A neurodevelopmental signature of parkinsonism in schizophrenia

Abstract

While sensorimotor abnormalities in schizophrenia (SZ) are of increasing scientific interest, little is known about structural changes and their developmental origins that may underlie parkinsonism. This multimodal magnetic resonance imaging (MRI) study examined healthy controls (HC, n = 20) and SZ patients with (SZ-P, n = 38) and without (SZ-nonP, n = 35) parkinsonism, as defined by Simpson-Angus Scale total scores of ≥4 or ≤1, respectively. Using the Computational Anatomy Toolbox (CAT12), voxel- and surface-based morphometry were applied to investigate cortical and subcortical gray matter volume (GMV) and three cortical surface markers of distinct neurodevelopmental origin: cortical thickness (CTh), complexity of cortical folding (CCF) and sulcus depth. In a subgroup of patients (29 SZ-nonP, 25 SZ-P), resting-state fMRI data were also analyzed using a regions-of-interest approach based on fractional amplitude of low frequency fluctuations (fALFF). SZ-P patients showed increased CCF in the left supplementary motor cortex (SMC) and decreased left postcentral sulcus (PCS) depth compared to SZ-nonP patients (p < 0.05, FWE-corrected at cluster level). In SMC, CCF was associated negatively with activity, which also differed significantly between the patient groups and between patients and HC. In regression models, severity of parkinsonism was associated negatively with left middle frontal CCF and left anterior cingulate CTh. These data provide novel insights into altered trajectories of cortical development in SZ patients with parkinsonism. These cortical surface changes involve the sensorimotor system, suggesting abnormal neurodevelopmental processes tightly coupled with cortical activity and subcortical morphology that convey increased risk for sensorimotor abnormalities in SZ.