Objective Children at familial high risk for psychosis (FHR) are at substantially increased risk for psychotic disorders and other serious mental illnesses. Identifying risk subgroups within FHR youth may enhance prediction models to identify children at greatest risk for potential intervention. This study investigated psychosis-linked symptoms and structural brain patterns in neurocognitive subgroups among FHR children in the Adolescent Brain Cognitive Development (ABCD) Study using baseline, 2-year, and 4-year follow-up data. Methods Among children with first- and second-degree family history of psychosis, neurocognitive subgroups were defined using NIH Toolbox Cognitive Battery baseline age-corrected total scores: children with low (FHR-LC, 0-33%, n=234), moderate (FHR-MC, 33-66%, n=261), and high (FHR-HC, 66-100%, n=277) cognitive performance. Psychiatric symptoms were assessed using Prodromal Questionnaire-Brief Child Version (PQ-BC) and Childhood Behavior Checklist (CBCL). Regional vulnerability indices (SSD-RVIs), which quantify the similarity of participants' structural brain patterns to the patterns found in adults with schizophrenia spectrum disorders, were calculated using cortical thickness measures following rigorous quality control. Results At baseline, FHR-LC had significantly higher PQ-BC and CBCL scores, and trend-level higher SSD-RVIs compared to FHR-HC. Longitudinally, PQ-BC and CBCL scores decreased with age across all FHR participants, while SSD-RVIs remained stable. No longitudinal cognitive subgroup-by-age interactions were observed, indicating that subgroup differences persisted over time. Conclusion Children at FHR who have concurrent poor cognitive performance exhibit elevated and stable clinical and imaging psychosis risk markers. This suggests that they may represent a risk subgroup with elevated vulnerability, presenting an opportunity for early identification and intervention.

The authors have declared no competing interest.

This work has been supported by the Brain and Behavior Research Foundation Young Investigator Grant (PI: Dr. Turkozer). Additionally, Dr. Turkozer is supported by Harvard Medical School's Dupont Warren and Livingston Fellowships. Dr. Karcher is supported by the National Institute of Mental Health (NIMH) (K23 MH121792). Dr. Clauss is supported by the Maryland Psychiatric Research Center and the Chen Institute Mass General Neuroscience Transformative Scholar Award. Dr. Roffman is supported by NIMH (R01MH124694) and the Mass General Early Brain Development Initiative. Dr. Ongur is supported by NIMH (P50MH115846).

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Data used in the preparation of this article were obtained from the Adolescent Brain Cognitive Development (ABCD) Study (https://abcdstudy.org), held in the NIMH Data Archive (NDA). This is a multisite, longitudinal study designed to recruit more than 10,000 children ages 9-10 and follow them over 10 years into early adulthood. The ABCD Study is supported by the National Institutes of Health and additional federal partners under award numbers U01DA041022, U01DA041025, U01DA041028, U01DA041048, U01DA041089, U01DA041093, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, and U24DA041147. A full list of supporters is available at https://abcdstudy.org/nih-collaborators. A listing of participating sites and a complete listing of the study investigators can be found at https://abcdstudy.org/principal-investigators.html. ABCD consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in analysis or writing of this report. This manuscript reflects the views of the authors and may not reflect the opinions or views of the NIH or ABCD consortium investigators. The ABCD data repository grows and changes over time. The ABCD data used in this report came from https://nda.nih.gov/study.html?id=2313.

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Data used in the preparation of this article were obtained from the Adolescent Brain Cognitive Development (ABCD) Study (https://abcdstudy.org), held in the NIMH Data Archive (NDA). The ABCD data used in this report came from https://nda.nih.gov/study.html?id=2313.