The Co-Development of Adiposity, Inflammation and Depressive Symptoms Across Adolescence: A Focus on Sex Differences, Developmental Trajectories and Bidirectional Associations

There is recognized comorbidity of obesity and depression, and research suggests chronic low-grade inflammation as a potential shared mechanism connecting these two health conditions. However, this hypothesis is mainly based on cross-sectional studies with adult clinical samples, which limits understanding of the developmental nature of these constructs. Furthermore, there is a debate on the directionality of these associations. Recent research also suggests that there are sex differences not only in the individual developmental trajectories of depression, obesity and inflammation across adolescence, but also in the associations among them. Examining the co-development of these constructs in adolescence is particularly important given the high prevalence of first onset-depression during adolescence. Biological mechanisms are critical to consider because obesity and inflammation are associated with endocrine processes which are salient during puberty, and sex differences may be especially apparent during this period. However, few studies have examined these questions in a prospective longitudinal manner throughout adolescent development. Thus, the current study aimed to examine the co-development of adiposity, inflammation and depressive symptoms in the period from pre-adolescence to early adulthood, and to examine whether these associations differ between boys and girls. These questions were explored in a subset of data from the Avon Longitudinal Studies of Parents and Children (ALSPAC; N=6,525). Fat Mass Index (FMI) was used as a measure of general adiposity. C-reactive protein (CRP) was used as a marker of systemic inflammation. Depressive symptoms were assessed by the Short Mood and Feelings Questionnaire (SMFQ; Angold et al., 1995). Each was measured at 4 time points between 9 and 24 years. A combination of both cross-lagged panel analyses and parallel-processes latent growth curve models were used to examine their associations. The most robust and consistent findings emerged for the relations between FMI and CRP. The development of these two constructs was clearly linked across adolescence, and although girls and boys had different developmental trajectories of FMI and CRP, for both there was greater evidence for earlier adiposity driving later inflammation than for the converse. CRP was not clearly linked with depression across adolescence, and in fact, for both boys and girls, CRP was inversely associated with depression at different points in development. Considering associations with adiposity, the findings from the 3-level cross-lagged model indicated that preadolescents with elevated depressive symptoms may be at greater risk for increasing adiposity, and for girls, increasing inflammation, in the transition into adolescence. However, this pattern does not seem to continue in the later phases of adolescence and emerging adulthood. These findings demonstrate that the mechanisms underlying the relations between adiposity, inflammation and depression are clearly different in adolescents compared to adults. There is no evidence that systemic inflammation is a shared mechanism between depression and obesity in adolescents. In fact, the null and inverse associations found between CRP and depression in this study call into question the notion that CRP can be used as a biomarker for depression. Consistent with the model proposed by Byrne and colleagues (2015), the study provides limited support to the hypothesis that adiposity and inflammation are consequences rather than antecedents of adolescent-onset depression, and that preadolescent depressed girls may be at greater risk for developing physical health problems in adulthood. To reach a better understanding of the mechanisms at play during adolescence, future research on this topic would benefit from including multiple measures of inflammation and adiposity, measuring sex and stress hormones, and collecting date on diet, exercise, body image, stress and sub-types or symptoms of depression