Psychosis-linked Symptoms and Structural Brain Patterns in Cognitive Subgroups among Familial High-Risk Children in the ABCD Study

Halide Bilge Türközer; Nicole R. Karcher; Jacqueline Clauss; Merete Nordentoft; Kathryn E. Lewandowski; Joshua L. Roffman; Dost Öngür

doi:10.1101/2025.01.31.25321486

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Psychosis-linked Symptoms and Structural Brain Patterns in Cognitive Subgroups among Familial High-Risk Children in the ABCD Study

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Psychosis-linked Symptoms and Structural Brain Patterns in Cognitive Subgroups among Familial High-Risk Children in the ABCD Study

Halide Bilge Türközer, Nicole R. Karcher, Jacqueline Clauss, Merete Nordentoft, Kathryn E. Lewandowski, Joshua L. Roffman and Dost Öngür

medRxiv

Cold Spring Harbor Laboratory Press, 1.1

02/02/2025

DOI: 10.1101/2025.01.31.25321486

PMCID: PMC11838667

PMID: 39974081

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https://doi.org/10.1101/2025.01.31.25321486View

Preprint (Author's original) This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

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. 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. 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. 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.

Psychiatry and Clinical Psychology

Details

Title: Subtitle: Psychosis-linked Symptoms and Structural Brain Patterns in Cognitive Subgroups among Familial High-Risk Children in the ABCD Study
Creators: Halide Bilge Türközer - Harvard University
Nicole R. Karcher - Department of Psychiatry, Washington University School of Medicine
Jacqueline Clauss - University of Maryland, Baltimore
Merete Nordentoft - University of Copenhagen
Kathryn E. Lewandowski - Harvard University
Joshua L. Roffman - Harvard University
Dost Öngür - Harvard University
Resource Type: Preprint
Publication Details: medRxiv
Edition: 1.1
DOI: 10.1101/2025.01.31.25321486
PMID: 39974081
PMCID: PMC11838667
Publisher: Cold Spring Harbor Laboratory Press
Number of pages: 23
Language: English
Date posted: 02/02/2025
Academic Unit: Psychiatry
Record Identifier: 9985223616302771

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