# Metabolomic Profiles of Depression and Social Isolation in Midlife.

> **NIH NIH R03** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $77,666

## Abstract

Project Abstract
Major depression is a mental disorder reported to affect approximately 16.2 million adults aged 18 years or older in the United States in 2016. Heritability estimates of 31-42% and 48% for depression and loneliness, respectively, indicate a substantial role for genetic and environmental factors in their etiology. Untargeted metabolomics is an emerging approach to quantify large numbers of low molecular weight compounds in a biological sample. Multiple pathways and functional classes are represented, providing a source of biomarkers that can reveal physiologic and cellular processes implicated in the coordinated response to DNA sequence variation and environmental influences occurring over the lifespan. It has previously been demonstrated that this technology can be used to reveal changes in metabolite levels in individuals with common diseases and conditions including cardiovascular disease, type 2 diabetes, chronic kidney disease, cognitive decline, and Alzheimer’s disease and dementia. In this study, we propose to analyze the association of serum metabolites and depression, social isolation, and perceived social support in midlife. This will be accomplished in the setting of the Atherosclerosis Risk in Communities (ARIC) Study, a prospective biracial cohort study of atherosclerosis that enrolled 15,792 European American and African American men and women 45 to 64 years at baseline in 1987-1989. ARIC investigators and others have previously shown that these psychosocial  factors were associated with increased susceptibility to chronic diseases of late adulthood including cardiovascular disease, and Alzheimer’s disease and dementia. In order to determine whether interindividual variation in metabolite levels is a biological determinant of depression and social isolation the following specific aims will be pursued:  identify  serum  metabolites  that  are  associated  with  depression,  social  isolation, and social support (Aim  1);  evaluate the relationship  of  common and rare  DNA sequence  variation with  the  metabolomic  signatures  associated  with  depression,  social  isolation,  and  social  support  in  Aim  1  by analyzing whole exome sequencing data already available in the ARIC study (Aim 2a), and establish whether the metabolomic signatures  identified  in  Aim  1  are  causally  related  by  examining  the association  between  the  genetic  variants  identified  in  Aim  2a  and  the  corresponding  psychosocial  factor using a  Mendelian  randomization  approach  (Aim  2b);  examine  the  association  between  the genetic variants found to be related to depression, social isolation, and social  support  in  Aim  2b  and incident cardiovascular disease, incident hospitalized  dementia,  and  prevalent  Alzheimer’s  disease classified based on a comprehensive neurocognitive assessment in all ARIC participants with exome sequencing (Aim 3). The long-term goals of this research are to further understand the underly...

## Key facts

- **NIH application ID:** 9991723
- **Project number:** 5R03AG064520-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Jan Bressler
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $77,666
- **Award type:** 5
- **Project period:** 2019-08-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991723

## Citation

> US National Institutes of Health, RePORTER application 9991723, Metabolomic Profiles of Depression and Social Isolation in Midlife. (5R03AG064520-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9991723. Licensed CC0.

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