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Featured researches published by Constance Guille.


Archives of General Psychiatry | 2010

A Prospective Cohort Study Investigating Factors Associated with Depression during Medical Internship

Srijan Sen; Henry R. Kranzler; John H. Krystal; Heather Speller; Grace Chan; Joel Gelernter; Constance Guille

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.


JAMA Internal Medicine | 2013

Effects of the 2011 Duty Hour Reforms on Interns and Their Patients: A Prospective Longitudinal Cohort Study

Srijan Sen; Henry R. Kranzler; Aashish Didwania; Ann C. Schwartz; Sudha Amarnath; Joseph C. Kolars; Gregory W. Dalack; Breck Nichols; Constance Guille

IMPORTANCE In 2003, the first phase of duty hour requirements for US residency programs recommended by the Accreditation Council for Graduate Medical Education (ACGME) was implemented. Evidence suggests that this first phase of duty hour requirements resulted in a modest improvement in resident well-being and patient safety. To build on these initial changes, the ACGME recommended a new set of duty hour requirements that took effect in July 2011. OBJECTIVE To determine the effects of the 2011 duty hour reforms on first-year residents (interns) and their patients. DESIGN As part of the Intern Health Study, we conducted a longitudinal cohort study comparing interns serving before (2009 and 2010) and interns serving after (2011) the implementation of the new duty hour requirements. SETTING Fifty-one residency programs at 14 university and community-based GME institutions. PARTICIPANTS A total of 2323 medical interns. MAIN OUTCOME MEASURES Self-reported duty hours, hours of sleep, depressive symptoms, well-being, and medical errors at 3, 6, 9, and 12 months of the internship year. RESULTS Fifty-eight percent of invited interns chose to participate in the study. Reported duty hours decreased from an average of 67.0 hours per week before the new rules to 64.3 hours per week after the new rules were instituted (P < .001). Despite the decrease in duty hours, there were no significant changes in hours slept (6.8 → 7.0; P = .17), depressive symptoms (5.8 → 5.7; P = .55) or well-being score (48.5 → 48.4; P = .86) reported by interns. With the new duty hour rules, the percentage of interns who reported concern about making a serious medical error increased from 19.9% to 23.3% (P = .007). CONCLUSIONS AND RELEVANCE Although interns report working fewer hours under the new duty hour restrictions, this decrease has not been accompanied by an increase in hours of sleep or an improvement in depressive symptoms or well-being but has been accompanied by an unanticipated increase in self-reported medical errors.


JAMA | 2016

Prevalence of Depression, Depressive Symptoms, and Suicidal Ideation Among Medical Students: A Systematic Review and Meta-Analysis

Lisa S. Rotenstein; Marco A. Ramos; Matthew Torre; J. Bradley Segal; Michael J. Peluso; Constance Guille; Srijan Sen; Douglas A. Mata

Importance Medical students are at high risk for depression and suicidal ideation. However, the prevalence estimates of these disorders vary between studies. Objective To estimate the prevalence of depression, depressive symptoms, and suicidal ideation in medical students. Data Sources and Study Selection Systematic search of EMBASE, ERIC, MEDLINE, psycARTICLES, and psycINFO without language restriction for studies on the prevalence of depression, depressive symptoms, or suicidal ideation in medical students published before September 17, 2016. Studies that were published in the peer-reviewed literature and used validated assessment methods were included. Data Extraction and Synthesis Information on study characteristics; prevalence of depression or depressive symptoms and suicidal ideation; and whether students who screened positive for depression sought treatment was extracted independently by 3 investigators. Estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were estimated using stratified meta-analysis and meta-regression. Main Outcomes and Measures Point or period prevalence of depression, depressive symptoms, or suicidal ideation as assessed by validated questionnaire or structured interview. Results Depression or depressive symptom prevalence data were extracted from 167 cross-sectional studies (n = 116 628) and 16 longitudinal studies (n = 5728) from 43 countries. All but 1 study used self-report instruments. The overall pooled crude prevalence of depression or depressive symptoms was 27.2% (37 933/122 356 individuals; 95% CI, 24.7% to 29.9%, I2 = 98.9%). Summary prevalence estimates ranged across assessment modalities from 9.3% to 55.9%. Depressive symptom prevalence remained relatively constant over the period studied (baseline survey year range of 1982-2015; slope, 0.2% increase per year [95% CI, -0.2% to 0.7%]). In the 9 longitudinal studies that assessed depressive symptoms before and during medical school (n = 2432), the median absolute increase in symptoms was 13.5% (range, 0.6% to 35.3%). Prevalence estimates did not significantly differ between studies of only preclinical students and studies of only clinical students (23.7% [95% CI, 19.5% to 28.5%] vs 22.4% [95% CI, 17.6% to 28.2%]; P = .72). The percentage of medical students screening positive for depression who sought psychiatric treatment was 15.7% (110/954 individuals; 95% CI, 10.2% to 23.4%, I2 = 70.1%). Suicidal ideation prevalence data were extracted from 24 cross-sectional studies (n = 21 002) from 15 countries. All but 1 study used self-report instruments. The overall pooled crude prevalence of suicidal ideation was 11.1% (2043/21 002 individuals; 95% CI, 9.0% to 13.7%, I2 = 95.8%). Summary prevalence estimates ranged across assessment modalities from 7.4% to 24.2%. Conclusions and Relevance In this systematic review, the summary estimate of the prevalence of depression or depressive symptoms among medical students was 27.2% and that of suicidal ideation was 11.1%. Further research is needed to identify strategies for preventing and treating these disorders in this population.


Psychological Medicine | 2014

Depression is more than the sum score of its parts: individual DSM symptoms have different risk factors

Eiko I. Fried; Randolph M. Nesse; Constance Guille; Srijan Sen

BACKGROUND For diagnostic purposes, the nine symptoms that compose the DSM-5 criteria for major depressive disorder (MDD) are assumed to be interchangeable indicators of one underlying disorder, implying that they should all have similar risk factors. The present study investigates this hypothesis, using a population cohort that shifts from low to elevated depression levels. METHOD We assessed the nine DSM-5 MDD criterion symptoms (using the Patient Health Questionnaire; PHQ-9) and seven depression risk factors (personal and family MDD history, sex, childhood stress, neuroticism, work hours, and stressful life events) in a longitudinal study of medical interns prior to and throughout internship (n = 1289). We tested whether risk factors varied across symptoms, and whether a latent disease model could account for heterogeneity between symptoms. RESULTS All MDD symptoms increased significantly during residency training. Four risk factors predicted increases in unique subsets of PHQ-9 symptoms over time (depression history, childhood stress, sex, and stressful life events), whereas neuroticism and work hours predicted increases in all symptoms, albeit to varying magnitudes. MDD family history did not predict increases in any symptom. The strong heterogeneity of associations persisted after controlling for a latent depression factor. CONCLUSIONS The influence of risk factors varies substantially across DSM depression criterion symptoms. As symptoms are etiologically heterogeneous, considering individual symptoms in addition to depression diagnosis might offer important insights obfuscated by symptom sum scores.


The Lancet Psychiatry | 2015

Heterogeneity of postpartum depression: a latent class analysis

Karen T. Putnam; Emma Robertson-Blackmore; Katherine M. Sharkey; Jennifer L. Payne; Veerle Bergink; Trine Munk-Olsen; Kristina M. Deligiannidis; Margaret Altemus; J. Newport; Gisèle Apter; A. Vikorin; Patrik K. E. Magnusson; Paul Lichtenstein; Brenda W.J.H. Penninx; Anne Buist; Justin L C Bilszta; Michael W. O'Hara; Scott Stuart; Rebecca L. Brock; Sabine J. Roza; Henning Tiemeier; Constance Guille; C.N. Epperson; Deborah R. Kim; Peter T. Schmidt; Pedro E. Martinez; Katherine L. Wisner; Zachary N. Stowe; Ian Jones; David R. Rubinow

BACKGROUND Maternal depression in the postpartum period confers substantial morbidity and mortality, but the definition of postpartum depression remains controversial. We investigated the heterogeneity of symptoms with the aim of identifying clinical subtypes of postpartum depression. METHODS Data were aggregated from the international perinatal psychiatry consortium Postpartum Depression: Action Towards Causes and Treatment, which represents 19 institutions in seven countries. 17,912 unique subject records with phenotypic data were submitted. We applied latent class analyses in a two-tiered approach to assess the validity of empirically defined subtypes of postpartum depression. Tier one assessed heterogeneity in women with complete data on the Edinburgh postnatal depression scale (EPDS) and tier two in those with postpartum depression case status. FINDINGS 6556 individuals were assessed in tier one and 4245 in tier two. A final model with three latent classes was optimum for both tiers. The most striking characteristics associated with postpartum depression were severity, timing of onset, comorbid anxiety, and suicidal ideation. Women in class 1 had the least severe symptoms (mean EPDS score 10·5), followed by those in class 2 (mean EPDS score 14·8) and those in class 3 (mean EPDS score 20·1). The most severe symptoms of postpartum depression were significantly associated with poor mood (mean EPDS score 20·1), increased anxiety, onset of symptoms during pregnancy, obstetric complications, and suicidal ideation. In class 2, most women (62%) reported symptom onset within 4 weeks postpartum and had more pregnancy complications than in other two classes (69% vs 67% in class 1 and 29% in class 3). INTERPRETATION PPD seems to have several distinct phenotypes. Further assessment of PPD heterogeneity to identify more precise phenotypes will be important for future biological and genetic investigations. FUNDING Sources of funding are listed at the end of the article.


Psychoneuroendocrinology | 2013

Cortisol at the emergency room rape visit as a predictor of PTSD and depression symptoms over time

Kate Walsh; Nicole R. Nugent; Amelia Kotte; Ananda B. Amstadter; Sheila Wang; Constance Guille; Ron Acierno; Dean G. Kilpatrick; Heidi S. Resnick

BACKGROUND Dysregulation of the hypothalamic-pituitary-adrenal axis, typically reflected by alterations in cortisol responsivity, has been associated with exposure to traumatic events and the development of stress-related disorders such as posttraumatic stress disorder (PTSD) and depression. METHODS Serum cortisol was measured at the time of a post sexual assault medical exam among a sample of 323 female victims of recent sexual assault. Analyses were conducted among 235 participants who provided data regarding history of previous assault as well as PTSD and depression symptoms during at least one of the three follow-ups. RESULTS Growth curve models suggested that prior history of assault and serum cortisol were positively associated with the intercept and negatively associated with the slope of PTSD and depression symptoms after controlling for covariates. Prior history of assault and serum cortisol also interacted to predict the intercept and slope of PTSD and depression symptoms such that women with a prior history of assault and lower ER cortisol had higher initial symptoms that decreased at a slower rate relative to women without a prior history and those with higher ER cortisol. CONCLUSIONS Prior history of assault was associated with diminished acute cortisol responsivity at the emergency room visit. Prior assault history and cortisol both independently and interactively predicted PTSD and depression symptoms at first follow-up and over the course a 6-month follow-up.


Journal of Graduate Medical Education | 2010

Utilization and Barriers to Mental Health Services Among Depressed Medical Interns: A Prospective Multisite Study

Constance Guille; Heather Speller; Rachel Laff; C. Neill Epperson; Srijan Sen

BACKGROUND Compared with graduate students and young adults in the general population, depression is more prevalent among training physicians, yet physicians are often reluctant to seek mental health treatment. The purpose of this study is to identify perceived barriers to mental health treatment among depressed training physicians. METHODS Subjects for this study were drawn from intern classes during the 2007-2008 and 2008-2009 academic years from 6 and 13 participating community and university hospitals, respectively. At 3-month intervals throughout the intern year, participants completed the Patient Health Questionnaire regarding current depressive symptoms and questions regarding current mental health treatment. We explored potential barriers to mental health treatment at the end of the intern year and determined the proportion of subjects screening positive for depression and seeking treatment through analysis of subject responses. Stepwise binary logistic regression was conducted to compare baseline characteristics among depressed interns who sought mental health treatment and those that did not. RESULTS Of the 42.5% (278 of 654) of interns who screened positive for depression, 22.7% (63 of 278) reported receiving treatment during the intern year. The most frequently cited barriers to seeking treatment were time (91.5%), preference to manage problems on their own (75.1%), lack of convenient access (61.8%), and concerns about confidentiality (57.3%). Interns who had previously sought treatment for depression were more likely to seek treatment during internship. CONCLUSIONS Despite high rates of depression, few interns appear to seek mental health treatment due to time constraints, lack of convenient access, concerns about confidentiality, and a preference to manage problems on their own. By identifying barriers to mental health treatment we can begin to remove obstacles to the delivery of evidence-based treatments and implement prevention, screening, and early detection programs to improve the mental health of physicians in training.


Acta Psychiatrica Scandinavica | 2015

The differential influence of life stress on individual symptoms of depression

Eiko I. Fried; Randolph M. Nesse; Constance Guille; Srijan Sen

Life stress consistently increases the incidence of major depression. Recent evidence has shown that individual symptoms of major depressive disorder (MDD) differ in important dimensions such as their genetic and etiological background, but the impact of stress on individual MDD symptoms is not known. Here, we assess whether stress affects depression symptoms differentially.


PLOS ONE | 2013

Well-Being and the Risk of Depression under Stress

Faren Grant; Constance Guille; Srijan Sen

Improving our ability to accurately predict individual risk for depression would have profound public health benefits. While there has been growing interest in understanding the relation between measures of positive emotion, such as well-being, and depression, it is not clear whether low well-being is an independent predictor of short term depression risk. We assessed whether low well-being is a risk factor for depressive symptoms. Medical internship is a well-established period of stress when levels of depressive symptoms increase dramatically. 1621 individuals beginning medical internship were assessed for well-being, depressive symptoms, and a set of psychological and demographic traits prior to starting internship year and again for depressive symptoms at 3 month intervals during the year. Low subjective well-being significantly predicted increased depression symptom scores during the stress of medical internship and accounted for individual level inter-variability in depression symptom trends across time. Assessing well-being may have utility in predicting future depression risk.


Epilepsy & Behavior | 2008

The role of sex steroids in catamenial epilepsy and premenstrual dysphoric disorder: Implications for diagnosis and treatment

Constance Guille; Susan S. Spencer; Idil Cavus; C. Neill Epperson

Despite our understanding of hormonal influences on central nervous system (CNS) function, there is still much to learn about the pathogenesis of menstrual cycle-linked disorders. A growing literature suggests that the influence of sex steroids on neurological and psychiatric disorders is in part mediated by an aberrant CNS response to neuroactive steroids. Although sex steroids such as estradiol, progesterone, and the progesterone derivative allopregnanolone (ALLO) influence numerous neurotransmitter systems, it is their potent effect on the brains primary inhibitory and excitatory neurotransmitters gamma-aminobutyric acid (GABA) and glutamate that links the study of premenstrual dysphoric disorder (PMDD) and catamenial epilepsy (CE). After providing an overview of these menstrual cycle-linked disorders, this article focuses on the preclinical and clinical research investigating the role of estradiol and progesterone (via ALLO) in the etiology of PMDD and CE. Through exploration of the phenomenological and neurobiological overlap between CE and PMDD, we aim to highlight areas for future research and development of treatments for menstrual cycle-linked neuropsychiatric disorders.

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Srijan Sen

University of Michigan

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C. Neill Epperson

University of Pennsylvania

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Douglas A. Mata

Brigham and Women's Hospital

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Kristina M. Deligiannidis

University of Massachusetts Medical School

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Roger B. Newman

Medical University of South Carolina

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Jenna L. McCauley

Medical University of South Carolina

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Karen T. Putnam

University of North Carolina at Chapel Hill

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