Neuroanatomical correlates of psychiatric manifestations in Wilson disease: the role of age

Objective To investigate gray matter volume (GMV) differences related to psychiatric manifestations in patients with Wilson disease (WD) and to examine the effect of age. Methods In 102 patients with WD, 3.0T T1-weighted MRI scans were analyzed using voxel-based morphometry. Patients were divided into younger (≤30 years) and older (>30 years) groups and were further grouped according to psychiatric manifestations. Patients with a UWDRS psychiatric subscale (UWDRS-PSY) score of 0 were classified as having no psychiatric manifestations, and those with a score >0 were classified as having psychiatric manifestations. Two-way ANCOVA was performed with total intracranial volume, sex, and education as covariates. Cluster-level family-wise error (FWE) correction was applied. Mean GMV values were extracted from significant caudate clusters and correlated with UWDRS-PSY scores as exploratory analyses. Results Significant interactions between age group and psychiatric manifestations were found in the left insula/Rolandic operculum and right inferior temporal gyrus. Lower GMV in these regions was mainly found in younger patients with psychiatric manifestations. A main effect of psychiatric manifestations was found in the bilateral caudate nuclei, with lower GMV in patients with psychiatric manifestations. Lower caudate GMV was also associated with higher UWDRS-PSY scores. Conclusions Psychiatric manifestations in WD are associated with distinct gray matter patterns that vary with age, while bilateral caudate involvement may represent a more consistent structural correlate. These findings highlight the potential importance of considering age when examining the neuroanatomical correlates of psychiatric manifestations in WD.