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Sex Differences in the Pathways to Major Depression: A Study of Opposite-Sex Twin Pairs
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OBJECTIVE: The authors sought to clarify the nature of sex differences in the etiologic pathways to major depression. METHOD: Retrospective and prospective assessments of 20 developmentally organized risk factors and the occurrence of past-year major depression were conducted at two waves of personal interviews at least 12 months apart in 1,057 opposite-sex dizygotic twin pairs from a population-based register. Analyses were conducted by structural modeling, examining within-pair differences. RESULTS: Sixty percent of all paths in the best-fit model exhibited sex differences. Eleven of the 20 risk factors differed across sexes in their impact on liability to major depression. Five had a greater impact in women: parental warmth, neuroticism, divorce, social support, and marital satisfaction. Six had a greater impact in men: childhood sexual abuse, conduct disorder, drug abuse, prior history of major depression, and distal and dependent proximal stressful life events. The life event categories responsible for the stronger effect in males were financial, occupational, and legal in nature. CONCLUSIONS: In a co-twin control design, which matches sisters and brothers on genetic and familial-environmental background, personality and failures in interpersonal relationships played a stronger etiologic role in major depression for women than for men. Externalizing psychopathology, prior depression, and specific "instrumental" classes of acute stressors were more important in the etiologic pathway to major depression for men. The results are consistent with previously proposed typologies of major depression that suggest two subtypes that differ in prevalence in women (deficiencies in caring relationships and interpersonal loss) and men (failures to achieve expected goals, with lowered self-worth).
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“Major depressive disorder was more prevalent among women, possibly related to gender discrimination, 50 differential exposure to childhood or adult adversities 51 such as sexual abuse, 52 differential exposure to a complex host of different developmentally organized risk factors, 53 or biologically different stress responses.54”
From Epidemiology of Adult DSM-5 Major Depressive Disorder and Its Specifiers in the United States (2018) · cites this paper as [52]
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“Although the inflated within-pair estimates in our study are difficult to interpret, findings from some previous genetically informative studies indicate that this association may be at least in part causal.”
From Stressful life events increase the risk of major depressive episodes: A population-based twin study (2023) · cites this paper as Kendler & Gardner, 2014
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“Kendler and Gardner (2014) found that the association between financial and occupational difficulties and depression risk were stronger in male twins discordant for depression compared with female twins.”
From Stressful life events increase the risk of major depressive episodes: A population-based twin study (2023) · cites this paper as Kendler & Gardner, 2014
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Metadata
- Authors
- Kendler, K. S., & Gardner, C. O.
- Affiliations
- Virginia Commonwealth University (US)
- Corresponding author
- Kendler, Kenneth S.
- ORCID
- Kendler, Kenneth S.
- Venue
- American Journal of Psychiatry
- Published
- 2014-04
- Volume
- 171
- Issue
- 4
- Pages
- 426-435
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC3972260
- OpenAlex
- W2155785248
- Cited by
- 307
- References
- 71
- Citations by year
- 2026: 13 · 2025: 14 · 2024: 17 · 2023: 18 · 2022: 33 · 2021: 33 · 2020: 34 · 2019: 30 · 2018: 23 · 2017: 18 · 2016: 27 · 2015: 30 · 2014: 15
- FWCI
- 35.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (MH-49492, R01MH049492)
- National Center for Research Resources (UL1RR031990)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Health Sciences › Medicine › Psychiatry and Mental health › Mental Health Treatment and Access
- Keywords
- major depressive disorder, sex differences, etiology of depression, co-twin control, risk factors, parental warmth, neuroticism, child sexual abuse, conduct disorder, drug abuse, life events, personality, interpersonal relationships, externalizing psychopathology, depression subtypes
- MeSH terms
- Adult, Child, Child Abuse, Sexual, Major Depressive Disorder, Depressive Disorder, Major, Diseases in Twins, Divorce, Female, Humans, Life Change Events, Male, Marriage, Middle Aged, Parent-Child Relations, Personal Satisfaction, Risk Factors, Sex Factors, Social Support, Twins, Dizygotic, Conduct Disorder, Substance-Related Disorders, Genetic Predisposition to Disease, Adult Survivors of Child Abuse, Gene-Environment Interaction
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