Sex differences in alcohol and tobacco use disorders among individuals with panic disorder: A cross-sectional analysis from the genomic psychiatry cohort

Anxiety disorders and substance use frequently co-occur, yet the moderating effects of sex and ancestry on these relationships remain understudied. This investigation examined associations between presumed panic disorder (pPD) and both presumed alcohol use disorder (pAUD) and tobacco use disorder (pTUD) in 10,953 individuals from the Genomic Psychiatry Cohort screened against severe mental illness. Our sample was demographically diverse (56% female; 55% European Ancestry, 45% African Ancestry), allowing robust comparison across these groups. Individuals with pPD ( n = 342) demonstrated significantly higher mean severity scores for both pAUD (1.26 vs. 0.33, p < 0.05) and pTUD (1.65 vs. 0.93, p < 0.05) compared with those without pPD. While female sex was associated with decreased risk for pAUD (B: −0.351, p < 0.05) compared with males, we observed no significant ancestry-based differences in substance use patterns among those with pPD. Two-way interaction analyses revealed that sex significantly moderated the relationship between pPD and pAUD (B: −0.97, p < 0.001), with the association being stronger among males than females. Additionally, comorbid presumed posttraumatic stress disorder was significantly associated with increased risk for both pAUD (B: 0.650, p < 0.05) and pTUD (B: 0.825, p < 0.05) but did not interact significantly with pPD. These findings advance our understanding of how biological sex influences the manifestation of comorbid panic and substance use disorders, offering clinical implications for assessment and treatment strategies that acknowledge sex-specific vulnerability patterns while highlighting the consistent relationship between these conditions across ancestral groups.