Cortical brain changes from early to mid-adolescence in offspring at familial high risk for schizophrenia or bipolar disorder
Year: 2026
Type: preprint
Abstract: Objective: Schizophrenia (SZ) and bipolar disorder (BP) emerge in late adolescence or adulthood. Offspring at familial high risk for SZ (FHR-SZ) or BP (FHR-BP) are more likely to develop psychiatric disorders. Prior work from the Danish High Risk and Resilience (VIA) Study found sex-specific volumetric brain differences in offspring at FHR-SZ and FHR-BP aged 11-12 years. This study builds upon these findings by testing whether they reflect group differences in rate of change or stable group differences from early to mid-adolescence. Methods: This study investigated MRI data from offspring at FHR-SZ, FHR-BP, and population- based controls (PBC) at baseline (11-12 years; n=288) and follow-up (15-16 years; n=249). FreeSurfer longitudinal processing derived total brain volume, cortical measures, and intracranial volume (ICV). Linear mixed-effects models tested group-by-age interactions and sex-specific group effects, as well as associations with psychotic experiences (PE) and lifetime Axis-I mental disorders. Results: The analysis did not detect group-by-age interactions, indicating similar developmental slopes across groups. However, at both time points, males at FHR-SZ demonstrated reduced brain and cortical volumes compared to PBC and FHR-BP males. These effects were attenuated after adjusting for ICV, which was reduced in males at FHR-SZ. The analysis additionally detected volumetric reductions in males with PE, after controlling for risk status. Conclusions: These results extend the previous findings to ages 15-16 years, indicating group differences are stable and persist into mid-adolescence. Associations with ICV suggest early neurodevelopmental effects, and volumetric reductions in males with PE suggest convergent effects with FHR-SZ.
Source: medRxiv
Authors: Adam Kaminski, Vasileios Ioakeimidis, William F.C. Baare, Kit Melissa Larsen, Line Korsgaard Johnsen, Nicoline Hemager, Martin Dietz, Lotte Veddum, Oskar Hougaard Jefsen, Aja Neergaard Greve, Mette Falkenberg Krantz, Maja Gregersen, Andreas Faergemand Laursen, Anette Faurskov Bundgaard, Doris Helena Bjarnadottir Streyma, Sinnika Birkehoej Rohd, Marta Schiavon Krabbe, Merete Birk, Torben E. Lund, Ole Mors, Anne Amalie Elgaard Thorup, Leif Oestergaard, Merete Nordentoft, Hartwig R. Siebner, Kathrine Skak Madsen
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7225755679
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