Exploring sex-specific symptom trajectories in psychosis following metacognitive training (MCT): Evidence from a large-scale retrospective harmonized database

Sex-related differences in the clinical presentation and course of schizophrenia spectrum disorders are increasingly recognized, yet it remains unclear whether biological sex moderates response to psychological interventions. Metacognitive Training for psychosis is an evidence-based psychological intervention targeting cognitive biases associated with psychotic symptoms, but evidence regarding sex-specific treatment effects remain limited. The present study examined whether biological sex influences symptom trajectories following Metacognitive Training in individuals with schizophrenia spectrum disorders. We analyzed harmonized retrospective data from an international consortium (PERMEPSY) including participants who received Metacognitive Training for psychosis in routine clinical or research settings. The sample comprised 573 participants diagnosed with schizophrenia spectrum disorders across different stages of illness. Control group data was not available due to the retrospective nature of the data and a lack of a standardised control group among included datasets. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale, including positive, negative, general, and total symptom scores. Repeated-measures analyses of variance were conducted to examine the effects of time, sex, and their interaction on symptom change. Across the full sample, Metacognitive Training for psychosis was associated with significant reductions in positive, negative, general, and overall psychotic symptoms. However, no significant moderation of symptom change by biological sex was detected, indicating comparable symptom improvement in males and females across all symptom domains. These findings are consistent with prior evidence supporting MCT as a broadly applicable psychological intervention for psychosis, with comparable symptom changes observed in males and females following treatment. Although sex-related differences in baseline symptom profiles were observed, biological sex did not influence the trajectory of symptom change following treatment. These results support the generalizability of Metacognitive Training and point to the relevance of examining more nuanced sex-related factors in future research.