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<p>Cortical brain morphology in early-onset psychosis (EOP; age of onset &lt;19 years) is poorly understood, partly due to recruitment constraints linked to its low incidence. We pooled T1-weighted magnetic resonance imaging (MRI) data from 387 adolescents with EOP (mean age=16.1 ± 1.5; 49.6% female) and 338 healthy controls (CTR; mean age=15.8 ± 1.9, 54.4% female) from nine research sites worldwide. Using harmonized processing protocols, we extracted cortical brain metrics from 34 bilateral regions. Univariate regression analyses revealed widespread lower bilateral cortical thickness (left/right hemisphere: <i>d</i> = −0.36/−0.31), surface area (left/right: <i>d</i> = −0.42/−0.41), cortical volume (left/right: <i>d</i> = −0.58/−0.56), and Local Gyrification Index (LGI; left/right: <i>d</i> = −0.39/−0.52) in EOP relative to CTR. Diagnostic subgroup analyses showed broader and more pronounced case-control differences in early-onset schizophrenia for area, volume, and LGI. We found no associations with antipsychotic medication use, illness duration, age of onset, or positive symptoms. Negative symptoms were related to smaller left lingual volume (partial <i>r</i> = −0.21; <i>p</i><sub><i>FDR</i></sub> = 0.014) and antidepressant users had smaller area (<i>d</i> = −0.43; <i>p</i><sub><i>FDR</i></sub> = 0.034) and volume (<i>d</i> = −0.50; <i>p</i><sub><i>FDR</i></sub> = 0.003) of the right rostral anterior cingulate compared to non-users. Cortical thickness alterations in EOP showed a similar pattern to those observed in prior studies on adults with schizophrenia (SCZ; <i>r</i> = 0.62) and bipolar disorders (BD; <i>r</i> = 0.61). However, surface area alterations were overall 1.5 times greater for EOP than adult SCZ and 4.6 times greater than adult BD. In the largest study of its kind, we observed a widespread pattern of cortical alterations in adolescents with psychotic disorders, highlighting the potential impact of aberrant neurodevelopment on cortical morphology in this clinical group.</p>

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Cerebral cortical alterations in adolescent early-onset psychosis: a surface-based morphometry mega-analysis

  • 期刊论文

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  • 发表日期：

    2026年5月19日

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  • Stener Nerland,
  • Claudia Barth,
  • Kjetil Nordbø Jørgensen,
  • Laura A. Wortinger,
  • Josefina Castro-Fornieles,
  • Covadonga M. Díaz-Caneja,
  • Joost Janssen,
  • Celso Arango,
  • Gisela Sugranyes,
  • Inmaculada Baeza,
  • Fabrizio Piras,
  • Nerisa Banaj,
  • Federica Piras,
  • Simone Elia,
  • Daniela Vecchio,
  • Mathias Lundberg,
  • Hannes Bohman,
  • Bjørn Rishovd Rund,
  • Elena de la Serna,
  • Adriana Fortea,
  • Christian K. Tamnes,
  • Lars T. Westlye,
  • Runar E. Smelror,
  • Dimitrios Andreou,
  • Erik G. Jönsson,
  • Matthew J. Kempton,
  • Shuqing Si,
  • Marinos Kyriakopoulos,
  • Carrie E. Bearden,
  • Kristen Laulette,
  • Saül Pascual-Diaz,
  • Anne-Kathrin J. Fett,
  • Katherine H. Karlsgodt,
  • Lydia Krabbendam,
  • Peter Kochunov,
  • Sophia I. Thomopoulos,
  • Neda Jahanshad,
  • Anthony James,
  • Sophia Frangou,
  • Anne M. Myhre,
  • Nils Eiel Steen,
  • Ole A. Andreassen,
  • Paul M. Thompson,
  • Ingrid Agartz

摘要

Cortical brain morphology in early-onset psychosis (EOP; age of onset <19 years) is poorly understood, partly due to recruitment constraints linked to its low incidence. We pooled T1-weighted magnetic resonance imaging (MRI) data from 387 adolescents with EOP (mean age=16.1 ± 1.5; 49.6% female) and 338 healthy controls (CTR; mean age=15.8 ± 1.9, 54.4% female) from nine research sites worldwide. Using harmonized processing protocols, we extracted cortical brain metrics from 34 bilateral regions. Univariate regression analyses revealed widespread lower bilateral cortical thickness (left/right hemisphere: d = −0.36/−0.31), surface area (left/right: d = −0.42/−0.41), cortical volume (left/right: d = −0.58/−0.56), and Local Gyrification Index (LGI; left/right: d = −0.39/−0.52) in EOP relative to CTR. Diagnostic subgroup analyses showed broader and more pronounced case-control differences in early-onset schizophrenia for area, volume, and LGI. We found no associations with antipsychotic medication use, illness duration, age of onset, or positive symptoms. Negative symptoms were related to smaller left lingual volume (partial r = −0.21; pFDR = 0.014) and antidepressant users had smaller area (d = −0.43; pFDR = 0.034) and volume (d = −0.50; pFDR = 0.003) of the right rostral anterior cingulate compared to non-users. Cortical thickness alterations in EOP showed a similar pattern to those observed in prior studies on adults with schizophrenia (SCZ; r = 0.62) and bipolar disorders (BD; r = 0.61). However, surface area alterations were overall 1.5 times greater for EOP than adult SCZ and 4.6 times greater than adult BD. In the largest study of its kind, we observed a widespread pattern of cortical alterations in adolescents with psychotic disorders, highlighting the potential impact of aberrant neurodevelopment on cortical morphology in this clinical group.