LEPTIN AS A NOVEL PREDICTOR OF DEPRESSION IN PATIENTS WITH THE METABOLIC SYNDROME

Transcription

1 LEPTIN AS A NOVEL PREDICTOR OF DEPRESSION IN PATIENTS WITH THE METABOLIC SYNDROME Diana A. Chirinos, Ronald Goldberg, Elias Querales-Mago, Miriam Gutt, Judith R. McCalla, Marc Gellman and Neil Schneiderman Behavioral Medicine Research Center and Department of Psychology. University of Miami, FL This research was funded by NHLBI PO1 HL36588

2 The Abstract was based on preliminary results of the Community Health and Riskreduction for the Metabolic Syndrome (CHARMS) study. The following results are more updated, complete and are focused on the Hispanic participants of our study. DISCLOSURE

3 METS AND DEPRESSION Hispanics have been found to be at increased risk for MetS and MDD. The association between MetS and depression has been extensively investigated. Waist Circum. HDL-cholesterol Triglycerides Metabolic Syndrome Depression Glucose Hypertension Gender Race SES

4 MECHANISTIC PATHWAYS The notion that inflammation may serve as a common mechanism has been supported by the literature. Inflammatory Markers Metabolic Syndrome Depression Leptin Recent reports indicate leptin may have a role in modulating the immune response and may also serve as a biomarker of depression.

5 THE PRESENT STUDY Aimed to: determine the association between circulating leptin levels and total depressive symptoms as well as depressive symptoms dimensions (cognitive and somatic) after controlling for important confounding factors such as age, insulin resistance, body mass index (BMI) and inflammation. Test the role of gender as a moderator of this relationship.

6 METHODS: Study Sample 119 Hispanic participants 60 women 59 men Recruited for the Community Health and Riskreduction for the Metabolic Syndrome (CHARMS) study All participants: met NCEP ATP III criteria for the MetS. Aged Excluded if they had type 1 or 2 diabetes mellitus or established cardiovascular disease.

7 METHODS: Measures Depressive Symptoms Beck Depression Inventory Separated 2 subscales: Cognitive & Somatic Inflammation Circulating C-reactive protein levels. Adiposity Body Mass Index (BMI) Leptin Leptin-specific immunoassay Insulin Resistance Homeostasis model assessment (HOMA) ISI 0, 120

8 DATA ANALYTIC PLAN Data Preparation Transformation: Internal consistency Normality Excluded values CRP levels greater than 10 mg/l were be excluded Descriptive Statistics Means and Standard deviations T-student test: continuous variables Chi-square test of independence: categorical variables Inferential analyses Separate models for BDI total, BDI cognitive and BDI somatic. Multiple Linear Regression Moderation analyses Test the effect of gender as a moderator Multiple group analyses: Structural equation Modeling Framework.

9 STUDY SAMPLE CHARACTERISTICS Table 1. Biological Variables by gender Median (IQR) Men (n=59) Women (n=60) P value Age, years 51 (44-57) 53 (48-57) Body Mass Index, kg/m ( ) ( ) Waist Circumference, cm ( ) (97-106) 0.000* Triglycerides, mg/dl 206 ( ) 193 ( ) LDL Cholesterol, mg/dl 122 ( ) ( ) HDL Cholesterol, mg/dl 34 (31-38) 41 (37-47) 0.000* C-Reactive Protein, mg/l 2.6 ( ) 4.5 ( ) 0.001* Leptin, ng/ml ( ) ( ) 0.000* HOMA 2.59 ( ) 2.81 ( ) ISI 0, ( ) 1.29 ( ) 0.381

10 STUDY SAMPLE CHARACTERISTICS Table 4. BDI Scores by gender Men (n=59) Median (IQR) Women (n=60) P value BDI Total Score 6 ( ) 11 (5-17.5) 0.003* BDI Cognitive 2 (1-6) 4 (1-9) BDI Somatic 3 (1.75-6) 6 (4-8) 0.001*

11 RESULTS: Total Depressive Symptoms Table 6. Leptin and total depressive symptoms Models using the HOMA index Models using the ISI 0,120 index Standardized β P value R 2 Standardized β P value R 2 Univariate Leptin (log) * * Multivariate Leptin (log) * * C-Reactive Protein (log) Insulin Resistance Body Mass Index Age

12 RESULTS: Cognitive Depressive Symptoms Table 6. Leptin and cognitive depressive symptoms Models using the HOMA index Models using the ISI 0,120 index Standardized β P value R 2 Standardized β P value R 2 Univariate Leptin (log) * * Multivariate Leptin (log) C-Reactive Protein (log) Insulin Resistance Body Mass Index Age

13 RESULTS: Somatic Depressive Symptoms Table 6. Leptin and somatic depressive symptoms Models using the HOMA index Models using the ISI 0,120 index Standardized β P value R 2 Standardized β P value R 2 Univariate Leptin (log) * * Multivariate Leptin (log) * * C-Reactive Protein (log) Insulin Resistance Body Mass Index Age * *

14 RESULTS: Moderation There was no evidence of the role of gender as a moderator in the relationship between leptin and: Total depressive symptoms Cognitive depressive symptoms, or Somatic depressive symptoms. Models were further adjusted for gender.

15 RESULTS: Gender as a control variable Table 7. Total depressive symptoms Models using the HOMA index Models using the ISI 0,120 index Standardized β P value R 2 Standardized β P value R 2 Final Model Leptin (log) CRP (log) Insulin Resistance Body Mass Index Age Gender

16 RESULTS: Gender as a control variable Table 7. Somatic depressive symptoms Models using the HOMA index Models using the ISI 0,120 index Standardized β P value R 2 Standardized β P value R 2 Final Model Leptin (log) * * CRP (log) Insulin Resistance Body Mass Index Age * * Gender

17 CONCLUSIONS The relationship between circulating leptin levels and somatic depressive symptoms was independent of gender, age, CRP, BMI and insulin resistance. There were no moderating effects of gender in the relationship between circulating leptin and total or cognitive depressive symptoms.

18 STRENGHTS & LIMITATIONS U.S. Hispanic sample: Highly understudied Fastest growing minority in the U.S. Relatively small sample size Cross sectional design Causal inferences can not be made

19 FUTURE DIRECTIONS It is important to replicate these findings: Healthy vs. MetS sample Population-based studies Across ethnicities (Caucasians/African Americans) Elucidate whether interventions aimed at reducing somatic depressive symptoms, both psychological and pharmacological, have an impact on circulating leptin levels.

20 FUTURE DIRECTIONS Further research is needed to understand the complex relationship among circulating leptin, CRP and depressive symptoms, as well as the directionality of the relationships. CRP IL-6 Leptin Somatic depressive symptoms

21 THANK YOU. ANY QUESTIONS?