Psychiatry Res Neuroimaging. 2026 Apr 24;360:112228. doi: 10.1016/j.pscychresns.2026.112228. Online ahead of print.
ABSTRACT
Neuroimaging studies in familial high-risk (FHR) individuals are vital for identifying vulnerability markers independent of overt illness. However, research on purely non-prodromal FHR cohorts using comparative multimodal approaches remains limited. This study addresses this gap through multimodal MRI analysis-including cortical morphometry, white matter microstructure, tractography, and functional connectivity-in non-prodromal FHR for psychosis (FHR-P, n = 18), bipolar disorder (FHR-BD, n = 19), and healthy controls (HC, n = 25). FHR-BD showed increased right inferior parietal surface area and right middle temporal volume compared to HC. Conversely, FHR-P exhibited reduced right superior frontal cortical thickness compared to FHR-BD and decreased left pallidum volume compared to HC. White matter analysis revealed significantly lower fractional anisotropy in FHR-P compared to both FHR-BD and HC. FHR-BD showed higher axial diffusivity than HC in the forceps minor, uncinate fasciculus, and right-fronto-occipital fasciculus. No significant differences were found in network-based statistics or graph theoretical measures. These findings reveal shared and distinct neurobiological alterations in non-prodromal FHR-P and FHR-BD, suggesting that grey and white matter disruptions constitute endophenotypes even without clinical symptoms. The lack of network-level findings may reflect the modest sample size, requiring further investigation in larger cohorts.
PMID:42070334 | DOI:10.1016/j.pscychresns.2026.112228
