Familial high-risk (FHR) for severe mental illness in clinical high-risk for psychosis (CHR-P): a systematic review and meta-analysis.

Preventive interventions for young help-seekers at clinical high risk for psychosis (CHR-P) critically depend on the progressive improvement of risk stratification. However, there is evidence that the transparent reporting of relevant variables plausibly affecting longitudinal outcomes (e.g. pre-assessment pharmacological exposure) remains suboptimal. In this study we focused on familial high-risk (FHR) for severe mental illness in CHR-P studies, as regards reporting habits, prevalence and possible role in the transition to psychosis. We performed a systematic review and meta-analysis on studies published on Medline and the Cochrane Library on CHR-P individuals with possible transition as outcome, and published from inception to March 31, 2024. The literature review identified 93 independent samples. Up to 26% of studies included information on first-degree relatives with psychosis. The estimated proportions of FHR for severe mental illness were 29.9% (95% CI: 28.2%-31.6%) for a broad family history of psychiatric illness, 21.0% (95% CI: 19.7%-22.4%) for a family history of psychosis in first-degree relatives, and 24.6% (95% CI: 21.7%-27.7%) for a family history of psychosis in either first- or second-degree relatives. In the small subgroup of studies reporting this information, a family history of psychosis in a first- or second-degree relative was negatively associated with the risk of transition to psychosis. No other significant associations were found between features of familial high risk (FHR) and transition to psychosis. Overall, FHR for severe mental illness is poorly reported in observational cohorts of CHR-P individuals, although it should be ordinarily screened during assessment according to validated instruments. Several limitations may account for the current lack of evidence, highlighting the need for further empirical investigation.