Neurocognitive deficits and prefrontal cortical atrophy in patients with schizophrenia

Rationale: Cognitive deficits are of particular importance in schizophrenia since they are strongly associated with poor prognosis. We investigated the relationship between prefrontal cortical atrophy as measured by MRI and the neuropsychological performance of participants diagnosed with DSM-IV-TR schizophrenia. Methods: Fourteen unmedicated adult patients and thirteen matched controls were studied. Subjects underwent MRI yielding 1 mm isotropic T1-weighted images. Voxel based morphometry was applied to all images using SPM5. The mean gray level of Brodmann area (BA) 9 was also extracted and evaluated using simple regression along with relative score differences on patients neuropsychological tests compared to controls. Results: Patients exhibited a poorer performance on the Controlled Word Association Task (COWAT), Wisconsin Card Sorting Test (WCST) and Trail Making Test (TMT). Patients also presented a greater level of apathy as indexed by the Apathy Evaluation Scale (AES). There was a significant decrease in gray matter volume in patients with schizophrenia in left supplementary motor area, bilateral superior frontal gyrus, left middle frontal gyrus, right opercular area, left angular gyrus, left superior temporal gyrus and left cerebellar hemisphere. Within the schizophrenia group, decreased BA9 gray matter volume was correlated with poorer performance on the WCST and TMT-B. Conclusion: Prefrontal gray matter abnormalities in schizophrenia patients may be associated with some symptoms including difficulties with set-shifting and decreased mental flexibility. Further studies evaluating prefrontal connectivity may clarify if such impairment results from abnormalities of the frontal area alone, or are a result of altered networks involving the frontal and extra-frontal areas.