Molecular Neuropsychiatry最新文献_第7页

Methylphenidate and Guanfacine Ameliorate ADHD-Like Phenotypes in Fez1-Deficient Mice. 哌甲酯和胍法辛可改善fez1缺陷小鼠adhd样表型。

Molecular Neuropsychiatry Pub Date : 2018-05-01 Epub Date: 2018-04-26 DOI: 10.1159/000488081

Akiko Sumitomo, Ayumi Saka, Keisho Ueta, Kouta Horike, Kazuko Hirai, Nao J Gamo, Takatoshi Hikida, Keiichi I Nakayama, Akira Sawa, Takeshi Sakurai, Toshifumi Tomoda

{"title":"Methylphenidate and Guanfacine Ameliorate ADHD-Like Phenotypes in Fez1-Deficient Mice.","authors":"Akiko Sumitomo, Ayumi Saka, Keisho Ueta, Kouta Horike, Kazuko Hirai, Nao J Gamo, Takatoshi Hikida, Keiichi I Nakayama, Akira Sawa, Takeshi Sakurai, Toshifumi Tomoda","doi":"10.1159/000488081","DOIUrl":"https://doi.org/10.1159/000488081","url":null,"abstract":"Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that, while prevalent, has a stagnant track record for advances in treatment. The limited availability of animal models with appropriate face and predictive validities has hampered progress in developing novel neurobiological hypotheses and testing new therapeutic options for this condition. Here, we report that mice deficient in Fez1, a gene specifically expressed in the nervous system with documented functions in neurodevelopment, show hyperactivity and impulsivity phenotypes, which are ameliorated by administering methylphenidate (MPH) or guanfacine (GFC), two pharmacological agents used for ADHD treatment. Fez1-knockout (KO) mice show reduced expression of tyrosine hydroxylase in the midbrain and the brain stem and have reduced levels of dopamine, norepinephrine, or their metabolites in both the nucleus accumbens and the prefrontal cortex. These neurochemical changes in Fez1-KO mice were normalized by MPH or GFC. We propose that Fez1-KO mice can be used as a model to evaluate the role of altered neurodevelopment in the manifestation of ADHD-like behavioral phenotypes, as well as to investigate the neurobiological mechanisms of existing and new pharmacotherapeutic agents for ADHD.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":"3 4","pages":"223-233"},"PeriodicalIF":0.0,"publicationDate":"2018-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000488081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36209636","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: 10

Differential Impact of Obesity on CD69 Expression in Individuals with Bipolar Disorder and Healthy Controls. 肥胖对双相情感障碍患者和健康对照者CD69表达的差异影响

Molecular Neuropsychiatry Pub Date : 2018-05-01 Epub Date: 2018-02-01 DOI: 10.1159/000486396

Ana S Yamagata, Lucas B Rizzo, Raphael O Cerqueira, Janine Scott, Quirino Cordeiro, Roger S McIntyre, Rodrigo B Mansur, Elisa Brietzke

{"title":"Differential Impact of Obesity on CD69 Expression in Individuals with Bipolar Disorder and Healthy Controls.","authors":"Ana S Yamagata, Lucas B Rizzo, Raphael O Cerqueira, Janine Scott, Quirino Cordeiro, Roger S McIntyre, Rodrigo B Mansur, Elisa Brietzke","doi":"10.1159/000486396","DOIUrl":"https://doi.org/10.1159/000486396","url":null,"abstract":"Preliminary evidence suggests that premature immunosenescence is involved in bipolar disorder (BD) pathophysiology. The cellular marker CD69 is expressed in T lymphocyte surface during their activation and its expression is negatively correlated with age. The objective of this study was to assess the moderating effects of obesity on the reduction of expression of CD69, a marker of immunosenescence. Forty euthymic patients with BD type I, aged 18-65 years, were included in this study. The healthy comparison group consisted of 39 volunteers who had no current or lifetime history of mental disorders, no use of psychotropic medications, and no known family history of mood disorders or psychosis. Peripheral blood mononuclear cells from BD patients and healthy controls were collected and isolated. The cells were allowed to grow in culture and stimulated for 3 days. CD69 was marked and read in flow cytometry. We found that the lower expression of CD69 in BD patients was moderated by body mass index (BMI) in both CD4+ (RR = 0.977, 95% CI 0.960-0.995, p = 0.013) and CD8+ cells (RR = 0.972, 95% CI 0.954-0.990, p = 0.003). Our findings indicate that BMI could potentially influence the process of premature aging in BD.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":"3 4","pages":"192-196"},"PeriodicalIF":0.0,"publicationDate":"2018-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000486396","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36209633","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

Mitochondrial Complex I Deficiency in Schizophrenia and Bipolar Disorder and Medication Influence. 精神分裂症和双相情感障碍的线粒体复合体I缺乏及其药物影响。

Molecular Neuropsychiatry Pub Date : 2018-02-01 Epub Date: 2017-11-30 DOI: 10.1159/000484348

Brandi L Rollins, Ling Morgan, Brooke E Hjelm, Adolfo Sequeira, Alan F Schatzberg, Jack D Barchas, Francis S Lee, Rick M Myers, Stanley J Watson, Huda Akil, Steven G Potkin, William E Bunney, Marquis P Vawter

{"title":"Mitochondrial Complex I Deficiency in Schizophrenia and Bipolar Disorder and Medication Influence.","authors":"Brandi L Rollins, Ling Morgan, Brooke E Hjelm, Adolfo Sequeira, Alan F Schatzberg, Jack D Barchas, Francis S Lee, Rick M Myers, Stanley J Watson, Huda Akil, Steven G Potkin, William E Bunney, Marquis P Vawter","doi":"10.1159/000484348","DOIUrl":"https://doi.org/10.1159/000484348","url":null,"abstract":"Subjects with schizophrenia (SZ) and bipolar disorder (BD) show decreased protein and transcript levels for mitochondrial complex I. In vitro results suggest antipsychotic and antidepressant drugs may be responsible. We measured complex I activity in BD, SZ, and controls and presence of antipsychotic and antidepressant medications, mitochondrial DNA (mtDNA) copy number, and the mtDNA \"common deletion\" in the brain. Complex I activity in the prefrontal cortex was decreased by 45% in SZ compared to controls (p = 0.02), while no significant difference was found in BD. Complex I activity was significantly decreased (p = 0.01) in pooled cases (SZ and BD) that had detectable psychotropic medications and drugs compared to pooled cases with no detectable levels. Subjects with age at onset in their teens and psychotropic medications showed decreased (p < 0.05) complex I activity compared to subjects with an adult age at onset. Both SZ and BD groups displayed significant increases (p < 0.05) in mtDNA copy number compared to controls; however, common deletion burden was not altered. Complex I deficiency is found in SZ brain tissue, and psychotropic medications may play a role in mitochondrial dysfunction. Studies of medication-free first-episode psychosis patients are needed to elucidate whether mitochondrial pathophysiology occurs independent of medication effects.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":" ","pages":"157-169"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000484348","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35957047","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: 36

Improved Scalability of Neuron-Based Phenotypic Screening Assays for Therapeutic Discovery in Neuropsychiatric Disorders. 神经精神疾病治疗发现中基于神经元的表型筛选测定的改进可扩展性。

Molecular Neuropsychiatry Pub Date : 2018-02-01 Epub Date: 2017-11-17 DOI: 10.1159/000481731

Timothy P Spicer, Christopher Hubbs, Thomas Vaissiere, Deanna Collia, Camilo Rojas, Murat Kilinc, Kyle Vick, Franck Madoux, Pierre Baillargeon, Justin Shumate, Kirill A Martemyanov, Damon T Page, Sathya Puthanveettil, Peter Hodder, Ronald Davis, Courtney A Miller, Louis Scampavia, Gavin Rumbaugh

{"title":"Improved Scalability of Neuron-Based Phenotypic Screening Assays for Therapeutic Discovery in Neuropsychiatric Disorders.","authors":"Timothy P Spicer, Christopher Hubbs, Thomas Vaissiere, Deanna Collia, Camilo Rojas, Murat Kilinc, Kyle Vick, Franck Madoux, Pierre Baillargeon, Justin Shumate, Kirill A Martemyanov, Damon T Page, Sathya Puthanveettil, Peter Hodder, Ronald Davis, Courtney A Miller, Louis Scampavia, Gavin Rumbaugh","doi":"10.1159/000481731","DOIUrl":"https://doi.org/10.1159/000481731","url":null,"abstract":"There is a pressing need to improve approaches for drug discovery related to neuropsychiatric disorders (NSDs). Therapeutic discovery in neuropsychiatric disorders would benefit from screening assays that can measure changes in complex phenotypes linked to disease mechanisms. However, traditional assays that track complex neuronal phenotypes, such as neuronal connectivity, exhibit poor scalability and are not compatible with high-throughput screening (HTS) procedures. Therefore, we created a neuronal phenotypic assay platform that focused on improving the scalability and affordability of neuron-based assays capable of tracking disease-relevant phenotypes. First, using inexpensive laboratory-level automation, we industrialized primary neuronal culture production, which enabled the creation of scalable assays within functioning neural networks. We then developed a panel of phenotypic assays based on culturing of primary neurons from genetically modified mice expressing HTS-compatible reporters that capture disease-relevant phenotypes. We demonstrated that a library of 1,280 compounds was quickly screened against both assays using only a few litters of mice in a typical academic laboratory setting. Finally, we implemented one assay in a fully automated high-throughput academic screening facility, illustrating the scalability of assays designed using this platform. These methodological improvements simplify the creation of highly scalable neuron-based phenotypic assays designed to improve drug discovery in CNS disorders.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":" ","pages":"141-150"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000481731","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35957538","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: 14

Erratum. 勘误表。

Molecular Neuropsychiatry Pub Date : 2018-02-01 Epub Date: 2018-01-11 DOI: 10.1159/000485222

引用次数: 0

A Genome-Wide Search for Bipolar Disorder Risk Loci Modified by Mitochondrial Genome Variation. 线粒体基因组变异修饰双相情感障碍风险位点的全基因组搜索。

Molecular Neuropsychiatry Pub Date : 2018-02-01 Epub Date: 2017-10-28 DOI: 10.1159/000464444

Euijung Ryu, Malik Nassan, Gregory D Jenkins, Sebastian M Armasu, Ana Andreazza, Susan L McElroy, Marquis P Vawter, Mark A Frye, Joanna M Biernacka

{"title":"A Genome-Wide Search for Bipolar Disorder Risk Loci Modified by Mitochondrial Genome Variation.","authors":"Euijung Ryu, Malik Nassan, Gregory D Jenkins, Sebastian M Armasu, Ana Andreazza, Susan L McElroy, Marquis P Vawter, Mark A Frye, Joanna M Biernacka","doi":"10.1159/000464444","DOIUrl":"https://doi.org/10.1159/000464444","url":null,"abstract":"Mitochondrial DNA mutations have been reported to be associated with bipolar disorder (BD). In this study, we performed genome-wide analyses to assess mitochondrial single-nucleotide polymorphism (mtSNP) effects on BD risk and early-onset BD (EOBD) among BD patients, focusing on interaction effects between nuclear SNPs (nSNPs) and mtSNPs. Common nSNP and mtSNP data from European American BD cases (n = 1,001) and controls (n = 1,034) from the Genetic Association Information Network BD study were analyzed to assess the joint effect of nSNP and nSNP-mtSNP interaction on the risk of BD and EOBD. The effect of nSNP-mtSNP interactions was also assessed. For BD risk, the strongest evidence of an association was obtained for nSNP rs1880924 in MGAM and mtSNP rs3088309 in CytB (pjoint = 8.2 × 10-8, pint = 1.4 × 10-4). Our results also suggest that the minor allele of the nSNP rs583990 in CTNNA2 increases the risk of EOBD among carriers of the mtSNP rs3088309 minor allele, while the nSNP has no effect among those carrying the mtSNP major allele (OR = 4.53 vs. 1.05, pjoint = 2.1 × 10-7, pint = 1.16 × 10-6). While our results are not statistically significant after multiple testing correction and a large-sample replication is required, our exploratory study demonstrates the potential importance of considering the mitochondrial genome for identifying genetic factors associated with BD.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":" ","pages":"125-134"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000464444","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35957536","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: 17

Interleukin-17 Alteration in First-Episode Psychosis: A Meta-Analysis. 首发精神病患者白细胞介素-17的改变:一项荟萃分析。

Molecular Neuropsychiatry Pub Date : 2018-02-01 Epub Date: 2017-10-28 DOI: 10.1159/000481661

Xinyu Fang, Yi Zhang, Weixing Fan, Wei Tang, Chen Zhang

引用次数: 25

Crossing the Worm-Brain Barrier by Using Caenorhabditis elegans to Explore Fundamentals of Human Psychiatric Illness. 利用秀丽隐杆线虫穿越虫脑屏障探索人类精神疾病的基本原理。

Molecular Neuropsychiatry Pub Date : 2018-02-01 Epub Date: 2018-01-11 DOI: 10.1159/000485423

Donard S Dwyer

{"title":"Crossing the Worm-Brain Barrier by Using Caenorhabditis elegans to Explore Fundamentals of Human Psychiatric Illness.","authors":"Donard S Dwyer","doi":"10.1159/000485423","DOIUrl":"https://doi.org/10.1159/000485423","url":null,"abstract":"Endophenotypes and Research Domain Criteria (RDoC) represent recent efforts to deconvolute psychiatric illnesses into fundamental symptom clusters or biological markers more closely linked to genetic influences. By taking this one step farther, these biomarkers can be reduced to protophenotypes - endophenotypes conserved during evolution - with counterparts in lower organisms including Caenorhabditis elegans and Drosophila. Striking conservation in C. elegans of genes that increase the risk for mental illness bolsters the relevance of this model system for psychiatric research. Here, I review the characterization of several protophenotypes that are relevant for asociality, avolition/anhedonia, prepulse inhibition, and anorexia. Interestingly, the analogous behavioral defects in C. elegans are also corrected by psychotropic drugs used to treat the corresponding symptoms in man and/or are mediated by the same neurotransmitters. Overall, there is much we can learn about the complex human brain by studying simpler nervous systems directing evolutionarily conserved behaviors. The potential for generating important new insights from model organisms appears limitless when we begin to recognize the vestiges of evolution in ourselves.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":" ","pages":"170-179"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000485423","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35957048","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

The COMT Val158Met Polymorphism and Exploratory Behavior in Bipolar Mania. COMT Val158Met多态性与双相躁狂症的探索性行为。

Molecular Neuropsychiatry Pub Date : 2018-02-01 DOI: 10.1159/000481822

Arpi Minassian, Jared W Young, Mark A Geyer, John R Kelsoe, William Perry

{"title":"The COMT Val158Met Polymorphism and Exploratory Behavior in Bipolar Mania.","authors":"Arpi Minassian, Jared W Young, Mark A Geyer, John R Kelsoe, William Perry","doi":"10.1159/000481822","DOIUrl":"https://doi.org/10.1159/000481822","url":null,"abstract":"Background: The catechol-O-methyltransferase (COMT) Val158Met gene influences cognition and behavior in psychiatric illnesses; its low-activity allele, methionine (Met), may be associated with behavior reflecting catecholamine overactivity. Heightened motor activity and increased positive valence are central features of bipolar disorder (BD) and have been quantified in the human Behavioral Pattern Monitor (hBPM), an exploration paradigm based upon the rodent open field. We examined whether hBPM behavior was related to the COMT gene in a small sample of manic BD patients.Methods: Twenty-six acutely hospitalized manic BD patients were genotyped for the COMT Val158Met polymorphism and tested in the hBPM, an unfamiliar room containing novel objects. Movements around the hBPM and object interactions were video-recorded for 15 min and rated.Results: Met homozygote BD patients demonstrated significantly more interactions with multiple objects and more time spent with objects in the hBPM. Valine (Val) homozygote patients exhibited the least object exploration, while heterozygote patients demonstrated intermediate levels.Conclusion: This preliminary study suggests that arousal and positive valence are influenced in a linear fashion by COMT, presumably due to increased catecholamine in frontal regions, but these findings require replication in a larger sample. The hBPM can enable cross-species and transdiagnostic studies to inform neurobiology of psychiatric disorders.","PeriodicalId":18957,"journal":{"name":"Molecular Neuropsychiatry","volume":"3 3","pages":"151-156"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000481822","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10343475","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: 7

Front & Back Matter 正面和背面

Molecular Neuropsychiatry Pub Date : 2018-01-24 DOI: 10.1159/000487097

J. Szepietowski, E. Weisshaar, Q. Nguyen, E. Rodrigues, M. Farah, W. Mieler, D. Do, O. Michielin, G. Coukos, W. Byerley, C. Barr, D. Mathalon, T. Petryshen

引用次数: 0