The growing interdisciplinarity of developmental psychopathology: Implications for science and training.

The field of developmental psychopathology has grown exponentially over the past decades, and has become increasingly multifaceted. The initial focus on understanding abnormal child psychology has broadened to the study of the origins of psychopathology, with the goals of preventing and alleviating disorder and promoting healthy development. In this paper, we discuss how technological advances and global events have expanded the questions that researchers in developmental psychopathology can address. We do so by describing a longitudinal study that we have been conducting for the past dozen years. We originally planned to examine the effects of early adversity on trajectories of brain development, endocrine function, and depressive symptoms across puberty; it has since become an interdisciplinary study encompassing diverse domains like inflammation, sleep, biological aging, the environment, and child functioning post-pandemic, that we believe will advance our understanding of neurobehavioral development. This increase in the breadth in our study emerged from an expansion of the field; we encourage researchers to embrace these dynamic changes. In this context, we discuss challenges, opportunities, and institutional changes related to the growing interdisciplinarity of the field with respect to training the next generation of investigators to mitigate the burden of mental illness in youth.

Corticostriatal Connectivity during Prosocial Decision-making Relates to Giving Behavior during Adolescence.

Prosocial behavior during adolescence becomes more differentiated based on the recipient of the action as well as the perceived value or benefit, relative to the cost to self, for the recipients. The current study investigated how functional connectivity of corticostriatal networks tracked the value of prosocial decisions as a function of target recipient (caregiver, friend, stranger) and age of the giver, and how they related to giving behavior. Two hundred sixty-one adolescents (9-15 and 19-20 years of age) completed a decision-making task in which they could give money to caregivers, friends, and strangers while undergoing fMRI. Results indicated that adolescents were more likely to give to others as the value of the prosocial decision (i.e., the difference between the benefit to other relative to the cost to self) increased; this effect was stronger for known (caregiver and friends) than unknown targets, and increased with age. Functional connectivity between the nucleus accumbens (NAcc) and OFC increased as the value of the prosocial decisions decreased for strangers, but not for known others, irrespective of choice. This differentiated NAcc-OFC functional connectivity during decision-making as a function of value and target also increased with age. Furthermore, regardless of age, individuals who evinced greater value-related NAcc-OFC functional connectivity when considering giving to strangers relative to known others showed smaller differentiated rates of giving between targets. These findings highlight the role of corticostriatal development in supporting the increasing complexity of prosocial development across adolescence.

Associations among early life adversity, sleep disturbances, and depressive symptoms in adolescent females and males: a longitudinal investigation.

BACKGROUND: Exposure to adversity early in life (ELA) has been associated with elevated risk for depression during adolescence, particularly for females; the mechanisms underlying this association, however, are poorly understood. One potential mechanism linking ELA and sex differences in depressive symptoms is sleep disturbances, which increase during adolescence and are more common in females. Here, we examined whether sleep disturbances mediate the association between ELA and increases in depressive symptoms during adolescence and whether this mediation differs by sex. METHODS: 224 (N = 132 females) youth were recruited at age 9-13 years and assessed every 2 years across three timepoints. At the first timepoint, we conducted extensive interviews about stressful events participants experienced; participants provided subjective severity ratings of events and we objectively scored the severity of each event. Self-reported sleep disturbances and depressive symptoms were assessed at all timepoints. We conducted linear mixed models to estimate both initial levels and changes in sleep disturbances and depressive symptoms, and moderated mediation analyses to test whether initial levels and/or changes in sleep disturbances mediated the association of ELA (objective and subjective) with increases in depressive symptoms across adolescence and whether the mediations differed by sex. RESULTS: While higher initial levels and increases in sleep problems were uniquely associated with increases in depressive symptoms for males and females, they were related to ELA differently by sex. For females, greater ELA (both objectively and subjectively rated) was associated with higher initial levels of sleep problems, which in turn were associated with increases in depressive symptoms from early to late adolescence. In contrast, for males, ELA exposure was not associated with either initial levels of, or increases in, sleep problems. CONCLUSIONS: These findings highlight the role of sleep disturbances during the transition to adolescence in mediating sex differences in the effects of ELA on depressive symptoms.

Effects of maternal childhood trauma on child emotional health: maternal mental health and frontoamygdala pathways.

BACKGROUND: Experiences of early life adversity pose significant psychological and physical health risks to exposed individuals. Emerging evidence suggests that these health risks can be transmitted across generations; however, the mechanisms underlying the intergenerational impacts of maternal early-life trauma on child health remain unknown. METHODS: The current study used a prospective longitudinal design to determine the unique and joint contributions of maternal childhood trauma (neglect and abuse) and maternal prenatal and postnatal mental health (anxiety and depressive symptoms) (N = 541) to children's resting frontoamygdala functional connectivity at 6 years (N = 89) and emotional health at 7-8 years, as indexed by parent-reported internalizing problems and child self-reported anxiety and depressive symptoms (N = 268-418). RESULTS: Greater maternal childhood neglect was indirectly associated with greater internalizing problems serially through a pathway of worse maternal prenatal and postnatal mental health (greater maternal anxiety and depressive symptoms). Worse maternal postnatal mental health was also uniquely associated with more negative child frontoamygdala resting-state functional connectivity, over and above maternal childhood trauma (both neglect and abuse) and prenatal mental health. More negative frontoamygdala functional connectivity was, in turn, associated with poorer child emotional health outcomes. CONCLUSIONS: Findings from the current study provide support for the existence of intergenerational influences of parental exposure to childhood trauma on childhood risk for psychopathology in the next generation and point to the importance of maternal factors proximal to the second generation (maternal prenatal and postnatal mental health) in determining the intergenerational impact of maternal early experiences.

Early life stress predicts trajectories of emotional problems and hippocampal volume in adolescence.

Exposure to early life stress (ELS) has been consistently associated with adverse emotional and neural consequences in youth. The development of brain structures such as the hippocampus, which plays a significant role in stress and emotion regulation, may be particularly salient in the development of psychopathology. Prior work has documented smaller hippocampal volume (HCV) in relation to both ELS exposure and risk for psychopathology. We used longitudinal k-means clustering to identify simultaneous trajectories of HCV and emotional problems in 155 youth across three assessments conducted approximately two years apart (mean baseline age = 11.33 years, 57% female). We also examined depressive symptoms and resilience approximately two years after the third timepoint. We identified three clusters of participants: a cluster with high HCV and low emotional problems; a cluster with low HCV and high emotional problems; and a cluster with low HCV and low emotional problems. Importantly, severity of ELS was associated with greater likelihood of belonging to the low HCV/high symptom cluster than to the low HCV/low symptom cluster. Further, low HCV/high symptom participants had more depressive symptoms and lower resilience scores than did participants in the low HCV/low symptom, but not than in the high HCV/low symptom cluster. Our findings suggest that smaller HCV indexes biological sensitivity to stress. This adds to our understanding of the ways in which ELS can affect hippocampal and emotional development in young people and points to hippocampal volume as a marker of susceptibility to context.

Parenting under pressure: Parental transmission and buffering of child fear during the COVID-19 pandemic.

The current study investigated the impacts of parental behaviors (threat communication and comforting) on children's COVID-19 fears and whether effects differed by age. Caregivers of 283 children (5.5-17 years, M = 10.17, SD = 3.25) from 186 families completed online measures assessing children's and parents' COVID-19-related fears, children's sources of COVID-19 threat information, and parents' engagement in behaviors to reduce child distress (i.e., comfort behaviors). Higher COVID-19 fear in parents was associated with greater communication of COVID-19 threat information, which was associated with higher COVID-19 fear in younger, but not older, children. Over and above parental fear and threat communication, greater exposure to COVID-19 threat information from community sources (e.g., media, school, friends) was associated with greater COVID-19 fear in children, regardless of age. Greater engagement of parental comfort behaviors buffered the association between community sources of COVID-19 threat information and COVID-19 fears in older, but not younger, children. These findings suggest that younger children might be more vulnerable to developing heightened COVID-19 fears as a result of increasing sources of COVID-19 threat information in their lives. This study highlights the importance of supporting the socioemotional well-being of children and families through the COVID-19 pandemic and beyond.

Physical home environment is associated with prefrontal cortical thickness in adolescents.

Biologically embedded experiences alter developmental trajectories in ways that can influence health, learning, and/or behavior. These systematic differences in experiences may contribute to different biological outcomes as individuals grow and develop, including at the neural level. Previous studies of biologically embedded experiences on neurodevelopment have focused on large-scale institutional or economic factors (e.g. socioeconomic status [SES]) and psychosocial factors (e.g. caregiving behavior). Less attention has focused on how the quality of the immediate home settings, such as the physical home environment (PHYS), influences neurodevelopment. Moreover, no study has investigated these effects in adolescents, who undergo significant physical maturation and neurodevelopment that may influence how they respond to their physical environments. The goal of the current study was to examine whether PHYS quality is biologically embedded in the developing adolescent brain as evidenced by cognitive achievement and cortical development in 56 (48% female) healthy adolescents (14-18 years (M = 16.83 years, SD = 1.17). Using in-home assessments of the physical home environment, anatomical brain scans, and indices of academic achievement, we found that adolescents who have more physical problems in the home (e.g. structural hazards, crowding, excessive noise, poorly lit) have thinner prefrontal cortices, which was associated with lower levels of reading achievement, independent of SES and psychosocial factors. By conducting home visits to assess physical characteristics of adolescents' home, we highlight a typically overlooked aspect of the home environment that has relevance for adolescents' cognitive and brain development.

Acute stress increases risky decisions and dampens prefrontal activation among adolescent boys.

Adolescence is characterized by increased risky decision-making, enhanced mesolimbic response to risk and reward, increased perceived stress, and heightened physiological response to stress relative to other age groups. In adults, evidence suggests that acute stress increases risky decision-making by stress-induced increases of dopamine in regions implicated in reward processing and decision-making. Acute stress also increases risky decision-making in adolescents, but the underlying neurobiological mechanisms remained unexplored. In this study, daily self-reports of stress were documented in adolescents and adults. Participants completed two fMRI visits during which they performed a risky decision-making task: once each when they endorsed a high and low level of stress. Results revealed that adolescent males took more advantageous risks under high stress relative to low stress whereas adult males took fewer non-advantageous risks under high stress relative to low stress. Adolescent males also showed a stress-related decrease in prefrontal activation when making risky decisions from high stress to low stress while adult males maintained prefrontal activation when making risky decisions across stress conditions. Adolescent and adult females did not exhibit stress-related changes in risky decisions. Moreover, greater prefrontal activation under stress was associated with fewer non-advantageous risks taken under stress. Implications for risk-taking under stress are discussed in light of these findings.

Effects of Pollution Burden on Neural Function During Implicit Emotion Regulation and Longitudinal Changes in Depressive Symptoms in Adolescents.

Background: Exposure to environmental pollutants early in life has been associated with increased prevalence and severity of depression in adolescents; however, the neurobiological mechanisms underlying this association are not well understood. In the current longitudinal study, we investigated whether pollution burden in early adolescence (9-13 years) was associated with altered brain activation and connectivity during implicit emotion regulation and changes in depressive symptoms across adolescence. Methods: One hundred forty-five participants (n = 87 female; 9-13 years) provided residential addresses, from which we determined their relative pollution burden at the census tract level, and performed an implicit affective regulation task in the scanner. Participants also completed questionnaires assessing depressive symptoms at 3 time points, each approximately 2 years apart, from which we calculated within-person slopes of depressive symptoms. We conducted whole-brain activation and connectivity analyses to examine whether pollution burden was associated with alterations in brain function during implicit emotion regulation of positively and negatively valenced stimuli and how these effects were related to slopes of depressive symptoms across adolescence. Results: Greater pollution burden was associated with greater bilateral medial prefrontal cortex activation and stronger bilateral medial prefrontal cortex connectivity with regions within the default mode network (e.g., temporoparietal junction, posterior cingulate cortex, precuneus) during implicit regulation of negative emotions, which was associated with greater increases in depressive symptoms across adolescence in those exposed to higher pollution burden. Conclusions: Adolescents living in communities characterized by greater pollution burden showed altered default mode network functioning during implicit regulation of negative emotions that was associated with increases in depressive symptoms across adolescence.

Exposure to environmental pollution is related to increased risk for depression in youth; however, the neurobiological mechanisms underlying this association are unknown. We found that adolescents living in neighborhoods with greater census tract­level pollution burden had stronger functional connectivity between the medial prefrontal cortex and regions within the default mode network during implicit regulation of negative emotions, which in turn was associated with greater increases in depressive symptoms across adolescence in these pollution-exposed youths.

The cortisol/DHEA ratio mediates the association between early life stress and externalizing problems in adolescent boys.

BACKGROUND: Despite evidence that early life stress (ELS) can influence the functioning of the hypothalamic-pituitary-adrenal (HPA) axis and increase maladaptive behaviors in adolescence, less attention has been paid to the role of the coordinated effects of the two primary adrenal hormones, cortisol and dehydroepiandrosterone (DHEA), in these associations. METHODS: 138 typically developing adolescents (76 females) reported the stressful events experienced during childhood and early adolescence across 30 domains. Two years later we assessed levels of externalizing problems and obtained salivary levels of cortisol and DHEA. Using causal moderated mediation analyses, we examined whether the ratio of cortisol to DHEA (CD ratio) mediates the association between ELS and subsequent externalizing problems. RESULTS: We found that ELS is associated with both a lower CD ratio and more externalizing problems. Importantly, a lower CD ratio mediated the association between ELS and externalizing problems in boys. CONCLUSIONS: An imbalance in adrenal hormones may be a mechanism through which ELS leads to an increase in externalizing problems in adolescent boys. These findings underscore the utility of using the CD ratio to index HPA-axis functioning.

Socioeconomic Disadvantage Moderates the Association of Systemic Inflammation with Amygdala Volume in Adolescents Over a Two-Year Interval: An Exploratory Study.

BACKGROUND: Research has demonstrated an association between elevated systemic inflammation and changes in brain function. Affective areas of the brain involved in processing threat (e.g., amygdala) and reward (e.g., nucleus accumbens [NAcc]) appear to be sensitive to inflammation. Early life stress (ELS), such as experiencing low socioeconomic status (SES), may also potentiate this association, but relevant evidence has come primarily from cross-sectional studies of brain function. It is unclear whether similar associations are present between ELS, inflammation, and brain structure, particularly in typically developing populations. METHODS: We recruited and assessed 50 adolescents (31F/19M) from the community (M±SD age=15.5±1.1; range=13.1-17.5 years ) and in exploratory analyses examined whether changes in C-reactive protein (ΔCRP) from blood spots predict changes in gray matter volumes (ΔGMV) in the bilateral amygdala and NAcc over a two-year period. We also investigated whether experiencing ELS, operationalized using a comprehensive composite score of SES disadvantage at the family and neighborhood levels, significantly moderated the association between ΔCRP and ΔGMV. RESULTS: We found that ΔCRP was negatively associated with ΔAmygdala GMV (i.e. increasing CRP levels were associated with decreasing amygdala volume; ß=-0.84; p=0.012). This effect was stronger in youth who experienced greater SES disadvantage (ß=-0.56; p=0.025). CONCLUSIONS: These findings suggest that increases in systemic inflammation are associated with reductions in amygdala GMV in adolescents, potentially signaling accelerated maturation, and that these neuroimmune processes are compounded in adolescents who experienced greater SES disadvantage. Our findings are consistent with theoretical frameworks of neuroimmune associations and suggest they may influence adolescent neurodevelopment.

Early life stress, sleep disturbances, and depressive symptoms during adolescence: The role of the cingulum bundle.

Adolescence is often characterized by sleep disturbances that can affect the development of white matter tracts implicated in affective and cognitive regulation, including the cingulate portion of the cingulum bundle (CGC) and the uncinate fasciculus (UF). These effects may be exacerbated in adolescents exposed to early life adversity (ELA). We examined the longitudinal relations between sleep problems and CGC and UF microstructure during adolescence and their relation to depressive symptoms as a function of exposure to ELA. We assessed self-reported sleep disturbances and depressive symptoms and acquired diffusion-weighted MRI scans twice: in early adolescence (9-13 years) and four years later (13-17 years) (N = 72 complete cases). Independent of ELA, higher initial levels and increases in sleep problems were related to increases in depressive symptoms. Further, increases in right CGC fractional anisotropy (FA) mediated the association between sleep problems and depressive symptoms for youth who experienced lower, but not higher, levels of ELA. In youth with higher ELA, higher initial levels of and steeper decreases in sleep problems were associated with greater decreases in right UF FA, but were unrelated to depressive symptoms. Our findings highlight the importance of sleep quality in shaping fronto-cingulate-limbic tract development and depressive symptoms during adolescence.

Sleep duration moderates the associations between immune markers and corticolimbic function during stress in adolescents.

Adolescence is characterized by biological changes in hormonal and circadian systems that, with concurrent psychosocial changes, result in increased sleep disturbances and stress sensitivity. Sleep disturbance has been associated with heightened stress sensitivity and elevated levels of inflammation in adults and adolescents, yet the neural correlates are unknown in adolescents. The current study investigated whether and how individual differences in peripheral immune markers (IL-6, TNF-α) related to neural response to stress in adolescents and whether these immune-brain associations were moderated by adolescents' sleep duration. Thirty-seven adolescents (14-15 years) who met quality control criteria for fMRI reported daily sleep duration for 7 days and performed a fMRI stressor task. A subsample of 23 adolescents additionally provided blood samples that were assayed for inflammatory markers using a multiplex assay. Results revealed that average sleep duration moderated associations between TNF-α and medial frontolimbic circuitry (amygdala, medial prefrontal cortex) during the stressor task such that, among adolescents who reported shorter sleep duration, higher levels of TNF-α were associated with greater deactivation in those regions during stress, which was associated with greater self-reported anxiety. These findings suggest that insufficient sleep duration coupled with greater levels of peripheral inflammation may promote a neural profile characterized by alterations in frontolimbic circuitry during stress, which can exacerbate sleep disturbances and/or peripheral inflammation.

Giving to others and neural processing during adolescence.

Adolescence is marked by an increased sensitivity to the social environment as youth navigate evolving relationships with family, friends, and communities. Prosocial behavior becomes more differentiated such that older adolescents increasingly give more to known others (e.g., family, friends) than to strangers. This differentiation may be linked with changes in neural processing among brain regions implicated in social decision-making. A total of 269 adolescents from 9-15 and 19-20 years of age completed a decision-making task in which they could give money to caregivers, friends, and strangers while undergoing functional magnetic resonance imaging (fMRI). Giving to caregivers and friends (at a cost to oneself) increased with age, but giving to strangers remained lower and stable across age. Brain regions implicated in cognitive control (dorsolateral and ventrolateral prefrontal cortex) showed increased blood-oxygen-level-dependent (BOLD) activation with increasing age across giving decisions to all recipients; regions associated with reward processing (ventral striatum and ventral tegmental area) showed increased activation across all ages when giving to all recipients. Brain regions associated with social cognition were either not active (dorsomedial prefrontal cortex) or showed reduced activation (temporal parietal junction and posterior superior temporal sulcus) when giving to others across all ages. Findings have implications for understanding the role of brain development in the increased complexity of social decision-making during adolescence.

Individual differences in accumbofrontal tract integrity relate to risky decisions under stress in adolescents and adults.

Psychosocial stress increases risky decision-making (DM). It is widely accepted that individual variation in neural phenotypes underlie variability in this behavioral tendency in adults, but is less examined in adolescents. Our goal was to test the hypothesis that the relation between neural phenotypes and stress-related risky DM is better characterized by individual variation than by age. Using diffusion tensor imaging (DTI) tractography to characterize the accumbofrontal tract, we determined if it uniquely moderated how stress affects risky DM, over and above age. A daily diary design monitored participants' daily stress for two weeks. Participants completed a DTI scan and performed a task in which decisions varied by expected value, once each on a day when they endorsed feeling higher (and lower) than usual levels of stress. Multilevel logistic regression analyses revealed that all participants were more likely to take risks as expected reward value increased; this behavior was greater under high versus low stress for individuals with low accumbofrontal tract integrity, whereas DM was less influenced by stress for individuals with high accumbofrontal tract integrity, regardless of age. Results suggest that individual differences in brain structure may be more germane to characterizing risky decisions in adolescents, rather than ontogeny.