Journal
MOLECULAR PSYCHIATRY
Volume 22, Issue 1, Pages 142-152Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2016.4
Keywords
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Funding
- National Medical Research Council under the Centre Grant Programme (Institute of Mental Health, Singapore) [NMRC/CG/004/2013]
- National Healthcare Group, Singapore [SIG/05004, SIG/05028]
- Singapore Bioimaging Consortium [RP C-009/2006]
- National Institute of Mental Health [K23MH076054, K23MH084059]
- Howard Hughes Medical Institute Physician Scientist Early Career Award
- Biomedical Research Council, Singapore [BMRC 04/1/36/372]
- Agency for Science, Technology, and Research (A*STAR)
- Duke-NUS Graduate Medical School Signature Research Program - Ministry of Health, Singapore
- Pamlab
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Volume deficits of the hippocampus in schizophrenia have been consistently reported. However, the hippocampus is anatomically heterogeneous; it remains unclear whether certain portions of the hippocampus are affected more than others in schizophrenia. In this study, we aimed to determine whether volume deficits in schizophrenia are confined to specific subfields of the hippocampus and to measure the subfield volume trajectories over the course of the illness. Magnetic resonance imaging scans were obtained from Data set 1: 155 patients with schizophrenia (mean duration of illness of 7 years) and 79 healthy controls, and Data set 2: an independent cohort of 46 schizophrenia patients (mean duration of illness of 18 years) and 46 healthy controls. In addition, follow-up scans were collected for a subset of Data set 1. A novel, automated method based on an atlas constructed from ultra-high resolution, post-mortem hippocampal tissue was used to label seven hippocampal subfields. Significant cross-sectional volume deficits in the CA1, but not of the other subfields, were found in the schizophrenia patients of Data set 1. However, diffuse cross-sectional volume deficits across all subfields were found in the more chronic and ill schizophrenia patients of Data set 2. Consistent with this pattern, the longitudinal analysis of Data set 1 revealed progressive illness-related volume loss (similar to 2-6% per year) that extended beyond CA1 to all of the other subfields. This decline in volume correlated with symptomatic worsening. Overall, these findings provide converging evidence for early atrophy of CA1 in schizophrenia, with extension to other hippocampal subfields and accompanying clinical sequelae over time.
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