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

Abstract

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 subfields in patients with chronic schizophrenia. It remains unclear whether these differences are already present during first-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. Methods: We recruited 58 first-episode psychosis (FEP) patients and 54 matched randomly selected general population controls. Patient sample included both non-affective and affective psychoses (DSM-IV). Hippocampal subfield volumes were measured using a novel segmentation protocol in FreeSurfer6. A general linear model was used to test for group differences in hippocampal subfield 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 excluding subjects with diabetes, we tested associations between fasting glucose (<6.2 mmol/l), insulin, HOMA-index, clinical symptoms, and the subfield volumes. Results: We found that several hippocampal subfields (ROI) were significantly smaller in FEP than in controls (ROI × Group P = .010, Partial η2 .039). In FEP patients particularly molecular layer (P = .001, left β = −38.95, right β = −27.81), subiculum (P = .028, left β = −19.71, right β = −13.35), CA1 (P = .016, left β = −29.73, right β = −28.58) and presubiculum (P = .004, left β = −14.01, right β = −13.92) were smaller than in the controls.Blood fasting glucose-dependent group interaction was found between FEP and control group (Group × 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, β = −25.13), left presubiculum (P = .004, β = −29.31) and right presubiculum (P = .038, β = −21.04). Cognitive tests or symptom severity were not associated with the hippocampal subfield volumes. Conclusion: We showed that hippocampal subregions are differently affected already in the first episode of psychosis. We found that several hippocampal subfields were differently associated with blood glucose levels in FEP and control group. The findings 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.