Voxel Based Morphometric Analysis of Regional Gray Matter Alterations Related with Duration of Illness, Number of Psychotic Episodes, Lifetime Antipsychotics Use in Patient with Schizophrenia

Abstract

Objective: Schizophrenia is known to be quite a heterogeneous disorder in terms of etiological factors, clinical features and, treatment response. Changes in gray matter areas with structural imaging studies seem to be a reflection of this diversity. The relationship of duration of illness, active psychosis periods,
 and antipsychotic treatment with structural changes in the brain has not been clarified yet. The aim of our study is to investigate the effects of the disease and disease-related processes (duration of illness, antipsychotic treatment, number of the psychotic episodes) on the brain structures.
 Material and Methods: Thirty three schizophrenic patients and 35 age, gender and education matched healthy volunteers participated in our study. Life-time antipsychotic exposure determined for the patients and inverted dose/year unit over equivalent chlorpromazine doses. Magnetic resonance images were acquired with a 3 Tesla-powered imaging unit. By using Statistical Parametric Mapping 8, images were compared with voxel-based morphometry (VBM) analysis. Independent samples t-test for statistical evaluation based on the data characteristics were used. By using the general linear model (GLM) age, gender, and total brain volume were included as confounding factors in the analyze matrix in VBM. In GLM, t-test was used to compare two groups and to investigate disease process-related GM changes, multiple regression analysis were applied. In VBM, p values of less than 0.001 and areas with a minimum expected number of voxels per cluster of 50 are required.
 Results: Compared to controls, patients showed decrements in gray matter density in the right middle and inferior temporal gyrus, bilateral middle frontal gyrus, left cingulate gyrus, left precentral gyrus, left supramarginal gyrus. Nevertheless, patients showed increased GM density in the right uncus, left caudate, and left posterior cingulate cortex as compared to controls. In the patient group, duration of illness was negatively associated with GM density in the left precentral gyrus and left postcentral gyrus. The lifetime exposure to antipsychotics correlated negatively and positively with gray matter density in, respectively; left inferior frontal gyrus and right precuneus. The number of psychotic episodes was positively associated with GM density in the left medial frontal gyrus, right precentral gyrus and left paracentral lobule whereas negatively in the uvula (cerebellum).
 Conclusion: It can be said that GM deficits in schizophrenic patients are prominent in frontal and temporal areas. Besides illness duration, antipsychotic treatment, and number of psychotic episodes seem to be associated with changes in brain GM. Further studies are needed to clarify the increase in the limbic lobe GM density.