# 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.

## Key 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.