CoChat
Sign Up
Cited by 480Genetic Associations and EpidemiologyTreatment of Major DepressionBipolar Disorder and Treatment

Genetic risk, number of previous depressive episodes, and stressful life events in predicting onset of major depression

Kendler, Kenneth S., Thornton, Laura M., Gardner, Charles O.·2001·American Journal of Psychiatry
DOI 10.1176/appi.ajp.158.4.582
Open this paper in CoChat — free account

Abstract

OBJECTIVE: The association between stressful life events and the onset of major depression decreases as the number of previous depressive episodes increases. How do genetic risk factors for major depression impact on this "kindling" phenomenon? In particular, do those at high genetic risk exhibit an increase in the speed of kindling, or are they "prekindled"? METHOD: Using discrete-time survival analysis, the authors examined the interaction between genetic risk, number of previous depressive episodes, and life event exposure in the prediction of episodes of major depression in female-female twin pairs from a population-based registry. The twins were interviewed four times over a 9-year period, producing 92,521 person-months of exposure. RESULTS: The decline in the association between stressful life events and risk for major depression as the number of previous depressive episodes increased was strongest in those at low genetic risk and was weak to absent in those at high genetic risk. In the absence of previous depressive episodes, those at high genetic risk frequently experienced depressive episodes without major environmental stressors. CONCLUSIONS: Genetic risk factors for depression produce a "prekindling" effect rather than increase the speed of kindling. The "kindled" state, wherein depressive episodes occur with little provocation, may be reached by two pathways: many previous depressive episodes, perhaps driven by multiple adversities, and high genetic risk.

Integrity signals

Registry

Crossref · 10.1176/appi.ajp.158.4.582

Cites

21 of 21 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In psychiatry, depression is conceptualized as heterogeneous, multifactorial in causation, and believed to arise from cumulative effects of genetics, adverse events in childhood, and ongoing life stressors.

    “Moreover, in psychiatry depression is conceptualized as heterogeneous, multifactorial in causation, and it is believed to arise from the cumulative effects [56–58] of genetics [59–62], adverse events in childhood [63–66], and ongoing life stressors [67–70].”

    From The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features (2017) · cites this paper as [56]

  • Not all subjects exhibiting increased inflammatory cytokines develop depression; there are vulnerability and resilience factors for cytokine-induced depression.

    “That is, not all subjects exhibiting increased inflammatory cytokines develop depression, and there are numerous vulnerability and resilience factors for cytokine-induced depression (Kendler et al., 2001, Caspi et al., 2003, Duman and Monteggia, 2006, Heim et al., 2008, Lotrich, 2011)”

    From Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications (2013) · cites this paper as Kendler et al., 2001

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Kendler, K. S., Thornton, L. M., & Gardner, C. O.
Affiliations
Virginia Commonwealth University (US)
ORCID
Venue
American Journal of Psychiatry
Publisher
American Psychiatric Association Publishing
Published
2001-04-01
Volume
158
Issue
4
Pages
582-586
ISSN
  • 0002-953X (ISSN-L)
  • 1535-7228
DOI
10.1176/appi.ajp.158.4.582
OpenAlex
W2141307005
Cited by
480
References
20
Citations by year
2026: 3 · 2025: 3 · 2024: 6 · 2023: 1 · 2022: 8 · 2021: 10 · 2020: 7 · 2019: 11 · 2018: 13 · 2017: 48 · 2016: 19 · 2015: 21 · 2014: 19 · 2013: 23 · 2012: 28
FWCI
11.50
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5k05mh001277-05)
  • National Institute on Alcohol Abuse and Alcoholism (R01AA009095, AA-09095)
  • National Institute of Mental Health (MH-01277, R01MH040828, MH 40828)
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, genetic risk, life events, kindling, depression onset, twin pairs, gene-environment interaction, adversity
MeSH terms
Adult, Depressive Disorder, Diseases in Twins, Female, Humans, Kindling, Neurologic, Life Change Events, Psychiatric Status Rating Scales, Recurrence, Registries, Risk Factors, Virginia, Genetic Predisposition to Disease

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 ›

Are you an author, or do you see a problem with this page? Request a review