Leveraging a Genetically-informative Study Design to Explore Depression As a Risk Factor for Type 2 Diabetes: Rationale and Participant Characteristics of the Mood and Immune Regulation in Twins Study

Background: Comorbidity between depression and type 2 diabetes is thought to arise from the joint effects of psychological, behavioral, and biological processes. Studies of monozygotic twins may provide a unique opportunity for clarifying how these processes inter-relate. This paper describes the rationale, characteristics, and initial findings of a longitudinal co-twin study aimed at examining the biopsychosocial mechanisms linking depression and risk of diabetes in mid-life.

Methods: Participants in the Mood and Immune Regulation in Twins (MIRT) Study were recruited from the Mid-Atlantic Twin Registry. MIRT consisted of 94 individuals who do not have diabetes at baseline, representing 43 twin pairs (41 monozygotic and 2 dizygotic), one set of monozygotic triplets, and 5 individuals whose co-twin did not participate. A broad set of variables were assessed including (e.g., lifetime history major depression (MD)); (e.g., stress perceptions and experiences); and , including indicators of metabolic risk (e.g., BMI, blood pressure (BP), HbA1c) and immune functioning (e.g., pro- and anti-inflammatory cytokines), as well as collection of RNA. Participants were re-assessed 6-month later. Intra-class correlation coefficients (ICC) and descriptive comparisons were used to explore variation in these psychological, social, and biological factors across time and within pairs.

Results: Mean age was 53 years, 68% were female, and 77% identified as white. One-third had a history of MD, and 18 sibling sets were discordant for MD. MD was associated with higher systolic (139.1 vs 132.2 mmHg, p=0.05) and diastolic BP (87.2 vs. 80.8 mmHg, p=0.002) and IL-6 (1.47 vs. 0.93 pg/mL, p=0.001). MD was not associated with BMI, HbA1c, or other immune markers. While the biological characteristics of the co-twins were significantly correlated, all within-person ICCs were higher than the within-pair correlations (e.g., HbA1c within-person ICC=0.88 vs. within-pair ICC=0.49; IL-6 within-person ICC=0.64 vs. within-pair=0.54). Among the pairs discordant for MD, depression was not substantially associated with metabolic or immune markers, but was positively associated with stress.

Conclusions: Twin studies have the potential to clarify the biopsychosocial processes linking depression and diabetes, and recently completed processing of RNA samples from MIRT permits future exploration of gene expression as a potential mechanism.