Rethinking childhood-onset schizophrenia: neurodevelopmental comorbidities shape the psychopathological profile

Childhood-onset schizophrenia (COS), defined by the onset of psychotic symptoms before the age of 13 years, is a rare and severe form of schizophrenia. Despite growing interest, little is known about how neurodevelopmental comorbidities shape its clinical presentation. This study aimed to examine whether COS with comorbid neurodevelopmental disorders differs in psychopathological profile from COS with psychiatric comorbidities and from COS without comorbidities.

Sixty-one children diagnosed with COS and evaluated at symptom onset in a specialized early psychosis service were included and classified into three subgroups: COS with neurodevelopmental comorbidities, COS with psychiatric comorbidities, and COS without comorbidities. Psychopathological dimensions were assessed using the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children - Present and Lifetime Version and the Structured Interview for Psychosis-Risk Syndromes and the Scale of Prodromal Symptoms (SIPS/SOPS). Group differences were examined using MANOVA and mixed-design repeated-measures ANOVA, repeated with IQ as a covariate, with False Discovery Rate correction across all SIPS measures. A secondary analysis separated intellectual disability from autism spectrum disorder and/or attention-deficit/hyperactivity disorder.

Children with COS and neurodevelopmental comorbidities showed an earlier age at onset, lower IQ, greater bizarre thinking and less social anhedonia. In contrast, COS with psychiatric comorbidity and COS without comorbidities exhibited largely overlapping profiles, marked by greater severity of negative symptoms and more organized thought processes. Within the neurodevelopmental group, the symptom pattern did not appear to be driven by specific diagnoses.

These preliminary findings are consistent with variation in the configuration of psychopathological features within COS along a continuum, and highlight the relevance of neurodevelopmental trajectories in shaping symptom expression. Accounting for neurodevelopmental comorbidities may be crucial for improving early diagnostic characterization and informing targeted therapeutic strategies in pediatric schizophrenia.