Low-grade inflammation as mediator between diet and behavioral disinhibition: A UK Biobank study

Abstract

Background: Dietary patterns have been associated with variations in behavior. However, evidence has been limited and mixed, and the underlying mechanism remains unclear.

Objective: Extend a previous study reporting significant associations between food patterns and behavioral disinhibition and explore whether low-grade inflammation is linked to behaviors and mediates the association between diet and behavioral disinhibition.

Design: Among participants of the UK Biobank (UKB) we extracted a single behavioral disinhibition principal component using the UKB touchscreen questionnaire, Mental Health Questionnaire (MHQ), and registered diagnoses. We identified four dietary patterns (prudent diet, elimination of wheat/dairy/eggs, meat-based diet, full-cream dairy consumption) by using the Food Frequency Questionnaire (FFQ). Immune biomarkers and an aggregated inflammation score (INFLA-score) were used to characterize low-grade inflammation. Associations between dietary patterns and immune biomarkers, between immune biomarkers and disinhibition were assessed, with adjustment for demographics, lifestyle factors, and somatic health conditions. Next, mediation analyses were run to examine whether the association between dietary patterns and disinhibition was partially explained by inflammatory levels. We also conducted subgroup analyses to explore whether associations and the mediation effect differed by sex, age, ethnicity/race, body-mass-index (BMI), and socioeconomic status (SES).

Results: The prudent diet was negatively, and the meat-based diet was positively associated with several pro-inflammatory biomarkers. Most immune biomarkers were positively associated with disinhibition (numbers of lymphocytes (β_standardized = 0.082, p < 0.001), monocytes (β_standardized = 0.043, p < 0.001), neutrophils (β_standardized = 0.071, p < 0.001), platelets (β_standardized = 0.022, p < 0.001), leukocytes (β_standardized = 0.093, p < 0.001), C-reactive protein (β_standardized = 0.051, p < 0.001), and for INFLA-score (β_standardized = 0.074, p < 0.001). In the mediation model, the INFLA-score mediated the association between prudent diet and meat-based diet and disinhibition score, with a significant indirect effect of low-grade inflammation for the prudent diet-disinhibition association (β_standardized = -0.007, p < 0.001) and for meat-disinhibition association (β_standardized = 0.001, p < 0.001)). Although all effects were small, covariates and interaction term adjustments did not attenuate the effects, and neither did most subgroup-only analyses.

Conclusions: The prudent diet was associated with a lower disinhibition score and this effect was partially mediated by the lower inflammation. Reversely, the meat-based diet was linked to more inflammation, which was associated with more disinhibition. Our findings suggest mediating effects of immune function in the relationship between diet and behavioral disinhibition. However further alternative designs such as interventional trials are needed to establish causal effects.

Keywords: Behavioral disinhibition; Compulsivity; Dietary pattern; Impulsivity; Low-grade inflammation; Mediation; Neuroinflammation.