Alterations in hippocampal subfield volumes among schizophrenia patients, their first-degree relatives and healthy subjects

Reduced hippocampal volumes feature prominently in schizophrenia patients (SCZ). Although several studies have investigated hippocampal volume alterations between unaffected first-degree relatives (FR) of SCZ and healthy controls (HC), the results were inconsistent. Furthermore, it remains unclear whether FR have specific alterations in hippocampal subfield volumes. Three-Tesla T1-weighted MP-RAGE brain scans were collected from 347 subjects (138 SCZ, 47 FR and 162 HC) and processed using the hippocampal subfields algorithm in Free Surfer v6.0. We investigated volumetric differences in the twelve hippocampal subfields bilaterally among SCZ, FR and HC. SCZ displayed bilateral reductions in whole hippocampal volume compared with FR and HC. The hippocampal volumes of FR did not differ from those of HC but exceeded those observed in SCZ. We found volumetric differences in specific hippocampal subfields, including the CA1, hippocampal fissure, presubiculum, molecular layer, fimbria and hippocampal-amygdala transitional area, among diagnostic groups. These alterations arose from differences in the hippocampal subfield volumes between SCZ and the other two diagnostic groups. However, right hippocampal fissure volumes linearly increased among the groups. In contrast, no significant volumetric differences were found in other hippocampal subfields between HC and FR. There were no significant intergroup differences in laterality in any hippocampal subfield volumes and no significant correlations between hippocampal subfield volumes and illness duration, psychiatric symptoms, antipsychotics or premorbid IQ in SCZ. Our findings suggest that volumetric alterations in hippocampal subfields (except the hippocampal fissure) in SCZ could be stable phenomena that are present at illness onset and minimally affected by antipsychotics.