Hypercortisolemic Depression and the Metabolic Syndrome in Late-Life

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1 Hypercortisolemic Depression and the Metabolic Syndrome in LateLife Results from the InChianti Study Nicole Vogelzangs 1, Kristen Suthers 2, Luigi Ferrucci 2, Eleanor Simonsick 2, Alexander Ble 2, Matthew Schrager 2, Stephania Bandinelli 3, Fulvio Lauretani 4, Sandra Giannelli 5, Jack Guralnik 5, Brenda Penninx 1 1 Psychiatry and EMGO institute, VU University Medical Center, Amsterdam, The Netherlands 2 National Institute on Aging, Baltimore, MD 3 Geriatric Rehabilitation, ASF, Florence, Italy 4 Tuscany Health Regional Agency, Florence, Italy 5 National Institute on Aging, Bethesda, MD

2 Background: Depression & Metabolic Syndrome o Depression is associated with cardiovascular disease and diabetes (Penninx et al. Am J Cardiol 98; Penninx et al. Arch Gen Psychiatry 01; Brown et al. Diabetes Care 05) o Metabolic syndrome might be part of the link between depression and CVD/diabetes (Vitaliano et al. Psychosom Med 02) o Depression has been associated with metabolic abnormalities such as hypertension, abdominal obesity, and insulin resistance (Raikkonen et al. Metabolism 96; Raikkonen et al. Hypertension 01) o Metabolic syndrome is major predictor of subsequent CVD/diabetes (Butler et al J Am Coll Cardiol 06; Holvoet et al. Diabetes 04; Klein et al. Diabetes Care 02)

3 Background: Role of Cortisol o Depression is linked with hyperactivity of the hypothalamuspituitaryadrenal (HPA)axis and increased cortisol levels (Heuser et al Am J Psych 96; Gotthardt Am J Physiol 95; Holsboer J Affect Disord 01) o Elevated cortisol levels have been associated with metabolic syndrome components, including abdominal obesity and glucose intolerance (Bjorntorp & Rosmond Ann N Y Acad Sci 99) o WeberHamann found increased visceral fat in hypercortisolemic depressed compared to normocortisolemic depressed persons (Psychosom Med 02)

4 Research Model Depression HPA axis (Cortisol) Metabolic Syndrome CVD/Diabetes Hypercortisolemic Depression Is (hypercortisolemic) depression associated with the metabolic syndrome? Does cortisol mediate the relationship between depression and the metabolic syndrome?

5 InChianti Study Invecchiare in Chianti = Aging in the Chianti area Prospective populationbased study 1,155 participants aged 65 years 867 included in present analyses Random selection from residents in 2 towns in the Chianti area (Greve and Bagno a Ripoli) Designed and supported by Laboratory of Clinical Epidemiology of the Italian National Research Council of Aging, and the US NIA

6 Depressed Mood Center for Epidemiological StudiesDepression Scale (CESD) continuous score (depressive symptoms) CESD 20 (depressed mood) 24hour Urinary Cortisol Represents biologically active (unbound) cortisol Measured with immunochemiluminescence method and an ADVIACentaur immunoassay system (Bayer Diagnostics)

7 Metabolic Syndrome 3 or more of the following: o Waist circumference > 102 cm (men) / > 88 cm (women) o Triglyceride level 150 mg/dl o HDL cholesterol < 40 mg/dl (men) / < 50 mg/dl (women) o Blood pressure 160/90 mmhg / antihypertensive drug use o Fasting glucose level 110 mg/dl / antidiabetic drug use

8 Statistical analyses o Logistic regression analyses were used for dichotomous outcomes and linear regression analyses were used for continuous outcomes o For continuous predictors OR is given per SD increase o Potential confounders: age, sex, years of education, smoking, alcohol use, number of chronic diseases, severe renal function impairment, urine volume (for analyses including cortisol)

9 Baseline Characteristics Age (years) 1 Current smoker, % 3 drinks a day, % # of chronic diseases (0.9) 1.3 (1.0) <.001 Urinary cortisol (µg) (43.2) (63.5).15 Metabolic syndrome, % 1 mean (SD) Nondepressed (N=688) 73.7 (6.6) Female, % <.001 Years of education (3.1) 5.1 (3.5) Depressed (N=179) 75.8 (6.3) P <.001 <

10 Depressed Mood, Urinary Cortisol & Metabolic Syndrome Age and Sexadjusted Adjusted* OR 95%CI P OR 95%CI P Total sample (N=867) Depressive symptoms Depressed mood Urinary cortisol *Adjusted for age, sex, years of education, smoking, alcohol use, number of chronic diseases, severe renal function impairment, and urine volume

11 Depressed Mood, Urinary Cortisol & Metabolic Syndrome Adjusted* Adjusted for cortisol OR 95%CI P OR 95%CI P Total sample (N=867) Depressive symptoms Depressed mood Urinary cortisol Interaction **.003 Nondepressed (N=688) Urinary cortisol Depressed (N=179) Urinary cortisol *Adjusted for age, sex, years of education, smoking, alcohol use, number of chronic diseases, severe renal function impairment, urine volume; ** depressed mood*urinary cortisol

12 Prevalence of Metabolic Syndrome % p= Depressed Nondepressed Low High Middle Urinary Cortisol Tertiles* * Lowest Tertile: <77 µg; Middle Tertile: µg; Highest Tertile: >111 µg

13 Adjusted OR for Metabolic Syndrome across Depression Status and Urinary Cortisol Tertiles OR Lowest Middle Highest Lowest Middle Highest No depression Depression *Lowest cortisol tertile: <77 µg; Middle cortisol tertile: µg; Highest cortisol tertile: >111 µg

14 Depression, Cortisol & Continuous Metabolic Syndrome Components* Waist Trigly HDL SBP DBP Glucose β β β β β β Total sample (N=867) Depressive symptoms Depressed mood Urinary cortisol Interaction ** (pvalue).08 < Nondepressed (N=688) Urinary cortisol Depressed (N=179) Urinary cortisol *Adjusted for age, sex, years of education, smoking, alcohol use, number of chronic diseases, severe renal function impairment, urine volume; ** depressed mood*urinary cortisol

15 Strengths o Large, randomly selected sample o 24hour urine measures of cortisol Limitations o Crosssectional analyses o No psychiatric diagnosis

16 Conclusions o Depression and urinary cortisol are both associated with the metabolic syndrome o The association between depression and the metabolic syndrome might be partially mediated by cortisol o Persons with hypercortisolemic depression in particular have an increased likelihood of having the metabolic syndrome o Hypercortisolemic depression may be especially associated with the obesityrelated measures of the metabolic syndrome