Recurrent major depression and right hippocampal volume: A bivariate linkage and association study: Recurrent Depression and Right Hippocampal Volume
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Previous work has shown that the hippocampus is smaller in the brains of individuals suffering from major depressive disorder (MDD) than those of healthy controls. Moreover, right hippocampal volume specifically has been found to predict the probability of subsequent depressive episodes. This study explored the utility of right hippocampal volume as an endophenotype of recurrent MDD (rMDD). We observed a significant genetic correlation between the two traits in a large sample of Mexican American individuals from extended pedigrees (ρg = -0.34, p = 0.013). A bivariate linkage scan revealed a significant pleiotropic quantitative trait locus on chromosome 18p11.31-32 (LOD = 3.61). Bivariate association analysis conducted under the linkage peak revealed a variant (rs574972) within an intron of the gene SMCHD1 meeting the corrected significance level (χ(2) = 19.0, p = 7.4 × 10(-5)). Univariate association analyses of each phenotype separately revealed that the same variant was significant for right hippocampal volume alone, and also revealed a suggestively significant variant (rs12455524) within the gene DLGAP1 for rMDD alone. The results implicate right-hemisphere hippocampal volume as a possible endophenotype of rMDD, and in so doing highlight a potential gene of interest for rMDD risk.
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Smaller hippocampal and medial prefrontal cortex volumes are consistently linked to a more recurrent or relapsing course of major depressive disorder.
“they have been consistently associated with markers of a progressive course of MDD characterized by more recurrent episodes/relapses (3,19–25)”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [25]
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Li, J., Lu, C.-L., Cheng, M.-C., Luu, S.-U., Hsu, S.-H., & Chen, C. (2012) · Psychiatry Research · doi:10.1016/j.psychres.2012.08.014 · Cited by 24 · see citing works
The link between stress disorders and autonomic dysfunction in muscular dystrophy
Sabharwal, R. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00025 · Cited by 20 · see citing works
Identification of two novel SMCHD1 sequence variants in families with FSHD-like muscular dystrophy
Winston, J., Duerden, L., Mort, M. E., Frayling, I. M., Rogers, M. T., & Upadhyaya, M. (2014) · European Journal of Human Genetics · doi:10.1038/ejhg.2014.58 · Cited by 20 · see citing works
Synaptic localization of SAPAP1, a synaptic membrane‐associated protein
Yao, I., Iida, J., Nishimura, W., & Hata, Y. (2003) · Genes to Cells · doi:10.1046/j.1365-2443.2003.00622.x · Cited by 20 · see citing works
Exonic resequencing of the DLGAP3 gene as a candidate gene for schizophrenia
Li, J.-M., Lu, C.-L., Cheng, M.-C., Luu, S.-U., Hsu, S.-H., & Chen, C. (2013) · Psychiatry Research · doi:10.1016/j.psychres.2012.12.015 · Cited by 17 · see citing works
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Belleau, E. L., Treadway, M. T., & Pizzagalli, D. A. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.09.031 · Cited by 550 · see citing works
The DLGAP family: neuronal expression, function and role in brain disorders
Rasmussen, A. H., Rasmussen, H. B., & Silahtaroglu, A. (2017) · Molecular Brain · doi:10.1186/s13041-017-0324-9 · Cited by 234 · see citing works
An, T., He, Z.-C., Zhang, X.-Q., Li, J., Chen, A.-L., Tan, F., Chen, H.-D., Lv, B.-H., Lian, J., Gao, S.-H., et al. (2019) · Chinese Medicine · doi:10.1186/s13020-019-0225-1 · Cited by 63 · see citing works
- Authors
- Mathias, S. R., Knowles, E. E. M., Kent, J. W., McKay, D. R., Curran, J. E., de Almeida, M. A. A., Dyer, T. D., Göring, H. H. H., Olvera, R. L., Duggirala, R., Fox, P. T., Almasy, L., Blangero, J., & Glahn, D. C.
- Affiliations
- Yale University (US)
- Texas Biomedical Research Institute (US)
- The University of Texas at San Antonio Health Science Center (US)
- South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio; Texas
- Corresponding author
- Mathias, Samuel R.
- ORCID
- Venue
- Human Brain Mapping
- Publisher
- Wiley
- Published
- 2015-10-20
- Volume
- 37
- Issue
- 1
- Pages
- 191-202
- ISSN
- 1065-9471 (ISSN-L)
- PMC
- PMC4981180
- OpenAlex
- W2137207059
- Cited by
- 28
- References
- 91
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 5 · 2017: 5 · 2016: 2
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Human Brain Mapping (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ScholarWorks @ UTRGV (The University of Texas Rio Grande Valley) (submittedVersion)
- Funders
- National Institute of Mental Health (MH078143, MH078111, MH083824, MH059490)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- recurrent major depressive disorder, endophenotypes, genetic correlation, SMCHD1, DLGAP1, Mexican American families, chromosome 18, hippocampal atrophy
- MeSH terms
- SAP90-PSD95 Associated Proteins, Adolescent, Adult, Aged, Aged, 80 and over, Chromosomal Proteins, Non-Histone, Major Depressive Disorder, Family Health, Female, Hippocampus, Humans, Image Processing, Computer-Assisted, Functional Laterality, Genetic Linkage, Magnetic Resonance Imaging, Male, Mental Status Schedule, Middle Aged, Mutation, Nerve Tissue Proteins, Recurrence, Mexican Americans, Genetic Predisposition to Disease, Young Adult, Endophenotypes
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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