Clinical, genomic, and neurophysiological correlates of lifetime suicide attempts among individuals with alcohol dependence

Author:

Barr Peter B.ORCID,Neale ZoeORCID,Schulman JessicaORCID,Mullins NiamhORCID,Zhang Jian,Chorlian David B.ORCID,Kamarajan Chella,Kinreich SivanORCID,Pandey Ashwini K.ORCID,Pandey GayathriORCID,Saenz de Viteri StaceyORCID,Acion LauraORCID,Bauer LanceORCID,Bucholz Kathleen K.ORCID,Chan GraceORCID,Chao Michael,Dick Danielle M.ORCID,Edenberg Howard J.ORCID,Foroud TatianaORCID,Goate AlisonORCID,Hesselbrock Victor,Johnson Emma C.ORCID,Kramer John,Lai Dongbing,Plawecki Martin H.ORCID,Salvatore Jessica E.ORCID,Wetherill LeahORCID,Agrawal ArpanaORCID,Porjesz Bernice,Meyers Jacquelyn L.ORCID

Abstract

AbstractResearch 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, 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) explored clinical risk factors associated with SA, 2) conducted a genome-wide association study of SA, 3) examined whether individuals with a SA had elevated polygenic scores for comorbid psychiatric conditions (e.g., alcohol use disorders, lifetime suicide attempt, and depression), and 4) explored differences in electroencephalogram neural functional connectivity between those with and without a SA. One gene-based finding emerged,RFX3(Regulatory Factor X, located on 9p24.2) which had supporting evidence in prior research of SA among individuals with major depression. Only the polygenic score for suicide attempts was associated with reporting a suicide attempt (OR = 1.20, 95% CI = 1.06, 1.37). Lastly, we observed decreased right hemispheric frontal-parietal theta and decreased interhemispheric temporal-parietal alpha electroencephalogram resting-state coherences among those participants who reported a SA 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.

Publisher

Cold Spring Harbor Laboratory

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