OBJECTIVE: Several studies have found associations between a diagnosis or symptoms of major depressive disorder and markers of cellular aging and dysfunction. These investigations, however, are predominantly cross-sectional and focus on adults. In the present study, we used a prospective longitudinal design to test the cross-sectional association between depressive symptoms in adolescents and telomere length (TL) as well as mitochondrial DNA copy number (mtDNA-cn). METHOD: A total of 121 adolescents (mean age = 11.38 years, SD = 1.03; 39% male adolescents and 61% female adolescents) were followed for approximately 2 years. At baseline and follow-up, participants provided saliva for DNA extraction, from which measures of TL and mtDNA-cn were obtained. Depressive symptoms were obtained via the Childrens Depression Inventory. RESULTS: There was no association between depressive symptoms and markers of cellular aging at baseline; however, depressive symptoms at baseline predicted higher rates of telomere erosion (β = -0.201, p = .016) and greater increases in mtDNA-cn (β = 0.190, p = .012) over the follow-up period. Markers of cellular aging at baseline did not predict subsequent changes in depressive symptoms. Furthermore, including the number of stressful life events did not alter these patterns of findings. CONCLUSION: These results indicate that depressive symptoms precede changes in cellular aging and dysfunction, rather than the reverse.

Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for the development of depression, with evidence that peer and academic difficulties mediate predictions of later depression from ADHD. In the present study, we hypothesized that parent-child relationship difficulties may be an additional potential mediator of this association. Academic, peer, and parent-child functioning were tested as mediators of the association of attention problems and depression in two distinctly different yet complementary samples. Study 1 was a cross-sectional sample of 5- to 10-year-old children (N = 230) with and without ADHD. Study 2 was a prospective longitudinal sample of 472 youth, followed prospectively from birth to age 20 years, at risk for depression. Despite differences in age, measures, and designs, both studies implicated peer and parent-child problems as unique mediators of depressive symptoms, whereas academic difficulties did not uniquely mediate the ADHD-depression association. Furthermore, inattention symptoms, but not hyperactivity, predicted depressive symptoms via the disruption of interpersonal functioning. The inclusion of oppositional defiant disorder into models impacted results and supported its independent role in parent-child problems. Implications include support for interventions that target interpersonal competence, which may effectively reduce the risk of depression among children with ADHD.

The interactions most supportive of positive child development take place in moments of close contact with others. In the earliest years of life, a child's caregivers are the primary partners in these important interactions. Little is known about the patterns of real-life physical interactions between children and their caregivers, in part due to an inability to measure these interactions as they occur in real time. We have developed a wearable, infrastructure-free device (TotTag) used to dynamically and unobtrusively measure physical proximity between children and caregivers in real time. We present a case-study illustration of the TotTag with data collected over two (12-hour) days each from two families: a family of four (30-month-old son, 61-month-old daughter, 37-year-old father, 37-year-old mother), and a family of three (12-month-old daughter, 35-year-old-father, 33-year-old mother). We explored patterns of proximity within each parent-child dyad and whether close proximity would indicate periods in which increased opportunity for developmentally critical interactions occur. Each child also wore a widely used wearable audio recording device (LENA) to collect time-synced linguistic input. Descriptive analyses reveal wide variability in caregiver-child proximity both within and across dyads, and that the amount of time spent in close proximity with a caregiver is associated with the number of adult words and conversational turns to which a child was exposed. This suggests that variations in proximity are linked to-though, critically, not synonymous with-the quantity of a child's exposure to adult language. Potential implications for deepening the understanding of early caregiver-child interactions are discussed.

Young adults (ages 18-26) with (n = 20) and without (n = 55) a history of child abuse (CA) completed self-report and laboratory-based measures of impulsivity and risk-taking. Relative to individuals without abuse histories, individuals with a history of CA self-reported a greater number of lifetime sexual partners as well as elevated trait impulsivity (specifically, elevated lack of premeditation and lack of perseverance). No group differences were observed for self-reported safety-related behaviors and risk-taking propensity. Notably, however, laboratory-based measures suggested that individuals with a history of CA showed significantly less impulsivity and risk-taking than individuals without abuse histories. These results suggest that self-report and laboratory measures of risk-taking and impulsivity measured in emerging adulthood may differentially relate to CA. Specifically, whereas laboratory-based measures may be influenced by hypervigilance or in the moment actions, self-report measures may assess more general behaviors related to real-world impulsivity and risk-taking.

Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for the development of depression, with evidence that peer and academic difficulties mediate predictions of later depression from ADHD. In the present study, we hypothesized that parent-child relationship difficulties may be an additional potential mediator of this association. Academic, peer, and parent-child functioning were tested as mediators of the association of attention problems and depression in two distinctly different yet complementary samples. Study 1 was a cross-sectional sample of 5- to 10-year-old children (N = 230) with and without ADHD. Study 2 was a prospective longitudinal sample of 472 youth, followed prospectively from birth to age 20 years, at risk for depression. Despite differences in age, measures, and designs, both studies implicated peer and parent-child problems as unique mediators of depressive symptoms, whereas academic difficulties did not uniquely mediate the ADHD-depression association. Furthermore, inattention symptoms, but not hyperactivity, predicted depressive symptoms via the disruption of interpersonal functioning. The inclusion of oppositional defiant disorder into models impacted results and supported its independent role in parent-child problems. Implications include support for interventions that target interpersonal competence, which may effectively reduce the risk of depression among children with ADHD.

Under typical conditions, medial prefrontal cortex (mPFC) connections with the amygdala are immature during childhood and become adult-like during adolescence. Rodent models show that maternal deprivation accelerates this development, prompting examination of human amygdala-mPFC phenotypes following maternal deprivation. Previously institutionalized youths, who experienced early maternal deprivation, exhibited atypical amygdala-mPFC connectivity. Specifically, unlike the immature connectivity (positive amygdala-mPFC coupling) of comparison children, children with a history of early adversity evidenced mature connectivity (negative amygdala-mPFC coupling) and thus, resembled the adolescent phenotype. This connectivity pattern was mediated by the hormone cortisol, suggesting that stress-induced modifications of the hypothalamic-pituitary-adrenal axis shape amygdala-mPFC circuitry. Despite being age-atypical, negative amygdala-mPFC coupling conferred some degree of reduced anxiety, although anxiety was still significantly higher in the previously institutionalized group. These findings suggest that accelerated amygdala-mPFC development is an ontogenetic adaptation in response to early adversity.

Early life stress (ELS) may accelerate frontoamygdala development related to socioemotional processing, serving as a potential source of resilience. Whether this circuit is associated with other proposed measures of accelerated development is unknown. In a sample of young adolescents, we examined the relations among ELS, frontoamygdala circuitry during viewing of emotional faces, cellular aging as measured by telomere shortening, and pubertal tempo. We found that greater cumulative severity of ELS was associated with stronger negative coupling between bilateral centromedial amygdala and the ventromedial prefrontal cortex, a pattern that may reflect more mature connectivity. More negative frontoamygdala coupling (for distinct amygdala subdivisions) was associated with slower telomere shortening and pubertal tempo over 2 years. These potentially protective associations of negative frontoamygdala connectivity were most pronounced in adolescents who had been exposed to higher ELS. Our findings provide support for the formulation that ELS accelerates maturation of frontoamygdala connectivity and provide novel evidence that this neural circuitry confers protection against accelerated biological aging, particularly for adolescents who have experienced higher ELS. Although negative frontoamygdala connectivity may be an adaptation to ELS, frontoamygdala connectivity, cellular aging, and pubertal tempo do not appear to be measures of the same developmental process.

Unlabelled

Early institutional care can be profoundly stressful for the human infant, and, as such, can lead to significant alterations in brain development. In animal models, similar variants of early adversity have been shown to modify amygdala-hippocampal-prefrontal cortex development and associated aversive learning. The current study examined this rearing aberration in human development. Eighty-nine children and adolescents who were either previously institutionalized (PI youth; N = 46; 33 females and 13 males; age range, 7-16 years) or were raised by their biological parents from birth (N = 43; 22 females and 21 males; age range, 7-16 years) completed an aversive-learning paradigm while undergoing functional neuroimaging, wherein visual cues were paired with either an aversive sound (CS+) or no sound (CS-). For the PI youth, better aversive learning was associated with higher concurrent trait anxiety. Both groups showed robust learning and amygdala activation for CS+ versus CS- trials. However, PI youth also exhibited broader recruitment of several regions and increased hippocampal connectivity with prefrontal cortex. Stronger connectivity between the hippocampus and ventromedial PFC predicted significant improvements in future anxiety (measured 2 years later), and this was particularly true within the PI group. These results suggest that for humans as well as for other species, early adversity alters the neurobiology of aversive learning by engaging a broader prefrontal-subcortical circuit than same-aged peers. These differences are interpreted as ontogenetic adaptations and potential sources of resilience.

Significance statement

Prior institutionalization is a significant form of early adversity. While nonhuman animal research suggests that early adversity alters aversive learning and associated neurocircuitry, no prior work has examined this in humans. Here, we show that youth who experienced prior institutionalization, but not comparison youth, recruit the hippocampus during aversive learning. Among youth who experienced prior institutionalization, individual differences in aversive learning were associated with worse current anxiety. However, connectivity between the hippocampus and prefrontal cortex prospectively predicted significant improvements in anxiety 2 years following scanning for previously institutionalized youth. Among youth who experienced prior institutionalization, age-atypical engagement of a distributed set of brain regions during aversive learning may serve a protective function.

Under typical conditions, medial prefrontal cortex (mPFC) connections with the amygdala are immature during childhood and become adult-like during adolescence. Rodent models show that maternal deprivation accelerates this development, prompting examination of human amygdala-mPFC phenotypes following maternal deprivation. Previously institutionalized youths, who experienced early maternal deprivation, exhibited atypical amygdala-mPFC connectivity. Specifically, unlike the immature connectivity (positive amygdala-mPFC coupling) of comparison children, children with a history of early adversity evidenced mature connectivity (negative amygdala-mPFC coupling) and thus, resembled the adolescent phenotype. This connectivity pattern was mediated by the hormone cortisol, suggesting that stress-induced modifications of the hypothalamic-pituitary-adrenal axis shape amygdala-mPFC circuitry. Despite being age-atypical, negative amygdala-mPFC coupling conferred some degree of reduced anxiety, although anxiety was still significantly higher in the previously institutionalized group. These findings suggest that accelerated amygdala-mPFC development is an ontogenetic adaptation in response to early adversity.