First- and second-generation antipsychotic drug treatment and subcortical brain morphology in schizophrenia

Antipsychotic medication may influence brain structure, but to what extent effects of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) differ is still not clear. Here we aimed to disentangle the effects of FGA and SGA on variation in volumes of subcortical structures in patients with long-term treated schizophrenia. Magnetic resonance images were obtained from 95 patients with schizophrenia and 106 healthy control subjects. Among the patients, 40 received only FGA and 42 received only SGA. FreeSurfer 5.3.0 was used to obtain volumes of 27 subcortical structures as well as total brain volume and estimated intracranial volume. Findings of reduced total brain volume, enlarged ventricular volume and reduced hippocampal volume bilaterally among patients were replicated, largely independent of medication class. In the basal ganglia, FGA users had larger putamen bilaterally and right caudate volume compared to healthy controls, and the right putamen was significantly larger than among SGA users. FGA and SGA users had similar and larger globus pallidus volumes compared to healthy controls. Post hoc analyses revealed that the difference between FGA and SGA could be attributed to smaller volumes in the clozapine users specifically. We therefore conclude that basal ganglia volume enlargements are not specific to FGA.