Journal of affective disorders最新文献

{"title":"Diverging trends in alcohol-related harms: The role of comorbid mental health, suicide and self-harm behaviors in ambulance attendances for alcohol intoxication during the COVID-19 pandemic in Victoria, Australia.","authors":"Rowan P Ogeil, Michael McGrath, Jasmin Grigg, Annette Peart, Jonathan Meddings, Christopher Greenwood, Ziad Nehme, Dan I Lubman","doi":"10.1016/j.jad.2024.11.012","DOIUrl":"https://doi.org/10.1016/j.jad.2024.11.012","url":null,"abstract":"<p><strong>Background: </strong>Alcohol harms changed significantly during COVID-19, but did not affect the population equally. Vulnerable groups including people with pre-existing mental health or suicidal behaviors may be at greater risk of alcohol-related harms, yet limited public health data are able to assess these.</p><p><strong>Methods: </strong>The present study utilised a novel, statewide surveillance system to examine ambulance attendances for alcohol intoxication over a four-year period prior to, and during the strictest lockdowns in Victoria, Australia.</p><p><strong>Results: </strong>While there was an overall reduction in alcohol-related attendances during lockdown (n = 15,064) compared to the 2018-19 period (n = 16,989), alcohol- intoxication attendances involving mental health symptoms increased by 40 % in Melbourne (IRR: 1.40 [1.30-1.51], p < 0.001), and by 25 % in regional Victoria (IRR: 1.25 [1.07-1.44], p = 0.005).There was also a 7 % increase in alcohol-intoxication attendances with co-morbid suicidal behaviors in Melbourne (IRR: 1.07 95%CI [1.02-1.13], p = 0.006), and a 21 % increase in regional Victoria (IRR: 1.21 [1.08-1.35], p = 0.001).</p><p><strong>Conclusions: </strong>These findings suggest that extra services and supports for individuals with co-morbid alcohol-related harms are required to ensure their clinical care needs are being met.</p>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural connectivity of thalamic subnuclei in major depressive disorder: An ultra-high resolution diffusion MRI study at 7-Tesla.","authors":"Weijian Liu, Jurjen Heij, Shu Liu, Luka Liebrand, Matthan Caan, Wietske van der Zwaag, Dick J Veltman, Lin Lu, Moji Aghajani, Guido van Wingen","doi":"10.1016/j.jad.2024.11.009","DOIUrl":"https://doi.org/10.1016/j.jad.2024.11.009","url":null,"abstract":"<p><strong>Background: </strong>The thalamus serves as a central relay station within the brain, and thalamic connectional anomalies are increasingly thought to be present in major depressive disorder (MDD). However, the use of conventional MRI scanners and acquisition techniques has prevented a thorough examination of the thalamus and its subnuclear connectional profile. We combined ultra-high field diffusion MRI acquired at 7.0 Tesla to map the white matter connectivity of thalamic subnuclei.</p><p><strong>Methods: </strong>Fifty-three MDD patients and 12 healthy controls (HCs) were involved in the final analysis. FreeSurfer was used to segment the thalamic subnuclei, and MRtrix was used to perform the preprocessing and tractography. Fractional anisotropy, axial diffusivity, mean diffusivity, radial diffusivity, and streamline count of thalamic subnuclear tracts were measured as proxies of white matter microstructure. Bayesian multilevel model was used to assess group differences in white matter metrics for each thalamic subnuclear tract and the association between these white matter metrics and clinical features in MDD.</p><p><strong>Results: </strong>Evidence was found for reduced whiter matter metrics of the tracts spanning from all thalamic subnuclei among MDD versus HC participants. Moreover, evidence was found that white matter in various thalamic subnuclear tracts is related to medication status, age of onset and recurrence in MDD.</p><p><strong>Conclusions: </strong>Structural connectivity was generally reduced in thalamic subnuclei in MDD participants. Several clinical characteristics are related to perturbed subnuclear thalamic connectivity with cortical and subcortical circuits that govern sensory processing, emotional function, and goal-directed behavior.</p>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between suicidal ideation and oxidative balance score (OBS): National Health and Nutrition Examination Survey (NHANES) 2005-2018.","authors":"Xinyu Zhang, Hangyu Liu, Chu Mi, Jieshen Mao, Dahong Zhang, Haibin Wei","doi":"10.1016/j.jad.2024.11.010","DOIUrl":"https://doi.org/10.1016/j.jad.2024.11.010","url":null,"abstract":"<p><strong>Background: </strong>The oxidative balance score (OBS) serves as an indicator of systemic oxidative stress status, where a higher OBS indicates significant exposure to antioxidants through dietary and lifestyle choices. Studies exploring the relationship between OBS and suicidal ideation are limited. Therefore, this study aimed to examine the association between OBS and suicidal ideation.</p><p><strong>Methods: </strong>This cross-sectional study selected 28,598 individuals aged ≥20 years from the 2005-2018 National Health and Nutrition Examination Survey dataset. The OBS was determined using 16 dietary components and 4 lifestyle components. Item 9 of the Patient Health Questionnaire-9 was used to evaluate suicidal ideation. The association between suicidal ideation and OBS, dietary OBS, and lifestyle OBS was examined using weighted logistic regression and restricted cubic spline. The subgroup analyses and interaction tests were further conducted to assess the robustness of these associations across different populations.</p><p><strong>Results: </strong>The prevalence of suicidal ideation was 3.35 %. OBS, dietary OBS, and lifestyle OBS were substantially and inversely linked with suicidal ideation in Models 1, 2, and 3 (P < 0.05). The odds ratio for the highest quartile of these variables and suicidal ideation in Model 3 was 0.44 [95 % confidence interval (CI): 0.30-0.65], 0.54 (95 % CI: 0.37-0.78), and 0.50 (95 % CI, 0.34-0.74), respectively, compared with the lowest quartile. The subgroup analyses revealed consistent connections between the three oxidative stress indices and suicidal ideation. The lifestyle OBS was negatively correlated with suicidal ideation, especially in women (P for interaction <0.05).</p><p><strong>Conclusions: </strong>The dietary and lifestyle OBSs may influence suicidal ideation by modulating oxidative balance. An antioxidant diet and lifestyle are crucial in mitigating suicidal ideation. These findings suggest a potential sex-specific suicide ideation risk, which significantly correlates with suicidal ideation in women but not in men.</p>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathways linking loneliness and depressive symptoms among Chinese adolescents: The mediating role of sleep disturbance.","authors":"Huiyu Cheng, Wanting Hu, Shengyu Luo, Xiangyu Feng, Zijie Chen, Xiangyue Yu, Huijun Li, Xiuqiong Feng, Weiqing Chen, Vivian Yawei Guo","doi":"10.1016/j.jad.2024.11.006","DOIUrl":"https://doi.org/10.1016/j.jad.2024.11.006","url":null,"abstract":"<p><strong>Background: </strong>Despite growing evidence linking loneliness and depressive symptoms, the underlying pathways remain unclear. This study aims to assess the impact of loneliness on depressive symptoms among Chinese adolescents and investigate the potential mediating role of sleep disturbance.</p><p><strong>Methods: </strong>A cross-sectional study was conducted between November and December 2021. Loneliness, depressive symptoms, and sleep disturbance were assessed using the UCLA Loneliness Scale, the 9-item Patient Health Questionnaire, and the Pittsburgh Sleep Quality Index questionnaire, respectively. Baron and Kenny's causal steps method and the Karlson-Holm-Breen method were applied to explore the mediating role of sleep disturbance. Subgroup analysis by gender was also conducted.</p><p><strong>Results: </strong>A total of 6838 adolescents were included, with 52.2 % boys and a mean age of 14.5 (SD = 1.6) years. Approximately 15.8 % of the adolescents reported depressive symptoms. Loneliness was positively associated with depressive symptoms after controlling for covariates (OR = 1.34, 95%CI = 1.31-1.36). After incorporating sleep disturbance into the model, the association was still significant (OR = 1.28, 95%CI = 1.25-1.31). Sleep disturbance partially mediated this association, contributing to 18.89 % of the total effects. The associations and mediation effects were consistent across both genders, with no moderating effect of gender observed.</p><p><strong>Limitations: </strong>The cross-sectional design limits the ability to establish causality.</p><p><strong>Conclusion: </strong>Loneliness was significantly associated with depressive symptoms in Chinese adolescents and this association was partially mediated by sleep disturbance. Interventions aimed at reducing loneliness and improving sleep quality may help lower the risk of depressive symptoms in Chinese adolescents, regardless of genders. Nevertheless, further randomized controlled trials are needed to confirm these findings.</p>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Joint effect of polysocial risk score, lifestyle and genetic susceptibility with the risk of dementia: A prospective cohort study.","authors":"Lichao Yang, Ziqing Sun, Qida He, Maosheng Zhu, Mengtong Sun, Hanqing Zhao, Yu Wang, Jianing Li, Yujie Shi, Zexin Lou, Boyan Liu, Miao Jiang, Yueping Shen","doi":"10.1016/j.jad.2024.11.005","DOIUrl":"https://doi.org/10.1016/j.jad.2024.11.005","url":null,"abstract":"<p><strong>Objectives: </strong>The comprehensive impact of polysocial risk score (PsRS)-encompassing multiple social determinants of health (SDoHs) with genetic and lifestyle factors on dementia incidence remains to be elucidated.</p><p><strong>Study design: </strong>This study aimed to clear the associations between PsRS and dementia incidence and evaluated how genetic and lifestyle factors modified these associations in the UK Biobank cohort.</p><p><strong>Methods: </strong>The detailed prospective study involved over 500,000 participants when recruited in 2006-2010. The PsRS was calculated by 12 SDoHs across psychosocial factors, socioeconomic status, and neighborhood and living environment. A healthy lifestyle score was constructed from physical activities, alcohol consumption, smoking status, and diet. A genetic risk score (GRS) was computed via genotype data from UK Biobank. The Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association between PsRS, lifestyle factors, GRS and dementia.</p><p><strong>Results: </strong>Results showed the participants with intermediate (HR = 1.32, 95%CI: 1.20-1.45) and high PsRS (HR = 2.10, 95 % CI: 1.91-2.32) were significantly associated with an increased risk of dementia compared with those with a low PsRS. Then, compared with participants with low PsRS and favorable lifestyle/low GRS, high PsRS and unfavorable lifestyle/high GRS had the highest risk of dementia (HR = 3.11,95%CI: 2.63-3.68)/(HR = 3.56, 95%CI: 2.62-4.85).</p><p><strong>Conclusions: </strong>Both high PsRS and GRS were significantly associated with higher dementia risk. A favorable lifestyle could reduce dementia incidence regardless of high PsRS or GRS. Additionally, focusing on the intervention of SDoHs would be positive in preventing dementia.</p>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The relationship between asthma and suggested alcohol dependence and heavy alcohol use in the Cooper Center longitudinal study: The role of depressive symptom severity.","authors":"Catherine D Agarwal, Kerem Shuval, Qing Li, Laura F DeFina, Carolyn E Barlow, David A Khan, E Sherwood Brown","doi":"10.1016/j.jad.2024.11.004","DOIUrl":"https://doi.org/10.1016/j.jad.2024.11.004","url":null,"abstract":"<p><strong>Background: </strong>Asthma appears to be associated with a variety of psychiatric illnesses including depression and alcohol use disorder. The current study examined the relationship between asthma, heavy alcohol intake and suggested alcohol dependence controlling for depressive symptom severity.</p><p><strong>Methods: </strong>Data from 33,253 adult patients at the Cooper Clinic who enrolled in the Cooper Center Longitudinal Study, completed a medical history questionnaire including information on asthma, depressive symptoms and alcohol use were used. The association between lifetime asthma and heavy alcohol intake, while accounting for depressive symptoms (10-item Center for Epidemiological Studies-Depression (CESD)), and demographic variables was examined employing logistic regression with heavy alcohol intake (yes/no) as the outcome. Logistic regression was similarly utilized to examine the association between asthma and suggested alcohol dependence (CAGE scores ≥2: yes/no) among current drinkers (n = 26,028).</p><p><strong>Results: </strong>Multivariable analysis revealed no significant association between asthma and heavy alcohol consumption with or without controlling for CES-D scores. Asthma was, however, associated with higher odds for suggested alcohol dependence (OR 1.18, CI 1.07, 1.31), which was attenuated but still significant when controlling for CES-D scores.</p><p><strong>Conclusion: </strong>Asthma was associated with higher risk for suggested alcohol dependence while current heaving drinking risk was not increased. The suggested drinking findings were slightly less strong when controlling for CES-D scores. The differences between current heavy drinking and CAGE findings might be due to differences in perception of problematic drinking by people with asthma or the timeframe of the assessments (current for drinking, lifetime for CAGE).</p>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction among negative mood, sleep, and diet habits in adolescents with non-suicidal self-injury: A cross-sectional network analysis.","authors":"Yunxiao Liu, Yating Yang, Ruitong Li, Qingqing Shen, Xiaoping Yuan, Jingwen Shang, Huanzhong Liu","doi":"10.1016/j.jad.2024.11.007","DOIUrl":"https://doi.org/10.1016/j.jad.2024.11.007","url":null,"abstract":"<p><strong>Background: </strong>Non-suicidal self-injury (NSSI) is a serious public health problem that can lead to adverse effects such as cognitive impairment, poor interpersonal relationships and violent crime. The progress of preventing and treating NSSI in adolescents depends on other changeable risk factors, such as negative mood, sleep, and diet habits. However, the risk factors for adolescent NSSI remain unclear. Therefore, this study explores the key factors influencing adolescents' non-suicidal self-injurious behavior through the use of network analysis.</p><p><strong>Methods: </strong>The study recruited 4040 middle school students aged 12-18 years old. From November 1st, 2023 to January 1st, 2024, paper questionnaires were utilized to investigate the participants' basic conditions, negative mood, NSSI, sleep conditions, and diet habits. Network analysis was used to explore the interrelationship among risk factors and discover the core factors.</p><p><strong>Results: </strong>In the network structure of adolescents with NSSI behavior, the most correlated nodes were negative emotions (CDI2) and low self-esteem (CDI3). Compared with adolescents without NSSI behavior, adolescents with NSSI behavior showed prominent anxiety symptoms related to injury avoidance (MASC1) and social anxiety (MASC2). Anhedonia (CDI1) was both the central node and the bridge node of the network.</p><p><strong>Limitation: </strong>The cross-sectional design of this study couldn't clarify the causal inference between independent variables and results.</p><p><strong>Conclusion: </strong>Anhedonia is the key factor affecting adolescents' emotion regulation. Furthermore, we hypothesize that adolescent non-suicidal self-injury is an emotional disorder, and anhedonia plays an important role in preventing and intervening in adolescent non-suicidal self-injury behavior.</p>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognition-related connectome gradient dysfunctions of thalamus and basal ganglia in drug-naïve first-episode major depressive disorder.","authors":"Qian Zhang, Aoxiang Zhang, Ziyuan Zhao, Qian Li, Yongbo Hu, Xiaoqi Huang, Weihong Kuang, Youjin Zhao, Qiyong Gong","doi":"10.1016/j.jad.2024.11.003","DOIUrl":"https://doi.org/10.1016/j.jad.2024.11.003","url":null,"abstract":"<p><strong>Background: </strong>Subcortical functional abnormalities are believed to contribute to clinical symptoms and cognitive impairments in major depressive disorder (MDD). By introducing functional gradient mapping, the present study evaluated subcortical gradients in MDD patients and their association with cognitive features.</p><p><strong>Methods: </strong>Organization patterns and between-group differences in the principal subcortical gradient were investigated in 145 never-treated first-episode MDD patients and 145 healthy controls (HCs) across limbic, thalamic, and basal ganglia (BG) systems and their structural and functional subregions. We also assessed the associations between significant gradient alterations and clinical characteristics and neuropsychological functioning.</p><p><strong>Results: </strong>Overall, MDD patients showed a relatively compressed and disturbed gradient organization than HCs, with limbic and BG regions located at the two extreme ends of the principal gradient. Specifically, MDD patients had lower principal gradient values in thalamus and limbic system but higher values in BG than HCs. These gradient alterations, associated with intrinsic Euclidian distance and functional connectivity patterns, manifested as spatial rearrangements of gradient values within each respective subregion. Lower gradient values in thalamic subregion projecting to default mode network were associated with higher principal gradient values in BG subregion projecting to ventral attention network, and these gradient alterations were correlated with poorer episodic memory performance in MDD patients.</p><p><strong>Limitations: </strong>The specific neuropathological mechanisms driving the gradient alterations still require further investigation.</p><p><strong>Conclusions: </strong>Opposing gradient alterations in the thalamic and BG regions synergistically impact episodic memory performance in MDD, revealing an internally differentiated and cognition related pattern of subcortical gradient dysfunction in MDD.</p>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of low-frequency repetitive transcranial magnetic stimulation in adolescents with first-episode major depressive disorder: A randomized, double-blind, sham-controlled pilot trial.","authors":"Li-Mei Gu, Can-Jin Deng, De-Wei Shang, Shan-Qing Huang, Sha Nie, Xin-Hu Yang, Yu-Ping Ning, Xing-Bing Huang, Lloyd Balbuena, Yu-Tao Xiang, Wei Zheng","doi":"10.1016/j.jad.2024.11.001","DOIUrl":"10.1016/j.jad.2024.11.001","url":null,"abstract":"<p><strong>Background: </strong>A few sham-controlled studies have examined the efficacy, safety, and tolerability of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) in adolescents with first-episode major depressive disorder (FE-MDD).</p><p><strong>Methods: </strong>Forty adolescents (aged 13-17 years) with FE-MDD were randomly assigned to receive active rTMS (n = 20) or sham rTMS (n = 20) for 10 sessions over two weeks. The severity of baseline depressive symptoms and their improvement on the day immediately after the second, fourth, sixth, eighth, and tenth sessions were assessed with the 17-item Hamilton Depression Rating Scale (HAMD-17).</p><p><strong>Results: </strong>After completing 10 rTMS treatment sessions, there was no significant difference in antidepressant response (70.0 % vs. 60.0 %, p > 0.05) and antidepressant remission (55.0 % vs. 35.0 %, p > 0.05) between rTMS groups. The linear mixed model analysis did not show a significant group-by-time interaction (F = 1.26; p > 0.05) in the HAMD-17 scores. There was a significant time main effect on the speed of processing (F = 13.61; p < 0.05), but this did not differ significantly between groups (p > 0.05). There were no other main effects and group-by-time interactions in the other MATRICS Consensus Cognitive Battery domains (all p > 0.05). All adverse event categories, such as fatigue and headache, were similar in the two groups (all p > 0.05).</p><p><strong>Conclusions: </strong>In this study that compared a combination of LF-rTMS + medication with sham + medication, LF-rTMS had higher response and remission rates than a sham procedure in adolescents with FE-MDD, but the change was not statistically significant. LF-rTMS is generally safe, with mild adverse effects and no negative impact on neurocognitive performance for adolescents with FE-MDD.</p><p><strong>Registration number: </strong>ChiCTR2000037878.</p>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the genetic underpinnings of neuroticism: A Mendelian randomization study of druggable gene targets.","authors":"Yanggang Hong, Yi Wang, Wanyi Shu","doi":"10.1016/j.jad.2024.11.002","DOIUrl":"10.1016/j.jad.2024.11.002","url":null,"abstract":"<p><strong>Background: </strong>Neuroticism, known for its association with a greater risk of psychiatric conditions such as depression and anxiety, is a critical focus of research.</p><p><strong>Methods: </strong>Cis-expression quantitative trait loci (eQTLs) from 31,684 whole blood samples provided by the eQTLGen Consortium, alongside data from a large neuroticism cohort, were analyzed to identify genes causally linked to neuroticism. To further explore the influence of gene expression changes on neuroticism, colocalization analysis was conducted. Identified drug targets were assessed for potential side effects using a phenome-wide association study (PheWAS). Additionally, we utilized multiple databases to explore the interactions between drugs and genes for drug prediction and assess the current medications for drug repurposing.</p><p><strong>Results: </strong>The analysis involved a total of 4473 druggable genes, with two-sample Mendelian randomization (MR) identifying 186 genes that are causally linked to neuroticism. Colocalization analysis highlighted 11 genes (TLR4, MMRN1, EP300, BRAF, ORM1, ACVR1B, LRRC17, NOS2, ADAMTS6, GPX1, and VCL) with a posterior probability of colocalization (PPH4) >0.8. PheWAS revealed that drugs targeting BRAF, LRRC17, ADAMTS6, and GPX1 were also associated with other traits. Notably, six of these genes (TLR4, MMRN1, BRAF, ACVR1B, NOS2, and GPX1) are already being explored for drug development in psychiatric and other diseases.</p><p><strong>Conclusion: </strong>This study pinpointed six genes as promising therapeutic targets for neuroticism. The repurposing and development of drugs targeting these genes hold potential for managing neuroticism and associated psychiatric disorders.</p>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}