: Psychosocial stressors have been suggested to precipitate psychotic episodes in patients with pre-existing psychosis and otherwise healthy subjects. However, such a risk has never been formally investigated in individuals with autism spectrum disorder (ASD). Sixty-nine autistic adolescents hospitalized for psychotic/manic symptoms (PSY) and other mental health issues (NPSY) over a 9-year period were compared with reference to their previous exposure to psychosocial stressors. ASD diagnoses satisfied the International Classification of Diseases (ICD)-10 criteria. Psychotic/manic symptom assessment followed the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS). Psychosocial stressor exposure was collected separately at each admission. Preliminarily, univariate between-group comparisons were conducted. Then, a binomial model was adopted to investigate associations with previous exposure to psychosocial stressors. Results were reported with a change in AIC (ΔAIC). PSY patients presented with higher previous exposure to adverse life events (30.43% vs. 6.52%, OR = 6.079 [1.209, 40.926], p = 0.013) and school/work difficulties (30.43% vs. 8.70%, OR = 4.478 [0.984, 23.846], p = 0.034) than NPSY ones. Admissions for psychotic/manic symptoms occurred more likely in the context of family disturbances (OR = 2.275 [1.045, 5.045], p = 0.030) and adverse life events (OR = 3.489 [1.194, 11.161], p = 0.014). The fitted binomial model was found to be significant compared to the random effects model (ΔAIC = -1.962; χ2 10 = 21.96, p = 0.015), with the risk of presenting psychotic/manic symptoms being increased by family disturbances (z = +4.118) and school/work difficulties (z = +2.455). The results suggest a potential psychosis-inducing effect of psychosocial stressors in ASD, which has clinical and policy implications.
