Neuropsychopharmacology最新文献_第4页

Genome-wide methylome-based molecular pathologies associated with depression and suicide. 与抑郁和自杀相关的全基因组甲基组分子病理学。

IF 6.6 1区医学

Neuropsychopharmacology Pub Date : 2024-12-07 DOI: 10.1038/s41386-024-02040-9

Yogesh Dwivedi, Bhaskar Roy, Praveen Kumar Korla

{"title":"Genome-wide methylome-based molecular pathologies associated with depression and suicide.","authors":"Yogesh Dwivedi, Bhaskar Roy, Praveen Kumar Korla","doi":"10.1038/s41386-024-02040-9","DOIUrl":"https://doi.org/10.1038/s41386-024-02040-9","url":null,"abstract":"Major depressive disorder (MDD) is a debilitating disorder. Suicide attempts are 5-times higher in MDD patients than in the general population. Interestingly, not all MDD patients develop suicidal thoughts or complete suicide. Thus, it is important to study the risk factors that can distinguish suicidality among MDD patients. The present study examined if DNA methylation changes can distinguish suicidal behavior among depressed subjects. Genome-wide DNA methylation was examined in the dorsolateral prefrontal cortex of depressed suicide (MDD+S; n = 15), depressed non-suicide (MDD-S; n = 17), and nonpsychiatric control (C; n = 16) subjects using 850 K Infinium Methylation EPIC BeadChip. The significantly differentially methylated genes were used to determine the functional enrichment of genes for ontological clustering and pathway analysis. Based on the number of CpG content and their relative distribution from specific landmark regions of genes, 32,958 methylation sites were identified across 12,574 genes in C vs. MDD+/-S subjects, 30,852 methylation sites across 12,019 genes in C vs. MDD-S, 41,648 methylation sites across 13,941 genes in C vs. MDD+S, and 49,848 methylation sites across 15,015 genes in MDD-S vs. MDD+S groups. A comparison of methylation sites showed 33,129 unique methylation sites and 5451 genes in the MDD-S group compared to the MDD+S group. Functional analysis suggested oxytocin, GABA, VGFA, TNFA, and mTOR pathways associated with suicide in the MDD group. Altogether, our data show a distinct pattern of DNA methylation, the genomic distribution of differentially methylated sites, gene enrichment, and pathways in MDD suicide compared to non-suicide MDD subjects.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The activation of the piriform cortex to lateral septum pathway during chronic social defeat stress is crucial for the induction of behavioral disturbance in mice. 慢性社会失败应激过程中梨状皮质向外侧隔膜通路的激活是诱导小鼠行为障碍的关键。

IF 6.6 1区医学

Neuropsychopharmacology Pub Date : 2024-12-05 DOI: 10.1038/s41386-024-02034-7

Yuki Okuda, Dongrui Li, Yuzuki Maruyama, Hirokazu Sonobe, Tomoyuki Mano, Kazuki Tainaka, Ryota Shinohara, Tomoyuki Furuyashiki

{"title":"The activation of the piriform cortex to lateral septum pathway during chronic social defeat stress is crucial for the induction of behavioral disturbance in mice.","authors":"Yuki Okuda, Dongrui Li, Yuzuki Maruyama, Hirokazu Sonobe, Tomoyuki Mano, Kazuki Tainaka, Ryota Shinohara, Tomoyuki Furuyashiki","doi":"10.1038/s41386-024-02034-7","DOIUrl":"https://doi.org/10.1038/s41386-024-02034-7","url":null,"abstract":"Chronic stress induces neural dysfunctions and risks mental illnesses. Clinical and preclinical studies have established the roles of brain regions underlying emotional and cognitive functions in stress and depression. However, neural pathways to perceive sensory stimuli as stress to cause behavioral disturbance remain unknown. Using whole-brain imaging of Arc-dVenus neuronal response reporter mice and machine learning analysis, here we unbiasedly demonstrated different patterns of contribution of widely distributed brain regions to neural responses to acute and chronic social defeat stress (SDS). Among these brain regions, multiple sensory cortices, especially the piriform (olfactory) cortex, primarily contributed to classifying neural responses to chronic SDS. Indeed, SDS-induced activation of the piriform cortex was augmented with repetition of SDS, accompanied by impaired odor discrimination. Axonal tracing and chemogenetic manipulation showed that excitatory neurons in the piriform cortex directly project to the lateral septum and activate it in response to chronic SDS, thereby inducing behavioral disturbance. These results pave the way for identifying a spatially defined sequence of neural consequences of stress and the roles of sensory pathways in perceiving chronic stress in mental illness pathology.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retraction Note: Disruption of lipid-raft localized Gαs/tubulin complexes by antidepressants: a unique feature of HDAC6 inhibitors, SSRI and tricyclic compounds 注：抗抑郁药破坏脂质筏定位的Gαs/微管蛋白复合物：HDAC6抑制剂、SSRI和三环化合物的独特特征。

IF 6.6 1区医学

Neuropsychopharmacology Pub Date : 2024-12-05 DOI: 10.1038/s41386-024-02039-2

Harinder Singh, Nathan Wray, Jeffrey M. Schappi, Mark M. Rasenick