Sex-specific clinical profiles and long-term outcomes in adolescents and young people at clinical high risk for psychosis: Findings from the PARMS program

Males with first episode psychosis (FEP) show poorer premorbid functioning, more severe psychopathology, and lower functional remission than females. Preliminary evidence suggests that even in Clinical High-Risk for Psychosis (CHR-P), males and females differ in clinical and psychosocial profiles. However, further investigations are needed, especially about outcomes and in adolescents. This study aimed to examine sex differences in clinical/functional presentation and longitudinal outcomes between CHR-P men and women assessing the impact of specialized "Early Intervention in Psychosis" (EIP) interventions over a two-year follow-up within an Italian program. 179 CHR-P men and women (90 females, 89 males; aged 12-25 years) were assessed using the Health of the Nation Outcome Scale and the Positive and Negative Syndrome Scale at baseline and annually for two years. Of them, 152 (76 males, 76 females) completed the follow-up. At baseline, males were older, had higher rates of substance use and unemployment, more severe negative symptoms, and poorer insight. They frequently suffered from brief limited, intermittent psychotic symptoms, whereas females predominantly from attenuated psychotic symptoms. Over two years, females showed a significantly higher rate of functional remission. Specialist EIP interventions increased across time and potentially contributed to improve outcomes in both sexes. Sex differences are evident at baseline in CHR-P participants, especially regarding psychopathology and social functioning. Nonetheless, clinical trajectories over time are largely comparable, except for greater functional recovery in females. These findings support the time effects of our early interventions regardless of sex but emphasize to further explore sex-specific pathways in psychosis risk and recovery.