present in schizophrenia. For example, clinical studies have shown patients with schizophrenia show increased presynaptic dopamine function in the associative striatum, rather than the limbic striatum as previously presumed...
January 31, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29382815/extended-amygdala-connectivity-changes-during-sustained-shock-anticipation
#17
REVIEW
Salvatore Torrisi, Adam X Gorka, Javier Gonzalez-Castillo, Katherine O'Connell, Nicholas Balderston, Christian Grillon, Monique Ernst
The bed nucleus of the stria terminalis (BNST) and central amygdala (CeA) of the extended amygdala are small, anatomically interconnected brain regions. They are thought to mediate responses to sustained, unpredictable threat stimuli and phasic, predictable threat stimuli, respectively. They perform these operations largely through their interconnected networks. In two previous studies, we mapped and contrasted the resting functional connectivity networks of the BNST and CeA at 7 Tesla with high resolution...
January 31, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29382814/social-affective-context-reveals-altered-network-dynamics-in-schizophrenia-patients
#18
Talma Hendler, Gal Raz, Solnik Shimrit, Yael Jacob, Tamar Lin, Leor Roseman, Wahid Madah Wahid, Ilana Kremer, Marina Kupchik, Moshe Kotler, Maya Bleich-Cohen
Impairments in social cognition and interactions are core psychopathologies in schizophrenia, often manifesting as an inability to appropriately relate to the intentions and feelings of others. Neuroimaging has helped to demarcate the dynamics of two distinct functional connectivity circuits underlying the social-affective processes related to mentalization (known as Theory of Mind, ToM) and somatic-affiliation (known as Embodied Simulation, ES). While evidence points to abnormal activation patterns within these networks among those suffering from schizophrenia, it is yet unclear however, if these patients exhibit this abnormal functional connectivity in the context of social-affective experiences...
January 31, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29362444/treatment-of-bipolar-depression-with-minocycline-and-or-aspirin-an-adaptive-2%C3%A3-2-double-blind-randomized-placebo-controlled-phase-iia-clinical-trial
#19
Jonathan B Savitz, T Kent Teague, Masaya Misaki, Matt Macaluso, Brent E Wurfel, Matt Meyer, Douglas Drevets, William Yates, Ondria Gleason, Wayne C Drevets, Sheldon H Preskorn
Given evidence of chronic inflammation in bipolar disorder (BD), we tested the efficacy of aspirin and minocycline as augmentation therapy for bipolar depression. Ninety-nine depressed outpatients with BD were enrolled in a 6 week, double-blind, placebo-controlled trial, and randomized to one of four groups: active minocycline (100 mg b.i.d.) + active aspirin (81 mg b.i.d.) (M + A); active minocycline + placebo aspirin (M + P); placebo-minocycline + active aspirin (A + P); and placebo-minocycline + placebo aspirin (P + P)...
January 24, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29362440/the-real-life-costs-of-emotion-regulation-in-anorexia-nervosa-a-combined-ecological-momentary-assessment-and-fmri-study
#20
Maria Seidel, Joseph A King, Franziska Ritschel, Ilka Boehm, Daniel Geisler, Fabio Bernardoni, Larissa Holzapfel, Stefan Diestel, Kersten Diers, Alexander Strobel, Thomas Goschke, Henrik Walter, Veit Roessner, Stefan Ehrlich
Regulation of emotions is necessary for successful attainment of short-term and long-term goals. However, over-regulation may also have its costs. In anorexia nervosa (AN), forgoing food intake despite emaciation and endocrine signals that promote eating is an example of "too much" self-control. Here we investigated whether voluntary emotion regulation in AN patients comes with associated disorder-relevant costs. Thirty-five patients with acute AN and thirty-five age-matched healthy controls (HCs) performed an established emotion regulation paradigm during functional magnetic resonance imaging after an overnight fast...
January 24, 2018: Translational Psychiatry
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