Abstract
Small hippocampal size, especially in CA1 may be implicated in the pathogenesis and psychopathology of schizophrenia (SCZ). However, does the volume of hippocampal subfields like CA1 in SCZ patients affect response to antipsychotic treatment? In this study, we used risperidone to treat first-episode and drug naïve (FEDN) SCZ patients for 12 weeks, and then explored the relationship between differences in baseline hippocampal subfield volumes, as well as any changes in the volumes of these hippocampal structures during treatment, and improvement in their psychopathological symptoms. By adopting a state-of the-art automated algorithm, the hippocampal subfields were segmented in 43 FEND SCZ inpatients at baseline and in 26 of them after 12 weeks of risperidone monotherapy, as well as in 30 matched healthy controls. We adopted the Positive and Negative Syndrome Scale (PANSS) to assess psychopathological symptoms in 43 SCZ patients at baseline and in 40 of them at post-treatment. Our results showed that before treatment, schizophrenia patients had no significant differences in total or subfield hippocampal volumes compared with healthy volunteers (all p>0.05). However, at baseline smaller volumes of the left CA1, right molecular layer of the dentate, left hippocampal tail and left pre-subiculum were significantly correlated with worse PANSS negative symptom scores, accounting for 41% of its variance. We also found a significant correlation between a larger left CA1 at baseline and a worse PANSS total score and general psychopathology sub-score at post-treatment (both p<0.05). Furthermore, the left CA1 at baseline was significantly smaller in responders, who had >50% improvement in PANSS total score, than in non-responders (p<0.05). Our results suggest that FEDN SCZ patients with smaller left CA1 had greater negative psychotic symptoms at baseline and more of them had a >50% improvement in PANSS total score after 12 weeks of risperidone treatment. Thus, smaller left CA1 volume may be a predicator for improvement in psychotic symptoms of FEDN SCZ patients, but hippocampal volumes overall did not differ in size from normal controls and did not change during treatment.