Neurophysiological correlates of metabolic syndrome and cognitive impairment in schizophrenia: a structural equation modeling approach.

Objective: We aimed to investigate the brain functional substrate underlying relationships between metabolic syndrome (MetS) and cognitive impairment in schizophrenia.

Methods: In this cross-sectional study, we collected socio-demographic, clinical, anthropometric, blood, and cognition data and performed brain 99mTc-ECD-SPECT imaging of cerebral blood flow in patients with schizophrenia. Patients were grouped according to the absence or presence of MetS. Whole-brain perfusion SPECTs were compared at voxel level between these two groups, and voxel-wise interregional correlation was performed to compare functional connectivity (voxel level significance of p<0.005, uncorrected; p<0.05 for the cluster, uncorrected; using SPM8). A structural equation model (SEM) was applied to examine the relationships between brain perfusion, connectivity between brain areas, and cognition.

Results: Of the 55 patients, 17 had MetS. They performed significantly worse than patients without MetS on tests of executive functions (processing speed p=0.005 for TMT-A; and reactive flexibility p=0.014 for TMT-B), attention (D2 attention task p=0.007), and memory (California Verbal Learning Test p=0.039). In comparison to patients without MetS, those with MetS exhibited significant hypoperfusion within the left orbital prefrontal cortex and greater functional connectivity from this left frontal cluster within the left insula and middle/superior frontal gyrus. SEM confirmed the effect on executive functions of brain hypoperfusion and of increased connectivity, suggesting possible compensatory networks in patients with MetS.

Conclusion: Our study identifies the brain functional impact of MetS on cognition, with orbital prefrontal impairment and possible compensatory networks.