Molecular Neuropsychiatry最新文献_第5页

Front & Back Matter 正面和背面

Molecular Neuropsychiatry Pub Date : 2018-12-01 DOI: 10.1159/000495995

C. Barr, D. Mathalon

引用次数: 0

The Sex Chromosome Hypothesis of Schizophrenia: Alive, Dead, or Forgotten? A Commentary and Review. 精神分裂症的性染色体假说:活着，死了，还是被遗忘了?A评论与回顾。

Molecular Neuropsychiatry Pub Date : 2018-10-01 Epub Date: 2018-08-20 DOI: 10.1159/000491489

William K Bache, Lynn E DeLisi

{"title":"The Sex Chromosome Hypothesis of Schizophrenia: Alive, Dead, or Forgotten? A Commentary and Review.","authors":"William K Bache, Lynn E DeLisi","doi":"10.1159/000491489","DOIUrl":"https://doi.org/10.1159/000491489","url":null,"abstract":"The X chromosome has long been an intriguing site for harboring genes that have importance in brain development and function. It has received the most attention for having specific genes underlying the X-linked inherited intellectual disabilities, but has also been associated with schizophrenia in a number of early studies. An X chromosome hypothesis for a genetic predisposition for schizophrenia initially came from the X chromosome anomaly population data showing an excess of schizophrenia in Klinefelter's (XXY) males and triple X (XXX) females. Crow and colleagues later expanded the X chromosome hypothesis to include the possibility of a locus on the Y chromosome and, specifically, genes on X that escaped inactivation and are X-Y homologous loci. Some new information about possible risk loci on these chromosomes has come from the current large genetic consortia genome-wide association studies, suggesting that perhaps this hypothesis needs to be revisited for some schizophrenias. The following commentary reviews the early and more recent literature supporting or refuting this dormant hypothesis and emphasizes the possible candidate genes still of interest that could be explored in further studies.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":"4 2","pages":"83-89"},"PeriodicalIF":0.0,"publicationDate":"2018-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000491489","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36650404","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: 9

Altered White Matter Diffusivity of the Cingulum Angular Bundle in Posttraumatic Stress Disorder. 创伤后应激障碍中扣带角束白质弥漫性改变。

Molecular Neuropsychiatry Pub Date : 2018-10-01 Epub Date: 2018-07-19 DOI: 10.1159/000490464

Christopher L Averill, Lynnette A Averill, Kristen M Wrocklage, J Cobb Scott, Teddy J Akiki, Brian Schweinsburg, Steven M Southwick, John H Krystal, Chadi G Abdallah

{"title":"Altered White Matter Diffusivity of the Cingulum Angular Bundle in Posttraumatic Stress Disorder.","authors":"Christopher L Averill, Lynnette A Averill, Kristen M Wrocklage, J Cobb Scott, Teddy J Akiki, Brian Schweinsburg, Steven M Southwick, John H Krystal, Chadi G Abdallah","doi":"10.1159/000490464","DOIUrl":"https://doi.org/10.1159/000490464","url":null,"abstract":"Purpose of the study: Prior studies showed posttraumatic stress disorder (PTSD)-related alterations in white matter integrity, but most of these studies have used region-based approaches. We address this limitation by investigating the relationship between PTSD severity and fractional anisotropy (FA) using a tract-based approach.Procedures: Structural and diffusion magnetic resonance imaging were acquired from 67 combat-exposed US Veterans and processed using FSL/FreeSurfer TRActs Constrained by UnderLying Anatomy. Partial correlations were conducted between PTSD severity and FA of the cingulum and uncinate fasciculi covarying for age, sex, and head motion.Results: Only FA of the left cingulum angular bundle (CAB) was positively correlated with PTSD symptom severity (r = 0.433, p = 0.001, df = 57) and remained significant after Bonferroni correction.Conclusions: This finding may imply greater organization of the CAB with increasing PTSD severity. The CAB connects directly to the cingulate cortex and the hippocampal subiculum, critical nodes of the default mode network, as well as being implicated in neurodegeneration pathology, decision-making, and executive functions, which may help explain previously shown alterations in this network in PTSD.Message of the paper: Further study of white matter tract integrity in PTSD is warranted, particularly to investigate whether the CAB connections with both higher-order cognitive functioning and emotion processing regions contribute to the pathophysiology and comorbidity of PTSD.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":"4 2","pages":"75-82"},"PeriodicalIF":0.0,"publicationDate":"2018-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000490464","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36650403","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: 18

Front & Back Matter 正面和背面

Molecular Neuropsychiatry Pub Date : 2018-10-01 DOI: 10.1159/000494372

C. Barr, D. Mathalon

引用次数: 0

Attenuated Mismatch Negativity in Attenuated Psychosis Syndrome Predicts Psychosis: Can Galantamine-Memantine Combination Prevent Psychosis? 减退性精神病综合征中减弱的错配负性可预测精神病：加兰他敏--吗啡联用药物能预防精神病吗？

Molecular Neuropsychiatry Pub Date : 2018-10-01 Epub Date: 2018-06-07 DOI: 10.1159/000488797

Maju Mathew Koola

{"title":"Attenuated Mismatch Negativity in Attenuated Psychosis Syndrome Predicts Psychosis: Can Galantamine-Memantine Combination Prevent Psychosis?","authors":"Maju Mathew Koola","doi":"10.1159/000488797","DOIUrl":"10.1159/000488797","url":null,"abstract":"Although first proposed in 1987, early diagnosis and intervention of psychotic disorders has only recently become a priority in the field. The interest in clinical high risk (CHR) for psychosis skyrocketed after attenuated psychosis syndrome (APS) was added to the DSM-5. There is evidence that in individuals with APS, attenuated mismatch negativity (MMN: functioning of the auditory sensory memory system) is a robust biomarker that can predict transition to psychosis. The underlying pathophysiological mechanism of MMN is via the interaction of N-methyl-D-aspartate (NMDA) and alpha-7 nicotinic acetylcholine (α-7nACh) receptors. Galantamine is an acetylcholinesterase inhibitor and a positive allosteric modulator of the α-7nACh receptors. Memantine is an NMDA receptor antagonist. Memantine has been shown to enhance MMN in people with schizophrenia. Although no studies with galantamine have measured MMN, encenicline, an α-7 nicotinic partial agonist, increased MMN in people with schizophrenia. MMN has been suggested as a potential biomarker with the galantamine-memantine combination for the treatment of neuropsychiatric disorders. Hence, the galantamine-memantine combination may enhance MMN, thereby preventing CHR to psychosis. With no treatments available, randomized controlled trials are warranted with the galantamine-memantine combination to delay or prevent conversion to psychosis in individuals with CHR.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":"4 2","pages":"71-74"},"PeriodicalIF":0.0,"publicationDate":"2018-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206967/pdf/mnp-0004-0071.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36696560","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

Epigenetic Age in Male Combat-Exposed War Veterans: Associations with Posttraumatic Stress Disorder Status. 接触过战斗的男性退伍军人的表观遗传年龄：创伤后应激障碍状态的相关性。

Molecular Neuropsychiatry Pub Date : 2018-10-01 Epub Date: 2018-09-05 DOI: 10.1159/000491431

Josine E Verhoeven, Ruoting Yang, Owen M Wolkowitz, Francesco S Bersani, Daniel Lindqvist, Synthia H Mellon, Rachel Yehuda, Janine D Flory, Jue Lin, Duna Abu-Amara, Iouri Makotkine, Charles Marmar, Marti Jett, Rasha Hammamieh

{"title":"Epigenetic Age in Male Combat-Exposed War Veterans: Associations with Posttraumatic Stress Disorder Status.","authors":"Josine E Verhoeven, Ruoting Yang, Owen M Wolkowitz, Francesco S Bersani, Daniel Lindqvist, Synthia H Mellon, Rachel Yehuda, Janine D Flory, Jue Lin, Duna Abu-Amara, Iouri Makotkine, Charles Marmar, Marti Jett, Rasha Hammamieh","doi":"10.1159/000491431","DOIUrl":"10.1159/000491431","url":null,"abstract":"DNA methylation patterns change with age and can be used to derive an estimate of \"epigenetic age,\" an indicator of biological age. Several studies have shown associations of posttraumatic stress disorder (PTSD) with worse somatic health and early mortality, raising the possibility of accelerated biological aging. This study examined associations between estimated epigenetic age and various variables in 160 male combat-exposed war veterans with (n = 79) and without PTSD (n = 81). DNA methylation was assessed in leukocyte genomic DNA using the Illumina 450K DNA methylation arrays. Epigenetic age was estimated using Horvath's epigenetic clock algorithm and Δage (epigenetic age-chronological age) was calculated. In veterans with PTSD (Δage = 3.2), Δage was on average lower compared to those without PTSD (Δage = 5.0; p = 0.02; Cohen's d = 0.42). This between-group difference was not explained by race/ethnicity, lifestyle factors or childhood trauma. Antidepressant use, however, explained part of the association. In the PTSD positive group, telomerase activity was negatively related to Δage (β = -0.35; p = 0.007). In conclusion, veterans with PTSD had significantly lower epigenetic age profiles than those without PTSD. Further, current antidepressant use and higher telomerase activity were related to relatively less epigenetic aging in veterans with PTSD, speculative of a mechanistic pathway that might attenuate biological aging-related processes in the context of PTSD.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":"4 2","pages":"90-99"},"PeriodicalIF":0.0,"publicationDate":"2018-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/55/ed/mnp-0004-0090.PMC6206951.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36650405","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

Perturbations of Neuron-Restrictive Silencing Factor Modulate Corticotropin-Releasing Hormone Gene Expression in the Human Cell Line BeWo. 神经元限制性沉默因子对人BeWo细胞促肾上腺皮质激素释放激素基因表达的干扰。

Molecular Neuropsychiatry Pub Date : 2018-10-01 Epub Date: 2018-09-19 DOI: 10.1159/000492635

Vasileios Kreouzis, Guo-Lin Chen, Gregory M Miller

{"title":"Perturbations of Neuron-Restrictive Silencing Factor Modulate Corticotropin-Releasing Hormone Gene Expression in the Human Cell Line BeWo.","authors":"Vasileios Kreouzis, Guo-Lin Chen, Gregory M Miller","doi":"10.1159/000492635","DOIUrl":"https://doi.org/10.1159/000492635","url":null,"abstract":"Stress exacerbates disease, and understanding its molecular mechanisms is crucial to the development of novel therapeutic interventions to combat stress-related disorders. The driver of the stress response in the hypothalamic-pituitary-adrenal axis (HPA) is corticotropin-releasing hormone (CRH), a neuropeptide synthesized in the paraventricular nucleus of the hypothalamus. Evidence supports that CRH expression is epigenetically modified at the molecular level by environmental stimuli, causing changes in the stress response. This effect is mediated by a concert of factors that translate environmental change into alterations in gene expression. An important regulator and epigenetic modulator of CRH expression is neuron-restrictive silencing factor (NRSF). Previously, our lab identified numerous splice variants of NRSF that are specific to humans and predictive of differential regulatory effects of NRSF variants on targeted gene expression. The human cell line BeWo has endogenous CRH and NRSF expression providing an in vitro model system. Here, we show that manipulation of NRSF expression through siRNA technology, overexpression by plasmid vectors, and direct cAMP induction that CRH expression is linked to changes in NRSF expression. Accordingly, this epigenetic regulatory pathway in humans might be a critical mechanism involved in the regulation of the stress response.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":"4 2","pages":"100-110"},"PeriodicalIF":0.0,"publicationDate":"2018-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000492635","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36650406","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: 1

Associations between the LEP -2548G/A Promoter and Baseline Weight and between LEPR Gln223Arg and Lys656Asn Variants and Change in BMI z Scores in Arab Children and Adolescents Treated with Risperidone. LEP -2548G/A启动子与基线体重的关系，LEPR Gln223Arg和Lys656Asn变异与接受利培酮治疗的阿拉伯儿童和青少年BMI z评分变化的关系

Molecular Neuropsychiatry Pub Date : 2018-10-01 Epub Date: 2018-10-05 DOI: 10.1159/000490463

Noor B Almandil, Rohit J Lodhi, Hongyan Ren, Frank M C Besag, David Rossolatos, Ruth Ohlsen, Caitlin Slomp, Diego L Lapetina, Giona Plazzotta, Macey L Murray, Abdulsalam A Al-Sulaiman, Paul Gringras, Ian C K Wong, Katherine J Aitchison

{"title":"Associations between the LEP -2548G/A Promoter and Baseline Weight and between LEPR Gln223Arg and Lys656Asn Variants and Change in BMI z Scores in Arab Children and Adolescents Treated with Risperidone.","authors":"Noor B Almandil, Rohit J Lodhi, Hongyan Ren, Frank M C Besag, David Rossolatos, Ruth Ohlsen, Caitlin Slomp, Diego L Lapetina, Giona Plazzotta, Macey L Murray, Abdulsalam A Al-Sulaiman, Paul Gringras, Ian C K Wong, Katherine J Aitchison","doi":"10.1159/000490463","DOIUrl":"https://doi.org/10.1159/000490463","url":null,"abstract":"Data on baseline (antipsychotics-naïve) age, weight, and height, and change in these at 3 subsequent follow-up time points up to 313.6 days (95% CI 303.5-323.7) were collected from 181 risperidone-treated children and adolescents (mean age 12.58 years, SD 4.99, range 2.17-17.7) attending a pediatric neurology clinic in Saudi Arabia. Owing to differences in genotypic distributions in the subsamples, results are reported for the white Arab population (n = 144). Age- and gender-normed body mass index (BMI)-standardized z scores (BMI z) were calculated (LMSgrowth program). Linear regression was performed for baseline weight and BMI z, while change in BMI z was assessed using random effects ordered logistic regression. The following single nucleotide polymorphisms (SNPs) were analyzed: rs7799039 in the LEP promoter, rs1805094 (previously rs8179183), rs1137100 and rs1137101 in the LEPR, and rs1414334 in HTR2C. We found a nominally significant association between rs7799309 and baseline weight, adjusting for height, age, gender, and diagnosis (A/G, p = 0.035, β = -3.62 vs. G/G). The rs1137101 (G/G, p = 0.018, odds ratio [OR] = 4.13 vs. A/A) and rs1805094 C allele carriers (p = 0.019, OR = 0.51) showed nominally significant associations with change in BMI z categories. Our data support and replicate previous relevant associations for these variants (including with weight gain when on risperidone), whilst being the first report of such associations in patients of Arab ethnicity.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":"4 2","pages":"111-117"},"PeriodicalIF":0.0,"publicationDate":"2018-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000490463","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36650407","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

Sequence Analysis of Drug Target Genes with Suicidal Behavior in Bipolar Disorder Patients. Sequence Analysis of Drug Target Genes with Suicidal Behavior in Bipolar Disorder Patients.

Molecular Neuropsychiatry Pub Date : 2018-06-01 Epub Date: 2018-05-03 DOI: 10.1159/000488029

Clement C Zai, Arun K Tiwari, Gwyneth C Zai, Vincenzo de Luca, Sajid A Shaikh, Nicole King, John Strauss, James L Kennedy, John B Vincent

{"title":"Sequence Analysis of Drug Target Genes with Suicidal Behavior in Bipolar Disorder Patients.","authors":"Clement C Zai, Arun K Tiwari, Gwyneth C Zai, Vincenzo de Luca, Sajid A Shaikh, Nicole King, John Strauss, James L Kennedy, John B Vincent","doi":"10.1159/000488029","DOIUrl":"https://doi.org/10.1159/000488029","url":null,"abstract":"Background: A number of genes have been implicated in recent genome-wide association studies of suicide attempt in bipolar disorder. More focused investigation of genes coding for protein targets of existing drugs may lead to drug repurposing for the treatment and/or prevention of suicide.Methods: We analyzed 2,457 DNA variants across 197 genes of interest to GlaxoSmithKline across the pipeline in our sample of European patients suffering from bipolar disorder (N = 219). We analyzed these variants for a possible association with the suicide severity score (ranging from suicidal ideation/plan to serious suicide attempt) from the Schedule for Clinical Assessment in Neuropsychiatry. We conducted tests of individual variants and gene-based tests.Results: We found a number of DNA variants in the transforming growth factor beta receptor 1 gene (TGFBR1) to be suggestively associated with suicide severity scores (p < 0.005). The gene-based tests also pointed to TGFBR1 to be associated with suicide severity (p = 0.0001). However, these findings were not replicated in an independent bipolar disorder sample.Conclusions: We report no significant association between DNA sequences of drug target genes and suicidal behavior. Additional larger sequencing studies could further interrogate associations between variants in drug target genes and suicidal behavior.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":"4 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000488029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36306650","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: 2

Front & Back Matter 正面和背面

Molecular Neuropsychiatry Pub Date : 2018-06-01 DOI: 10.1159/000490631

C. Barr, D. Mathalon, Rakesh Karmacharya, T. Kash

引用次数: 0