Barr Peter, Neale Zoe, Chatzinakos Chris, Schulman Jessica, Mullins Niamh, Zhang Jian, Chorlian David, Kamarajan Chella, Kinreich Sivan, Pandey Ashwini, Pandey Gayathri, de Viteri Stacey Saenz, Acion Laura, Bauer Lance, Bucholz Kathleen, Chan Grace, Dick Danielle, Edenberg Howard, Foroud Tatiana, Goate Alison, Hesselbrock Victor, Johnson Emma, Kramer John, Lai Dongbing, Plawecki Martin, Salvatore Jessica, Wetherill Leah, Agrawal Arpana, Porjesz Bernice, Meyers Jacquelyn
SUNY Downstate Health Sciences University.
Icahn School of Medicine.
Res Sq. 2024 Feb 9:rs.3.rs-3894892. doi: 10.21203/rs.3.rs-3894892/v1.
Research has identified clinical, genomic, and neurophysiological markers associated with suicide attempts (SA) among individuals with psychiatric illness. However, there is limited research among those with an alcohol use disorder (AUD), despite their disproportionately higher rates of SA. We examined lifetime SA in 4,068 individuals with DSM-IV alcohol dependence from the Collaborative Study on the Genetics of Alcoholism (23% lifetime suicide attempt; 53% female; 17% Admixed African American ancestries; mean age: 38). We 1) conducted a genome-wide association study (GWAS) of SA and performed downstream analyses to determine whether we could identify specific biological pathways of risk, and 2) explored risk in aggregate across other clinical conditions, polygenic scores (PGS) for comorbid psychiatric problems, and neurocognitive functioning between those with AD who have and have not reported a lifetime suicide attempt. The GWAS and downstream analyses did not produce any significant associations. Participants with an AUD who had attempted suicide had greater rates of trauma exposure, major depressive disorder, post-traumatic stress disorder, and other substance use disorders compared to those who had not attempted suicide. Polygenic scores for suicide attempt, depression, and PTSD were associated with reporting a suicide attempt (ORs = 1.22-1.44). Participants who reported a SA also had decreased right hemispheric frontal-parietal theta and decreased interhemispheric temporal-parietal alpha electroencephalogram resting-state coherences relative to those who did not, but differences were small. Overall, individuals with alcohol dependence who report SA appear to experience a variety of severe comorbidities and elevated polygenic risk for SA. Our results demonstrate the need to further investigate suicide attempts in the presence of substance use disorders.
研究已确定了与精神疾病患者自杀未遂(SA)相关的临床、基因组和神经生理学标志物。然而,对于患有酒精使用障碍(AUD)的人群,尽管他们的自杀未遂率高得不成比例,但相关研究却很有限。我们对来自酒精中毒遗传学合作研究的4068名患有DSM-IV酒精依赖的个体进行了终生自杀未遂情况调查(23%有终生自杀未遂经历;53%为女性;17%有非裔美国人混合血统;平均年龄:38岁)。我们1)开展了自杀未遂的全基因组关联研究(GWAS),并进行了下游分析,以确定是否能识别出特定的风险生物学途径,以及2)探讨了在其他临床状况、共病精神问题的多基因评分(PGS)以及报告有或没有终生自杀未遂经历的酒精依赖者之间的神经认知功能等方面的总体风险。GWAS及下游分析未产生任何显著关联。与未尝试自杀的酒精使用障碍患者相比,曾尝试自杀的患者有更高的创伤暴露率、重度抑郁症、创伤后应激障碍及其他物质使用障碍发生率。自杀未遂、抑郁症和创伤后应激障碍的多基因评分与报告自杀未遂相关(比值比=1.22 - 1.44)。与未报告自杀未遂的参与者相比,报告有自杀未遂经历的参与者右半球额顶叶θ波减少,半球间颞顶叶α波静息态相干性降低,但差异较小。总体而言,报告有自杀未遂经历的酒精依赖个体似乎经历了各种严重的共病情况,且自杀未遂的多基因风险升高。我们的结果表明,需要在存在物质使用障碍的情况下进一步研究自杀未遂情况。