بررسی رابطه اختلال در نظم محور هیپوتالاموس-هیپوفیز-آدرنال و مقاومت به انسولین در بیماران مسن مبتلا به افسردگی
|کد مقاله||سال انتشار||مقاله انگلیسی||ترجمه فارسی||تعداد کلمات|
|29729||2015||5 صفحه PDF||سفارش دهید||4281 کلمه|
Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)
Journal : Psychiatry Research, Volume 226, Issues 2–3, 30 April 2015, Pages 494–498
Cortisol dysregulation has been proposed to be involved in depression. Hypothalamic–pituitary–adrenal (HPA) axis dysregulation associated with major depressive disorder (MDD) was previously reported to be higher in the elderly. Furthermore, insulin resistance and the prevalence of type 2 diabetes are known to increase with aging. The aim of the present study was to determine whether a relationship existed between plasma cortisol levels following the dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test and insulin resistance evaluated by the homeostasis model assessment of insulin resistance (HOMA-R) in elderly MDD subjects. Fifteen unmedicated MDD inpatients and 17 age- and sex-matched healthy controls participated in this study. After overnight fasting, blood samples were collected to measure plasma glucose and insulin concentrations, estimate HOMA-R, and perform the DEX/CRH test to evaluate HPA axis function. The value of the area under the time curve of plasma cortisol concentrations (CortAUC) and peak cortisol values (Cortpeak) following the administration of DEX/CRH both correlated with HOMA-R in MDD group. In contrast, neither CortAUC nor Cortpeak correlated with HOMA-R in controls. This is the first study to directly demonstrate the relationship between HPA axis dysregulation assessed with the DEX/CRH test and the index of insulin resistance estimated as HOMA-R in elderly MDD patients.
A relationship has been identified between MDD and type 2 diabetes, which have also been proposed to partially share a common etiology (Iwata et al., 2013); MDD was shown to increase the incidence of type 2 diabetes (relative hazard [RH] 1.63, 95% CI 1.31–2.02) (Golden et al., 2004) and the comorbidity rate of MDD in type 2 diabetic patients was estimated to be higher than that in the non-diabetic population (Gavard et al., 1993). A meta-analysis performed by Gavard et al. (1993) revealed that the prevalence of depression in current diabetic patients ranged between 8.5% and 27.3% (mean=14.0%), which was three-fold higher than the prevalence of MDD in the general adult population. The risk factors for MDD in diabetic patients include the burden of diabetes management and arteriosclerosis (Schillerstrom et al., 2008). On the other hand, the risk factors for diabetes in patients with depression involve reduced daily activities, overeating, and hypercortisolemia (Pariante and Lightman, 2008). Hypercortisolemia has been attributed to hypothalamic–pituitary–adrenal (HPA) axis dysregulation, which is one of the most reliable biological findings of MDD (Pariante and Lightman, 2008), has been implicated in the development of insulin resistance (Manoudi et al., 2012), and is a risk factor for type 2 diabetes (Brown et al., 2004). However, evidence for the relationship between hypercortisolemia and insulin resistance is limited to a cross-sectional study that only recruited normal volunteers (Rizza et al., 1982). This study demonstrated that cortisol-induced insulin resistance was caused by a decrease in both hepatic and extrahepatic sensitivity to insulin. HPA axis dysregulation associated with MDD was previously shown to be more prevalent in the elderly (Hatzinger et al., 2011), and insulin resistance and the prevalence of type 2 diabetes have both been reported to increase with aging (Rowe et al., 1983). Regarding depression, community-based studies identified a relationship between aging and prevalence of MDD (Beekman et al., 1999 and Naismith et al., 2012). Moreover, a meta-analysis revealed that aging itself may be an important risk factor for MDD (Snowdon, 2001). A previous study also found that the prevalence of type 2 diabetes was the highest in the elderly (Danaei et al., 2011). Taken together, these findings suggested that a positive relationship exists between hypercortisolemia arising from HPA axis dysregulation and insulin resistance in elderly MDD patients. Elevated cortisol levels have been shown to worsen glucose tolerance (Di Dalmazi et al., 2012). Insulin resistance may aggravate type 2 diabetes and cardiovascular disease, but not hypercortisolemia, which may develop due to the excess secretion of adrenocorticotrophic hormone (ACTH) or administration of a glucocorticoid treatment, but not directly from insulin resistance (Meigs, 2003 and Prague et al., 2013). Therefore, we hypothesized that depression or depressive episodes may have effects on cortisol dysregulation and also that the resultant hypercortisolemia may subsequently lead to the development of insulin resistance in patients with depression. In the present study, we investigated whether hypercortisolemia resulting from HPA axis dysregulation was directly associated with insulin resistance in elderly MDD patients. The primary aim of the present study was to determine whether plasma cortisol levels following the dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test correlated with insulin resistance evaluated with HOMA-R in elderly MDD subjects.