The Effect of Antipsychotic Treatment on Cortical Gray Matter Changes in Schizophrenia: Does the Class Matter? A Meta-analysis and Meta-regression of Longitudinal Magnetic Resonance Imaging Studies

Abstract

Background: Deficits in cortical gray matter (GM) have been found in patients with schizophrenia, with evidence of progression over time. The aim of this study was to determine the role of potential moderators of such changes, in particular of the amount and type of antipsychotic medication intake.

Methods: Longitudinal magnetic resonance imaging studies comparing changes in the volume of cortical GM over time between patients with schizophrenia and healthy control subjects published between January 1, 1983, and March 31, 2014, were analyzed. Hedges' g was calculated for each study and volume changes from baseline to follow-up were analyzed. Meta-regression statistics were applied to investigate the role of potential moderators of the effect sizes.

Results: Eighteen studies involving 1155 patients with schizophrenia and 911 healthy control subjects were included. Over time, patients with schizophrenia showed a significantly higher loss of total cortical GM volume. This was related to cumulative antipsychotic intake during the interval between scans in the whole study sample. Subgroup meta-analyses of studies on patients treated with second-generation antipsychotics and first-generation antipsychotics revealed a different and contrasting moderating role of medication intake on cortical GM changes: more progressive GM loss correlated with higher mean daily antipsychotic intake in patients treated with at least one first-generation antipsychotic and less progressive GM loss with higher mean daily antipsychotic intake in patients treated only with second-generation antipsychotics.

Conclusions: These findings add useful information to the controversial debate on the brain structural effects of antipsychotic medication and may have both clinical relevance and theoretical implications.

Keywords: Cortical gray matter; First generation antipsychotics; Magnetic resonance imaging; Schizophrenia; Second generation antipsychotics; Structural brain changes.