Anatomic abnormalities of hippocampal subfields in never-treated and antipsychotic-treated patients with long-term...

Hippocampal volume deficits have been reported in chronically-treated schizophrenia patients, however, the longer-term effects of antipsychotic medications on hippocampal anatomy are unclear. This case-control study investigated volume differences in hippocampal subfields of never-treated and antipsychotic-treated patients with long-term schizophrenia. High spatial-resolution T1-weighted magnetic resonance images were collected from 29 never-treated and 40 antipsychotic-treated patients with long-term schizophrenia matched for illness duration (all ≥ 5 years), and 40 demographically-matched healthy controls. Hippocampal subfield volumes were measured using FreeSurfer v6.0, compared across groups and between hemispheres, and correlated with clinical features. Volume reductions were found in both patient groups compared to healthy controls in 8 of 26 hippocampal subfields (Cohen's d = 0.46 - 1.17, P = < .001 - .03), and more diffusely and obviously in never-treated than treated patients (Cohen's d = 0.50 - 0.90, P = < .001 - .04). Greater right-than-left volumes were seen in treated patients and healthy controls in 11 of 13 subfields (T = 2.30 - 7.29, P = < .001 - .03), but not in never-treated patients, in whom the volumes were reduced more on the right than on the left. Subfield volumes were negatively correlated with symptom severity and illness duration, and declined with age in never-treated patients. Findings indicate clinically-relevant and age-related volume reductions in hippocampal subfields of never-treated patients with long-term schizophrenia. Broader and greater subfield deficits in never-treated than treated patients, especially in the right hippocampus, suggest that long-term antipsychotic treatment may benefit hippocampal structures over the longer-term course of illness.