Objective: Schizophrenia is a heterogeneous psychiatric disease with a vast array of clinical symptoms. It is thought that this large spectrum of symptoms is associated with different etiological factors and treatment response. Therefore, it is not surprising to come across inconsistent neuroimaging findings in patients, as those findings are reflections of symptoms. To clarify the effect of the disease (e.g., duration of illness) and nuisance (e.g. antipsychotic treatment) factors would help us to interpret the current findings in schizophrenia patients. The aim of our study is to investigate the effects of the disease and disease-related clinical parameters (duration of illness, antipsychotic treatment, number of psychotic episode) on the brain structures.
Methods: Thirty-three schizophrenic patients and 35 age-, gender- and education-matched healthy volunteers participated in our study. Patients and healthy controls were given a questionnaire assessing sociodemographic characteristics. Structured Clinical Interview for DSM IV (SCID-I) was applied to the patients. Lifetime antipsychotic exposure was 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. T-test, Chi-square test and MannWhitney U test for statistical evaluation based on the data characteristics were used. By using 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 was applied. In VBM, p values <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 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 left precentral gyrus and left postcentral gyrus. The lifetime exposure to antipsychotics correlated negatively and positively with gray matter density in, respectively, the left inferior frontal gyrus and the 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 and negatively in the uvula (cerebellum).
Conclusion: Our data suggested that GM deficits in schizophrenic patients are prominent in frontal and temporal areas. Furthermore, illness duration, antipsychotic treatment and number of psychotic episodes were associated with changes in brain GM. Further studies are needed to clarify the increase in the limbic lobe GM density.