SA88. Hippocampal Subfield Volumes in First-Episode Psychosis: Association With Glucose Metabolism

Abstract

Background: It is well documented that the hippocampal volume is reduced in schizophrenia. Latest studies suggest that the reduction is more robust in certain hippocampal subfelds in patients with chronic schizophrenia. It remains unclear whether these differences are already present during frst-episode of psychosis. Furthermore, the clinical correlates of these brain abnormalities have remained elusive. Since impaired glucose tolerance has known detrimental effect on the central nervous system, we tested if glucose metabolism could underlie the changes seen in the hippocampus. Method(s): We recruited 58 frst-episode psychosis (FEP) patients and 54 matched randomly selected general population controls. Patient sample included both non-affective and affective psychoses (DSM-IV). Hippocampal subfeld volumes were measured using a novel segmentation protocol in FreeSurfer6. A general linear model was used to test for group differences in hippocampal subfeld volumes. All tests were corrected for age, sex, body mass index, and total intracranial volume, and test within the FEP group were also corrected for antipsychotic medication. After exclud-ing subjects with diabetes, we tested associations between fasting glucose (<6.2 mmol/l), insulin, HOMA-index, clinical symptoms, and the subfeld volumes. Result(s): We found that several hippocampal subfelds (ROI) were signifcantly smaller in FEP than in controls (ROI x Group P =.010, Partial eta 2.039). In FEP patients particularly molecular layer (P =.001, left beta =-38.95, right beta =-27.81), subiculum (P =.028, left beta =-19.71, right beta =-13.35), CA1 (P =.016, left beta =-29.73, right beta =-28.58) and presubiculum (P =.004, left beta =-14.01, right beta =-13.92) were smaller than in the controls. Blood fasting glucose-dependent group interaction was found between FEP and control group (Group x Glucose P =.038). Glucose correlated positively with hippocampal volumes in the controls but not in the FEP. In FEP group, fasting glucose levels correlated negatively with volumes in right subiculum (P =.033, beta =-25.13), left presubiculum (P =.004, beta =-29.31) and right presubiculum (P =.038, beta =-21.04). Cognitive tests or symptom severity were not associated with the hippocampal subfeld volumes. Conclusion(s): We showed that hippocampal subregions are differently affected already in the frst episode of psychosis. We found that several hip-pocampal subfelds were differently associated with blood glucose levels in FEP and control group. The fndings do not provide evidence for causal relationships but suggest that hippocampal subregions are differently involved in the regulation of glucose metabolism in FEP and control group. The results suggest FEP patients are susceptible to the negative effects of impaired glucose metabolism.