Depression is the most common psychiatric disorder worldwide. The burden of disease for depression goes beyond functioning and quality of life and extends to somatic health. Depression has been shown ...to subsequently increase the risk of, for example, cardiovascular, stroke, diabetes and obesity morbidity. These somatic consequences could partly be due to metabolic, immuno-inflammatory, autonomic and hypothalamic-pituitary-adrenal (HPA)-axis dysregulations which have been suggested to be more often present among depressed patients. Evidence linking depression to metabolic syndrome abnormalities indicates that depression is especially associated with its obesity-related components (for example, abdominal obesity and dyslipidemia). In addition, systemic inflammation and hyperactivity of the HPA-axis have been consistently observed among depressed patients. Slightly less consistent observations are for autonomic dysregulation among depressed patients. The heterogeneity of the depression concept seems to play a differentiating role: metabolic syndrome and inflammation up-regulations appear more specific to the atypical depression subtype, whereas hypercortisolemia appears more specific for melancholic depression. This review finishes with potential treatment implications for the downward spiral in which different depressive symptom profiles and biological dysregulations may impact on each other and interact with somatic health decline.
Although the association between depression and excess mortality has been well established, it is not clear whether this is greater in major depression than in subthreshold depression.
To compare ...excess mortality in major depression with that in subthreshold depression.
We searched bibliographic databases and included prospective studies in which both major and subthreshold depression were examined at baseline and mortality was measured at follow-up.
A total of 22 studies were included. People with major depression had a somewhat increased chance of dying earlier than people with subthreshold depression but this difference was not significant, although there was a trend (relative risk 1.13, 95% CI 0.98-1.30, P = 0.1). The population attributable fraction was 7% for major depression and an additional 7% for subthreshold depression.
Although excess mortality may be somewhat higher in major than in subthreshold depression, the difference is small and the overall impact on excess mortality is comparable.
Abstract Systemic inflammation has emerged as a potential pathway linking depressive and anxiety disorders with disease risk. Short and long sleep duration, as well as insomnia, are common among ...psychiatric populations and have previously been related to increased inflammation. The aim of the present study was to investigate associations between sleep duration and insomnia with biomarkers of inflammation and to explore whether these associations varied by psychiatric diagnostic status. To this end, self-reported measures of sleep duration, insomnia symptoms, and markers of inflammation, including C-reactive protein (CRP), interleukin-(IL)-6, and tumor necrosis factor (TNF)-α, were obtained in 2553 adults (aged 18–65 years) diagnosed with current/recent or remitted depressive and/or anxiety disorders and healthy controls enrolled in the Netherlands Study of Depression and Anxiety (NESDA). Regression analyses revealed associations between sleep duration and levels of CRP and IL-6 with higher levels observed in long sleepers. These associations remained statistically significant after controlling for age, gender, education, body mass index, smoking, alcohol consumption, medical comorbidities, medication use, psychotropic medication use, and psychiatric diagnostic status. There were no clear associations between insomnia symptoms and levels of inflammation. Relationships between sleep duration and inflammation did not vary as a function of psychiatric diagnostic status. These findings suggest that elevated levels of systemic inflammation may represent a mechanism linking long sleep duration and disease risk among those with and without depressive and anxiety disorders.
Summary Background Several studies have suggested that induced tryptophan (TRP) degradation through the kynurenine (KYN) pathway by the enzyme indoleamine 2,3-dioxygenase (IDO) is implicated in the ...relation between depression and inflammation. We investigated the role of tryptophan degradation in the relationship between inflammatory markers and depressive symptoms in the Netherlands Study of Depression and Anxiety (NESDA) and hypothesized that tryptophan degradation would mediate (part of) this association. Methods 2812 Participants of NESDA were included in this study including 1042 persons with current major depressive disorder (MDD). Assessments of C-reactive protein (CRP), interleukin (IL)-6, tumor-necrosis factor (TNF)-α, KYN and TRP were obtained from fasting blood samples at the baseline assessment. Tryptophan degradation was estimated by calculating the ratio KYN/TRP. Depressive symptoms were measured with the Inventory of Depressive Symptomatology. Results Significant associations between inflammation and depressive symptoms were found for CRP and IL-6, for the total group and the subgroup of patients with current MDD. Adjustment for KYN/TRP did not attenuate these associations. There were no significant indirect effects for CRP on depressive symptoms mediated by KYN/TRP for the whole group ( B = −0.032; 95% CI: −0.103 to 0.028) and for the subgroup of patients with current MDD ( B = 0.059; 95% CI: −0.037 to 0.165). Also IL-6 did not indirectly affect depressive symptoms through KYN/TRP in the total group ( B = −0.023; 95% CI: −0.093 to 0.045) and in the MDD subgroup B = 0.052; 95% CI: −0.019 to 0.144). Finally, no significant relation between depressive symptoms and KYN/TRP was found in the whole group ( β = −0.019, p = 0.311) nor in the subgroup with MDD ( β = 0.025, p = 0.424). Conclusions We did not find indications for tryptophan degradation, measured by KYN/TRP, to mediate the relationship between inflammation and depressive symptoms.
Context: The stress hormone cortisol has been linked with unfavorable cardiovascular risk factors, but longitudinal studies examining whether high levels of cortisol predict cardiovascular mortality ...are largely absent.
Objective: The aim of this study was to examine whether urinary cortisol levels predict all-cause and cardiovascular mortality over 6 yr of follow-up in a general population of older persons.
Design and Setting: Participants were part of the InCHIANTI study, a prospective cohort study in the older general population with 6 yr of follow-up.
Participants: We studied 861 participants aged 65 yr and older.
Main Outcome Measure: Twenty-four-hour urinary cortisol levels were assessed at baseline. In the following 6 yr, all-cause and cardiovascular mortality was ascertained from death certificates. Cardiovascular mortality included deaths due to ischemic heart disease and cerebrovascular disease.
Results: During a mean follow-up of 5.7 (sd = 1.2) yr, 183 persons died, of whom 41 died from cardiovascular disease. After adjustment for sociodemographics, health indicators, and baseline cardiovascular disease, urinary cortisol did not increase the risk of noncardiovascular mortality, but it did increase cardiovascular mortality risk. Persons in the highest tertile of urinary cortisol had a five times increased risk of dying of cardiovascular disease (hazard ratio = 5.00; 95% confidence interval = 2.02–12.37). This effect was found to be consistent across persons with and without cardiovascular disease at baseline (p interaction = 0.78).
Conclusions: High cortisol levels strongly predict cardiovascular death among persons both with and without preexisting cardiovascular disease. The specific link with cardiovascular mortality, and not other causes of mortality, suggests that high cortisol levels might be particularly damaging to the cardiovascular system.
High cortisol levels predict cardiovascular death among persons with and without pre-existing cardiovascular disease.
The mechanisms that underlie the association between abdominal obesity and depression risk in older persons are not well known, but the "leptin hypothesis" of depression suggests that leptin ...resistance may be involved in mood regulation. We tested whether high circulatory concentration of leptin, alone and in combination with visceral adiposity, is associated with onset of depression in a sample of older persons.
Participants were 1,220 men and 1,282 women aged 70-79 years and enrolled in the Health, Aging, and Body Composition study. Serum concentration of leptin and abdominal visceral fat, ascertained by computed tomography, were assessed at baseline (April 1997-June 1998). Onset of depression, the primary outcome measure, was defined as a Center for Epidemiologic Studies-depression scale 10-item score ≥ 10 and/or new antidepressant medication use at any annual visit over a 5-year follow-up.
Higher leptin level was associated with the risk of depression onset in men with high levels of visceral fat (hazard ratio HR = 1.25; 95% CI, 1.06-1.46; P = .01) but not in those with normal visceral fat (HR = 0.98; 95% CI, 0.80-1.19; P = .80) (leptin-by-visceral fat, P = .04). No interaction between leptin and visceral fat was detected in the analysis focusing on women (P = .90).
In older men, high leptin level was associated with an increased onset of depressive symptoms, especially in the presence of abdominal obesity, suggesting that underlying leptin resistance may play a role in this link. Differences in visceral fat levels and metabolic consequences may explain the absence of this association in women. These findings suggest a potential biological link between depression, obesity, and their joint association with negative health outcomes.
Studies on hypothalamic-pituitary-adrenal axis (HPA-axis) function amongst patients with chronic pain show equivocal results and well-controlled cohort studies are rare in this field. The goal of our ...study was to examine whether HPA-axis dysfunction is associated with the presence and the severity of chronic multi-site musculoskeletal pain.
Data are from the Netherlands Study of Depression and Anxiety including 1125 subjects with and without lifetime depressive and anxiety disorders. The Chronic Pain Grade questionnaire was used to determine the presence and severity of chronic multi-site musculoskeletal pain. Subjects were categorized into a chronic multi-site musculoskeletal pain group (n = 471) and a control group (n = 654). Salivary cortisol samples were collected to assess HPA-axis function (awakening level, 1-h awakening response, evening level, diurnal slope and post-dexamethasone level).
In comparison with the control group, subjects with chronic multi-site musculoskeletal pain showed significantly lower cortisol level at awakening, lower evening level and a blunted diurnal slope. Lower cortisol level at awakening and a blunted diurnal slope appeared to be restricted to those without depressive and/or anxiety disorders, who also showed a lower 1-h awakening response.
Our results suggest hypocortisolemia in chronic multi-site musculoskeletal pain. However, if chronic pain is accompanied by a depressive or anxiety disorder, typically related to hypercortisolemia, the association between cortisol levels and chronic multi-site musculoskeletal pain appears to be partly masked. Future studies should take psychopathology into account when examining HPA-axis function in chronic pain.
ABSTRACT
Aims To identify independent risk factors of the recurrence of alcohol dependence (AD) in people with a remitted disorder at baseline and persistence of AD in people with a current disorder ...at baseline.
Design Prospective cohort study with assessments at baseline and 2‐year follow‐up.
Setting Recruitment from the general population, primary care and out‐patient mental health‐care services.
Participants People with remitted AD (n = 253) and current AD (n = 135).
Measurements Recurrence and persistence of AD during 2‐year follow‐up were established using the Composite International Diagnostic Interview (CIDI) interview based on DSM‐IV. Logistic regression analyses were performed to explore the role of potential risk factors (i.e. baseline severity of alcohol problems, measures for depression and anxiety, socio‐demographics, vulnerability factors and addiction‐related factors) as independent predictors of a negative course.
Findings Overall recurrence and persistence rates of AD were 14.6 and 40.7%, respectively, and were highly conditional on the severity of alcohol problems adjusted odds ratio (OR) per standard deviation (SD) increase: OR = 3.64, 95% confidence interval (CI): 2.21–6.01 and OR = 2.12, 95% CI: 1.32–3.40, respectively). Severity of depressive/anxiety symptoms was an additional independent predictor of the recurrence of AD, whereas male gender and high education were significant independent risk factors of the persistence of AD.
Conclusions Alcohol dependence has a dynamic course, with only moderate levels of diagnostic stability. Both recurrence and persistence of alcohol dependence are highly dependent on severity of baseline alcohol problems, whereas severity of depressive/anxiety symptoms predicts only the recurrence of alcohol dependence. Both measures may be useful in identifying people at an increased risk of a negative course and who could be targeted by prevention strategies.
It has been hypothesized that cellular damage caused by oxidative stress is associated with late-life depression but epidemiological evidence is limited. In the present study we evaluated the ...association between urinary 8-iso-prostaglandin F2α (8-iso-PGF2α), a biomarker of lipid peroxidation, and depressed mood in a large sample of community-dwelling older adults. Participants were selected from the Health, Aging and Body Composition study, a community-based longitudinal study of older persons (aged 70-79 years). The present analyses was based on a subsample of 1027 men and 948 women free of mobility disability. Urinary concentration of 8-iso-PGF2α was measured by radioimmunoassay methods and adjusted for urinary creatinine. Depressed mood was defined as a score greater than 5 on the 15-item Geriatric Depression Scale and/or use of antidepressant medications. Depressed mood was present in 3.0% of men and 5.5% of women. Depressed men presented higher urinary concentrations of 8-iso-PGF2α than non-depressed men even after adjustment for multiple sociodemographic, lifestyle and health factors (p = 0.03, Cohen's d = 0.30). This association was not present in women (depressed status-by-sex interaction p = 0.04). Our study showed that oxidative damage may be linked to depression in older men from a large sample of the general population. Further studies are needed to explore whether the modulation of oxidative stress may break down the link between late-life depression and its deleterious health consequences.
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