Inflammatory and Insulinemic Potential of Diet and Risk of Suicide Among Midlife and Older U.S. Adults

The goal of this project is to advance knowledge of biological mechanisms underlying risk of suicide using easily measurable and potentially modifiable factors such as diet. Suicide is a global public health problem that claimed nearly 45,000 lives in the US in 2020. In the past decade, interest in the relationship between diet and mental health outcomes including suicide has grown. The emerging role of inflammation and insulin resistance/hyperinsulinemia in suicide pathophysiology has generated increasing interest; targeting these biological pathways using modifiable factors, such as diet, may offer a path to suicide prevention among midlife and older adults. To date, evidence regarding the role of inflammatory and insulinemic diet on suicide mortality is lacking. Thus, we will address this question using data from prospective cohorts including 121,701 women in the Nurses' Health Study (NHS, 1984-2019), 51,529 men enrolled in the Health Professionals Follow-up Study (HPFS, 1986-2018), and 116,430 women in the NHS-II (1991-2019). Using data from repeated administration of food frequency questionnaires, we will establish an empirical dietary inflammatory pattern (EDIP) and an empirical dietary index for hyperinsulinemia (EDIH) "“ food-based indices that characterize dietary inflammatory or insulinemic potential based on circulating biomarkers of inflammation or C-peptide, respectively. The primary outcome is suicide mortality; ~600 suicides occurred over three decades in these cohorts. Suicide deaths were classified with codes E950 through E959 according to the World Health Organization International Classification of Diseases (ICD), Eighth and Ninth Revisions (ICD-8 for NHS; ICD-9 for HPFS & NHS-II). There are two Specific Aims: 1) Determining whether a higher intake of an inflammatory diet (EDIP) will be associated with a higher risk of suicide; 2) Determining whether a higher intake of an insulinemic diet (EDIH) will be associated with an increased risk of suicide. Secondarily, we will investigate depression as a key mediator for longitudinal associations of inflammatory and insulinemic diets and suicide risk; this will provide empirical evidence underlying risk pathways related to suicide. A deliverable from this study is to refine understanding of how high inflammation and insulin levels, as reflected by dietary pattern scores, may be relevant to suicide risk and prevention. This project will provide novel evidence on how biologically-informed diets can reduce burden of suicide among midlife and older adults. Furthermore, this proposal will shed light on developing potential tools for suicide prevention strategies among those at high-risk for suicide. Findings from this project could be validated in other cohorts (e.g., those with high racial/ethnic diversity). This proposal will ensure that this AFSP fellowship applicant is positioned for a career that addresses risk and modifiable targets in mental disorders and conditions, including suicide, and is well-prepared to conduct innovative research on suicide in the era of precision medicine.