Depression and 24-hour urinary cortisol in medical outpatients with coronary heart disease: The Heart and Soul Study

Otte, Christian; Marmar, Charles R.; Pipkin, Sharon; Moos, Rudolf H.; Browner, Warren S.; Whooley, Mary A.

doi:10.1016/j.biopsych.2004.06.003

Cited by 117 publications

(78 citation statements)

References 60 publications

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“…In turn, norepinephrine enhances forebrain CRF activity, possibly closing a feed-forward loop leading to higher activity of both norepinephrine and CRF in depressed patients (37). Indeed, in this study group, we also found increased cortisol levels in depressed patients (42), consistent with this model of norepinephrine-CRF interaction (10).…”

Section: Discussionsupporting

confidence: 83%

Depressive Symptoms and 24-Hour Urinary Norepinephrine Excretion Levels in Patients With Coronary Disease: Findings From the Heart and Soul Study

Otte¹,

Neylan²,

Pipkin³

et al. 2005

AJP

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Objective-Depressive symptoms are associated with an increased risk of cardiac events in patients with heart disease. Elevated catecholamine levels may contribute to this association, but whether depressive symptoms are associated with catecholamine levels in patients with heart disease is unknown. Method-The authors examined the association between depressive symptoms (defined by a PatientHealth Questionnaire score ≥10) and 24-hour urinary norepinephrine, epinephrine, and dopamine excretion levels in 598 subjects with coronary disease.Results-A total of 106 participants (18%) had depressive symptoms. Participants with depressive symptoms had greater mean norepinephrine excretion levels than those without depressive symptoms (65 μg/day versus 59 μg/day, with adjustment for age, sex, body mass index, smoking, urinary creatinine levels, comorbid illnesses, medication use, and cardiac function). In logistic regression analyses, participants with depressive symptoms were more likely than those without depressive symptoms to have norepinephrine excretion levels in the highest quartile and above the normal range. Depressive symptoms were not associated with dopamine or epinephrine excretion levels.Conclusions-In patients with coronary disease, depressive symptoms are associated with elevated norepinephrine excretion levels. Future longitudinal studies are needed to determine whether elevations in norepinephrine contribute to adverse cardiac outcomes in patients with depressive symptoms.Coronary disease and major depression are the two leading causes of disability worldwide (1). Depressive symptoms occur in about 20% of patients with coronary disease (2,3) and are associated with an increased risk of future cardiac events and mortality (4-7). However, the mechanisms linking depressive symptoms with subsequent cardiac events are unknown (8).Enhanced activity of the sympathetic nervous system with increased concentrations of catecholamines has been proposed as one possible mechanism by which depressive symptoms may increase morbidity and mortality (7-9). This hypothesis is based on evidence suggesting that depressed patients without heart disease have elevated catecholamine levels (10-12). Previous studies have also found alterations of the sympathetic nervous system in depressed NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript patients with coronary heart disease, including increased heart rate (13) and decreased heart rate variability (14). High catecholamine levels can damage cardiac myocytes (15,16) and have been associated with cardiac events and mortality in a variety of clinical and population-based samples (17)(18)(19)(20)(21)(22). Thus, altered autonomic tone may contribute to adverse cardiac outcomes in patients with depression.The Heart and Soul Study is an ongoing prospective cohort study of psychosocial factors and health outcomes in patients with coronary disease (3). We examined the association of depressive symptoms with 24-hour levels of uri-nary norepinephrine, epinephr...

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Section: Discussionsupporting

confidence: 83%

Depressive Symptoms and 24-Hour Urinary Norepinephrine Excretion Levels in Patients With Coronary Disease: Findings From the Heart and Soul Study

Otte¹,

Neylan²,

Pipkin³

et al. 2005

AJP

Self Cite

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“…Our study provides evidence for the proposition that elevated cortisol levels increase the risk of the metabolic syndrome. An association between urinary cortisol and metabolic parameters was not observed in a study by Otte et al (2004); however this study did not investigate the metabolic syndrome as a whole and did not examine depression*cortisol interactions. Most importantly, our study confirmed the hypothesis that when both depression and high cortisol levels are present, the odds of the metabolic syndrome is increased.…”

Section: Discussionmentioning

confidence: 72%

Hypercortisolemic depression is associated with the metabolic syndrome in late-life

Vogelzangs

Suthers

Ferrucci

et al. 2007

Psychoneuroendocrinology

195

168

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“…Details regarding our recruitment procedures have been published previously (23)(24)(25). In brief, we used administrative databases to identify outpatients with documented coronary disease at two Department of Veterans Affairs (VA) medical centers in California (San Francisco VA Medical Center and VA Palo Alto Health Care System), one university medical center (University of California, San Francisco), and nine public health clinics in the Community Health Network of San Francisco.…”

Section: Methods Participantsmentioning

confidence: 99%

Association of a Serotonin Transporter Polymorphism (5-HTTLPR) With Depression, Perceived Stress, and Norepinephrine in Patients With Coronary Disease: The Heart and Soul Study

Otte

McCaffery²,

Ali³

et al. 2007

AJP

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134

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Objective-The short allele of a functional polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) has been shown to interact with stressful life events to predict depression in otherwise healthy individuals. Whether the short allele increases risk for depression associated with the stress of a chronic illness has not been established.Method-In a cross-sectional genetic association study, the authors examined the association of 5-HTTLPR with current depression (measured by the Computerized Diagnostic Interview Schedule), perceived stress (measured by the Perceived Stress Scale), and 24-hour urinary norepinephrine excretion in 557 outpatients with chronic coronary disease.Results-Among individuals carrying an s allele, 25% (97 of 383) had current depression, compared with 17% (29 of 174) of l/l homozygotes. The unadjusted odds ratio was 1.6, with a 95% confidence interval (CI) of 1.0-2.6; the age-and gender-adjusted odds ratio was also 1.6 (95% CI= 1.0-2.5). Participants carrying an s allele had a higher mean score for perceived stress than l/l homozygotes (5.4 versus 4.7) and a higher rate of moderate or high perceived stress (adjusted odds ratio=1.6, 95% CI=1.1-2.3). Mean 24-hour norepinephrine excretion was higher in s allele carriers (55.6 versus 50.2 μg/day), who were more likely to have norepinephrine values in the highest quartile (adjusted odds ratio=1.7, 95% CI=1.0-3.0).Conclusions-Among patients with chronic illness, carriers of the s allele of 5-HTTLPR are more vulnerable to depression, perceived stress, and high norepinephrine secretion. These factors may contribute to worse cardiovascular outcomes in these patients.The serotonin, or 5-HT (5-hydroxytryptamine), system is critically involved in the pathophysiology of mood and anxiety disorders, and drugs that target serotonergic neurotransmission are efficacious for the treatment of these disorders (1). The serotonin transporter (5-HTT) plays an important role in serotonergic neurotransmission by facilitating reuptake of 5-HT from the synaptic cleft. A repeat of 20-23 base pairs has been observed as a motif within a polymorphic region of the serotonin transporter gene, and it occurs as two prevalent alleles: one consisting of 14 repeats (the short allele variant) and another of 16 repeats (the long allele variant). This functional polymorphism in the 5-regulatory promoter region, termed 5-HTTLPR (5-HTT-gene-linked polymorphic region), alters transcription of the serotonin transporter gene (2). Specifically, the short allele of the 5-HTTLPR polymorphism is thought to reduce transcription efficiency for the gene, resulting in decreased expression of the serotonin transporter and decreased serotonin uptake in lymphoblast cell lines and blood platelets (3,4) and decreased availability of the serotonin transporter in human imaging studies (5). The s allele appears to exert its effect independent of s allele load, i.e., in a dominant manner (6).With remarkable consistency (exceptions are studies by Surtees et al. [7] and Gill...

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Depression and 24-hour urinary cortisol in medical outpatients with coronary heart disease: The Heart and Soul Study

Cited by 117 publications

References 60 publications

Depressive Symptoms and 24-Hour Urinary Norepinephrine Excretion Levels in Patients With Coronary Disease: Findings From the Heart and Soul Study

Depressive Symptoms and 24-Hour Urinary Norepinephrine Excretion Levels in Patients With Coronary Disease: Findings From the Heart and Soul Study

Hypercortisolemic depression is associated with the metabolic syndrome in late-life

Association of a Serotonin Transporter Polymorphism (5-HTTLPR) With Depression, Perceived Stress, and Norepinephrine in Patients With Coronary Disease: The Heart and Soul Study

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