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A Prospective Cohort Study Investigating Factors Associated With Depression During Medical Internship
Open accessAbstract
CONTEXT: Although the prevalence of depression among medical interns substantially exceeds that of the general population, the specific factors responsible are not well understood. Recent reports of a moderating effect of a genetic polymorphism (5-HTTLPR) in the serotonin transporter protein gene on the likelihood that life stress will precipitate depression may help to understand the development of mood symptoms in medical interns. OBJECTIVES: To identify psychological, demographic, and residency program factors that are associated with depression among interns and to use medical internship as a model to study the moderating effects of this polymorphism. DESIGN: A prospective cohort study. SETTING: Thirteen US hospitals. PARTICIPANTS: Seven hundred forty interns entering participating residency programs. MAIN OUTCOME MEASURES: Subjects were assessed for depressive symptoms using the 9-item Patient Health Questionnaire (PHQ-9), a series of psychological traits, and the 5-HTTLPR genotype prior to internship and then assessed for depressive symptoms and potential stressors at 3-month intervals during internship. RESULTS: The PHQ-9 depression score increased from 2.4 prior to internship to a mean of 6.4 during internship (P < .001). The proportion of participants who met PHQ-9 criteria for depression increased from 3.9% prior to internship to a mean of 25.7% during internship (P < .001). A series of factors measured prior to internship (female sex, US medical education, difficult early family environment, history of major depression, lower baseline depressive symptom score, and higher neuroticism) and during internship (increased work hours, perceived medical errors, and stressful life events) was associated with a greater increase in depressive symptoms during internship. In addition, subjects with at least 1 copy of a less-transcribed 5-HTTLPR allele reported a greater increase in depressive symptoms under the stress of internship (P = .002). CONCLUSIONS: There is a marked increase in depressive symptoms during medical internship. Specific individual, internship, and genetic factors are associated with the increase in depressive symptoms.
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“These longitudinal data, collected in the context of a chronic stressor that triggers new onset depression in a substantial number of those exposed (Mata et al., 2015; Sen et al., 2010), add weight to the idea that hypercortisolemia is neither a cause nor direct correlate of depressive symptom states, at least in the context of a non-clinical sample.”
From Chronic Stress, Hair Cortisol and Depression: A Prospective and Longitudinal Study of Medical Internship (2018) · cites this paper as Sen et al., 2010
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“an established model of stress and depression (Sen et al., 2010).”
From Chronic Stress, Hair Cortisol and Depression: A Prospective and Longitudinal Study of Medical Internship (2018) · cites this paper as Sen et al., 2010
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“These longitudinal data, collected in the context of a chronic stressor that triggers new onset depression in a substantial number of those exposed (Mata et al., 2015; Sen et al., 2010), add weight to the idea that hypercortisolemia is neither a cause nor direct correlate of depressive symptom states, at least in the context of a non-clinical sample.”
From Chronic Stress, Hair Cortisol and Depression: A Prospective and Longitudinal Study of Medical Internship (2018) · cites this paper as Sen et al., 2010
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Soller, M. V., & Lashen, G. (2026) · Springer eBooks · doi:10.1007/978-3-032-14062-3_21
Anzia, J. M. (2026) · Springer eBooks · doi:10.1007/978-3-032-14062-3_10
The Case for Life Beyond Medicine: A Niche Outside of Medicine for Residents and Fellows
Ayyad, M. (2026) · American Journal of Psychiatry Residents Journal · doi:10.1176/appi.ajp-rj.2026.210407
Metadata
- Authors
- Sen, S., Kranzler, H. R., Krystal, J. H., Speller, H., Chan, G., Gelernter, J., & Guille, C.
- Affiliations
- University of Michigan (US)
- University of Connecticut (US)
- Yale University (US)
- Medical University of South Carolina (US)
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2010-06-01
- Volume
- 67
- Issue
- 6
- Pages
- 557
- ISSN
- 0003-990X (ISSN-L)
- PMC
- PMC4036806
- OpenAlex
- W2063172343
- Cited by
- 411
- References
- 79
- Citations by year
- 2026: 17 · 2025: 44 · 2024: 29 · 2023: 35 · 2022: 30 · 2021: 38 · 2020: 25 · 2019: 40 · 2018: 24 · 2017: 30 · 2016: 22 · 2015: 22 · 2014: 14 · 2013: 13 · 2012: 15
- FWCI
- 23.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (K23MH095109)
- Topics
- Health Sciences › Health Professions › General Health Professions › Healthcare professionals’ stress and burnout
- Social Sciences › Education › Innovations in Medical Education
- Health Sciences › Medicine › Psychiatry and Mental health › Mental Health Treatment and Access
- Keywords
- depression, medical interns, residency training, 5-HTTLPR, serotonin transporter gene, genetic polymorphism, life events, depressive symptoms, neuroticism, working hours, female sex, family environment
- MeSH terms
- Adult, Depression, Major Depressive Disorder, Depressive Disorder, Female, Genotype, Health Status, Humans, Internship and Residency, Life Change Events, Male, Medicine, Prospective Studies, Surveys and Questionnaires, Risk Factors, Stress, Psychological, Students, Medical, Cohort Studies, Prevalence, Polymorphism, Single Nucleotide, Serotonin Plasma Membrane Transport Proteins
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