Lifespan brain structural variation reveals shared organization across mental health conditions

This study highlights that structural brain deviations in various mental health conditions may follow a shared organizational pattern, but individual variability remains significant.

Summary and findings

This study examined brain structural variations in individuals with neurodevelopmental and psychiatric conditions compared to reference participants. A total of 10,135 individuals with various disorders and 11,998 reference participants were analyzed. The findings suggest that structural deviations in the brain are organized along specific axes that reflect connectome organization and vary across diagnoses.

Abstract

Elucidating the neurobiological basis of neurodevelopmental and psychiatric conditions (NDPCs) remains challenging because brain alterations vary within diagnoses and overlap across them. Whether diverse alterations follow a systematic organization that may reflect shared vulnerabilities remains unknown. Here, we assembled 10,135 individuals with schizophrenia, autism, bipolar, obsessive-compulsive, generalized anxiety, and major depressive disorders, and 11,998 reference participants across six continents through the ENIGMA consortium. Using normative modeling, we quantified individual deviations in cortical thickness, surface area, and subcortical volumes relative to lifespan reference trajectories (5 to 80 years). We show that structural deviations converged along cortical axes reflecting connectome organization, maturation, and cytoarchitectonic diversity. These axes mirrored typical population variation, but their expression differed across diagnoses and partly scaled with symptom severity. Even rare and highly individualized extreme deviations followed this organization, concentrating in densely connected regions. Finally, brain structural deviations overlapped substantially across diagnoses, while differences between them increased toward the association cortex. Together, we provide large-scale evidence that structural deviations across NDPCs are systematically constrained by the brain’s intrinsic architecture. This shared organization provides a framework for reconciling individual variability with transdiagnostic similarities and motivates an integrative, systems-level understanding of mental health.

Limitations

Not reported in abstract.

Elsewhere in the PT-141 (Bremelanotide) corpus