Common and disorder-specific cortical thickness alterations in internalizing, externalizing and thought disorders during early adolescence: an Adolescent Brain and Cognitive Development study.

Background: A growing body of neuroimaging studies has reported common neural abnormalities among mental disorders in adults. However, it is unclear whether the distinct disorder-specific mechanisms operate during adolescence despite the overlap among disorders.
Methods: We studied a large cohort of more than 11 000 preadolescent (age 9-10 yr) children from the Adolescent Brain and Cognitive Development cohort. We adopted a regrouping approach to compare cortical thickness (CT) alterations and longitudinal changes between healthy controls ( n = 4041) and externalizing ( n = 1182), internalizing ( n = 1959) and thought disorder ( n = 347) groups. Genome-wide association study (GWAS) was performed on regional CT across 4468 unrelated European youth.
Results: Youth with externalizing or internalizing disorders exhibited increased regional CT compared with controls. Externalizing ( p = 8 × 10 ^-4 , Cohen d = 0.10) and internalizing disorders ( p = 2 × 10 ^-3 , Cohen d = 0.08) shared thicker CT in the left pars opercularis. The somatosensory and the primary auditory cortex were uniquely affected in externalizing disorders, whereas the primary motor cortex and higher-order visual association areas were uniquely affected in internalizing disorders. Only youth with externalizing disorders showed decelerated cortical thinning from age 10-12 years. The GWAS found 59 genome-wide significant associated genetic variants across these regions. Cortical thickness in common regions was associated with glutamatergic neurons, while internalizing-specific regional CT was associated with astrocytes, oligodendrocyte progenitor cells and GABAergic neurons.
Limitations: The sample size of the GWAS was relatively small.
Conclusion: Our study provides strong evidence for the presence of specificity in CT, developmental trajectories and underlying genetic underpinnings among externalizing and internalizing disorders during early adolescence. Our results support the neurobiological validity of the regrouping approach that could supplement the use of a dimensional approach in future clinical practice.
Competing Interests: Competing interests: B.J. Sahakian reports grants from Lundbeck Foundation and Leverhulme Trust; royalties from PopReach; consulting fees from Cambridge Cognition; and honoraria from the Alberta Psychiatric Association. She is a member of the Human Brain Project Science and Infrastructure Advisory Board, the academic representative for the National Institute for Health and Care Excellence guidelines on harmful gambling, and a member of the EBRAINS Science and Technology Committee. T.W. Robbins reports consultancies with Cambridge Cognition, Arcadia, Greenfield Bioventures, Heptares, Takeda, Lundbeck, Merck, Sharp and Dohme; and royalties from Cambridge Cognition. Research Grants with Shionogi and GlaxoSmithKline and editorial honoraria with Springer Nature and Elsevier. L. Palaniyappan reports personal fees from Janssen Canada, Otsuka Canada, SPMM Course Limited UK and the Canadian Psychiatric Association; book royalties from Oxford University Press; and investigator-initiated educational grants from Janssen Canada, Sunovion and Otsuka Canada outside the submitted work. He is also co-editor-in-chief of JPN; he was not involved in the review or decision to accept this manuscript for publication. None of the above-listed companies or funding agencies had any influence on the content of this article. No other competing interests were declared.
(© 2023 CMA Impact Inc. or its licensors.)