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

Introduction 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-immune-metabolic 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 immune-metabolic 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. 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. Competing Interest Statement The authors have declared no competing interest. Funding Statement Research reported on this publication was funded by the National Institute on Aging of the National Institutes of Health under Award Numbers R01AG054073, R01AG058533, R01AG070862, P41EB015922, and U19AG078109. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Procedures contributing to this work were all compliant with the Helsinki Declaration of 1975, as revised in 2013, and with the ethical standards of the relevant national and institutional committees on human experimentation. Ethical approval was obtained from the local institutional review board (University of North Texas Health Science Center). Written informed consent was obtained from every participant. The current research consists of a secondary analysis of anonymized data. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes Conflict of interest: None. Clinical trial number: Not applicable. ↵* HABS-HD MPIs: Sid E O’Bryant, Kristine Yaffe, Arthur Toga, Robert Rissman, & Leigh Johnson; HABS-HD Investigators: Meredith Braskie, Kevin King, James R Hall, Melissa Petersen, Raymond Palmer, Robert Barber, Yonggang Shi, Fan Zhang, Rajesh Nandy, Roderick McColl, David Mason, Bradley Christian, Nicole Phillips, Stephanie Large, Joe Lee, Badri Vardarajan, Monica Rivera Mindt, Amrita Cheema, Lisa Barnes, Mark Mapstone, Annie Cohen, Amy Kind, Ozioma Okonkwo, Raul Vintimilla, Zhengyang Zhou, Michael Donohue, Rema Raman, Matthew Borzage, Michelle Mielke, Beau Ances, Ganesh Babulal, Jorge Llibre-Guerra, Carl Hill and Rocky Vig.