Molecular Neuropsychiatry最新文献_第9页

Front & Back Matter 正面和背面

Molecular Neuropsychiatry Pub Date : 2017-07-01 DOI: 10.1159/000479830

Q. Nguyen, E. Rodrigues, M. Farah, W. Mieler, D. Do, O. Michielin, G. Coukos, G. Coscas, J. Cunha-Vaz, A. Loewenstein, G. Soubrane, K. Priftis, M. Anthracopoulos, W. Byerley, C. Barr, D. Mathalon, T. Petryshen

引用次数: 0

WNT/β-Catenin Pathway and Epigenetic Mechanisms Regulate the Pitt-Hopkins Syndrome and Schizophrenia Risk Gene TCF4. WNT/β-Catenin通路及其表观遗传机制调控Pitt-Hopkins综合征和精神分裂症风险基因TCF4。

Molecular Neuropsychiatry Pub Date : 2017-07-01 Epub Date: 2017-07-14 DOI: 10.1159/000475666

Krista M Hennig, Daniel M Fass, Wen-Ning Zhao, Steven D Sheridan, Ting Fu, Serkan Erdin, Alexei Stortchevoi, Diane Lucente, Jannine D Cody, David Sweetser, James F Gusella, Michael E Talkowski, Stephen J Haggarty

{"title":"WNT/β-Catenin Pathway and Epigenetic Mechanisms Regulate the Pitt-Hopkins Syndrome and Schizophrenia Risk Gene TCF4.","authors":"Krista M Hennig, Daniel M Fass, Wen-Ning Zhao, Steven D Sheridan, Ting Fu, Serkan Erdin, Alexei Stortchevoi, Diane Lucente, Jannine D Cody, David Sweetser, James F Gusella, Michael E Talkowski, Stephen J Haggarty","doi":"10.1159/000475666","DOIUrl":"https://doi.org/10.1159/000475666","url":null,"abstract":"Genetic variation within the transcription factor TCF4 locus can cause the intellectual disability and developmental disorder Pitt-Hopkins syndrome (PTHS), whereas single-nucleotide polymorphisms within noncoding regions are associated with schizophrenia. These genetic findings position TCF4 as a link between transcription and cognition; however, the neurobiology of TCF4 remains poorly understood. Here, we quantitated multiple distinct TCF4 transcript levels in human induced pluripotent stem cell-derived neural progenitors and differentiated neurons, and PTHS patient fibroblasts. We identify two classes of pharmacological treatments that regulate TCF4 expression: WNT pathway activation and inhibition of class I histone deacetylases. In PTHS fibroblasts, both of these perturbations upregulate a subset of TCF4 transcripts. Finally, using chromatin immunoprecipitation sequencing in conjunction with genome-wide transcriptome analysis, we identified TCF4 target genes that may mediate the effect of TCF4 loss on neuroplasticity. Our studies identify new pharmacological assays, tools, and targets for the development of therapeutics for cognitive disorders.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":"3 1","pages":"53-71"},"PeriodicalIF":0.0,"publicationDate":"2017-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000475666","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35479351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 19

A Preliminary Study of the Opioid System and Personality Traits Using Positron Emission Tomography. 用正电子发射断层扫描对阿片系统和人格特征的初步研究。

Molecular Neuropsychiatry Pub Date : 2017-07-01 Epub Date: 2017-03-11 DOI: 10.1159/000452417

Alexandra M Rodman, Thilo Deckersbach, Tina Chou, Jian Kong, Randy L Gollub, Darin D Dougherty

{"title":"A Preliminary Study of the Opioid System and Personality Traits Using Positron Emission Tomography.","authors":"Alexandra M Rodman, Thilo Deckersbach, Tina Chou, Jian Kong, Randy L Gollub, Darin D Dougherty","doi":"10.1159/000452417","DOIUrl":"https://doi.org/10.1159/000452417","url":null,"abstract":"Background: Personality traits, such as Neuroticism and Extraversion, have been implicated in the processing of emotion. The neural correlates most often associated with Neuroticism and Extraversion are the insular cortex, orbitofrontal cortex, amygdala, and ventral striatum.Objective: The aim of the current study was to explore neurotransmitter systems underlying those neural correlates and investigate the relationship between personality traits and opioid receptor binding potential.Method: Twelve healthy participants completed an [11C]diprenorphine positron emission tomography scan at rest. Endogenous opioid levels as indicated by opioid receptor binding potential was examined in relation to personality phenotype.Results: A high score of Neuroticism, a personality trait characterized by negative affect, was found to be associated with high opioid receptor binding in the right anterior insula. Conversely, a high score of Extraversion, a personality trait characterized by positive affect, was found to be associated with low opioid receptor binding in the left posterior insula.Conclusions: While preliminary, the results of this study suggest that the expression of Neuroticism and Extraversion is related to baseline function of the opioid neurotransmitter system in the insular cortex. These findings may help elucidate the neural mechanisms underlying the expression of personality traits, particularly those implicated in affective processing.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":"3 1","pages":"12-18"},"PeriodicalIF":0.0,"publicationDate":"2017-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000452417","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35331456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Positive Traits in the Bipolar Spectrum: The Space between Madness and Genius. 双相情感谱系中的积极特质：疯狂与天才之间的空间

Molecular Neuropsychiatry Pub Date : 2017-02-01 Epub Date: 2016-12-09 DOI: 10.1159/000452416

Tiffany A Greenwood

{"title":"Positive Traits in the Bipolar Spectrum: The Space between Madness and Genius.","authors":"Tiffany A Greenwood","doi":"10.1159/000452416","DOIUrl":"10.1159/000452416","url":null,"abstract":"Bipolar disorder is a severe, lifelong mood disorder for which little is currently understood of the genetic mechanisms underlying risk. By examining related dimensional phenotypes, we may further our understanding of the disorder. Creativity has a historical connection with the bipolar spectrum and is particularly enhanced among unaffected first-degree relatives and those with bipolar spectrum traits. This suggests that some aspects of the bipolar spectrum may confer advantages, while more severe expressions of symptoms negatively influence creative accomplishment. Creativity is a complex, multidimensional construct with both cognitive and affective components, many of which appear to reflect a shared genetic vulnerability with bipolar disorder. It is suggested that a subset of bipolar risk variants confer advantages as positive traits according to an inverted-U-shaped curve with clinically unaffected allele carriers benefitting from the positive traits and serving to maintain the risk alleles in the population. The association of risk genes with creativity in healthy individuals (e.g., NRG1), as well as an overall sharing of common genetic variation between bipolar patients and creative individuals, provides support for this model. Current findings are summarized from a multidisciplinary perspective to demonstrate the feasibility of research in this area to reveal the mechanisms underlying illness.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":"2 4","pages":"198-212"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318923/pdf/mnp-0002-0198.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34798460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neurodevelopmental Perspectives on Wnt Signaling in Psychiatry. 精神病学中Wnt信号的神经发育观点。

Molecular Neuropsychiatry Pub Date : 2017-02-01 Epub Date: 2017-01-13 DOI: 10.1159/000453266

Kimberly A Mulligan, Benjamin N R Cheyette

{"title":"Neurodevelopmental Perspectives on Wnt Signaling in Psychiatry.","authors":"Kimberly A Mulligan, Benjamin N R Cheyette","doi":"10.1159/000453266","DOIUrl":"https://doi.org/10.1159/000453266","url":null,"abstract":"Mounting evidence indicates that Wnt signaling is relevant to pathophysiology of diverse mental illnesses including schizophrenia, bipolar disorder, and autism spectrum disorder. In the 35 years since Wnt ligands were first described, animal studies have richly explored how downstream Wnt signaling pathways affect an array of neurodevelopmental processes and how their disruption can lead to both neurological and behavioral phenotypes. Recently, human induced pluripotent stem cell (hiPSC) models have begun to contribute to this literature while pushing it in increasingly translational directions. Simultaneously, large-scale human genomic studies are providing evidence that sequence variation in Wnt signal pathway genes contributes to pathogenesis in several psychiatric disorders. This article reviews neurodevelopmental and postneurodevelopmental functions of Wnt signaling, highlighting mechanisms, whereby its disruption might contribute to psychiatric illness, and then reviews the most reliable recent genetic evidence supporting that mutations in Wnt pathway genes contribute to psychiatric illness. We are proponents of the notion that studies in animal and hiPSC models informed by the human genetic data combined with the deep knowledge base and tool kits generated over the last several decades of basic neurodevelopmental research will yield near-term tangible advances in neuropsychiatry.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":"2 4","pages":"219-246"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000453266","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34798405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 63

Pharmacogenetic Analysis of Functional Glutamate System Gene Variants and Clinical Response to Clozapine. 功能性谷氨酸系统基因变异及氯氮平临床反应的药理学分析。

Molecular Neuropsychiatry Pub Date : 2017-02-01 Epub Date: 2016-10-12 DOI: 10.1159/000449224

Danielle L Taylor, Arun K Tiwari, Jeffrey A Lieberman, Steven G Potkin, Herbert Y Meltzer, Joanne Knight, Gary Remington, Daniel J Müller, James L Kennedy

{"title":"Pharmacogenetic Analysis of Functional Glutamate System Gene Variants and Clinical Response to Clozapine.","authors":"Danielle L Taylor, Arun K Tiwari, Jeffrey A Lieberman, Steven G Potkin, Herbert Y Meltzer, Joanne Knight, Gary Remington, Daniel J Müller, James L Kennedy","doi":"10.1159/000449224","DOIUrl":"https://doi.org/10.1159/000449224","url":null,"abstract":"Altered glutamate neurotransmission is implicated in the etiology of schizophrenia (SCZ) and the pharmacogenetics of response to clozapine (CLZ), which is the drug of choice for treatment-resistant SCZ. Response to antipsychotic therapy is highly variable, although twin studies suggest a genetic component. We investigated the association of 10 glutamate system gene variants with CLZ response using standard genotyping procedures. GRM2 (rs4067 and rs2518461), SLC1A2 (rs4354668, rs4534557, and rs2901534), SLC6A9 (rs12037805, rs1978195, and rs16831558), GRIA1 (rs2195450), and GAD1 (rs3749034) were typed in 163 European SCZ/schizoaffective disorder patients deemed resistant or intolerant to previous pharmacotherapy. Response was assessed following 6 months of CLZ monotherapy using change in Brief Psychiatric Rating Scale (BPRS) scores. Categorical and continuous response variables were analyzed using χ2 tests and analysis of covariance, respectively. We report no significant associations following correction for multiple testing. Prior to correction, nominally significant associations were observed for SLC6A9, SLC1A2, GRM2, and GRIA1. Most notably, CC homozygotes of rs16831558 located in the glycine transporter 1 gene (SLC6A9) exhibited an allele dose-dependent improvement in positive symptoms compared to T allele carriers (puncorrected = 0.008, pcorrected = 0.08). To clarify the role of SLC6A9 in clinical response to antipsychotic medication, and CLZ in particular, this finding warrants further investigation in larger well-characterized samples.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":"2 4","pages":"185-197"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000449224","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34798562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13

Front & Back Matter 正面和背面

Molecular Neuropsychiatry Pub Date : 2017-02-01 DOI: 10.1159/000458716

Q. Nguyen, E. Rodrigues, M. Farah, W. Mieler, D. Do, O. Michielin, G. Coukos, G. Coscas, J. Cunha-Vaz, A. Loewenstein, G. Soubrane, K. Priftis, M. Anthracopoulos, D. Mathalon, T. Petryshen

引用次数: 0

Analysis of Shared Haplotypes amongst Palauans Maps Loci for Psychotic Disorders to 4q28 and 5q23-q31. 帕劳人共享单倍型分析将精神疾病基因座定位于4q28和5q23-q31。

Molecular Neuropsychiatry Pub Date : 2017-02-01 Epub Date: 2016-10-12 DOI: 10.1159/000450726

Corneliu A Bodea, Frank A Middleton, Nadine M Melhem, Lambertus Klei, Youeun Song, Josepha Tiobech, Pearl Marumoto, Victor Yano, Stephen V Faraone, Kathryn Roeder, Marina Myles-Worsley, Bernie Devlin, William Byerley

{"title":"Analysis of Shared Haplotypes amongst Palauans Maps Loci for Psychotic Disorders to 4q28 and 5q23-q31.","authors":"Corneliu A Bodea, Frank A Middleton, Nadine M Melhem, Lambertus Klei, Youeun Song, Josepha Tiobech, Pearl Marumoto, Victor Yano, Stephen V Faraone, Kathryn Roeder, Marina Myles-Worsley, Bernie Devlin, William Byerley","doi":"10.1159/000450726","DOIUrl":"https://doi.org/10.1159/000450726","url":null,"abstract":"To localize genetic variation affecting risk for psychotic disorders in the population of Palau, we genotyped DNA samples from 203 Palauan individuals diagnosed with psychotic disorders, broadly defined, and 125 control subjects using a genome-wide single nucleotide polymorphism array. Palau has unique features advantageous for this study: due to its population history, Palauans are substantially interrelated; affected individuals often, but not always, cluster in families; and we have essentially complete ascertainment of affected individuals. To localize risk variants to genomic regions, we evaluated long-shared haplotypes, ≥10 Mb, identifying clusters of affected individuals who share such haplotypes. This extensive sharing, typically identical by descent, was significantly greater in cases than population controls, even after controlling for relatedness. Several regions of the genome exhibited substantial excess of shared haplotypes for affected individuals, including 3p21, 3p12, 4q28, and 5q23-q31. Two of these regions, 4q28 and 5q23-q31, showed significant linkage by traditional LOD score analysis and could harbor variants of more sizeable risk for psychosis or a multiplicity of risk variants. The pattern of haplotype sharing in 4q28 highlights PCDH10, encoding a cadherin-related neuronal receptor, as possibly involved in risk.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":"2 4","pages":"173-184"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000450726","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34798561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Evidence of AS3MT^d2d3-Associated Variants within 10q24.32-33 in the Genetic Risk of Major Affective Disorders. 10q24.32-33内as3mtd2d3相关变异与主要情感障碍遗传风险的证据

Molecular Neuropsychiatry Pub Date : 2017-02-01 Epub Date: 2016-12-14 DOI: 10.1159/000452998

Lingyi Li, Hong Chang, Tao Peng, Ming Li, Xiao Xiao

引用次数: 16

Contents Vol. 2, 2016 目录2016年第2卷

Molecular Neuropsychiatry Pub Date : 2017-02-01 DOI: 10.1159/000456093

F. Middleton, S. Faraone, M. Myles‐Worsley, B. Devlin, W. Byerley, C. Bodea, N. Melhem, L. Klei, Youeun Song, J. Tiobech, V. Yano, K. Roeder, P. Marumoto, B. Cheyette, Kimberly A. Mulligan, T. Greenwood, Lingyi Li, Hong Chang, T. Peng, Ming Li, Xiao Xiao, A. Tiwari, S. Potkin, D. Müller, J. Kennedy, Dani Taylor, J. Lieberman, H. Meltzer, Joanne Knight, G. Remington, Mengensatzproduktion, Druckerei Stückle

引用次数: 0