Hippocampal volume and hippocampal neuron density, number and size in schizophrenia: a systematic review and meta-analysis of postmortem studies
- 28 July 2020
- journal article
- review article
- Published by Springer Science and Business Media LLC in Molecular Psychiatry
- Vol. 26 (7), 3524-3535
- https://doi.org/10.1038/s41380-020-0853-y
Abstract
Reduced hippocampal volume is a consistent finding in neuroimaging studies of individuals with schizophrenia. While these studies have the advantage of large-sample sizes, they are unable to quantify the cellular basis of structural or functional changes. In contrast, postmortem studies are well suited to explore subfield and cellular alterations, but low sample sizes and subject heterogeneity impede establishment of statistically significant differences. Here we use a meta-analytic approach to synthesize the extant literature of hippocampal subfield volume and cellular composition in schizophrenia patients and healthy control subjects. Following pre-registration (PROSPERO CRD42019138280), PubMed, Web of Science, and PsycINFO were searched using the term: (schizophrenia OR schizoaffective) AND (post-mortem OR postmortem) AND hippocampus. Subjects were adult men and women with schizophrenia or schizoaffective disorder or non-psychiatric control subjects, and key outcomes, stratified by hippocampal hemisphere and subfield, were volume, neuron number, neuron density, and neuron size. A random effects meta-analysis was performed. Thirty-two studies were included (413 patients, 415 controls). In patients, volume and neuron number were significantly reduced in multiple hippocampal subfields in left, but not right hippocampus, whereas neuron density was not significantly different in any hippocampal subfield. Neuron size, averaged bilaterally, was also significantly reduced in all calculated subfields. Heterogeneity was minimal to moderate, with rare evidence of publication bias. Meta-regression of age and illness duration did not explain heterogeneity of total hippocampal volume effect sizes. These results extend neuroimaging findings of smaller hippocampal volume in schizophrenia patients and further our understanding of regional and cellular neuropathology in schizophrenia.Keywords
Funding Information
- U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (K23MH116339, R01MH70560)
- U.S. Department of Health & Human Services | NIH | National Institute of Mental Health
This publication has 88 references indexed in Scilit:
- Brain Volumes in Schizophrenia: A Meta-Analysis in Over 18 000 SubjectsSchizophrenia Bulletin, 2012
- Increased ratio of calcineurin immunoreactive neurons in the caudate nucleus of patients with schizophreniaProgress in Neuro-Psychopharmacology and Biological Psychiatry, 2012
- Asymmetric Development of the Hippocampal Region Is Common: A Fetal MR Imaging StudyAmerican Journal of Neuroradiology, 2011
- Hippocampal interneurons are abnormal in schizophreniaSchizophrenia Research, 2011
- Brain Volume Changes After Withdrawal of Atypical Antipsychotics in Patients With First-Episode SchizophreniaJournal of Clinical Psychopharmacology, 2011
- Increased density of GAD65/67 immunoreactive neurons in the posterior subiculum and parahippocampal gyrus in treated patients with chronic schizophreniaThe World Journal of Biological Psychiatry, 2011
- Are the Dorsal and Ventral Hippocampus Functionally Distinct Structures?Neuron, 2010
- Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophreniaTrends in Neurosciences, 2008
- Quantifying heterogeneity in a meta-analysisStatistics in Medicine, 2002
- Hippocampal neurons in schizophreniaJournal of Neural Transmission, 2002