Bipolar disorder: Trimodal age-at-onset distribution

Objective Bipolar disorder (BD) is a chronic mental health disorder with significant morbidity and mortality. Age at onset (AAO) may be a key variable in delineating more homogeneous subgroups of BD patients. However, no known research has systematically assessed how BD age-at-onset subgroups should be defined. Methods We systematically searched the following databases: Cochrane Central Register of Controlled Trials, PsycINFO, MEDLINE, Embase, CINAHL, Scopus, Proquest Dissertations and Theses, Google Scholar and BIOSIS Previews. Original quantitative English language studies investigating AAO in BD were sought. Results A total of 9454 unique publications were identified. Twenty-one of these were included in data analysis (n = 22981 BD participants). Fourteen of these studies (67%, n = 13626 participants) found a trimodal AAO distribution: early-onset (mu = 17.3, sigma = 1.19, 45% of sample), mid-onset (mu = 26.0, sigma= 1.72, 35%), and late-onset (mu = 41.9, sigma= 6.16, 20%). Five studies (24%, n = 1422 participants) described a bimodal AAO distribution: early-onset (mu = 24.3, sigma = 6.57, 66% of sample) and late-onset (mu = 46.3, sigma = 14.15, 34%). Two studies investigated cohort effects on BD AAO and found that when the sample was not split by cohort, a trimodal AAO was the winning model, but when separated by cohort a bimodal distribution fit the data better. Conclusions We propose that the field conceptualises bipolar disorder age-at-onset subgroups as referring broadly to life stages. Demarcating BD AAO groups can inform treatment and provide a framework for future research to continue to investigate potential mechanisms of disease onset.