The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Stressful Life Events and Previous Episodes in the Etiology of Major Depression in Women: An Evaluation of the “Kindling” Hypothesis
Abstract
OBJECTIVE: Although previous evidence has suggested that the etiologic role of stressful life events in major depression is reduced in recurrent versus first-onset cases, this question deserves reexamination because of potential methodological limitations of the previous studies. METHOD: Members of female-female twin pairs from a population-based registry (N=2,395), who were interviewed four times over a period of 9 years, formed a study group that contained 97,515 person-months and 1,380 onsets of major depression. Discrete-time survival, proportional hazards model, and piece-wise regression analyses were used to examine the interaction between life event exposure and number of previous depressive episodes in the prediction of episodes of major depression. RESULTS: For those with zero to nine previous depressive episodes, the depressogenic effect of stressful life events declined substantially with increasing episode number. However, the association between stressful life events and major depression was not substantially influenced by additional episodes. This pattern of results was robust to the addition of indices of event severity, measures of genetic risk, and restriction to independent stressful life events. The same pattern was also seen upon examining within-person changes in number of episodes. CONCLUSIONS: The association between previous number of depressive episodes and the pathogenic impact of stressful life events on major depression is likely causal and biphasic. Through approximately nine episodes, the association between stressful life event exposure and risk of major depression progressively declines but is largely unchanged with further episodes. These results are consistent with the kindling hypothesis but suggest a threshold at which the mind/brain is no longer additionally sensitized to the depressive state.
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“A more liberal estimate, which includes any type of preonset major life event, raises the risk estimate several fold to an odds ratio of 9.38 for a first lifetime episode of MDD”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Kendler, Thornton, & Gardner, 2000
In the citing paper
“Many of the factors reported on here appear to have robust properties as predictors of relapse or recurrence risk independent of medication discontinuation: number of previous episodes (Berlanga et al. 1999; Kendler et al. 2000; Burcusa & Iacono, 2007; Hardeveld et al. 2010), residual symptoms (Hardeveld et al. 2010; Nierenberg et al. 2010) and other factors all robustly increase the risk of rela”
From Predicting relapse after antidepressant withdrawal – a systematic review (2017) · cites this paper as Kendler et al. 2000
In the citing paper
“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 [57]
In the citing paper
“The course of MDD shows a worsening pattern, with each episode occurring sooner, increasing in severity and becoming more resistant to effective treatments.10”
In the citing paper
“These results are consistent with the substantial literature on the “kindling hypothesis” for MD in which, over episodes, MD becomes more autonomous and less associated with prior stressors”
From The development of an environmental risk score using Swedish National Registers and its impact on subsequent episodes of major depression (2025) · cites this paper as Kendler, Thornton, & Gardner, 2000
In the citing paper
“research suggests that in many individuals, depressive episodes show a worsening pattern over the course of repeated episodes, characterised by increased severity, frequency, autonomy (i.e. episodes are less clearly precipitated by psychosocial stress) and lack of responsiveness to initially effective treatments (Kendler 2000; Post 1992).”
From Interventions for preventing relapse and recurrence of a depressive disorder in children and adolescents (2012) · cites this paper as Kendler 2000
In the citing paper
“There is compelling evidence that intervention in this early stage may prevent the development of cognitive factors associated with recurrent episodes (Kendler 2000; Lewinsohn 1999; Ma 2004).”
From Interventions for preventing relapse and recurrence of a depressive disorder in children and adolescents (2012) · cites this paper as Kendler 2000
In the citing paper
“Moreover, there is commonly a dose-response relationship between the number of types of adversity associated and the magnitude of the risk for depression.4-11”
From Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function (2014) · cites this paper as [9]
In the citing paper
“A higher number of previous episodes (Berwian, Walter, Seifritz, & Huys, 2017; Kendler, Thornton, & Gardner, 2000), more residual symptoms (Berwian et al., 2017; Nierenberg et al., 2010), and failure to reach remission after acute antidepressant treatment (APA, 2010; Rush et al., 2006) are associated with a greater risk of relapse”
From Relapse prevention with levomilnacipran ER in adults with major depressive disorder: a multicenter, randomized, double-blind, placebo-controlled study (2019) · cites this paper as Kendler, Thornton, & Gardner, 2000
Citations
Cites
A Coefficient of Agreement for Nominal Scales
Cohen, J. (1960) · Educational and Psychological Measurement · doi:10.1177/001316446002000104 · Cited by 42,398
Applied Linear Statistical Models
Kutner, M., Nachtsheim, C. J., Neter, J., & Li, W. (1997) · Technometrics · doi:10.1080/00401706.1997.10485141 · Cited by 7,186
Social Origins of Depression: A Study of Psychiatric Disorder in Women.
Schnitzer, P. K., Brown, G. W., & Harris, T. (1980) · Contemporary Sociology A Journal of Reviews · doi:10.2307/2065631 · Cited by 3,053
Survival analysis using the SAS system : a practical guide
Allison, P. D. (1995) · Medical Entomology and Zoology · Cited by 2,402
THE EFFECTS OF STRESSFUL LIFE EVENTS ON DEPRESSION
Kessler, R. C. (1997) · Annual Review of Psychology · doi:10.1146/annurev.psych.48.1.191 · Cited by 2,111
Discrete-Time Methods for the Analysis of Event Histories
Allison, P. D. (1982) · Sociological Methodology · doi:10.2307/270718 · Cited by 2,080
Transduction of psychosocial stress into the neurobiology of recurrent affective disorder
(1992) · American Journal of Psychiatry · doi:10.1176/ajp.149.8.999 · Cited by 1,848
Manic-Depressive Insanity and Paranoia.
(1921) · JAMA · doi:10.1001/jama.1921.02630330070026 · Cited by 1,612
Large sample standard errors of kappa and weighted kappa.
Fleiss, J. L., Cohen, J., & Everitt, B. S. (1969) · Psychological Bulletin · doi:10.1037/h0028106 · Cited by 1,536
Stressful life events, genetic liability, and onset of an episode of major depression in women
(1995) · American Journal of Psychiatry · doi:10.1176/ajp.152.6.833 · Cited by 1,063
Self-citationCovariance Analysis of Censored Survival Data Using Log-Linear Analysis Techniques
Laird, N. M., & Olivier, D. (1981) · Journal of the American Statistical Association · doi:10.1080/01621459.1981.10477634 · Cited by 580
The prediction of major depression in women: toward an integrated etiologic model.
(1993) · American Journal of Psychiatry · doi:10.1176/ajp.150.8.1139 · Cited by 554
Self-citationA Population-Based Twin Study of Lifetime Major Depression in Men and Women
Kendler, K. S., & Prescott, C. A. (1999) · Archives of General Psychiatry · doi:10.1001/archpsyc.56.1.39 · Cited by 512
Self-citationSurvival Analysis Using the SAS System
Ziegel, E. R., & Allison, P. D. (1997) · Technometrics · doi:10.2307/1271161 · Cited by 506
Applied Linear Statistical Models (3rd ed.).
Lorenz, F. O., Neter, J., Wasserman, W., & Kutner, M. (1992) · Journal of the American Statistical Association · doi:10.2307/2290239 · Cited by 478
A Population-Based Twin Study of Major Depression in Women
Kendler, K. S. (1992) · Archives of General Psychiatry · doi:10.1001/archpsyc.1992.01820040009001 · Cited by 451
Self-citationKENDLER, K. S., KARKOWSKI, L. M., & PRESCOTT, C. A. (1998) · The Journal of Nervous & Mental Disease · doi:10.1097/00005053-199811000-00001 · Cited by 380
Self-citationA Hospital-Based Twin Register of the Heritability of DSM-IV Unipolar Depression
McGuffin, P. (1996) · Archives of General Psychiatry · doi:10.1001/archpsyc.1996.01830020047006 · Cited by 373
Contribution of life events to causation of psychiatric illness
Paykel, E. S. (1978) · Psychological Medicine · doi:10.1017/s003329170001429x · Cited by 372
The genetics of mood disorders
Tsuang, M. T., & Faraone, S. V. (1990) · DigitalGeorgetown (Georgetown University Library) · Cited by 349
Life-events and psychiatric disorders Part 1: some methodological issues
Brown, G. W., Sklair, F., Harris, T. O., & Birley, J. L. T. (1973) · Psychological Medicine · doi:10.1017/s0033291700046365 · Cited by 343
The Lifetime History of Major Depression in Women: Reliability of Diagnosis and Heritability
Kendler, K. S. (1993) · Archives of General Psychiatry · doi:10.1001/archpsyc.1993.01820230054003 · Cited by 326
Self-citationSocial factors associated with depression: a retrospective community study
Costello, C. G. (1982) · Psychological Medicine · doi:10.1017/s0033291700046663 · Cited by 260
Stability of Psychiatric Diagnoses
Rice, J. P. (1992) · Archives of General Psychiatry · doi:10.1001/archpsyc.1992.01820100068012 · Cited by 253
Long-term Reliability of Diagnosing Lifetime Major Depression in a Community Sample
Bromet, E. J. (1986) · Archives of General Psychiatry · doi:10.1001/archpsyc.1986.01800050033004 · Cited by 242
Segal, Z. V., Williams, J. M., Teasdale, J. D., & Gemar, M. C. (1996) · Psychological Medicine · doi:10.1017/s0033291700034760 · Cited by 235
Life Events and Endogenous Depression: A Puzzle Reexamined
Brown, G. W. (1994) · Archives of General Psychiatry · doi:10.1001/archpsyc.1994.03950070017006 · Cited by 230
Blindness and Reliability in Lifetime Psychiatric Diagnosis
Mazure, C. M. (1979) · Archives of General Psychiatry · doi:10.1001/archpsyc.1979.01780050031002 · Cited by 187
Understanding the Clinical Heterogeneity of Major Depression Using Family Data
Weissman, M. M. (1986) · Archives of General Psychiatry · doi:10.1001/archpsyc.1986.01800050028003 · Cited by 162
Akiskal, H. S., Cassano, G., Musetti, L., Perugi, G., Tundo, A., & Mignani, V. (2010) · Psychopathology · doi:10.1159/000284607 · Cited by 158
Self-report psychiatric symptoms in twins and their nontwin relatives: are twins different?
Kendler, K., Martin, N. G., Heath, A. C., & Eaves, L. (1995) · American journal of medical genetics · doi:10.1002/ajmg.1320600622 · Cited by 158
Self-citationClinical Characteristics of Major Depression That Predict Risk of Depression in Relatives
Kendler, K. S., Gardner, C. O., & Prescott, C. A. (1999) · Archives of General Psychiatry · doi:10.1001/archpsyc.56.4.322 · Cited by 144
Self-citationCassano, G., Akiskal, H. S., Musetti, L., Perugi, G., Soriani, A., & Mignani, V. (2010) · Psychopathology · doi:10.1159/000284608 · Cited by 136
Brown, G. W. (1989) · Cited by 136
Recurrent and Nonrecurrent Depression
Bland, R. C. (1986) · Archives of General Psychiatry · doi:10.1001/archpsyc.1986.01800110071009 · Cited by 128
Misfortune and resilience: a community study of women
Bebbington, P., Sturt, E., Tennant, C., & Hurry, J. (1984) · Psychological Medicine · doi:10.1017/s0033291700003603 · Cited by 118
Life events and the onset of affective disorder A longitudinal general population study
SURTEES, P., MILLER, P., INGHAM, J., KREITMAN, N., RENNIE, D., & SASHIDHARAN, S. (1986) · Journal of Affective Disorders · doi:10.1016/0165-0327(86)90047-9 · Cited by 108
Kendler, K. S., Pedersen, N. L., Farahmand, B. Y., & Persson, P. (1996) · Psychological Medicine · doi:10.1017/s0033291700035856 · Cited by 89
Self-citationFixed-Effects Partial Likelihood for Repeated Events
Allison, P. D. (1996) · Sociological Methods & Research · doi:10.1177/0049124196025002003 · Cited by 76
Perris, H. (1984) · Journal of Affective Disorders · doi:10.1016/0165-0327(84)90061-2 · Cited by 74
Validation of criteria for major depression through controlled family study
Gershon, E. S., Weissman, M. M., Guroff, J. J., Prusoff, B. A., & Leckman, J. F. (1986) · Journal of Affective Disorders · doi:10.1016/0165-0327(86)90018-2 · Cited by 65
Psychosocial factors and episode number in depression
Ezquiaga, E., Gutiérrez, J. L., & López, A. G. (1987) · Journal of Affective Disorders · doi:10.1016/0165-0327(87)90005-x · Cited by 61
Life Events, Depression and Hypothalamic–Pituitary–Adrenal Axis Function
Dolan, R. J., Galloway, S., Fonagy, P., Souza, F. V. A. D., & Wakeling, A. (1985) · The British Journal of Psychiatry · doi:10.1192/bjp.147.4.429 · Cited by 61
The Clinical Characteristics of Major Depression as Indices of the Familial Risk to Illness
Kendler, K. S., Neale, M. C., Kessler, R. C., Heath, A. C., & Eaves, L. J. (1994) · The British Journal of Psychiatry · doi:10.1192/bjp.165.1.66 · Cited by 58
Self-citationLife Events and the Recurrence of Depression
Ghaziuddin, M., Ghaziuddin, N., & Stein, G. S. (1990) · The Canadian Journal of Psychiatry · doi:10.1177/070674379003500307 · Cited by 47
Karkowski, L. M., & Kendler, K. S. (1997) · Psychiatric Genetics · doi:10.1097/00041444-199700740-00004 · Cited by 34
Self-citationKarkowski, L. M., & Kendler, K. S. (1997) · Psychiatric Genetics · doi:10.1097/00041444-199724000-00004 · Cited by 1
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Cytokines sing the blues: inflammation and the pathogenesis of depression
Raison, C. L., Capuron, L., & Miller, A. H. (2006) · Trends in Immunology · doi:10.1016/j.it.2005.11.006 · Cited by 3,009
Hammen, C. (2005) · Annual Review of Clinical Psychology · doi:10.1146/annurev.clinpsy.1.102803.143938 · Cited by 2,979
Slavich, G. M., & Irwin, M. R. (2014) · Psychological Bulletin · doi:10.1037/a0035302 · Cited by 2,206
The Evolution of the Cognitive Model of Depression and Its Neurobiological Correlates
Beck, A. T. (2008) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2008.08050721 · Cited by 1,537
Nanni, V., Uher, R., & Danese, A. (2012) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.11020335 · Cited by 1,480
Metadata
- Authors
- Kendler, K. S., Thornton, L. M., & Gardner, C. O.
- Affiliations
- Virginia Commonwealth University (US)
- Venue
- American Journal of Psychiatry
- Published
- 2000-08-01
- Volume
- 157
- Issue
- 8
- Pages
- 1243-1251
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2150355913
- Cited by
- 721
- References
- 47
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 13 · 2023: 21 · 2022: 27 · 2021: 29 · 2020: 28 · 2019: 27 · 2018: 30 · 2017: 27 · 2016: 46 · 2015: 45 · 2014: 40 · 2013: 33 · 2012: 36
- FWCI
- 11.21
- 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
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Mental Health Research Topics
- Keywords
- major depressive disorder, life events, recurrent depression, women, depressive episodes, etiology of depression, twin pairs, genetic risk, event severity, within-person change
- MeSH terms
- Adult, Depressive Disorder, Diseases in Twins, Female, Humans, Kindling, Neurologic, Life Change Events, Longitudinal Studies, Models, Psychological, Recurrence, Research Design, Risk Factors, Proportional Hazards Models, Odds Ratio, Survival Analysis, Genetic Predisposition to Disease
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