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Cerebral cortical alterations in adolescent early-onset psychosis: a surface-based morphometry mega-analysis
Stener Nerland1,2, Claudia Barth3,4,5, Kjetil Nordbø Jørgensen6,7
1Division of Mental Health and Substance Abuse, Diakonhjemmet Hospital, Oslo, Norway. stener.nerland@medisin.uio.no.
Molecular Psychiatry
|May 19, 2026
Summary
Adolescents with early-onset psychosis show widespread differences in brain cortical morphology, including reduced thickness, surface area, and volume compared to healthy peers. These findings suggest aberrant neurodevelopment impacts cortical structure in this population.
Area of Science:
- Neuroscience
- Developmental Psychology
- Psychiatry
Background:
- Early-onset psychosis (EOP) brain morphology is understudied due to low incidence and recruitment challenges.
- Understanding EOP's neurobiological underpinnings is crucial for early intervention.
Purpose of the Study:
- To investigate cortical brain morphology differences in adolescents with EOP compared to healthy controls.
- To explore associations between cortical alterations and clinical factors in EOP.
Main Methods:
- Pooled T1-weighted MRI data from 387 adolescents with EOP and 338 healthy controls across nine international research sites.
- Harmonized processing protocols to extract cortical thickness, surface area, volume, and Local Gyrification Index (LGI) from 34 bilateral regions.
- Univariate regression analyses and diagnostic subgroup analyses were performed.
Main Results:
- Adolescents with EOP exhibited significantly lower bilateral cortical thickness, surface area, volume, and LGI compared to controls.
- Early-onset schizophrenia subgroup showed more pronounced differences in area, volume, and LGI.
- Cortical thickness alterations in EOP mirrored adult schizophrenia and bipolar disorder findings, but surface area alterations were more pronounced in EOP.
Conclusions:
- Widespread cortical alterations are present in adolescents with psychotic disorders, indicating aberrant neurodevelopment.
- Findings highlight significant differences in cortical morphology in EOP, particularly in surface area.
- No associations were found with medication, illness duration, age of onset, or positive symptoms; negative symptoms were linked to left lingual volume, and antidepressant use to right rostral anterior cingulate alterations.
