Sex-Specific Cortical Brain Differences in Children at Familial High Risk for Schizophrenia or Bipolar Disorder

Area of Science:

• Neuroscience
• Psychiatry
• Genetics

Background:

• Familial high risk (FHR) is the strongest predictor for schizophrenia (SZ) and bipolar disorder (BP).
• Children at FHR offer a unique window to identify early brain markers of vulnerability.
• Sex-specific brain developmental trajectories necessitate investigation of sex differences in FHR populations.

Purpose of the Study:

• To investigate sex-specific group differences in brain morphometry among 11-12-year-old children at FHR-SZ or FHR-BP.
• To identify potential sex-specific endophenotypic markers of risk for SZ and BP.
• To highlight the importance of considering sex in neurodevelopmental psychiatric research.

Main Methods:

• Included 278 children: 101 FHR-SZ, 64 FHR-BP, and 113 population-based controls (PBCs).
• Structural MRI scans were acquired on 3T scanners.
• Brain volume, cortical volume, surface area, and cortical thickness were extracted using FreeSurfer.

Main Results:

• Significant group-by-sex interactions were found for brain, cortical, and intracranial volume, and surface area.
• Males at FHR-SZ showed smaller brain, cortical, and intracranial volumes and surface area compared to PBC males.
• Females at FHR-BP exhibited larger brain and cortical volumes than PBC females.

Conclusions:

• Children at FHR-SZ and FHR-BP display sex-specific morphometric brain differences.
• These differences may represent sex-specific endophenotypic markers of risk.
• Future longitudinal studies are needed to track neuroanatomical changes and their predictive value.