DepressionNCT01809080
Intern Health Study
An observational study of Depression, run by University of Michigan at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Depression
- How many people
- 25,000 participants
- Where
- 1 siteUnited States
- Study dates
- May 2007to Jul 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Medical internship is an attractive model to bypass some limitations of previous studies. Internship is well chronicled as a time of high stress (Butterfield 1988; Addison et al 2004). Interns are faced with long work hours, sleep deprivation, loss of autonomy and extreme emotional situations (Shanafelt \& Habermann 2002). Many physicians recall internship as among the most stressful years of their lives (Duffy 2005). The stress of internship is often uncontrollable, unpredictable and chronic; features that are particularly linked to the development of depression (Kendler et al 2003; Cryan et al 2004). Several studies have estimated the point prevalence of depression among interns at 28%-37% (Valko \& Clayton 1975; Reuben 1985; Cohen et al 2006), in contrast to a point prevalence of 5% in general population (Murphy et al 2000). There is also evidence that physicians have underlying personality traits that predispose to depression (McDonough 1990; Hojat et al 1999).
Who may be able to join
- 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.
Who cannot join
- None.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
University of Michigan Medical School
Ann Arbor, Michigan, 48109
About this study
Official title: Investigation Into the Interaction Between Genes and Stress in the Etiology of Depression in Interns
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.
Read the detailed description
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:
- Assess the point prevalence of depression among interns in a large sample.
- Determine the change in depressive symptoms through the course of the intern year
- 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
- 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.
- 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.
- Conditions
- Depression
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 2020 | Not described | |
| 2019 | Not described | |
| 2018 | Not described | |
| 2017 | Not described | |
| 2016 | Not described | |
| 2015 | Not described | |
| 2014 | Not described | |
| 2013 | Not described | |
| 2012 | Not described | |
| 2011 | Not described | |
| 2010 | Not described | |
| 2009 | Not described | |
| 2008 | Not described | |
| 2007 | Not described | |
| 2021 | Not described | |
| 2022 | Not described | |
| 2023 | Not described | |
| 2024 | Not described | |
| 2025 | Not described | |
| 2026 | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess the change in rates of depression among medical interns.
The point prevalence of depression at various points through internship will be determined using subject responses to DSM-IV major depression items at the 0, 3-month, 6-month and 12-month assessments. To investigate whether there is a significant change in depressive symptoms through intern year, the investigators will compare PHQ (baseline) and PHQ (6 month) depression scores through a paired T-test. The effect of baseline psychological traits (neuroticism, resilience, personal history of depression, family history of depression, early family environment, social supports) on the development of depression will also be explored through linear regression analyses with each of the psychological factors as independent variables and PHQ (change) [PHQ (6 month) - PHQ (baseline)] as the dependent variable. The investigators will use linear regression to investigate correlations between training program characteristics (average work hours, specialty) and PHQ (change).
Measured: Months 0, 3, 6, and 12 of Intern Year
Secondary outcomes (3)
Evaluate the presence of genotype x stress interaction among this sample.
As a baseline analysis, the investigators will investigate association between each variant/haplotype and PHQ (baseline) scores using linear regression. To explore gene x environment interactions, the investigators will assess for association between each variant/haplotype and PHQ change scores (Mean (3,6,9 and 12 month PHQ score) - Baseline (PHQ score)).
Measured: Sample within first 6 months of Intern Year (Because DNA sequence generally does not change with time, the exact timing of sample collection is not critical to the analysis)
Evaluate the relationship between serum factors and changes in depressive symptoms under stress.
For each of the proteins assessed (IL-1beta, IL-6, IL-10, hs-CRP and TNF-alpha), Pearson correlation will be used to assess the relationship between serum and saliva levels. The investigators will assess whether there is a significant change in the serum levels of endothelial and inflammatory markers and endothelial function using a within-subject paired T-test, with baseline values (low stress) paired with internship stress values (high stress). To assess whether the change in endothelial and inflammatory markers correlate with a change in depressive symptoms, the investigators will utilize a linear regression, with the change in marker level used as explanatory variables and the change in depressive symptoms score (PHQ (change) = mean residency depressive symptoms - baseline depressive symptoms) used as the outcome variable
Measured: Months 0 and 10 of Intern Year
Examine the temporal relationship between hair cortisol level changes, stress exposure and changes in depressive symptoms
Statistical analysis will be conducted using Generalized Estimating Equation (GEE) analysis. To assess whether there is a change in hair cortisol indices with internship stress, the investigators will perform a paired T-test, with pre-internship factor cortisol level paired with post-internship factor cortisol level. To determine the relationship between hair-related factors (hair color, hair treatment, washing frequency), transient mediating factors (work hours, outside stressful life events, recent exercise, sleep and illness), long-term mediating factors (BMI, regular exercise schedule, smoking behavior) and long-term cortisol, the investigators will assess whether the difference in level of these factors between the two assessments shows a significant correlation with the difference in cortisol level. Next, the investigators will identify whether that change in hair cortisol is associated with the change in depressive symptoms while accounting for related variables.
Measured: Months 0, 4, 8, 12 of Intern Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2013 (estimated)
- Study startMay 2007
- Primary completionJul 2027 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 25,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Srijan Sen, University of Michigan
- Investigators
- Srijan Sen, MD, PhD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01809080
- Sponsor's protocol ID
- MH-095109
- Status last verified
- Aug 2026
- First submitted
- 1 Mar 2013
- Last updated
- 7 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
Publications
Karg K, Sen S. Gene x environment interaction models in psychiatric genetics. Curr Top Behav Neurosci. 2012;12:441-62. doi: 10.1007/7854_2011_184.
PubMed 22241248Guille C, Sen S. Prescription drug use and self-prescription among training physicians. Arch Intern Med. 2012 Feb 27;172(4):371-2. doi: 10.1001/archinternmed.2011.791. No abstract available.
PubMed 22371930Guille C, Speller H, Laff R, Epperson CN, Sen S. Utilization and barriers to mental health services among depressed medical interns: a prospective multisite study. J Grad Med Educ. 2010 Jun;2(2):210-4. doi: 10.4300/JGME-D-09-00086.1.
PubMed 21975622Sen S, Kranzler HR, Krystal JH, Speller H, Chan G, Gelernter J, Guille C. A prospective cohort study investigating factors associated with depression during medical internship. Arch Gen Psychiatry. 2010 Jun;67(6):557-65. doi: 10.1001/archgenpsychiatry.2010.41. Epub 2010 Apr 5.
PubMed 20368500Karg K, Burmeister M, Shedden K, Sen S. The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: evidence of genetic moderation. Arch Gen Psychiatry. 2011 May;68(5):444-54. doi: 10.1001/archgenpsychiatry.2010.189. Epub 2011 Jan 3.
PubMed 21199959
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation Into the Interaction Between Genes and Stress in the Etiology of Depression in Interns
- ClinicalTrials.gov ID
- NCT01809080
- Acronym / sponsor ID
- MH-095109
- Conditions
- Depression
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 25,000 participants (estimated)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Study start
- May 2007 (actual)
- Primary completion
- Jul 2027 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 12 Mar 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- Assess the point prevalence of depression among interns in a large sample.
- Determine the change in depressive symptoms through the course of the intern year
- 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
- 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.
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 20
| Arm | Type | Receives |
|---|---|---|
| 2020 | – | – |
| 2019 | – | – |
| 2018 | – | – |
| 2017 | – | – |
| 2016 | – | – |
| 2015 | – | – |
| 2014 | – | – |
| 2013 | – | – |
| 2012 | – | – |
| 2011 | – | – |
| 2010 | – | – |
| 2009 | – | – |
| 2008 | – | – |
| 2007 | – | – |
| 2021 | – | – |
| 2022 | – | – |
| 2023 | – | – |
| 2024 | – | – |
| 2025 | – | – |
| 2026 | – | – |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Medical internship is an attractive model to bypass some limitations of previous studies. Internship is well chronicled as a time of high stress (Butterfield 1988; Addison et al 2004). Interns are faced with long work hours, sleep deprivation, loss of autonomy and extreme emotional situations (Shanafelt \& Habermann 2002). Many physicians recall internship as among the most stressful years of their lives (Duffy 2005). The stress of internship is often uncontrollable, unpredictable and chronic; features that are particularly linked to the development of depression (Kendler et al 2003; Cryan et al 2004). Several studies have estimated the point prevalence of depression among interns at 28%-37% (Valko \& Clayton 1975; Reuben 1985; Cohen et al 2006), in contrast to a point prevalence of 5% in general population (Murphy et al 2000). There is also evidence that physicians have underlying personality traits that predispose to depression (McDonough 1990; Hojat et al 1999).
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- None.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Assess the change in rates of depression among medical interns.
Time frame: Months 0, 3, 6, and 12 of Intern Year
The point prevalence of depression at various points through internship will be determined using subject responses to DSM-IV major depression items at the 0, 3-month, 6-month and 12-month assessments. To investigate whether there is a significant change in depressive symptoms through intern year, the investigators will compare PHQ (baseline) and PHQ (6 month) depression scores through a paired T-test. The effect of baseline psychological traits (neuroticism, resilience, personal history of depression, family history of depression, early family environment, social supports) on the development of depression will also be explored through linear regression analyses with each of the psychological factors as independent variables and PHQ (change) [PHQ (6 month) - PHQ (baseline)] as the dependent variable. The investigators will use linear regression to investigate correlations between training program characteristics (average work hours, specialty) and PHQ (change).
3 secondary outcomes
Evaluate the presence of genotype x stress interaction among this sample.
Time frame: Sample within first 6 months of Intern Year (Because DNA sequence generally does not change with time, the exact timing of sample collection is not critical to the analysis)
Evaluate the relationship between serum factors and changes in depressive symptoms under stress.
Time frame: Months 0 and 10 of Intern Year
Examine the temporal relationship between hair cortisol level changes, stress exposure and changes in depressive symptoms
Time frame: Months 0, 4, 8, 12 of Intern Year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2026.
- Background: PubMed 22241248Karg K, Sen S. Gene x environment interaction models in psychiatric genetics. Curr Top Behav Neurosci. 2012;12:441-62. doi: 10.1007/7854_2011_184.
- Results publication: PubMed 22371930Guille C, Sen S. Prescription drug use and self-prescription among training physicians. Arch Intern Med. 2012 Feb 27;172(4):371-2. doi: 10.1001/archinternmed.2011.791. No abstract available.
- Results publication: PubMed 21975622Guille C, Speller H, Laff R, Epperson CN, Sen S. Utilization and barriers to mental health services among depressed medical interns: a prospective multisite study. J Grad Med Educ. 2010 Jun;2(2):210-4. doi: 10.4300/JGME-D-09-00086.1.
- Results publication: PubMed 20368500Sen S, Kranzler HR, Krystal JH, Speller H, Chan G, Gelernter J, Guille C. A prospective cohort study investigating factors associated with depression during medical internship. Arch Gen Psychiatry. 2010 Jun;67(6):557-65. doi: 10.1001/archgenpsychiatry.2010.41. Epub 2010 Apr 5.
- Results publication: PubMed 21199959Karg K, Burmeister M, Shedden K, Sen S. The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: evidence of genetic moderation. Arch Gen Psychiatry. 2011 May;68(5):444-54. doi: 10.1001/archgenpsychiatry.2010.189. Epub 2011 Jan 3.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Srijan Sen, MD, PhD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Depression, run by University of Michigan at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 7 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess the change in rates of depression among medical interns. (time frame: Months 0, 3, 6, and 12 of Intern Year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01809080, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2026.