UI.

CAPSUL

Depression and Fat Distribution in Adolescents

1-2 M.D. , 1 B.S. , 3 Ph.D. ,

Chadi Calarge, Brandon Butcher, Trudy Burns, MPH, 4 1 Janet Schlechte, M.D. , and William Coryell, M.D. 1 2 3 4 The University of Iowa, Departments of Psychiatry , Pediatrics , Epidemiology , and Internal Medicine

The authors report no competing interests.

Introduction
Background: Obesity is a well-established cardiovascular risk factor (1). It is associated with a number of cardiometabolic abnormalities, including the accumulation of visceral adipose tissue (VAT). Studies in community and clinical samples have found an association between depression and obesity, in general, and central obesity in particular (2,3). The causal link underlying this association is likely bidirectional as depression may promote adipose tissue deposition through a number of direct (e.g., hypothalamic-pituitaryadrenal axis activation) and indirect (e.g., increased appetite and reduced physical activity) pathways (4). On the other hand, obesity may cause various abnormalities (e.g., subclinical inflammation) that may precipitate depression. Objective: To investigate the association between depression and fat distribution in a well-characterized sample of adolescents and young adults.

Results
Table: Clinical and Demographic Characteristics of the Sample [meansd unless noted otherwise] MDD (n=151) No MDD (n=71) Age, years 19.01.5 19.11.4 Female Sex, n (%) 111 (73) 42 (59) Caucasian, n (%) 132 (87) 63 (89) Hispanic, n (%) 18 (12) 2 (3) SSRI Use, n (%) 101 (67) 10 (14) Duration of SSRI Trial, days 25.09.4 26.26.4 Weeks Meeting Depression 0.570.39 0.020.11 Criteria GAD, n (%) 94 (62) 15 (21) Weeks Meeting GAD Criteria 0.660.43 0.160.33 Physical Activity Score 2.20.8 2.20.8 Daily Caloric Intake, Kcal 1734941 1849993 Alcohol Use, n (%) 103 (70) 52 (73) Cigarette Use, n (%) 21 (14) 12 (17) Height z score 0.350.9 0.150.8 BMI z score 0.381.0 0.410.9 Overweight, n (%) 23 (15) 19 (27) Obese, n (%) 21 (14) 9 (13) Overweight/Obese, n (%) 44 (29) 28 (40) Waist Circumference, cm 88.913.6 89.3312.1 Whole Body Lean Mass, kg 49.49.3 51.411.7 Whole Body Fat % 27.69.0 26.28.6 Visceral Adipose Tissue (cc) 287190 278126 Android Fat (kg) 1.41.0 1.30.8 Gynoid Fat (kg) 3.91.7 3.71.5 Android/Gynoid Ratio 0.330.10 0.330.10
Figure 1: Visceral Adipose Tissue Least Squares Means 300 250 VAT (cc) 200 150 100 50 0 No MDD MDD 0.4 p = 0.06 0.35 0.3 0.25 AGR 0.2 p = 0.07

p -value 0.40 0.03 0.20 0.03 < 0.0001 0.59 < 0.0001 < 0.0001 < 0.0001 0.92 0.41 0.58 0.56 0.12 0.80 0.17 0.17 0.14 0.84 0.20 0.30 0.67 0.75 0.51 0.71

After controlling for age (years), sex, physical activity, alcohol use, cigarette use, and BMI category, participants with MDD had marginally larger VAT volume (=0.17, p=0.06) and higher AGR (=0.04, p=0.07) compared to those without MDD. In fact, those with MDD had 2% larger VAT volume (Cohens d=0.33, Fig 1) and 6% higher AGR (Cohens d=0.26, Fig 2) than those without. In overweight/obese, but not normal-BMI, participants, the proportion of weeks meeting full DSM-IV-TR criteria for major depressive episode was positively associated with VAT volume, AGR, and waist circumference (p0.01, Fig 3). Figure 3: VAT Least Squares Means by BMI Category 500 VAT (cc) 400 300 200 100 0 Proportion of Weeks Meeting MDE Criteria
0 0.29 0.57 0.88 Normal Overweight/Obese

Methods
Participants: Participants, 15 to 20 years old, either within a month of starting a selective serotonin reuptake inhibitor (SSRI) or unmedicated were enrolled. No earlier SSRI use was allowed in the two years prior to enrollment and cumulative SSRI exposure could not exceed six months in prior years. The Beck Depression (BDI) and Anxiety Inventory (BAI), the Inventory of Depressive Symptomatology (IDS), and the Longitudinal Interval Follow-up Evaluation (A-LIFE) quantified depression and anxiety symptoms. Diagnoses for Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD) were based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). Daily total caloric intake was estimated using the 2005 Block Food Frequency Questionnaire. Physical Activity was estimated using the Physical Activity Questionnaire for Adolescents (PAQ-A). At study entry, height, weight, and waist circumference were measured following standard procedures. All participants underwent a whole-body Dual-energy x-ray absorptiometry (DXA) scan using a Hologic QDR 4500 Delphi-A unit. Hologic Visceral Fat Software was used to estimate VAT volume (cc). The study was approved by the local IRB and written consents and assents were obtained. Statistical Analysis: Age-sex-specific height and body mass index (BMI) z scores were computed using the 2000 CDC normative data. Proportion of weeks meeting full DSM-IV-TR criteria for a major depressive episode or GAD was defined as the ratio of the number of weeks rated a 5 or 6 in the four months preceding study entry. Continuous and categorical variables were compared across participants with vs. without MDD using Students t-test and Chisquare test. Multivariable linear regression analysis was used to examine the association between MDD, on the one hand, and VAT, the ratio of android over gynoid fat mass (AGR), waist circumference, and whole body fat percentage, on the other, while adjusting for potential confounders. All DXA-based fat measures were natural logarithm transformed.

The presence of an anxiety disorder, the proportion of weeks meeting DSM-IV-TR criteria for GAD, and the scores on the BDI, BAI, and IDS were not significantly associated with either VAT or AGR. The proportion of weeks meeting DSM-IV-TR criteria for GAD was positively associated with a larger waist circumference (=0.03, p<0.04) while the presence of MDD was marginally associated with it (=0.02, p=0.09).

Conclusions
The occurrence of MDD in adolescents and young adults may be associated with increased central obesity. This finding is concerning as both depression and VAT increase morbidity and mortality. Longitudinal follow-up will examine whether persistent MDD or SSRI treatment is associated with the development of significant central obesity.
References:
1. Daniels SR, Arnett DK, Eckel RH, et al. Overweight in children and adolescents: Pathophysiology, consequences, prevention, and treatment. Circulation. 2005;111(15):1999-2012. 2. Blaine B. Does depression cause obesity?: A meta-analysis of longitudinal studies of depression and weight control. J Health Psychol. 2008;13(8):11907. 3. Eskandarii F, Mistry S, Martinez PE, et al. Younger, premenopausal women with major depression disorder have more abdominal fat and increased serum levels of prothrombotic factors: implications for greater cardiovascular risk. Metabolism. 2005;54(7):918-24. 4. Miller GE, Freedland KE, Carney RM, et al. Pathways linking depression, adiposity, and inflammatory markers in healthy young adults. Brain Behav Immun. 2003;17(4):276-85. Acknowledgements: This work was funded by the NIMH (R01MH090072) and the NCRR (2UL1TR000442-06). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

Figure 2: Android-Gynoid Ratio Least Squares Means

0.15 0.1 0.05 0 No MDD MDD

Contact: chadi-calarge@uiowa.edu