Sex differences in outcomes of an early intervention service for first-episode psychosis

Ilaria Domenicano¹Alice Onofrio^2*Martina Citton¹Ludovica Vecchioni¹Domenico De Donatis¹Raffaella Bertelli³Franca Emanuelli³Luigi Grassi^1,3Maria Ferrara^1,3,4

• ¹Universita degli Studi di Ferrara, Ferrara, Italy
• ²University of Ferrara, Ferrara, Italy
• ³Azienda Unita Sanitaria Locale di Ferrara Dipartimento Assistenziale Integrato Salute Mentale Dipendenze Patologiche, Ferrara, Italy
• ⁴Yale School of Medicine Department of Psychiatry, New Haven, United States

Early intervention services (EIS) for first-episode psychosis (FEP) play a key role in shaping a better disease trajectory for psychosis. Psychotic disorders tend to present sex differences both from an epidemiological and clinical perspective.The aim of this study is to investigate sex-based differences in outcome of patients admitted to EIS , analysing clinical differences and recovery rates during a 24 months long follow-up.A longitudinal cohort study was conducted. Patients were those admitted to the EIS in Ferrara between 2012 and 2025 who met the following criteria: (a) diagnosed with affective or non-affective FEP; (b) not being treated for more than 24 months; (c) absence of intellectual disability; (d) aged between 18 and 35 years; (e) absence of organic psychosis. Socio-demographic and clinical characteristics were collected at program admission. The HoNOS (Health of the Nation Outcome Scale) was administered at baseline and every six months for the 24 months follow-up to compare sex differences in terms of symptoms severity and clinical recovery (HoNOS total score < 8). Outcomes over time were compared between groups using mixed effects models repeated measures analysis of variance. A total of 174 patients were included, most were males (74.1%). At admission, men had significantly higher rates of cannabis use (56.6% vs 22.2%), tobacco use (62% vs 28.9%), and alcohol misuse (51.2% vs 15.5%) (p < 0.001). Men, compared to women, at 6 and 12 months showed significantly lower clinical severity (11.9 vs 14.5, p = 0.03; 9.4 vs 11.9, p = 0.05 respectively), and higher probability of being in recovery at 12 months (p=0.04), indicating a faster clinical improvement. At 24-month, more men than women were Not in Education or Employment (26.3% vs 8%, p = 0.04). Our study highlighted significant sex differences both at admission as well as in outcomes. Men tend to improve more rapidly than women, then reaching a plateau with no substantial differences between sexes at 24 months. Further studies should identify sexspecific outcome predictors that could help in early patients' identification, thus leading to improve clinical trajectories and long-term prognosis.