Intern Health Study

Specific Aims Retrospective studies have established a strong correlation between reports of
life stress and depression. Investigators have begun to further explore this relationship by
examining the role of gene x stress interactions in the pathogenesis of depression. In a
recent landmark study, Caspi and colleagues (2003) reported an interaction between a
serotonin transporter promoter polymorphism and life stress in the development of depression.
This finding has been replicated in some but not all follow up studies. Despite the initial
promise of these results, the ability to draw definitive conclusions is compromised by
significant study design limitations: 1) retrospective design 2) a focus on acute rather than
chronic stress 3) substantial variation in the character and intensity of stress between
subjects. Medical internship is a period filled with predictable and high levels of chronic
uncontrolled stress. Rates of depression among interns are elevated compared to the general
population. In this study, we aim to utilize the predictable and consistent stress of
internship to investigate the relationship between stress, genes and depression with a
prospective study design that bypasses some of the pitfalls of previous studies.

Goal 1) Assess the prevalence and development of depression among medical interns

Although small studies have assessed the point prevalence of depression among medical
residents, no study has prospectively followed the development of depressive symptoms through
residency. We will collect baseline psychological profiles of incoming interns prior to the
commencement of residency duties and subsequently assess for depressive symptoms at 3-month
intervals throughout internship. This data will allow us to:

1. Assess the point prevalence of depression among interns in a large sample.

2. Determine the change in depressive symptoms through the course of the intern year

3. Evaluate stable psychological factors that associate with the development of depression
in the face of life stress.

Goal 2) Evaluate the presence of genotype x stress interaction among this sample

1. There is conflicting evidence concerning the presence of an interaction between the
serotonin transporter promoter polymorphism (5-HTTLPR) and life stress in the
development of depression. We will assess the presence and strength of this interaction
in the sample of medical interns using a study design that avoids many of the pitfalls
affecting previous studies.

2. We will explore novel putative interactions between stress and genetic variants in
additional genes including BDNF, CRH, COMT, serotonin 1A and serotonin 2A receptor
variants in the development of depression.

Goal 3) Evaluate the relationship between serum endothelial and immune factors and the
development of depressive symptoms under stress.

The identification biomarkers that predict the onset of depression can facilitate more timely
and accurate identification of individuals at high risk for the disorder. Unfortunately
appropriate studies are lacking, largely because it is difficult to know exactly when a
depressive episode will occur. Medical internship represents a rare situation where we can
prospectively predict when a cohort of individuals shift will shift from a low stress
environment to a high stress environment and thus predict when this cohort will experience a
dramatic increase in depressive symptoms.

Goal 4) Examine the temporal relationship between hair cortisol levels, stress exposure and
development of depressive symptoms.A novel technique allows us to assess chronic HPA axis
activity by measuring cortisol in the growing hair, providing an integrated measure of total
cortisol secretion over extended periods of time (1-3 months).

By incorporating this novel method into an established longitudinal study of a chronic
stressor that dramatically increases rates of depression, we have a unique opportunity to
determine a) whether cortisol levels prior to stress exposure predict risk of depression in
response to the stressor (b) whether cortisol rise in response to stress exposure precedes
and perhaps contributes to development of depressive symptoms or whether cortisol elevations
in depression develop after symptom onset and perhaps reflect a consequence of depression.

Inclusion Criteria:

- Subjects for our study will be drawn from incoming interns in the traditional and
primary care internal medicine, general surgery, pediatrics, obstetrics/gynecology,
neurology and psychiatry residency programs at participating University and Community
residency programs, as well as fourth year medical students at participating medical
schools.

Exclusion Criteria: