Pre-onset risk characteristics for mania among young people at clinical high risk for psychosis

Importance: Psychosis and mania share conceptual, genetic, and clinical features, which suggest the possibility that they have common antecedents. Participants identified to be atrisk for psychosis might also be at-risk for mania.

Objective: We aimed to identify the rate and predictors of transition to mania in a cohort of youth at clinical high-risk for psychosis.

Design: Five to 13-year longitudinal follow-up study

Setting: Tertiary mental health service for young people in Melbourne, Australia
Participants: Among a cohort of 416 young people at clinical high-risk for psychosis defined using the Ultra-High-Risk (UHR) criteria, 74.7% were followed up between 5 and 13 years from their baseline assessment.

Exposures: Clinical characteristics and risk factors at baseline included i) the presence of threshold or subthreshold manic and depressive symptoms ii) medications and substance use iii) the severity of depression, anxiety, overall symptomatology, and positive and negative psychotic symptoms, iv) psychosocial functioning and v) family history. Main outcomes and measures: Transition to mania, the outcome of interest, was determined
using either a structured clinical interview, or diagnoses from a state-wide public mental health contact registry. The presence of subthreshold symptoms, syndromes and treatments were established using the Structured Clinical Interview for Diagnosis as well as clinical notes. Family history was established using the Family Interview for Genetic Studies. Severity of depression, anxiety and general psychopathology were determined using Hamilton Depression and Anxiety Rating scales as well as the Brief Psychiatric Rating Scale. Functioning was measured using the Global Assessment of Functioning scale. These
measures were compared between those who transitioned to mania and a subgroup of comparison participants who were individually matched on age, gender and baseline study.

Results: Eighteen participants developed mania (UHR-M, 4.3%). In comparison with participants matched on age, gender and baseline-study who developed neither mania nor psychosis, more UHR-M participants had more subthreshold manic symptoms, more antidepressant use, and had lower psychosocial functioning at baseline.

Conclusions and Relevance: In addition to the UHR criteria, additional features such as subthreshold manic symptoms and antidepressant use may help identify broader at-risk groups that predict the onset of mania in addition to transition to psychosis.