Predicting bipolar disorder I/II in individuals at clinical high-risk: Results from a systematic review

Introduction: No systematic review has estimated the consistency and the magnitude of the risk of developing bipolar disorder I-II (BD-I/II) in individuals at clinical high risk for bipolar disorder (CHR-BD). Methods: PubMed and Web of Science databases were searched until April 2022 in this pre-registered (PROSPERO CRD42022346515) PRISMA-compliant systematic review to identify longitudinal studies in individuals meeting pre-defined CHR-BD criteria. The risk of bias was assessed using the Newcastle-Ottawa Scale, and results were systematically synthesized around CHR-BD criteria across follow-up periods and different subgroups. Results: Altogether, 13 studies were included reporting on nine prospective independent cohorts (n = 678 individuals at CHR-BD). The mean age of participants was 15.7 years (range 10.1-22.6 years), and 54.2 % were females. The most common CHR-BD subgroup was subthreshold mania (55.5 %), followed by BD-Not Otherwise Specified (BD-NOS: 33.3 %). Development of BD I/II ranged from 7.1 % to 23.4 % after 2 years. Development of BD-I ranged from 3.4 % at 4 years to 23 % at 8 years. Development of BD-II ranged from 10 % at 2 years to 63.8 % at 4 years. The risk of developing BD-I appeared highest in those meeting BD-NOS criteria (23 % at eight years). Predictors of development of BD were identified but remained mostly unreplicated. The quality of the included studies was moderate (NOS = 5.2 ± 1.1). Conclusions: Emerging data from research studies point towards the promising utility of CHR-BD criteria. These studies may pave the way to the next generation of research, implementing detection, prognostication, and preventive interventions in individuals at CHR-BD identified and followed in clinical practice.