The development of depressive symptoms during medical internship stress predicts worsening vascular function

Fiedorowicz, Jess G.; Ellingrod, Vicki L.; Kaplan, Mariana J.; Sen, Srijan

doi:10.1016/j.jpsychores.2015.06.004

Cited by 15 publications

(13 citation statements)

References 23 publications

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“…[6,7] In a year-long prospective study of 37 participants in medical internship, those who developed depressive symptoms, as measured with Patient Health Questionnaire (PHQ-9) every three months, also had reduced endothelial function when symptomatic. [8] Similar findings were seen in a cross-sectional study of adolescent girls, presumably without atherosclerosis, but here their depressive symptoms were measured using the Beck Depression Inventory. [9] Although these two studies measured depressive symptoms by a different method, endothelial function was measured with the same methodology: using finger plethysmography and subsequent determination of a reactive hyperemia index.…”

Section: Introductionsupporting

confidence: 72%

“…[46] The previously mentioned Fiedorowicz et al study on endothelial dysfunction during medical internship investigated changes in reactive hyperemia index at baseline and one year later, another indication that changes in vascular function need to be studied over a longer period of time. [8] The sample was not aggressively treated with only two participants achieving remission (MADRS<10) and followed for only eight weeks. [47] Nonetheless the study sample's depressive symptoms did improve over the course of the study; so, the researchers could appropriately address the question of whether immediate depressive symptom improvement is associated with improved measures of cardiovascular risk, presuming the effects were observable within eight weeks and didn't require remission of symptoms to resolve.…”

Section: Discussionmentioning

confidence: 99%

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Inflammatory and Vascular Correlates of Mood Change Over 8 Weeks

et al. 2019

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Background-Mood disorders have been associated with a variety of cardiovascular disease risk factors, including inflammation and large artery stiffness, particularly while depressed although longitudinal studies have been limited. Methods-With measurements at baseline and 8 weeks, the researchers prospectively assessed mood, levels of inflammatory markers (hsCRP and TNF-α), serum lipids, and large artery stiffness in a cohort of 26 participants with a diagnosis of a mood disorder, enriched for current depression. Depressive symptoms were measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline and 8 weeks. Associations between depressive symptoms and other measures were assessed using linear mixed models, unadjusted and adjusted for age and BMI. Results-The mean age of the participants (n=26) was 41.6 (standard deviation [SD] 12.8) years, and 81% were female. During the study, there was a mean (SD) MADRS score improvement of 9.5 (9.4) from baseline to eight weeks. Reductions in the primary outcome TNF-α with improvement in depression fell short of significance (P=0.076). In secondary analyses, there was a statistically significant association between improved cholesterol ratio (P=0.038) and triglycerides (P=0.042) with depression improvement. There was no statistically significant change in large artery stiffness during the study. Conclusion-Improved depressive symptoms were associated with improved cholesterol ratios even after adjustment, suggesting possible mechanism by which acute mood states may influence cardiovascular disease risk. Future longitudinal studies with extended and intensive follow-up investigating cardiovascular disease risk related to acute changes and persistence of mood symptoms is warranted.

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Section: Introductionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Inflammatory and Vascular Correlates of Mood Change Over 8 Weeks

et al. 2019

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“…Although multiple factors undoubtedly contribute, extensive evidence indicates that vascular dysfunction plays a pathogenic role in depression-CVD comorbidity. MDD is associated with impairments in vascular function graded in relation to the severity of depressive symptoms [8][9][10][11] . Depression-induced impairments in brachial artery endothelium-dependent dilation [flow-mediated dilation (FMD)] are indicative of reductions in vascular nitric oxide (NO) bioavailability and function 8,[11][12][13][14] .…”

Section: Introductionmentioning

confidence: 99%

Oxidative Stress Contributes to Microvascular Endothelial Dysfunction in Men and Women With Major Depressive Disorder

Greaney

Saunders

Santhanam

et al. 2019

Circulation Research

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Rationale: In rodent models of depression, oxidative stress-induced reductions in nitric oxide (NO) bioavailability contribute to impaired endothelium-dependent dilation. Endothelial dysfunction is evident in Major Depressive Disorder (MDD); however, the molecular mediators remain undefined. Objective: We sought to translate preclinical findings to humans by testing the role of oxidative stress in mediating microvascular endothelial dysfunction, including potential modulatory influences of sex, in MDD. Methods and Results: Twenty-four treatment-naïve, otherwise healthy, young adults with MDD (14 women; 18-23 yrs) and twenty healthy adults (HC; 10 women; 19-30 yrs) participated. Red blood cell flux (laser Doppler flowmetry) was measured during graded intradermal microdialysis perfusion of the endothelium-dependent agonist acetylcholine, alone and in combination with an NO synthase inhibitor (L-NAME), a superoxide scavenger (Tempol), and an NADPH oxidase inhibitor (apocynin), as well as during perfusion of the endothelium-independent agonist sodium nitroprusside. Tissue oxidative stress markers (e.g., nitrotyrosine abundance, superoxide production) were also quantified. Endothelium-dependent dilation was blunted in MDD and mediated by reductions in NO-dependent dilation. Endothelium-independent dilation was likewise attenuated in MDD. In MDD, there were no sex differences in either NO-mediated endothelium-dependent dilation or endothelium-independent dilation. Acute scavenging of superoxide or inhibition of NADPH oxidase improved NO-dependent dilation in MDD. Expression and activity of oxidative stress markers were increased in MDD. In a subset of adults with MDD treated with a selective serotonin reuptake inhibitor for their depressive symptoms and in remission (n=8; 7 women; 19-37 yrs), NO-mediated endothelium-dependent dilation was preserved, but endothelium-independent dilation was impaired, compared to HC.

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“…Indeed, medical internship year is a difficult transition marked by high stress [33,34], long workdays and burnout [35,36], and inadequate sleep [37][38][39][40][41][42]. Prior studies have shown these factors to create an environment fertile for developing psychiatric illness [13,[43][44][45][46][47]. Significantly, nearly one-fifth of training physicians report significant sleep disturbance complaints in the months preceding intern year, and these disturbed sleepers are at more than twice the odds to develop depression during internship than good sleepers [39].…”

Section: Introductionmentioning

confidence: 99%

Insomnia symptoms and short sleep predict anxiety and worry in response to stress exposure: a prospective cohort study of medical interns

et al. 2019

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Study objectives: While anxiety rates are alarmingly high in short sleeping insomniacs, the relationship between insomnia and anxiety symptoms has not been extensively studied, especially in comparison to the relationship between insomnia and depressive symptoms. Using residency training as a naturalistic stress exposure, we prospectively assessed the role of sleep disturbance and duration on anxiety-risk in response to stress. Methods: Web-based survey data from 1336 first-year training physicians (interns) prior to and then quarterly across medical internship. Using mixed effects modeling, we examined how preinternship sleep disturbance and internship sleep duration predicted symptoms of anxiety, using an established tool for quantifying symptom severity in generalized anxiety disorder (GAD). Results: Pre-internship poor sleepers are at more than twice the odds of having short sleep (≤6 h) during internship as good sleepers (OR = 2.38, 95% CI = 1.61, 3.57). Poor sleepers were also at twice the odds for screening positive for probable GAD diagnosis (OR = 2.08, 95% CI = 1.26, 3.45). Notably, sleep onset insomnia strongly predicted anxiety development under stress (OR = 3.55, 95% CI = 1.49, 8.45). During internship, short sleep associated with concurrent anxiety symptoms (b = −0.26, 95% CI = −0.38, −0.14) and predicted future anxiety symptoms even more strongly (b = −0.39, 95% CI = −0.76, −0.03). Conclusions: Poor sleepers, particularly those with sleep onset insomnia symptoms, are vulnerable to short sleep and GAD anxiety and worry during chronic stress.

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The development of depressive symptoms during medical internship stress predicts worsening vascular function

Cited by 15 publications

References 23 publications

Inflammatory and Vascular Correlates of Mood Change Over 8 Weeks

Inflammatory and Vascular Correlates of Mood Change Over 8 Weeks

Oxidative Stress Contributes to Microvascular Endothelial Dysfunction in Men and Women With Major Depressive Disorder

Insomnia symptoms and short sleep predict anxiety and worry in response to stress exposure: a prospective cohort study of medical interns

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