Unraveling the Pathogenesis of the Depression–Diabetes Link

Ismail, Khalida

doi:10.1002/9780470667309.ch2

Cited by 15 publications

(18 citation statements)

References 128 publications

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“…These include increased pro-inflammatory cytokines, abnormalities of the hypothalamic pituitary axis (HPA), changes in homeostasis between the sympathetic and parasympathetic nervous systems and changes in metabolism [16-19]. …”

Section: Discussionmentioning

confidence: 99%

Endocrine and inflammatory profiles in type 2 diabetic patients with and without major depressive disorder

et al. 2013

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BackgroundThere is a high prevalence of depression in individuals with type 2 diabetes mellitus. Depressive disorders are associated with increased medical morbidity and mortality in individuals with diabetes. It has been demonstrated that there is a higher prevalence of diabetic complications among individuals with diabetes and depression compared to those without depression. Several biological alterations have been reported in individuals with depressive disorders, particularly abnormal levels of endocrine-inflammatory markers.This study aims to determine the prevalence of major depressive disorder (MDD) in type 2 diabetes patients, the prevalence of cardiovascular events in individuals with and without MDD and to compare the endocrine-inflammatory profile between groups.MethodsThe study was approved by the “Comité de Etica de Protocolos de Investigación del Departamento de Docencia e Investigación del Hospital Italiano de Buenos Aires” with the number “1262” and included only patients who provided written informed consent. The study was conducted in accordance with the Declaration of Helsinki and the Habeas Data law on protection of personal data (Law Nª 25326, Argentina).Type 2 diabetes patients (n = 61) were included and they were classified as having MDD or not according to DSM-IV. Macrovascular disease was obtained from the medical history. Additionally, the intima-media thickness of the common carotid, carotid bifurcations and internal carotid arteries was measured non-invasively by two-dimensional ultrasound imaging. Fasting glucose, fasting lipid profile, inflammatory (CRP, TNF-α) and endocrine (urine free cortisol and saliva cortisol) markers. Student t tests were used to compare means for normally distributed variables and Mann-Whitney test for variables without normal distribution. Relative frequencies were calculated and a chi-square analysis was conducted. Data were expressed as mean ± standard deviation (SD) or median and interquartile range. Multivariable logistic regression was used to determine the relative odds of clinical cardiovascular disease in individuals with compared to those without depression. Differences were considered significant using a two-sided p < 0.05.Results21 patients (34%) had MDD and 40 patients (66%) didn’t have MDD. Diabetic patients with MDD had significantly higher CRP levels (4.1(1.9-7.6) vs 1.5(0.5-4.4) mg/l; p = 0.02) and 24-hour urine free cortisol (71.4 ± 21.3 vs 59.8 ± 29.3 ug/24 h; p = 0.03). The other metabolic and inflammatory parameters were not statistically different between groups. There was a significantly higher prevalence of cardiovascular events in individuals with MDD: 38% for the depressive group vs 15% for non-depressive group, p = 0.04). Patients with MDD had a 3.5-fold greater odd of having cardiovascular disease.ConclusionsDiabetic patients with depression are more likely to have cardiovascular events, and different factors can determine this high association.

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Section: Discussionmentioning

confidence: 99%

Endocrine and inflammatory profiles in type 2 diabetic patients with and without major depressive disorder

et al. 2013

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“…Although the mechanisms responsible for producing the high rates of depression and dementia in diabetes are not well understood, the overlap of numerous physiological and non-physiological factors likely account for the pathogenesis of their comorbidity (Ismail, 2010). Non-physiological factors, such as sedentary lifestyle, diet, lack of self-care and history of substance abuse, contribute to the development of diabetes.…”

Section: Introductionmentioning

confidence: 99%

Effects of diabetes on hippocampal neurogenesis: Links to cognition and depression

Sommers

Lucki

2013

Neuroscience & Biobehavioral Reviews

220

160

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Diabetes often leads to a number of complications involving brain function, including cognitive decline and depression. In addition, depression is a risk factor for developing diabetes. A loss of hippocampal neuroplasticity, which impairs the ability of the brain to adapt and reorganize key behavioral and emotional functions, provides a framework for understanding this reciprocal relationship. The effects of diabetes on brain and behavioral functions in experimental models of type 1 and type 2 diabetes are reviewed, with a focus on the negative impact of impaired hippocampal neurogenesis, dendritic remodeling and increased apoptosis. Mechanisms shown to regulate neuroplasticity and behavior in diabetes models, including stress hormones, neurotransmitters, neurotrophins, inflammation and aging, are integrated within this framework. Pathological changes in hippocampal function can contribute to the brain symptoms of diabetes-associated complications by failing to regulate the hypothalamic-pituitary-axis, maintain learning and memory and govern emotional expression. Further characterization of alterations in neuroplasticity along with glycemic control will facilitate the development and evaluation of pharmacological interventions that could successfully prevent and/or reverse the detrimental effects of diabetes on brain and behavior.

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“…The mechanisms for this bidirectional relationship between depressive symptoms and diabetes are not well understood (10). We are investigating activated innate immunity as the common antecedent for the parallel development of diabetes and depression, and for cardiovascular disease (which is a common comorbidity of diabetes and depression), since there is evidence for the involvement of innate immunity in the pathogenesis of all three.…”

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confidence: 99%

The Association Between Depressive Symptoms and Systemic Inflammation in People With Type 2 Diabetes: Findings From the South London Diabetes Study

et al. 2014

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OBJECTIVEThe prevalence of depression and depressive symptoms is increased twofold in people with type 2 diabetes compared with the general population and is associated with worse biomedical outcomes and increased mortality. Type 2 diabetes, cardiovascular disease, and depression in nondiabetes subjects are independently associated with raised concentrations of circulating inflammatory markers, but it is not known if a similar association is observed in type 2 diabetes. We tested the hypothesis that higher depressive symptom scores in newly diagnosed type 2 diabetes patients were associated with higher concentrations of inflammatory markers. RESEARCH DESIGN AND METHODSDepressive symptoms in adults with newly diagnosed type 2 diabetes recruited from primary care were assessed using the Patient Health Questionnaire-9. RESULTSThe baseline cohort consisted of 1,790 participants. After adjusting for covariates, CRP (B = 0.13, P < 0.001), IL-1b (B = 0.06, P = 0.047), IL-1RA (B = 0.13, P < 0.001), MCP-1 (B = 0.11, P = 0.001), WBC (B = 0.13, P < 0.001), and TG (B = 0.10, P < 0.001) were associated with depressive symptoms. CONCLUSIONSIncreased inflammation may be involved in the pathogenesis of depressive symptoms in type 2 diabetes and contribute to the increased risk of complications and mortality in this group.

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Unraveling the Pathogenesis of the Depression–Diabetes Link

Cited by 15 publications

References 128 publications

Endocrine and inflammatory profiles in type 2 diabetic patients with and without major depressive disorder

Endocrine and inflammatory profiles in type 2 diabetic patients with and without major depressive disorder

Effects of diabetes on hippocampal neurogenesis: Links to cognition and depression

The Association Between Depressive Symptoms and Systemic Inflammation in People With Type 2 Diabetes: Findings From the South London Diabetes Study

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