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.

Unpredictability, an aspect of early life adversity, creates significant disruptions for children and adolescents’ psychosocial development throughout their lifetime. Despite growing evidence highlighting the importance of predictable caregiving in fostering long-term healthy development, there is still limited understanding of proximal unpredictability within caregiver-child relationships. Given that both early childhood and adolescence are dynamic periods characterized by increasing self-regulation capacities and susceptibility to mental health disorders, this dissertation aimed to address three critical gaps in understanding caregiver unpredictability and its implications for child and youth adjustment: whether it is domain general or specific, the cascade between distal and proximal experiences of unpredictability and the developmental systems most influenced by caregiver unpredictability during childhood and adolescence.Study 1 examined the relations among family instability, maternal and paternal mood unpredictability, and youths' mental health problems in a sample of Mexican-origin families. Using random intercept cross-lagged models to disentangle between- and within-family differences, results showed that family instability was positively related to maternal and paternal mood unpredictability, and that maternal mood unpredictability was positively associated with youths' internalizing problems across adolescence. However, there was little evidence of reciprocal relations, suggesting a lack of transactional associations at the within-family level over time. Study 2 was designed to extend prior research on caregivers’ sensory signal unpredictability with infants, by (1) developing and validating an observational measure of caregiver affective and behavioral unpredictability in early childhood, and (2) exploring its implications for preschoolers’ development of biobehavioral self-regulation. Results demonstrated that caregiver unpredictability was related to only a subset of indices of biobehavioral regulation. At age four, caregiver affective and behavioral unpredictability was linked to greater respiratory sinus arrhythmia (RSA) suppression (i.e., decrease in RSA) during the Day/Night task, and to greater effortful control in a non-linear, inverted U-shape pattern. At age six, children whose caregivers exhibited greater sensory signal unpredictability had stronger RSA suppression during the Day/Night task. Conversely, children whose caregivers demonstrated lower and higher levels of affective and behavioral unpredictability had RSA augmentation relative to children whose caregivers were moderately unpredictable. However, neither sensory signals nor affective or behavioral unpredictability was associated with children's inhibitory control or behavioral adjustment. Together, these studies emphasize the importance of developing and validating methods to capture the dynamic and nuanced nature of caregiver unpredictability, as well as considering its domain specificity. This dissertation also raises questions about the appropriate temporal lens for examining caregiver unpredictability, the significance of developmental timing, and the impact of unique experiences and vulnerabilities among Mexican-origin families living in unpredictable environments. In conclusion, this research program provides valuable insights into the effects of unpredictability on early childhood development and adolescent mental health. Systematic empirical and translational progress in understanding unpredictability will enhance efforts to ensure continuity and stability in children's lives, particularly for families experiencing other environmental adversities that threaten children’s and adolescents’ well-being.

All youth have the capacity to thrive during adolescence by actively seeking internal and external resources to navigate the core developmental tasks characterizing this pivotal transition. Positive Youth Development (PYD) theories emphasize the role of adolescents’ self-regulation and relational context in supporting this process, leading researchers to investigate which person-by-environment interactions confer optimal benefits. However, few empirical studies have explored PYD trajectories among ethnic/racial minority samples, including Latinx youth of Mexican-origin, leaving gaps in our understanding of specific individual, familial, and sociocultural factors enabling youth of color to flourish. Furthermore, research integrating cultural influences and neurobiological development within PYD trajectories in youth exposed to adversity are scarce. This dissertation aimed to address these gaps by investigating: (1) whether the Five Cs model of PYD accurately reflects PYD in Latinx youth, (2) the extent to which cultural orientation promotes Latinx PYD, (3) whether PYD factors moderate the impact of family stress on adolescent stress physiology, and (4) the moderating role of adolescent demographics within these associations. Study 1 provides robust evidence supporting the Five Cs model of PYD in Latinx youth, highlighting ethnic pride and cultural values as potent promoters of PYD for Mexican-origin youth. Study 2 reveals differential associations between family stress exposure and adrenocortical regulation based on adolescent gender and endorsement of the Five Cs, suggesting a potentially stronger biological link between the Five Cs and adrenocortical functioning in adolescent girls compared to boys. Taken together, these studies offer a culturally-sensitive and neurobiologically-informed understanding of PYD pathways and resilience processes unfolding in the lives of Mexican-origin youth, underscoring the importance of integrating across bioecological and relational systems when conducting PYD research.

Suicide is the second leading cause of death for youth in the United States and the rates are continuing to rise. Unfortunately, national policy efforts to combat this increase in youth deaths by suicide have made little difference. Suicidal thoughts and behaviors (STB) disproportionately affect female adolescents, and youth of color, including Latino youth. To date, there have been few longitudinal studies of adolescent STB in Latino adolescents, thus, many of the prospective risk factors for suicidality in these populations are not well understood. Additionally, there is limited research which has examined the neurobiological predictors of STB in community or clinical adolescent samples across all genders and ethnicities. Given this imminent and intensifying public health crisis, additional investigations are needed to examine and understand both proximal and distal factors related to the increase in adolescent STB. Moreover, as the US becomes more ethnically diverse, risk and protective factors which influence both the general population as well as specific ethnic minorities should be examined, including environmental, social, and biological factors which may act to either ameliorate or exacerbate rates of youth STB. This dissertation investigated: (1) the associations between psychosocial and culturally specific factors and the growth of STB from early to late adolescence; (2) the role of the autonomic nervous system (ANS) in stress activation during social exclusion and its relation to concurrent and prospective STB in late adolescence; and (3) whether pubertal timing moderates the link between parasympathetic stress activity and concurrent and subsequent STB in clinically high-risk adolescent females. In Paper 1, female sex and later generation status were associated with increasing prevalence in STB across adolescence, and family conflict and peer conflict predicted increased STB whereas greater familism predicted less STB, in Mexican-origin youth. In Paper 2, prior STB was associated with lower sympathetic activity at baseline and during social exclusion, and prospective STB was predicted by lower basal ANS activity paired with greater ANS activation during social exclusion, in Mexican-origin youth. In paper 3, lower baseline parasympathetic activity and earlier pubertal timing were associated with prior STB, whereas girls with later pubertal timing and higher parasympathetic activity during a speech task were buffered from endorsing STB one year later. In summary, this body of research suggests that interpersonal processes, especially within the family, are critical for understanding suicidality risk in Mexican-origin adolescents. Additionally, basal autonomic activity may be a biomarker or a physiological “scar” of prior suicidality whereas certain patterns of autonomic stress activation may confer greater risk for prospective STB years in advance. Lastly, the female pubertal transition confers risk for STB and later pubertal timing may provide a protective buffer against STB for those youth who display dysregulated physiological responses to stress.