Gray matter in first-episode schizophrenia before and after antipsychotic drug treatment. Anatomical likelihood estimation meta-analyses with sample size weighting

Abstract

Background: Cerebral morphological abnormalities in schizophrenia may be modulated by treatment, chronicity, and duration of illness. Comparing brain imaging studies of individuals with first-episode schizophrenia and neuroleptic naive (NN-FES) with that of their neuroleptic-treated counterparts (NT-FES) can help to dissect out the effect of these potential confounders.

Methods: We used the anatomical likelihood estimation method to compare voxel-based morphometric studies of NN-FES (n = 162 patients) and NT-FES (n = 336 patients) studies. The analysis included a sample size weighting step based on the Liptak-Stouffer method to reflect the greater power of larger studies.

Results: Patient samples were matched for age, gender, and duration of illness. An extensive network of gray matter deficits in frontal, temporal, insular, striatal, posterior cingulate, and cerebellar regions was detected in the NN-FES samples as compared with healthy controls. Major deficits were detected in the frontal, superior temporal, insular, and parahippocampal regions for the NT-FES group compared with the NN-FES group. In addition, the NT-FES group showed minor deficits in the caudate, cingulate, and inferior temporal regions compared with the NN-FES group. There were no regions with gray matter volumetric excess in the NT-FES group.

Conclusion: Frontal, striato-limbic, and temporal morphological abnormalities are present in the early stage of schizophrenia and are unrelated to the effects of neuroleptic treatment, chronicity, and duration of illness. There may be dynamic effects of treatment on striato-limbic and temporal, but not frontal, regional gray matter volumes of the brain.

Fig. 1.

Gray Matter Deficits in Neuroleptic-Naive and Neuroleptic-Treated FES Compared With Healthy Controls With ALEn. Significant clusters were thresholded with a false discovery rate P<.05 and a cluster extent of 150 voxels. The left side (L) of each axial section represents the left side of the brain. FES, first-episode schizophrenia; ALEn, anatomical likelihood estimation weighted by number of subjects.

Fig. 2.

Gray Matter Deficits in Neuroleptic-Treated FES Compared With Neuroleptic-Naive FES by Subtraction Analysis with ALEn. Significant clusters were thresholded with a false discovery rate P < .05 and a cluster extent of 150 voxels. The left side (L) of each axial section represents the left side of the brain. FES, first-episode schizophrenia; ALEn, anatomical likelihood estimation weighted by number of subjects.