Examining the Moderating Effect of Sex on the Association Between Asthma and Age of Onset in Bipolar Disorder and Schizophrenia.

Background: Asthma, characterized by chronic inflammatory burden, may increase the risk of developing bipolar disorder (BD) and schizophrenia (SZ). Emerging evidence suggests that sex differences can further influence the presentation and course of these conditions.

Objective: To investigate the impact of antecedent asthma diagnosis on the clinical trajectory and age at first episode of mania (FEM) or psychosis (FEP) in individuals and explore sex differences in these associations.

Methods: We identified patients with FEM or FEP within the Rochester Epidemiology Project. Patient demographics, psychiatric antecedents, and prior medical diagnoses were collected. Antecedent asthma diagnoses were extracted using International Classification of Diseases-10 codes via the Rochester Epidemiology Project records-linkage system.

Results: Among 201 patients with FEM (n = 72) or FEP (n = 129), 50 (24.9%) had a prior diagnosis of asthma. There was no difference in asthma prevalence by diagnosis (24.8% BD vs. 25.0% SZ; P = 0.976) or sex (male 22.4% vs. female 31.5%, P = 0.189). Patients with asthma were more likely to have an antecedent psychiatric disorder prior to their first episode (P = 0.008), particularly depressive disorders (P = 0.006). A significant interaction effect was found between sex and asthma on age at first episode, with females with asthma experiencing a significantly earlier illness onset (F [1197] = 8.20, P = 0.006). These findings remained significant in sensitivity analyses excluding patients without at least one year of follow-up prior to the first episode.

Conclusions: Antecedent asthma was prevalent in our cohort and associated with increased psychiatric illness burden and an earlier age of onset in females with BD or SZ. These findings highlight important comorbidity patterns to consider in the antecedent illness trajectory and the need for further research into the inflammatory and sex-specific mechanisms underlying serious mental illness.