Hippocampal CA1 deformity is related to symptom severity and antipsychotic dosage in schizophrenia

Abstract

Abnormalities of the hippocampus are intricately involved in the pathophysiology of schizophrenia. Hippocampal volume decrease is present at disease onset and has mainly been observed in the anterior and posterior part of the hippocampus. Nevertheless, an association between regionally specific hippocampal shape deformities putatively affecting a pathophysiologically crucial region, i.e. cornu ammonis field 1 (CA1), and symptomatology as well as required maintenance medication has not been observed. The aim of this study was to characterize the relationship between CA1-specific hippocampal surface deformations and symptom severity. Furthermore, we aimed to explore whether such specific morphological hippocampus abnormalities statistically predict the maintenance dosage of antipsychotic medication. Hippocampal shape and volume were determined by manual segmentation of high resolution, whole brain, three-dimensional structural magnetic resonance imaging scans. Associations between hippocampal volume, specific shape deformities in CA1, and positive and negative symptoms were assessed in 32 patients with schizophrenia and compared with 34 healthy control subjects. In addition to volume reductions of the left hippocampus, patients with schizophrenia displayed specific shape deformities in the left anterior and posterior CA1 subfield. Overall, the severity of positive symptoms was closely associated to these morphological deformities, specifically delusions and hallucinations. In addition, CA1 deformity was linked to the required antipsychotic dosage. Findings were replicated in a second, independent sample. Hippocampal CA1 deformity, possibly reflecting shrinkage, might result from a specific hyperactivity, leading to a circumscribed volume loss. Owing to its physiological function, deficits in CA1 may be directly involved in the pathogenesis of hallucinations and delusions, core symptoms in schizophrenia.