Hypercortisolemic Depression Is Associated With Increased Intra-Abdominal Fat BETTINA WEBER-HAMANN, MD, FRANK HENTSCHEL, MD, ANJA KNIEST, MD, MICHAEL DEUSCHLE, MD, MICHAEL COLLA, MD, FLORIAN LEDERBOGEN, MD, AND ISABELLA HEUSER, MD Objective: Similar to patients with a metabolic syndrome, patients with major depression are at increased risk of developing cardiovascular disorders. Interestingly, both disorders share a specific endocrine syndrome that pro- motes the accumulation of visceral fat, which again is considered a marker of increased cardiovascular morbidity and mortality. Methods: Intra-abdominal fat was measured in 22 postmenopausal depressed women and 23 age-matched healthy women by computer tomography at the level of lumbar vertebrae 1 (L1) and 4 (L4). Saliva was taken in patients and control subjects at 08:00 hours over a period of 7 drug-free days for the measurement of free cortisol. In patients only we performed an oral glucose tolerance test. Results: Compared with control subjects, depressed patients with elevated free cortisol concentrations showed similar visceral fat depots at L1 (113.0  41.6 vs. 94.3  53.2 cm 2 ). Hypercortisolemic depressed patients also showed greater fat depots in this area (74.5  55.5 cm 2 , p = .04) than the normocortisolemic patients. However, a comparison of all patients with control subjects revealed no difference in fat accumulation at either L1 or L4. Finally, glucose concentrations during the glucose tolerance test were higher in hypercortisolemic than in normocortisolemic patients, whereas their insulin levels showed only a tendency toward being increased. Conclusions: Hypercortisolemic depressed patients suffer from resistance to insulin and increased visceral fat. The fact that hypercortisolemia reverses depression-related fat loss, particularly in the visceral area, might partially explain why major depression can be considered a risk factor for cardiovascular disorders. Key words: major depression, hypercortisolemia, visceral fat, insulin resistance. BMI = body mass index; HAM-D = Hamilton Depres- sion Scale; HPA = hypothalamic-pituitary-adrenal; L1 = lumbar vertebra 1; L4 = lumbar vertebra 4; OGTT = oral glucose tolerance test. INTRODUCTION Distribution of body fat is an important predictor of the development of cardiovascular disorders. In con- trast to subcutaneous body fat, intra-abdominal body fat is associated with diabetes mellitus Type 2, hyper- tension, and dyslipidemia. This cluster of symptoms is called “metabolic syndrome” and has also been named the “deadly quartet” because of its association with an increased risk of myocardial infarction and stroke (1). Accumulation of intra-abdominal fat is thought to be promoted by several endocrine abnormalities that are triggered by an overactivity of the hypothalamic- pituitary-adrenal (HPA) system, resulting in elevated glucocorticoids. Thus, in subjects with increased intra- abdominal fat, concentrations of the lipid-accumulat- ing hormones cortisol and insulin are elevated, over- riding the lipid-mobilizing hormones testosterone and growth hormone, which are suppressed (2). Epidemiological studies have revealed an increased risk of cardiovascular disorders, particularly myocar- dial infarction, in patients with major depression (3). Because major depression and the metabolic syndrome share a number of endocrine-metabolic characteristics, these features might provide information about the underlying mechanisms for the above-mentioned observations. Interestingly, the endocrine imbalance associated with hypercortisolemia, hyperinsulinemia, low growth hormone, and low testosterone, all typical of metabolic syndrome, mirrors that in patients with severe major depression (4 –7). To date, one small-scale study has already demonstrated increased intra-abdominal adipose tissue in premenopausal hypercortisolemic women with major depression (8). These results prompted us to fur- ther explore the hypothesis that in patients with depres- sion, hypercortisolemia is related to visceral fat accumu- lation and might at least partially explain the increased morbidity and mortality due to cardiovascular disorders associated with major depression. METHODS Subjects This study was approved by the local ethics committee, and all subjects gave written informed consent. Enrollment was limited to postmenopausal female inpatients with major depression. Inclusion criteria were 1) major depression according to DSM-IV criteria (9), 2) a score of at least 18 points on the 21-item Hamilton Depression Scale (HAM-D) (10), 3) no history of substance abuse or dependency, 4) absence of neurological or relevant medical disorders, and 5) body mass index (BMI) lower than 30 kg/m 2 . Patients took no medications with the exception of zolpidem, which was prescribed for patients with sleep difficulties. From the Central Institute of Mental Health (B.W.-H., F.H., A.K., M.D., M.C., F.L., I.H.), Mannheim; and Department of Psychiatry, Free University of Berlin (I.H.), University Hospital Benjamin Frank- lin, Berlin, Germany. Address reprint requests to: Isabella Heuser, Department of Psychi- atry, Free University of Berlin, University Hospital Benjamin Franklin, Eschenallee 3, 14050 Berlin, Germany. Email: isabella.heuser@ medizin.fu-berlin.de Received for publication August 29, 2000; revision received June 25, 2001. 274 Psychosomatic Medicine 64:274 –277 (2002) 0033-3174/02/6402-0274 Copyright © 2002 by the American Psychosomatic Society