Clinical outcomes of youth at familial risk for bipolar disorder: A 2-year longitudinal, observational study

BACKGROUND: Functional status may predict mood outcomes in youth at familial risk for bipolar disorder (BD). This study examined whether baseline functional status of at-risk youth is linked to clinical outcomes over 2-years. METHOD: Aretaeus (named for Aretaeus of Cappadocia) is a multicenter, prospective, observational study. Participants (15-25 years), all offspring of a parent with BD, were stratified by Global Assessment of Function (GAF) score into functionally impaired (GAF ≤ 70; Low-GAF) or not-impaired (GAF > 70; High-GAF) groups. The primary outcome was difference in time spent with clinically significant mood symptoms ([hypo]mania, depression) between groups, assessed using Longitudinal Interval Follow-up Evaluation Psychiatric Status Rating (LIFE-PSR). Outcomes were evaluated at baseline and every 3-months for 24-months. RESULTS: Of 223 eligible participants, 156 (70 %) completed the study. Completion rates were lower in the Low- vs. High-GAF group (60 % vs. 76 %; p = 0.008). Time spent with clinically significant mood symptoms was higher in Low- vs. High-GAF group at baseline (28 vs. 6 weeks, p < 0.0001) and 24-months (30 vs. 11 weeks, p = 0.009). Serious psychiatric adverse events (7.0 % vs. 1.0 %) and psychiatric medication use were more frequent in Low- vs. High-GAF group. BD and new-onset major depressive disorder diagnoses were similar between groups over 24-months. CONCLUSIONS: Baseline Functional impairment in at-risk youth was linked to more time spent with clinically relevant depressive symptoms. Low-GAF participants experienced mood symptoms for a greater period of time than High-GAF participants, suggesting that early functional impairment relates to poorer-clinical course. Assessing psychosocial function in at-risk individuals may help guide future care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03017781.