Spatial patterns of individual morphological deformation in schizophrenia: Putative cortical compensatory of unaffected sibling.

Background: Neuroimaging advancements have revealed morphological deformation across various indicators, illuminating the neuropathological origins of schizophrenia. However, consolidating the findings across indicators and assessing regional global deformation at individual-level poses a significant challenge.

Methods: We propose individual morphological deformation index (IMDI) as potential biomarker for schizophrenia leveraging a distance algorithm that incorporates three key indicators (cortical thickness, gyrification, and volume), and applied it for 199 schizophrenia patients, 218 healthy controls, and 47 unaffected siblings. Additionally, we studied the relationships between polygenic risks, symptomology, cognition, social functioning and regional IMDI.

Results: Our findings reveal significantly higher IMDI in specific brain regions (bilateral pars opercularis, lateral orbitofrontal, left superior parietal, right pars orbitalis, and superior temporal) in patients, demonstrating two distinct spatial patterns linked to either isolated indicator reduction or concurrent declines across multiple indicators. Notably, unaffected siblings exhibited higher IMDI than controls, primarily due to cortical volume expansion in the right pars opercularis and superior temporal regions. Patients with higher IMDI had more severe positive symptoms, impaired cognition, reduced social functioning and selfcare ability. Participants with higher polygenic scores showed higher IMDI specifically in left caudal middle frontal regions.

Conclusions: The proposed IMDI biomarker offers an objective, interpretable way to quantify global regional deformation and integrate disparate neuroimaging indicators. Our results indicate that schizophrenia-related cortical deformations encompass sensorimotor, attention, default mode, and frontoparietal networks, exhibiting at least two spatial patterns. Moreover, siblings may exhibit compensation in cortical volume. These insights offer a novel perspective on the neuroanatomical underpinnings of schizophrenia.