{"title":"The efficacy and cerebral mechanism of intradermal acupuncture for major depressive disorder: a multicenter randomized controlled trial","authors":"Xiaoting Wu, Mingqi Tu, Zelin Yu, Zhijian Cao, Siying Qu, Nisang Chen, Junyan Jin, Sangsang Xiong, Jiajia Yang, Shuangyi Pei, Maosheng Xu, Jia Wang, Yan Shi, Lishu Gao, Jian Xie, Xinwei Li, Jianqiao Fang, Xiaomei Shao","doi":"10.1038/s41386-024-02036-5","DOIUrl":"10.1038/s41386-024-02036-5","url":null,"abstract":"New combinations or alternative therapies for major depressive disorder (MDD) are necessary. Intradermal acupuncture (IA) shows promise but requires further investigation regarding its efficacy, safety, and mechanisms. Conducted across 3 centers from November 2022 to January 2024, our randomized controlled trial included 120 participants with moderate to severe MDD, divided into the selective serotonin reuptake inhibitors (SSRIs), SSRIs plus sham IA (SSRIs + SIA), and SSRIs plus active IA (SSRIs + AIA) groups. Acupuncture groups received 10 sessions over 6 weeks at Shenmen (HT7), Neiguan (PC6), Sanyinjiao (SP6) and Taichong (LR3) bilaterally, followed by a 4-week follow-up. The primary outcome was changes in Hamilton Depression Rating Scale-17 (HAMD-17) scores at week 6. Furthermore, healthy controls (HCs) and MDD patients underwent magnetic resonance imaging (MRI) scans for functional connectivity (FC) analysis. After 6 weeks of treatment, the SSRIs + AIA group showed a greater reduction in HAMD-17 score than the SSRIs + SIA group (MD, −4.9 [CI, −7.6 to −2.2], P < 0.001) and SSRIs group (MD, −5.1 [CI, −7.8 to −2.3], P < 0.001). No serious adverse events occurred. SSRIs + AIA resulted in lower incidences of palpitations (vs.SSRIs + SIA: OR, 0.1% [CI, 0.0–1.0%]; vs. SSRIs: OR, 0.1% [CI, 0.0–0.7%]; P < 0.05), somnolence (vs.SSRIs + SIA: OR, 0.1% [CI, 0.0–0.9%]; vs.SSRIs: OR, 0.1% [CI, 0.0–0.7%]; P < 0.05), and nausea (vs.SSRIs + SIA: OR, 0.1% [CI, 0.0–1.0%]; vs. SSRIs: OR, 0.1% [CI, 0.0–0.9%]; P < 0.05). MDD patients showed abnormal FCs, and IA enhanced FCs between striatum and frontal_inf_tri, and striatum and cerebellum in the MRI study. Overall, IA as adjunctive therapy provides clinical efficacy and safety for MDD, and it may exert antidepressant effects by modulating striatal FCs.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 7","pages":"1075-1083"},"PeriodicalIF":6.6,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41386-024-02036-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"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":"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":"50 4","pages":"705-716"},"PeriodicalIF":6.6,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11845511/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"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":"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":"50 5","pages":"828-840"},"PeriodicalIF":6.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41386-024-02034-7.pdf","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Harinder Singh, Nathan Wray, Jeffrey M. Schappi, Mark M. Rasenick
{"title":"Retraction Note: Disruption of lipid-raft localized Gαs/tubulin complexes by antidepressants: a unique feature of HDAC6 inhibitors, SSRI and tricyclic compounds","authors":"Harinder Singh, Nathan Wray, Jeffrey M. Schappi, Mark M. Rasenick","doi":"10.1038/s41386-024-02039-2","DOIUrl":"10.1038/s41386-024-02039-2","url":null,"abstract":"","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 3","pages":"608-608"},"PeriodicalIF":6.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}