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Understanding schizophrenia

Anil P S Ori, Merel H M Bot, Remco T Molenhuis, Loes M Olde Loohuis, Roel A Ophoff
BACKGROUND: Common psychiatric disorders are characterized by complex disease architectures with many small genetic effects that contribute and complicate biological understanding of their etiology. There is therefore a pressing need for in vitro experimental systems that allow for interrogation of polygenic psychiatric disease risk to study the underlying biological mechanisms. METHODS: We have developed an analytical framework that integrates genome-wide disease risk from genome-wide association studies with longitudinal in vitro gene expression profiles of human neuronal differentiation...
September 6, 2018: Biological Psychiatry
Yan Zhao, Xiao Liang, Feng Zhu, Yan Wen, Jiawen Xu, Jian Yang, Miao Ding, Bolun Cheng, Mei Ma, Lu Zhang, Shiqiang Cheng, Cuiyan Wu, Sen Wang, Xi Wang, Yujie Ning, Xiong Guo, Feng Zhang
Attention deficit hyperactivity disorder (ADHD), bipolar disorder (BP) and schizophrenia (SCZ) are complex psychiatric disorders. We conducted a large-scale integrative analysis of genome-wide association studies (GWAS) and life course consistent methylation quantitative trait loci (meQTLs) datasets. The GWAS data of ADHD (including 20,183 cases and 35,191 controls), BP (including 7,481 cases and 9,250 controls) and SCZ (including 36,989 cases and 113,075 controls) were derived from published GWAS. Life course consistent meQTLs dataset was obtained from a longitudinal meQTLs analysis of 1,018 mother-child pairs...
October 16, 2018: Neuroscience and Biobehavioral Reviews
Mariangela Chisari, Timothy J Wilding, Samuel Brunwasser, Kathiresan Krishnan, Mingxing Qian, Ann Benz, James E Huettner, Charles F Zorumski, Douglas F Covey, Steven Mennerick
Positive modulators of NMDA receptors are important candidates for therapeutic development to treat psychiatric disorders including autism and schizophrenia. Sulfated neurosteroids have been studied as positive allosteric modulators of NMDA receptors for years, but we understand little about the cellular fate of these compounds, an important consideration for drug development. Here we focus on a visualizable sulfated neurosteroid analogue, KK-169. As expected of a pregnenolone sulfate analogue, the compound strongly potentiates NMDA receptor function, is an antagonist of GABAA receptors, exhibits occlusion with pregnenolone sulfate potentiation, and requires receptor domains important for pregnenolone sulfate potentiation...
October 14, 2018: Neuropharmacology
Zhen Liang, Chen Xu, Yi Cao, Hai-Dong Kan, Ren-Jie Chen, Chun-Yan Yao, Xiao-Ling Liu, Ying Xiang, Na Wu, Long Wu, Ya-Fei Li, Ai-Ling Ji, Tong-Jian Cai
Schizophrenia is a devastating neuropsychiatric disorder with increasing concern. Limited studies have been conducted to assess the relationship between short-term exposure to ambient air pollution and schizophrenia attacks. This study aimed to investigate the associations between short-term air pollution exposure and schizophrenia outpatient visits based on a time-series study performed in China. Daily data of schizophrenia outpatient admissions and air pollution from 1 October 2010 to 31 December 2013 were collected in Xi'an, a heavily-polluted city in China...
October 3, 2018: Environmental Pollution
Bill Deakin, John Suckling, Thomas R E Barnes, Kelly Byrne, Imran B Chaudhry, Paola Dazzan, Richard J Drake, Annalisa Giordano, Nusrat Husain, Peter B Jones, Eileen Joyce, Emma Knox, Carl Krynicki, Stephen M Lawrie, Shôn Lewis, Danuta M Lisiecka-Ford, Naghmeh Nikkheslat, Carmine M Pariante, Richard Smallman, Andrew Watson, Steven C R Williams, Rachel Upthegrove, Graham Dunn
BACKGROUND: The antibiotic minocycline has neuroprotective and anti-inflammatory properties that could prevent or reverse progressive neuropathic changes implicated in recent-onset schizophrenia. In the BeneMin study, we aimed to replicate the benefit of minocycline on negative symptoms reported in previous pilot studies, and to understand the mechanisms involved. METHODS: In this randomised, double-blind, placebo-controlled trial, we recruited people with a schizophrenia-spectrum disorder that had begun within the past 5 years with continuing positive symptoms from 12 National Health Service (NHS) trusts...
October 12, 2018: Lancet Psychiatry
Paul H Lysaker, Emily Gagen, Abigail Wright, Jenifer L Vohs, Marina Kukla, Phillip T Yanos, Ilanit Hasson-Ohayon
The integrated model of insight in schizophrenia suggests that poor insight is the result of multiple factors which compromise persons' abilities to integrate streams of information into a personal awareness of psychiatric challenges, and make adaptive responses. This model hypothesizes that metacognitive deficits, or difficulties forming a complex and integrated understanding of the self and others, influence insight, regardless of other proximal causes including clinical profile. To explore this possibility, we performed a latent class analysis on 324 adults with schizophrenia or schizoaffective disorder...
October 15, 2018: Schizophrenia Bulletin
Amanda M Maple, Rachel K Rowe, Jonathan Lifshitz, Fabian Fernandez, Amelia L Gallitano
Up to 80% of people meeting DSM-IV definitions for schizophrenia will exhibit difficulties with sleep, along with a breakdown in circadian entrainment and rhythmicity. The changes to the sleep and circadian systems in this population are thought to be interdependent, as evidenced by the frequent use of the combined term "sleep and circadian rhythm disruption" or "SCRD" to describe their occurrence. To understand links between sleep and circadian problems in the schizophrenia population, we analyzed the duration and rhythmicity of sleep behavior in mice lacking function of the immediate early gene early growth response 3 ( Egr3)...
October 15, 2018: Journal of Biological Rhythms
Serena B Gumusoglu, Hanna E Stevens
Early disruptions to neurodevelopment are highly relevant to understanding both psychiatric risk and underlying pathophysiology that can be targeted by new treatments. Much convergent evidence from the human literature associates inflammation during pregnancy with later neuropsychiatric disorders in offspring. Preclinical models of prenatal inflammation have been developed to examine the causal maternal physiological and offspring neural mechanisms underlying these findings. Here we review the strengths and limitations of preclinical models used for these purposes and describe selected studies that have shown maternal immune impacts on the brain and behavior of offspring...
August 27, 2018: Biological Psychiatry
Cristina P Garcia, Lauren T Catalano, Kristen R Dwyer, Julie M McCarthy, Melanie E Bennett, Jack J Blanchard
Social affiliation, or engagement in positive social interactions, is often profoundly impaired in individuals with schizophrenia. Valid measures of social affiliation are needed to understand these impairments and their symptom and functional correlates; however, such measures are limited and have not been validated. This pilot study evaluated one such measure-the video-based Social Affiliation Interaction Task (SAIT)-and a novel in vivo behavioral measure, the Affiliative Conversation Task (ACT). Twenty participants with schizophrenia or schizoaffective disorder (SZ) and 35 nonpsychiatric controls (CT) completed both tasks and measures of negative symptoms and functioning...
November 2018: Behavior Therapy
G Singh, V Singh, J S Schneider
Sex differences in the risk for and expression of various brain disorders have been known for some time. Yet, the molecular underpinnings of these sex differences as well as how sex modifies normal brain development are still poorly understood. It has recently become known that epigenetic mechanisms play an essential role in establishing and maintaining sex differences in neurodevelopment and disease susceptibility. Epigenetic mechanisms such as post-translational modifications of histones (histone PTMs) integrate various hormonal and external environmental influences to affect genomic output, and this appears to occur in a sex-dependent manner...
October 10, 2018: Biochimica et biophysica acta. Molecular basis of disease
Raphaelle Winsky-Sommerer, Paula de Oliveira, Sally Loomis, Keith Wafford, Derk-Jan Dijk, Gary Gilmour
The high prevalence of sleep disturbance in neurodegenerative and psychiatric conditions is often interpreted as evidence for both sleep's sensitivity to and causal involvement in brain pathology. Nevertheless, how and which aspects of sleep contribute to brain function remains largely unknown. This review provides a critical evaluation of clinical and animal literature describing sleep and circadian disturbances in two distinct conditions and animal models thereof: Alzheimer's disease and schizophrenia. Its goal is to identify commonalities and distinctiveness of specific aspects of sleep disturbance and their relationship to symptoms across conditions...
October 9, 2018: Neuroscience and Biobehavioral Reviews
Maria Arioli, Chiara Crespi, Nicola Canessa
Social cognition refers to a set of processes, ranging from perception to decision-making, underlying the ability to decode others' intentions and behaviors to plan actions fitting with social and moral, besides individual and economic considerations. Its centrality in everyday life reflects the neural complexity of social processing and the ubiquity of social cognitive deficits in different pathological conditions. Social cognitive processes can be clustered in three domains associated with (a) perceptual processing of social information such as faces and emotional expressions (social perception), (b) grasping others' cognitive or affective states (social understanding), and (c) planning behaviors taking into consideration others', in addition to one's own, goals (social decision-making)...
2018: BioMed Research International
Erin Relyea, Brooke MacDonald, Christina Cattaruzza, Denise Marshall
Schizophrenia is a serious chronic mental illness that results in marginalization and stigma for sufferers. It is the seventh leading cause for disability worldwide. The symptoms of the illness, including hallucinations, delusions, and extremely disordered thinking and behavior, may also introduce barriers to accessing treatment, education, housing, and employment. Little is known about end-of-life care for individuals with schizophrenia. To address this gap, a scoping review was conducted to enhance understanding of hospice and palliative care for patients with schizophrenia...
October 10, 2018: Journal of Palliative Care
Barnaly Rashid, Jiayu Chen, Ishtiaque Rashid, Eswar Damaraju, Jingyu Liu, Robyn Miller, Oktay Agcaoglu, Theo G M van Erp, Kelvin O Lim, Jessica A Turner, Daniel H Mathalon, Judith M Ford, James Voyvodic, Bryon A Mueller, Aysenil Belger, Sarah McEwen, Steven G Potkin, Adrian Preda, Juan R Bustillo, Godfrey D Pearlson, Vince D Calhoun
Multimodal, imaging-genomics techniques offer a platform for understanding genetic influences on brain abnormalities in psychiatric disorders. Such approaches utilize the information available from both imaging and genomics data and identify their association. Particularly for complex disorders such as schizophrenia, the relationship between imaging and genomic features may be better understood by incorporating additional information provided by advanced multimodal modeling. In this study, we propose a novel framework to combine features corresponding to functional magnetic resonance imaging (functional) and single nucleotide polymorphism (SNP) data from 61 schizophrenia (SZ) patients and 87 healthy controls (HC)...
October 6, 2018: NeuroImage
Jennifer A Honeycutt, James J Chrobak
A marked decrease in parvalbumin (PV), a calcium-binding protein specific to a subset of GABAergic neurons, is a consistent finding in postmortem schizophrenic brain tissue. This reduction is selective to PV and is regionally specific, occurring primarily in the prefrontal cortex and hippocampus (HPC) of patients. Rodent models of NMDA receptor hypofunction utilizing NMDA antagonist treatments - e.g. ketamine (KET) - show schizophrenia-like cognitive and behavioral impairments with parallel changes in PV. While decreased PV is considered a hallmark of neuropathology in schizophrenia, previous work elucidating the effects of KET administration on PV are contradictory, with findings suggesting decreased, increased, or no change in PV expression...
October 6, 2018: Neuroscience
Atsushi Takata
Owing to recent advances in DNA sequencing technology, a number of large-scale comprehensive analyses of genetic variations in protein-coding regions (i.e., whole-exome sequencing studies), have been conducted for neuropsychiatric and neurodevelopmental disorders, such as autism spectrum disorders, intellectual disability, and schizophrenia. These studies, especially those focusing on de novo (newly arising) mutations and extremely rare variants, have successfully identified previously unrecognized disease genes/mutations with a large effect size and deepen our understanding of the biology of neuropsychiatric diseases...
October 6, 2018: Psychiatry and Clinical Neurosciences
Janelle M Painter, Jennifer E Stellar, Erin K Moran, Ann M Kring
OBJECTIVES: Emotion deficits are well documented in people with schizophrenia. Far less is known about their ability to implement emotion regulation strategies. We sought to explore whether people with schizophrenia can modify their emotion responses similar to controls. METHODS: People with (n = 25) and without (n = 21) schizophrenia were instructed to amplify positive-emotion expression, reappraise negative emotion experience, and suppress physiological response...
October 6, 2018: Journal of Clinical Psychology
Soumya Sivaraman, Nina V Kraguljac, David M White, Charity J Morgan, Sara S Gonzales, Adrienne C Lahti
Schizophrenia is a chronic, often progressive, disorder. Understanding the underlying neurobiology present in the early stages of the illness is as a pivotal step in designing targeted interventions aimed at arresting disease progression. The aim of our study was to examine neurometabolic changes in the dopamine rich associative striatum in medication-naïve first episode psychosis (FEP). We quantified neurometabolites in 14 FEP and 18 healthy controls (HC) matched on key demographic characteristics. Spectra from the voxel in the left associative striatum were acquired using a PRESS sequence (TR/TE = 2000/80 ms; 512 averages)...
June 9, 2018: Psychiatry research. Neuroimaging
Zhen Zheng, Peng Zheng, Xiaobing Zou
Schizophrenia and autism spectrum disorder (ASD) are significant public health problems. Scientists have recently explored the association between schizophrenia and ASD, but the findings are inconsistent. Thus, we conducted a systematic review and meta-analysis of epidemiological studies to examine the association between schizophrenia and ASD. PubMed, Embase, and the Cochrane Library were used for literature searches to identify eligible studies published in English before October 2, 2017. Relevant studies estimating the association between schizophrenia and ASD were included...
October 3, 2018: Autism Research: Official Journal of the International Society for Autism Research
Gaelle E Doucet, Dominik A Moser, Maxwell J Luber, Evan Leibu, Sophia Frangou
Although schizophrenia is considered a brain disorder, the role of brain organization for symptomatic improvement remains inadequately defined. We investigated the relationship between baseline brain morphology, resting-state network connectivity and clinical response after 24-weeks of antipsychotic treatment in patients with schizophrenia (n = 95) using integrated multivariate analyses. There was no significant association between clinical response and measures of cortical thickness (r = 0.37, p = 0...
October 3, 2018: Molecular Psychiatry
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