Self‐Reported Everyday Psychosocial Stressors Are Associated With Greater Impairments in Endothelial Function in Young Adults With Major Depressive Disorder

Greaney, Jody L.; Koffer, Rachel; Saunders, Erika F.H.; Almeida, David M.; Alexander, Lacy M.

doi:10.1161/jaha.118.010825

Cited by 28 publications

(21 citation statements)

References 61 publications

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“…Fourteen otherwise healthy nonmedicated adults with MDD were screened; of these, 12 patients (8 women) met the inclusion criteria for study enrollment (Table 1). Three of these adults with MDD participated in previous studies in our laboratory (15,16). Twelve healthy adults (8 women) without any history of major psychiatric illness, also recruited from campus using standard recruitment strategies, served as the control group.…”

Section: Methodsmentioning

confidence: 99%

“…Twelve healthy adults (8 women) without any history of major psychiatric illness, also recruited from campus using standard recruitment strategies, served as the control group. All participants underwent the structured clinical Mini-International Neuropsychiatric Interview (41), and a diagnosis of MDD was confirmed by a psychiatrist according to DSM-5 criteria (15,16). Exclusion criteria included comorbid current psychiatric disorders (e.g., psychosis, schizophrenia, bipolar disorder, panic disorder, etc.…”

Section: Methodsmentioning

confidence: 99%

“…The PHQ-9 rates the nine symptoms of depression on a four-point scale, ranging from 0 ϭ "not at all" to 3 ϭ "nearly every day." Response options are used to calculate a total score (maximum ϭ 27) and symptom severity is quantified as none (0 -4), mild (5-9), moderate (10 -14), moderately severe (15)(16)(17)(18)(19), or severe (20 -27).…”

Section: Methodsmentioning

confidence: 99%

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Peripheral microvascular serotoninergic signaling is dysregulated in young adults with major depressive disorder

Greaney

Dillon

Saunders

et al. 2020

Journal of Applied Physiology

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Dysfunction of the brain serotonergic system is implicated in the pathogenesis of major depressive disorder (MDD). Serotonin is also a vasoactive signaling molecule, the effects of which are modulated by both nitric oxide (NO) and the serotonin transporter [the primary target of selective serotonin reuptake inhibitors (SSRIs)]. Despite its role in the neurobiology of depression, serotoninergic signaling mechanisms in the microvasculature of adults with MDD are unknown. We hypothesized that 1) cutaneous microvascular responsiveness to serotonin would be attenuated in MDD and mediated by reductions in both 2) NO-dependent and 3) serotonin reuptake-dependent mechanisms. In 12 adults with MDD (nonmedicated) and 12 nondepressed adults, red cell flux (laser-Doppler flowmetry) was measured during graded intradermal microdialysis perfusion of 1) serotonin (10−10 to 10−1 mol/L) alone and in combination with a nonselective NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME; 15 mmol/L) and the SSRI paroxetine (10 μmol/L); and 2) paroxetine ( n = 6; 10−9 to 10−2 M) alone and in combination with l-NAME. Serotonin-induced vasodilation was preserved in MDD. The NO-dependent component of serotonin-induced vasodilation was not different between groups. Paroxetine augmented vasodilatory responsiveness to serotonin via NO-dependent mechanisms in both groups; however, the magnitude was blunted in MDD. The NO contribution to direct paroxetine-induced vasodilation was also reduced in adults with MDD. Collectively, these preliminary data suggest that cutaneous microvascular serotoninergic signaling is dysregulated in adults with MDD and mediated by NO-dependent and serotonin reuptake-dependent mechanisms, providing initial mechanistic insight to the purported vasculoprotective effect of chronic SSRI treatment. NEW & NOTEWORTHY Cutaneous microvascular vasodilatory responsiveness to serotonin was preserved in adults with major depressive disorder (MDD). However, the contribution of serotonin reuptake-dependent mechanisms to serotonin-induced dilation was reduced in MDD. Direct perfusion of the selective serotonin reuptake inhibitor (SSRI) paroxetine elicited vasodilation that is partially mediated by nitric oxide (NO)-dependent mechanisms, but these responses were blunted in MDD, reflective of a diminished contribution of NO to the direct effects of a SSRI on the cutaneous microvasculature.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Peripheral microvascular serotoninergic signaling is dysregulated in young adults with major depressive disorder

Greaney

Dillon

Saunders

et al. 2020

Journal of Applied Physiology

Self Cite

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“…A link between neurovascular dysfunction and MDD pathology is supported by studies assessing peripheral vascular endothelial dysfunction in patients with depressive symptoms. For instance, MDD is associated with greater impairments in vascular conductance as measured by endothelium-dependent dilatation (Greaney, Koffer, Saunders, Almeida & Alexander, 2019). Furthermore, a prospective study of subjects with various depressive disorders has shown a lower relative uptake ratio (RUR) of blood flow in the brachial artery of MDD patients in comparison with non-depressed controls (Lavoie, Pelletier, Arsenault, Dupuis & Bacon, 2010).…”

Section: Neurovascular Adaptations In Human Depressionmentioning

confidence: 99%

Neurobiology of resilience in depression: immune and vascular insights from human and animal studies

Dudek

Dion‐Albert

Kaufmann

et al. 2019

Eur J of Neuroscience

100

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“…25 These JAMA Network Open | Cardiology shown to be associated with perceived stress in patients with cardiovascular disease. 26 To examine whether chronic stress was associated with mortality, independent of baseline depressive symptoms, we performed a secondary analysis that adjusted for baseline PHQ-8 score in the Cox proportional hazards regression model. To understand whether baseline stress moderated the association between chronic stress and mortality, we assessed the interaction between baseline stress and chronic stress toward the outcome of mortality.…”

Section: Discussionmentioning

confidence: 99%

Association of Perceived Stress Levels With Long-term Mortality in Patients With Peripheral Artery Disease

et al. 2020

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IMPORTANCE Identifying modifiable risk factors, such as stress, that could inform the design of peripheral artery disease (PAD) management strategies is critical for reducing the risk of mortality. Few studies have examined the association of self-perceived stress with outcomes in patients with PAD. OBJECTIVE To examine the association of high levels of self-perceived stress with mortality in patients with PAD. DESIGN, SETTING, AND PARTICIPANTS This cohort study analyzed data from the registry of the Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories (PORTRAIT) study, a multicenter study that enrolled patients with new or worsening symptoms of PAD who presented to 16 subspecialty clinics across the US, the Netherlands, and Australia from June 2, 2011, to December 3, 2015. However, the present study included only patients in the US sites because assessments of mortality for patients in the Netherlands and Australia were not available. Data analysis was conducted from July 2019 to March 2020. EXPOSURE Self-perceived stress was quantified using the 4-item Perceived Stress Scale (PSS-4), with a score range of 0 to 16. A score of 6 or higher indicated high stress in this cohort. Missing scores were imputed using multiple imputation by chained equations with predictive mean matching. Stress was assessed at baseline and at 3-, 6-, and 12-month follow-up. Patients who reported high levels of stress at 2 or more follow-up assessments were categorized as having chronic stress. MAIN OUTCOMES AND MEASURES All-cause mortality was the primary study outcome. Such data for the subsequent 4 years after the 12-month follow-up were obtained from the National Death Index. RESULTS The final cohort included 765 patients, with a mean (SD) age of 68.4 (9.7) years. Of these patients, 57.8% were men and 71.6% were white individuals. High stress levels were reported in 65% of patients at baseline and in 20% at the 12-month follow-up. In an adjusted Cox proportional hazards regression model accounting for demographics, comorbidities, disease severity, treatment type, and socioeconomic status, exposure to chronic stress during the 12 months of follow-up was independently associated with increased risk of all-cause mortality in the subsequent 4 years (hazard ratio, 2.12; 95% CI, 1.14-3.94; P = .02). CONCLUSIONS AND RELEVANCE In thie cohort study of patients with PAD, higher stress levels in the year after diagnosis appeared to be associated with greater long-term mortality risk, even after adjustment for confounding factors. These findings suggest that, given that stress is a modifiable risk (continued) Key Points Question Is there an association between chronic stress and mortality risk in patients with peripheral artery disease? Findings In this cohort study of 765 patients with new symptoms of peripheral artery disease, higher stress levels in the year after diagnosis were independently associated with higher risk of mortality in the subsequent 4 years. Meaning The findings o...

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Self‐Reported Everyday Psychosocial Stressors Are Associated With Greater Impairments in Endothelial Function in Young Adults With Major Depressive Disorder

Cited by 28 publications

References 61 publications

Peripheral microvascular serotoninergic signaling is dysregulated in young adults with major depressive disorder

Peripheral microvascular serotoninergic signaling is dysregulated in young adults with major depressive disorder

Neurobiology of resilience in depression: immune and vascular insights from human and animal studies

Association of Perceived Stress Levels With Long-term Mortality in Patients With Peripheral Artery Disease

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