Cell Density and mRNA Expression of Inhibitory Interneurons in Schizophrenia: A Meta-Analysis

GABAergic inhibitory interneurons have been implicated in the pathophysiology of schizophrenia. However, there is conflicting evidence regarding the nature and extent of the deficits across brain areas and interneuron subtypes. To address these questions, we conducted a systematic search for immunohistochemistry and mRNA studies that examined parvalbumin, somatostatin, calbindin, and calretinin interneuron density or expression in schizophrenia patients and carried out a meta-analysis using a random-effects model. Data from 25 immunohistochemistry studies (311 control participants, 281 individuals with schizophrenia) revealed that the hippocampus and prefrontal cortex were characterized by GABAergic interneuron deficits; parvalbumin and somatostatin interneuron density was reduced in the hippocampus, while data from 21 mRNA studies (546 control participants, 551 individuals with schizophrenia) indicated reduced parvalbumin and somatostatin expression in the prefrontal cortex and hippocampus. Cortical layer-specific analyses demonstrated that parvalbumin interneuron density and somatostatin mRNA expression were most affected in superficial layers 2 and 3 of prefrontal cortex. We also identified significant reductions in subcortical calretinin interneuron density. Together, these data have important implications for the pathophysiology and computational models of circuit deficits in the disorder.