Clinical and genetic association of comorbid provisional PMDD and ADHD in female patients with bipolar disorder.

Abstract

Background: Premenstrual dysphoric disorder (PMDD) is a common comorbidity in bipolar disorder (BD), and its association with severe illness course and other comorbidity in BD has been reported.

Aims & objectives: This study aims to investigate clinical characteristics and polygenic risk features of the subgroup with DSM-5-based provisional PMDD in BD. Attention deficit/hyperactivity disorder (ADHD) symptoms and polygenic risk of ADHD were included in the analysis based on recent evidence suggesting the clinical and polygenic association between PMDD and ADHD in non-bipolar populations.

Methods: Female patients with BD were grouped into 'with PMDD' and 'without PMDD.' Clinical characteristics, including other comorbidities, and polygenic risk score (PRS) of major psychiatric disorders were compared between the two groups.

Results: Of the 423 participants, 187 (44.2%) met the DSM-5 criteria for provisional PMDD. Those with PMDD were more likely to have bipolar II disorder, had earlier illness onset, and experienced more frequent major depressive episodes. The prevalence of comorbid bulimia nervosa and ADHD symptom scores was higher in the PMDD group, compared to those without PMDD. In the analysis of genetic correlation using PRS for 5 major psychiatric disorders, the polygenic risk of ADHD was significantly associated with the severity of both PMDD symptom severity and ADHD symptoms.

Discussion & conclusion: Our findings indicate a clinical and genetic association between comorbid PMDD and ADHD symptoms in BD. It is suggested that pleiotropic expression of a common genetic vulnerability might constitute a unique subgroup of BD, characterized by multiple comorbidities with underlying mood dysregulation.