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

Abstract

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.

Figure 1

Polygenic Scores for AUD, DEP and SUI across those who have and have not reported a suicide attempt Panel A presents odds ratios (OR) for AUD, DEP, and SUI PGSs from logistic regression models in persons with AD who had and had not attempted suicide. Panel B presents OR from multinomial logistic models (no AD, no suicide attempt as reference group). All models include cohort, sex, PC1-PC3, array, and site as covariates. SEs adjusted for familial clustering using cluster-robust standard errors. AFR = African Ancestries, EUR = European Ancestries, AUD = alcohol use disorder polygenic score, DEP = depression polygenic score, = SUI suicide attempt polygenic score, SA− = no lifetime suicide attempt, AD− = does not meet criteria for alcohol dependence, SA+ = lifetime suicide attempt, AD+ = meets criteria for alcohol dependence.