Longitudinal Evidence of a Vicious Cycle Between Nucleus Accumbens Microstructure and Childhood Weight Gain.

ABSTRACT

PURPOSE: Pediatric obesity is a growing public health concern. Previous work has observed diet to impact nucleus accumbens (NAcc) inflammation in rodents, measured by the reactive proliferation of glial cells. Recent work in humans has demonstrated a relationship between NAcc cell density-a proxy for neuroinflammation-and weight gain in youth; however, the directionality of this relationship in the developing brain and association with diet remains unknown. METHODS: Waist circumference (WC) and NAcc cell density were collected in a large cohort of children (n > 2,000) participating in the Adolescent Brain Cognitive Development (ABCD) Study (release 3.0) at baseline (9-10 y) and at a Year 2 follow-up (11-12 y). Latent change score modeling (LCSM) was used to disentangle contributions of baseline measures to two-year changes in WC percentile and NAcc cellularity. In addition, the role of NAcc cellularity in mediating the relationship between diet and WC percentile was assessed using dietary intake data collected at Year 2. RESULTS: LCSM indicates that baseline WC percentile influences change in NAcc cellularity and that baseline NAcc cell density influences change in WC percentile. NAcc cellularity was significantly associated with WC percentile at Year 2 and mediated the relationship between dietary fat consumption and WC percentile. CONCLUSIONS: These results implicate a vicious cycle whereby NAcc cell density biases longitudinal changes in WC percentile and vice versa. Moreover, NAcc cell density may mediate the relationship between diet and weight gain in youth. These findings suggest that diet-induced inflammation of reward circuitry may lead to behavioral changes that further contribute to weight gain.