Networks and clusters of immunometabolic biomarkers and depression-associated features in middle-aged and older community-dwelling US adults with and without depression

TL;DR

This study explores how immunometabolic biomarkers are linked to depression features in older adults, aiming to improve risk assessment and treatment strategies.

Contribution

The study identifies specific immunometabolic clusters and their associations with depression features in multiethnic aging populations.

Findings

IL-6 and HbA1c were significantly associated with anhedonic and melancholic features.

Abdominal circumference and BMI were significantly associated with anhedonic features.

In non-depressed individuals, IL-6 and abdominal circumference remained linked to anhedonic features.

Abstract

Therapy-resistant depression is associated with higher levels of systemic inflammation and increased odds of metabolic disorders. It is, therefore, crucial to identify the biomarkers of high-risk individuals and understand the key features of depression-immunometabolic networks.

The multiethnic ≥50-year-old study population is a subset of the Health and Aging Brain Study: Health Disparities (HABS-HD) study. Spearman's rank correlation network analysis was performed between immunological, metabolic, and subscales of the Geriatric Depression Scale (GDS). Significant correlations were then evaluated using a multivariable linear regression analysis, including testing for non-linearity and clinical cutoffs.

Two clusters were formed: the first included the immunometabolic biomarkers, and the second included the different subscales of GDS. The two clusters were significantly correlated at six edges. IL-6 and HbA1c were significantly correlated with anhedonic and melancholic features. Abdominal circumference and BMI were significantly correlated with anhedonic features. In the subgroup without current depression, IL-6 and Abdominal circumference maintained a significant edge with anhedonic features. TNF-alpha/melancholia and IL-6/cognitive concerns were additional relevant edges in older adults. The observed correlations remained statistically significant in the confounder-adjusted regression analysis and followed specific patterns.

Symptom clustering showed its superiority over relying on dichotomized depression diagnoses for identifying relevant immunometabolic biomarkers. This study is a first step toward understanding the particularities of immunometabolic depression for better risk stratification and to direct personalized preventive and therapeutic strategies in multiethnic aging populations.

Image 1

•IL-6 and HbA1c were significantly associated with anhedonic and melancholic features.•Abdominal circumference and BMI were significantly associated with anhedonic features.•In the subgroup without current depression, IL-6 and Abdominal circumference were correlated with anhedonic features.

IL-6 and HbA1c were significantly associated with anhedonic and melancholic features.

Abdominal circumference and BMI were significantly associated with anhedonic features.

In the subgroup without current depression, IL-6 and Abdominal circumference were correlated with anhedonic features.

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