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      Risk of future depression in people who are obese but metabolically healthy: the English longitudinal study of ageing.

      Molecular Psychiatry
      Aging, metabolism, psychology, Blood Pressure, physiology, Body Mass Index, C-Reactive Protein, Cholesterol, Depression, blood, complications, physiopathology, Female, Health Status, Hemoglobin A, Glycosylated, Humans, Longitudinal Studies, Male, Metabolic Syndrome X, diagnosis, epidemiology, Middle Aged, Obesity, Psychiatric Status Rating Scales, Risk Factors

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          Abstract

          There is some evidence to suggest that obesity is a risk factor for the development of depression, although this is not a universal finding. This discordance might be ascribed to the existence of a 'healthy obese phenotype'--that is, obesity in the absence of the associated burden of cardiometabolic risk factors. We examined whether the association of obesity with depressive symptoms is dependent on the individual's metabolic health. Participants were 3851 men and women (aged 63.0±8.9 years, 45.1% men) from the English Longitudinal Study of Ageing, a prospective study of community dwelling older adults. Obesity was defined as body mass index ≥30 kg m(-2). Based on blood pressure, high-density lipoprotein cholesterol, triglycerides, glycated haemoglobin and C-reactive protein, participants were classified as 'metabolically healthy' (0 or 1 metabolic abnormality) or 'unhealthy' (≥2 metabolic abnormalities). Depressive symptoms were assessed at baseline and at 2 years follow-up using the 8-item Centre of Epidemiological Studies Depression (CES-D) scale. Obesity prevalence was 27.5%, but 34.3% of this group was categorized as metabolically healthy at baseline. Relative to non-obese healthy participants, after adjustment for baseline CES-D score and other covariates, the metabolically unhealthy obese participants had elevated risk of depressive symptoms at follow-up (odds ratio (OR)=1.50; 95% confidence interval (CI), 1.05-2.15), although the metabolically healthy obese did not (OR=1.38; 95% CI, 0.88-2.17). The association between obesity and risk of depressive symptoms appears to be partly dependent on metabolic health, although further work is required to confirm these findings.

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          Most cited references57

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          From inflammation to sickness and depression: when the immune system subjugates the brain.

          In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour. When activation of the peripheral immune system continues unabated, such as during systemic infections, cancer or autoimmune diseases, the ensuing immune signalling to the brain can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals. These phenomena might account for the increased prevalence of clinical depression in physically ill people. Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors.
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            A meta-analysis of cytokines in major depression.

            Major depression occurs in 4.4% to 20% of the general population. Studies suggest that major depression is accompanied by immune dysregulation and activation of the inflammatory response system (IRS). Our objective was to quantitatively summarize the data on concentrations of specific cytokines in patients diagnosed with a major depressive episode and controls. We performed a meta-analysis of studies measuring cytokine concentration in patients with major depression, with a database search of the English literature (to August 2009) and a manual search of references. Twenty-four studies involving unstimulated measurements of cytokines in patients meeting DSM criteria for major depression were included in the meta-analysis; 13 for tumor necrosis factor (TNF)-alpha, 9 for interleukin (IL)-1beta, 16 for IL-6, 5 for IL-4, 5 for IL-2, 4 for IL-8, 6 for IL-10, and 4 for interferon (IFN)-gamma. There were significantly higher concentrations of TNF-alpha (p < .00001), weighted mean difference (WMD) (95% confidence interval) 3.97 pg/mL (2.24 to 5.71), in depressed subjects compared with control subjects (438 depressed/350 nondepressed). Also, IL-6 concentrations were significantly higher (p < .00001) in depressed subjects compared with control subjects (492 depressed/400 nondepressed) with an overall WMD of 1.78 pg/mL (1.23 to 2.33). There were no significant differences among depressed and nondepressed subjects for the other cytokines studied. This meta-analysis reports significantly higher concentrations of the proinflammatory cytokines TNF-alpha and IL-6 in depressed subjects compared with control subjects. While both positive and negative results have been reported in individual studies, this meta-analytic result strengthens evidence that depression is accompanied by activation of the IRS. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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              Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies.

              Association between obesity and depression has repeatedly been established. For treatment and prevention purposes, it is important to acquire more insight into their longitudinal interaction. To conduct a systematic review and meta-analysis on the longitudinal relationship between depression, overweight, and obesity and to identify possible influencing factors. Studies were found using PubMed, PsycINFO, and EMBASE databases and selected on several criteria. Studies examining the longitudinal bidirectional relation between depression and overweight (body mass index 25-29.99) or obesity (body mass index > or =30) were selected. Unadjusted and adjusted odds ratios (ORs) were extracted or provided by the authors. Overall, unadjusted ORs were calculated and subgroup analyses were performed for the 15 included studies (N = 58 745) to estimate the effect of possible moderators (sex, age, depression severity). Obesity at baseline increased the risk of onset of depression at follow-up (unadjusted OR, 1.55; 95% confidence interval [CI], 1.22-1.98; P or =60 years) but not among younger persons (aged <20 years). Baseline depression (symptoms and disorder) was not predictive of overweight over time. However, depression increased the odds for developing obesity (OR, 1.58; 95% CI, 1.33-1.87; P < .001). Subgroup analyses did not reveal specific moderators of the association. This meta-analysis confirms a reciprocal link between depression and obesity. Obesity was found to increase the risk of depression, most pronounced among Americans and for clinically diagnosed depression. In addition, depression was found to be predictive of developing obesity.
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