# Inflammation, Social Networks, and Depression in Rural Uganda

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $342,132

## Abstract

PROJECT SUMMARY
Major depressive disorder is one of the top 5 contributors to years lived with disability among adults in sub-
Saharan Africa. Numerous studies have suggested a link between social networks and depression, but none
have measured actual changes in social network structure in relation to depression or have examined the
potential mediating role of inflammation. This is an important gap in the literature because negative social
interactions increase production of pro-inflammatory cytokines, and inflammation is believed to play an
important role in depression pathogenesis. Our scientific objective is to estimate the causal effect of social
networks on depression and to assess the extent to which inflammation causally mediates this effect. The
cytokine theory of depression is consistent with our strong preliminary data from rural Uganda showing that:
elevated C-reactive protein and interleukin-6 values correlate strongly with depression; reversals in tryptophan
catabolism, mediated by the activity of indoleamine 2,3-dioxygenase-1, explain improvements in depression
symptom severity over the course of early HIV antiretroviral treatment; and social networks provide a
moderating, or “buffering,” effect against the adverse mental health impacts of food insecurity. The proposed
study will leverage the resources of an ongoing, whole-population social network cohort study in Mbarara and
a long-term partnership with Mbarara University that is presently focused on characterizing the contributions of
social networks and HIV stigma to HIV care cascade outcomes. The sample of opportunity includes 3 waves of
existing survey data and biological specimens from this whole-population sample; the plasma samples are
currently in -80C storage. During the three-year study we propose here, we will test our currently held 3 years
of frozen plasma samples for inflammatory markers of interest, and collect an additional 3 years of survey and
biomarker data (total N=1,776, T=6). We will accomplish two specific aims: (1) Estimate the causal effect of
social networks on depression symptom severity; and (2) assess the extent to which inflammatory activity
mediates the causal effect of social networks on depression. Our expected contribution is detailed mechanistic
insight into the causal pathways linking social networks, inflammation, & major depressive disorder. Our key
innovation is that we will apply state-of-the-art methods of causal inference to whole-population social network
cohort data in rural Uganda to identify the causal effect of social networks on depression & the causal
mediation effects of inflammation. This contribution will have significant public health impact by providing novel
data linking social network structure to depression and therefore inform future social network-based
interventions; investigation of inflammatory mediators will inform the use of anti-inflammatory depression
treatment strategies or of inflammatory testing to predict depress...

## Key facts

- **NIH application ID:** 10328265
- **Project number:** 5R01MH125667-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** ALEXANDER C TSAI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $342,132
- **Award type:** 5
- **Project period:** 2021-01-13 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328265

## Citation

> US National Institutes of Health, RePORTER application 10328265, Inflammation, Social Networks, and Depression in Rural Uganda (5R01MH125667-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10328265. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*