Delineation of Two Genetic Pathways to Major Depression
Open accessAbstract
Background We sought to identify two sets of familial/genetic risk factors for major depression (MD): 1) high familial loading for MD, which we predicted would be most prominent in cases of MD with an early age at onset (AAO), and 2) high familial loading for vascular disease (VD), which should be strongest in MD cases with a late AAO.Methods We examined 4785 twin pairs from the Swedish Twin Registry, assessed at a mean age of 54.0 (SD = 7.4), where both members of the pair were evaluated by interview and at least one member reported a lifetime history of modified DSM-IV MD. Risk for VD was assessed from hospital discharge information and death certificates.Results Using Cox proportional hazard models and controlling for zygosity, age, and sex, early AAO in depressed twins predicted risk for MD in their cotwins, whereas late AAO predicted cotwin risk for VD. Using piecewise regression, the hazard ratio (HR) relating AAO per decade to risk for MD in cotwin was much stronger for AAO from 13-23 years (HR = .62) than for AAO 24-65 years (HR = 0.94). The HR relating AAO of MD in twin and risk for VD in cotwin was twice as strong for AAO from 47-65 years (HR = 1.17) as for AAO 13-46 years (1.08).Conclusions From a familial/genetic perspective, MD is etiologically heterogeneous. Early and late onset MD are indexed, respectively, by the risk for MD and VD in relatives.
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Depression with an early age of onset was associated with a family history of depression, whereas late-onset depression was associated with a family history of vascular disease.
“depression with an early age of onset was associated with a family history of depression, whereas late-onset depression was associated with a family history of vascular disease.”
From Association of depressive disorders, depression characteristics and antidepressant medication with inflammation (2012) · cites this paper as [28]
A distinct etiology in late-onset versus early-onset depression was found by Kendler et al.
“A distinct etiology in late-onset versus early-onset depression was also found by Kendler et al.28”
From Association of depressive disorders, depression characteristics and antidepressant medication with inflammation (2012) · cites this paper as [28]
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- Authors
- Kendler, K. S., Fiske, A., Gardner, C. O., & Gatz, M.
- Affiliations
- West Virginia University (US)
- University of Southern California (US)
- Karolinska Institutet (SE)
- Corresponding author
- Kendler, Kenneth S.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2009-05
- Volume
- 65
- Issue
- 9
- Pages
- 808-811
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC2744314
- OpenAlex
- W2087631857
- Cited by
- 89
- References
- 33
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 6 · 2021: 6 · 2020: 6 · 2019: 6 · 2017: 9 · 2016: 2 · 2015: 5 · 2014: 3 · 2013: 6 · 2012: 9
- FWCI
- 3.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (AG 08724, R01AG008724)
- National Institute of Mental Health (MH-49492, R01MH049492)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Keywords
- major depressive disorder, familial risk, genetic risk factors, age of onset, vascular disease, twin pairs, etiologic heterogeneity, Swedish Twin Registry
- MeSH terms
- Major Depressive Disorder, Diseases in Twins, Female, Humans, Male, Middle Aged, Risk Factors, Vascular Diseases, Proportional Hazards Models, Age of Onset, Genetic Predisposition to Disease
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