Document Type



Medicine and Health Sciences



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.


To identify psychological, demographic and residency program factors that associate with depression among interns and use medical internship as a model to study the moderating effects of this polymorphism using a prospective, within-subject design that addresses the design limitations of earlier studies.


Prospective cohort study


13 United States hospitals


740 interns entering participating residency programs

Main outcome measures

Subjects were assessed for depressive symptoms using the Patient Health Questionnaire (PHQ-9), a series of psychological traits and 5-HTTLPR genotype prior to internship and then assessed for depressive symptoms and potential stressors at 3-month intervals during internship.


The PHQ-9 depression score increased from 2.4 prior to internship to a mean of 6.4 during internship (p<0.001). 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<0.001). A series of factors measured prior to internship (female sex, U.S. 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) were associated with a greater increase in depressive symptoms during internship. In addition, subjects with at least one copy of a less transcribed 5-HTTLPR allele reported a greater increase in depressive symptoms under the stress of internship (p=0.002).


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.


Arch Gen Psychiatry. Author manuscript; available in PMC May 28, 2014. Published in final edited form as: Arch Gen Psychiatry. Jun 2010; 67(6): 557–565. Published online Apr 5, 2010. doi: 10.1001/archgenpsychiatry.2010.41 PMCID: PMC4036806 NIHMSID: NIHMS452400