Multi-environment gene interactions linked to the interplay between polysubstance dependence and suicidality.

Area of Science:

• Psychiatry
• Genetics
• Epidemiology

Background:

• Substance dependence diagnoses (SDs) are established risk factors for suicidality.
• Understanding the interplay between multiple SDs and suicidality is crucial for risk assessment and intervention.

Purpose of the Study:

• To investigate the associations between multiple SDs and various suicidality outcomes.
• To examine the moderating role of genetic background in these associations.

Main Methods:

• Utilized multivariate logistic regression in the Yale-Penn and Army STARRS cohorts.
• Employed structured linear mixed models (StructLMM) to analyze gene-environment interactions in the Yale-Penn cohort.

Main Results:

• In Yale-Penn, lifetime polysubstance dependence showed strong associations with suicidal ideation (OR=6.77) and suicide attempts (OR=3.61).
• In Army STARRS, multiple substance use disorders correlated with increased suicidality (SI OR=2.88, SA OR=3.92).
• Identified significant gene-environment interactions on chromosome 16 for various SDs and suicidal ideation in the Yale-Penn cohort.

Conclusions:

• Comorbidity of multiple SDs is a significant risk factor for suicidality.
• Heritability of suicidality is partially moderated by multivariate gene-environment interactions, suggesting complex genetic influences.