Secondary analyses of sex differences in attention improvements across three clinical trials of a digital therapeutic in children, adolescents, and adults with ADHD.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) remains underdiagnosed and undertreated in girls. Inattentive symptoms, often predominant in girls with ADHD, represent a key driver of impairment and often persist into adulthood. AKL-T01 is a regulated digital therapeutic targeting inattention. We examined potential sex differences in the efficacy of AKL-T01 in three separate trials for 1) children, 2) adolescents, and 3) adults. METHODS: We conducted secondary analyses of clinical outcomes by sex in three AKL-T01 randomized clinical trials in ADHD (n1 = 180 children 30.6% female, M(SD) age = 9.71 (1.32); n2 = 146 adolescents; 41.1% female, M(SD) age = 14.34 (1.26); n3 = 153 adults; 69.9% female, M(SD) age = 39.86 (12.84)). Active treatment participants used AKL-T01 for 25 min/day over 4-6 weeks. Primary outcomes included change in attention on the Test of Variables of Attention (TOVA) and symptom change on the clinician-rated ADHD Rating Scale (ADHD-RS). To evaluate study hypotheses, we conducted a series of robust linear regressions of TOVA and ADHD-RS change scores by sex, adjusting for baseline scores. RESULTS: In children, girls demonstrated greater improvement in objective attention relative to boys following AKL-T01 (TOVA Attentional Composite Score; Cohen's d = .36 and Reaction Time Mean Half; Cohen's d = .54), but no significant sex differences in ADHD rating scale change. We did not observe significant sex differences in outcomes in the adolescent or adult trials. Limitations include binary sex categorization and slight study design variation across the three samples. CONCLUSION: AKL-T01 might notably improve attentional functioning in girls with ADHD relative to boys. Objective attention measures may be particularly important in the assessment of attentional improvement in childhood, given known gender biases in ADHD symptom reporting. We emphasize the importance of considering sex and gender-specific factors in ADHD treatment evaluation. TRIAL REGISTRATIONS: STARS ADHD CHILD: ClinicalTrials.gov ID NCT03649074; STARS ADHD ADOLESCENT: ClinicalTrials.gov ID NCT04897074; STARS ADHD ADULT: ClinicalTrials.gov ID NCT05183919.

Behavioral and Neural Trajectories of Risk Taking for Peer and Parent in Adolescence.

One feature of adolescence is a rise in risk-taking behaviors, whereby the consequences of adolescents' risky action often impact their immediate surrounding such as their peers and parents (vicarious risk taking). Yet, little is known about how vicarious risk taking develops, particularly depending on who the risk affects and the type of risky behavior. In a 3-wave longitudinal fMRI study, 173 adolescents completed 1-3 years of a risky decision-making task where they took risks to win money for their best friend and parent (n with behavioral and fMRI data ranges from 139-144 and 100-116 participants, respectively, per wave). Results of this preregistered study suggest that adolescents did not differentially take adaptive (sensitivity to the expected value of reward during risk taking) and general (decision-making when the expected values of risk taking and staying safe are equivalent) risks for their best friend and parent from sixth to ninth grade. At the neural level, preregistered ROI analyses revealed no differences in the ventral striatum and ventromedial pFC during general nor adaptive risk taking for best friend versus parent over time. Furthermore, exploratory longitudinal whole-brain analyses revealed subthreshold differences between best friend and parent trajectories within regulatory regions during general vicarious risk taking and social-cognitive regions during adaptive vicarious risk taking. Our findings demonstrate that brain regions implicated in cognitive control and social-cognitive processes may distinguish behaviors involving peers and parents over time.

Concurrent and prospective associations between fitbit wearable-derived RDoC arousal and regulatory constructs and adolescent internalizing symptoms.

BACKGROUND: Adolescence is characterized by alterations in biobehavioral functioning, during which individuals are at heightened risk for onset of psychopathology, particularly internalizing disorders. Researchers have proposed using digital technologies to index daily biobehavioral functioning, yet there is a dearth of research examining how wearable metrics are associated with mental health. METHODS: We preregistered analyses using the Adolescent Brain Cognitive Development Study dataset using wearable data collection in 5,686 adolescents (123,862 person-days or 2,972,688 person-hours) to determine whether wearable indices of resting heart rate (RHR), step count, and sleep duration and variability in these measures were cross-sectionally associated with internalizing symptomatology. All models were also run controlling for age, sex, body mass index, socioeconomic status, and race. We then performed prospective analyses on a subset of this sample (n = 143) across 25 months that had Fitbit data available at baseline and follow-up in order to explore directionality of effects. RESULTS: Cross-sectional analyses revealed a small, yet significant, effect size (R2 = .053) that higher RHR, lower step count and step count variability, and greater variability in sleep duration were associated with greater internalizing symptoms. Cross-lagged panel model analysis revealed that there were no prospective associations between wearable variables and internalizing symptoms (partial R2 = .026), but greater internalizing symptoms and higher RHR predicted lower step count 25 months later (partial R2 = .010), while higher RHR also predicted lower step count variability 25 months later (partial R2 = .008). CONCLUSIONS: Findings indicate that wearable indices concurrently associate with internalizing symptoms during early adolescence, while a larger sample size is likely required to accurately assess prospective or directional effects between wearable indices and mental health. Future research should capitalize on the temporal resolution provided by wearable devices to determine the intensive longitudinal relations between biobehavioral risk factors and acute changes in mental health.

Adolescents Are More Likely to Help Others on Days They Take Risks and Crave Social Connections.

This study examined how adolescents' risk-taking behaviors were related to their prosocial behaviors on a daily level and how this association differed depending on adolescents' daily and average levels of sensation seeking and social craving. Adolescents (N = 212; Mage = 15 years) completed daily diaries for 14 days. Adolescents were more likely to engage in prosocial behavior on days when they also took risks, but only when they also felt high levels of social craving. The daily link between risk-taking and prosocial behavior did not vary based on daily or individual differences in sensation seeking. Results suggest that when adolescents feel highly motivated to connect with others, their risk-taking and prosocial tendencies co-occur on a daily basis.

Feeling left out or just surprised? Neural correlates of social exclusion and overinclusion in adolescence.

Social belonging is an important human drive that influences mood and behavior. Neural responses to social exclusion are well-characterized, but the specificity of these responses to processing rejection-related affective distress is unknown. The present study compares neural responses to exclusion and overinclusion, a condition that similarly violates fairness expectations but does not involve rejection, with a focus on implications for models of dorsal anterior cingulate cortex (dACC) and anterior insula (AI) function. In an fMRI adaptation of the Cyberball paradigm with adolescents aged 11.1-17.7 years (N = 69), we employed parametric modulators to examine scaling of neural signal with cumulative exclusion and inclusion events, an approach that overcomes arbitrary definitions of condition onsets/offsets imposed on fluid, continuous gameplay. We identified positive scaling of dACC and posterior insula response with cumulative exclusion events, but these same regions exhibited trending signal decreases with cumulative inclusion events. Furthermore, areas within the dACC and insula also responded to context incongruency (throws to the participant in the exclusion run; throws between computer players in the overinclusion run). These findings caution against interpretations that responses in these regions uniquely reflect the affective distress of exclusion within social interaction paradigms. We further identified that the left ventrolateral PFC, rostromedial PFC, and left intraparietal sulcus responded similarly to cumulative exclusion and inclusion. These findings shed light on which neural regions exhibit patterns of differential sensitivity to exclusion or overinclusion, as well as those that are more broadly engaged by both types of social interaction.

Expectations of Social Consequences Impact Anticipated Involvement in Health-Risk Behavior During Adolescence.

This study examined how individual differences in expectations of social consequences relate to individuals' expected involvement in health-risk behaviors (HRBs). A total of 122 adolescents (aged 11-17) reported their expected involvement in a number of risk behaviors and whether or not they expect to be liked more or less by engaging in the behavior: the expected social benefit. Higher perceived social benefit was associated with higher anticipated involvement in said behavior. This relationship was stronger for adolescents who reported a higher degree of peer victimization, supporting the hypothesis that experiencing victimization increases the social value of peer interactions. Findings suggest that adolescents incorporate expectations of social consequences when making decisions regarding their involvement in HRBs.

Novel insights from the Yellow Light Game: Safe and risky decisions differentially impact adolescent outcome-related brain function.

Changes across the span of adolescence in the adolescent reward system are thought to increase the tendency to take risks. While developmental differences in decision and outcome-related reward processes have been studied extensively, existing paradigms have largely neglected to measure how different types of decisions modulate reward-related outcome processes. We modified an existing decision-making paradigm (the Stoplight Task; Chein et al., 2011) to create a flexible laboratory measure of decision-making and outcome processing, including the ability to assess modulatory effects of safe versus risky decisions on reward-related outcome processes: the Yellow Light Game (YLG). We administered the YLG in the MRI scanner to 81 adolescents, ages 11-17 years, recruited from the community. Results showed that nucleus accumbens activation was enhanced for (1) risky > safe decisions, (2) positive > negative outcomes, and (3) outcomes following safe decisions compared to outcomes following risky decisions, regardless of whether these outcomes were positive or negative. Outcomes following risky decisions (compared to outcomes following safe decisions) were associated with enhanced activity in cortical midline structures. Furthermore, while there were no developmental differences in risk-taking behavior, more pubertally mature adolescents showed enhanced nucleus accumbens activation during positive > negative outcomes. These findings suggest that outcome processing is modulated by the types of decisions made by adolescents and highlight the importance of investigating processes involved in safe as well as risky decisions to better understand the adolescent tendency to take risks.

Polyvictimization and externalizing symptoms in foster care children: The moderating role of executive function.

Prior research has identified the role of childhood maltreatment in externalizing problems and executive function (EF) deficits, but minimal work has been done to characterize the effects of co-occurring maltreatment types, defined as polyvictimization. Here, we sought to characterize the association between polyvictimization and externalizing problems in a sample of foster care children aged 3-4 years (N = 84) and examine how EF may mediate or moderate that relationship. A moderation model was supported in that only polyvictimized children with EF scores 1.62 or more standard deviations below the mean were at heightened risk for clinically severe externalizing problems, while no association between polyvictimization and externalizing problems were observed for children who scored at the mean or above on the EF measure. Findings highlight that EF may serve as a resilience factor indicating that individual differences in polyvictimized children's EF skills help to predict variability in externalizing problems. Future research on designing and optimizing intervention programs that target EF skills may mitigate the development of maladaptive outcomes for polyvictimized children.

Comparing the multivariate relationships of conceptual adversity models and structural brain development in adolescent girls: A registered report.

Adverse experiences throughout development confer risk for a multitude of negative long-term outcomes, but the processes via which these experiences are neurobiologically embedded are still unclear. Adolescence provides an opportunity to understand how these experiences impact the brain's rapidly changing structure. Two models are central to current adversity conceptualizations: a cumulative risk model, where all types of experiences are combined to represent accumulating stress, and a dimensional model, where certain features of experience (e.g., threat or deprivation) exert unique neurophysiological influence. In this registered report, we extended upon previous research by using a form of representational similarity analysis to examine whether the dimensional and cumulative risk models of adversity predict cortical thinning in frontoparietal and frontotemporal networks and volumetric changes in subcortical regions throughout adolescence. Drawing from a longitudinal sample of 179 adolescent girls (ages 10-13 years at the first wave) from Lane County, Oregon, United States, and up to four waves of follow-up data, we found that operationalizing adversity by similarity in threat and deprivation provided better prediction of brain development than similarity in overall adversity. However, these dimensions do not exhibit unique associations with developmental changes in the hypothesized brain changes. These results underscore the significance of carefully defining adversity and considering its impact on the entire brain. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Telomere Erosion and Depressive Symptoms Across Development Following Institutional Care.

OBJECTIVE: A large literature has identified exposure to early caregiving adversities as a potent risk for developing affective psychopathology, with depression, in particular, increasing across childhood into adolescence. Evidence suggests telomere erosion, a marker of biological aging, may underlie associations between adverse early-life experiences and later depressive behavior; yet, little is understood about this association during development. METHOD: The current accelerated longitudinal study examined concurrent telomere length and depressive symptoms concurrently, 2 and 4 years later, from the preschool period through adolescence among children exposed (n =116) and not exposed (n = 242) to early previous institutional (PI) care. RESULTS: PI care was associated with shorter telomeres on average and with quadratic age-related growth in depressive symptoms, indicating a steeper association between PI care and depressive symptoms in younger age groups that leveled off in adolescence. Contrary to studies in adult samples, telomere length was not associated with depressive symptoms, and it did not predict future symptoms. CONCLUSION: These findings indicate that early caregiving disruptions increase the risk for both accelerated biological aging and depressive symptoms, although these variables did not correlate with each other during this age range.

Association of Habitual Checking Behaviors on Social Media With Longitudinal Functional Brain Development.

Importance: Social media platforms provide adolescents with unprecedented opportunities for social interactions during a critical developmental period when the brain is especially sensitive to social feedback. Objective: To explore how adolescents' frequency of checking behaviors on social media platforms is associated with longitudinal changes in functional brain development across adolescence. Design, Setting, and Participants: A 3-year longitudinal cohort study of functional magnetic resonance imaging (fMRI) among sixth- and seventh-grade students recruited from 3 public middle schools in rural North Carolina. Exposures: At wave 1, participants reported the frequency at which they checked Facebook, Instagram, and Snapchat. Main Outcome or Measure: Neural responses to the Social Incentive Delay task when anticipating receiving social feedback, measured annually using fMRI for 3 years. Participants saw a cue that indicated whether the social feedback (adolescent faces with emotional expressions) would be a reward, punishment, or neutral; after a delay, a target appeared and students responded by pressing a button as quickly as possible; a display of social feedback depended on trial type and reaction time. Results: Of 178 participants recruited at age 12 years, 169 participants (mean [SD] age, 12.89 [0.58] years; range, 11.93-14.52 years; 91 [53.8%] female; 38 [22.5%] Black, 60 [35.5%] Latinx, 50 [29.6%] White, 15 [8.9%] multiracial) met the inclusion criteria. Participants with habitual social media checking behaviors showed lower neural sensitivity to social anticipation at age 12 years compared with those with nonhabitual checking behaviors in the left amygdala, posterior insula (PI), and ventral striatum (VS; ß, -0.22; 95% CI, -0.33 to -0.11), right amygdala (ß, -0.19; 95% CI, -0.30 to -0.08), right anterior insula (AI; ß, -0.23; 95% CI, -0.37 to -0.09), and left dorsolateral prefrontal cortex (DLPFC; ß, -0.29; 95% CI, -0.44 to -0.14). Among those with habitual checking behaviors, there were longitudinal increases in the left amygdala/PI/VS (ß, 0.11; 95% CI, 0.04 to 0.18), right amygdala (ß, 0.09; 95% CI, 0.02 to 0.16), right AI (ß, 0.15; 95% CI, 0.02 to 0.20), and left DLPFC (ß, 0.19; 95% CI, 0.05 to 0.25) during social anticipation, whereas among those with nonhabitual checking behaviors, longitudinal decreases were seen in the left amygdala/PI/VS (ß, -0.12; 95% CI, -0.19 to -0.06), right amygdala (ß, -0.10; 95% CI, -0.17 to -0.03), right AI (ß, -0.13; 95% CI, -0.22 to -0.04), and left DLPFC (ß, -0.10, 95% CI, -0.22 to -0.03). Conclusions and Relevance: The results of this cohort study suggest that social media checking behaviors in early adolescence may be associated with changes in the brain's sensitivity to social rewards and punishments. Further research examining long-term associations between social media use, adolescent neural development, and psychological adjustment is needed to understand the effects of a ubiquitous influence on development for today's adolescents.

A CBT-based mobile intervention as an adjunct treatment for adolescents with symptoms of depression: a virtual randomized controlled feasibility trial.

Background: High rates of adolescent depression demand for more effective, accessible treatment options. A virtual randomized controlled trial was used to assess the feasibility and acceptability of a 5-week, self-guided, cognitive behavioral therapy (CBT)-based mobile application, Spark, compared to a psychoeducational mobile application (Active Control) as an adjunct treatment for adolescents with depression during the COVID-19 pandemic. Methods: A community sample aged 13-21, with self-reported symptoms of depression, was recruited nationwide. Participants were randomly assigned to use either Spark or Active Control (NSpark = 35; NActive Control = 25). Questionnaires, including the PHQ-8 measuring depression symptoms, completed before, during, and immediately following completion of the intervention, evaluated depressive symptoms, usability, engagement, and participant safety. App engagement data were also analyzed. Results: 60 eligible adolescents (female = 47) were enrolled in 2 months. 35.6% of those expressing interest were consented and all enrolled. Study retention was high (85%). Spark users rated the app as usable (System Usability Scalemean = 80.67) and engaging (User Engagement Scale-Short Formmean = 3.62). Median daily use was 29%, and 23% completed all levels. There was a significant negative relationship between behavioral activations completed and change in PHQ-8. Efficacy analyses revealed a significant main effect of time, F = 40.60, p < .001, associated with decreased PHQ-8 scores over time. There was no significant Group × Time interaction (F = 0.13, p = .72) though the numeric decrease in PHQ-8 was greater for Spark (4.69 vs. 3.56). No serious adverse events or adverse device effects were reported for Spark users. Two serious adverse events reported in the Active Control group were addressed per our safety protocol. Conclusion: Recruitment, enrollment, and retention rates demonstrated study feasibility by being comparable or better than other mental health apps. Spark was highly acceptable relative to published norms. The study's novel safety protocol efficiently detected and managed adverse events. The lack of significant difference in depression symptom reduction between Spark and Active Control may be explained by study design and study design factors. Procedures established during this feasibility study will be leveraged for subsequent powered clinical trials evaluating app efficacy and safety. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04524598.

Associations between multi-method latent factors of puberty and brain structure in adolescent girls.

Pubertal processes are associated with structural brain development, but studies have produced inconsistent findings that may relate to different measurements of puberty. Measuring both hormones and physical characteristics is important for capturing variation in neurobiological development. The current study explored associations between cortical thickness and latent factors from multi-method pubertal data in 174 early adolescent girls aged 10-13 years in the Transitions in Adolescent Girls (TAG) Study. Our multi-method approach used self-reported physical characteristics and hormone levels (dehydroepiandrosterone (DHEA), testosterone (T), and estradiol (E2) from saliva) to estimate an overall pubertal factor and for each process of adrenarche and gonadarche. There were negative associations between the overall puberty factor representing later stage and thickness in the posterior cortex, including the occipital cortices and extending laterally to the parietal lobe. However, the multi-method latent factor had weaker cortical associations when examining the adnearcheal process alone, suggesting physical characteristics and hormones capture different aspects of neurobiological development during adrenarche. Controlling for age weakened some of these associations. These findings show that associations between pubertal stage and cortical thickness differ depending on the measurement method and the pubertal process, and both should be considered in future confirmatory studies on the developing brain.

Meaningful engagement: A crossfunctional framework for digital therapeutics.

Digital mental health interventions, or digital therapeutics, have the potential to transform the field of mental health. They provide the opportunity for increased accessibility, reduced stigma, and daily integration with patient's lives. However, as the burgeoning field continues to expand, there is a growing concern regarding the level and type of engagement users have with these technologies. Unlike many traditional technology products that have optimized their user experience to maximize the amount of time users spend within the product, such engagement within a digital therapeutic is not sufficient if users are not experiencing an improvement in clinical outcomes. In fact, a primary challenge within digital therapeutics is user engagement. Digital therapeutics are only effective if users sufficiently engage with them and, we argue, only if users meaningfully engage with the product. Therefore, we propose a 4-step framework to assess meaningful engagement within digital therapeutics: (1) Define the measure of value (2) Operationalize meaningful engagement for your digital therapeutic (3) Implement solutions to increase meaningful engagement (4) Iteratively evaluate the solution's impact on meaningful engagement and clinical outcomes. We provide recommendations to the common challenges associated with each step. We specifically emphasize a cross-functional approach to assessing meaningful engagement and use an adolescent-focused example throughout to further highlight developmental considerations one should consider depending on their target users.

Differential neural sensitivity to social inclusion and exclusion in adolescents in foster care.

OBJECTIVES: Adolescents in foster care may exhibit differential patterns of brain functioning that contribute to their pervasive socioemotional challenges. However, there has been limited investigation of implicated neural processes, particularly in the social domain. Thus, the current study investigated neural responses to exclusionary and inclusionary peer interactions in adolescents in foster-care. METHODS: Participants comprised adolescents aged 11-18 years in foster care (N = 69) and a community sample (N = 69). They completed an fMRI adaptation of Cyberball, a virtual ball-throwing paradigm, that included periods of exclusion and over-inclusion. To investigate neural sensitivity to peer social experiences, we quantified neural responses that scaled with consecutive inclusionary and exclusionary interactions (using parametric modulators). RESULTS: Relative to the community sample, adolescents in foster care exhibited increasing response to consecutive exclusionary events in lateral prefrontal regions and decreasing response to consecutive inclusionary events in the intraparietal sulcus and temporo-occipital cortex. Further, exploratory analyses revealed that dorsolateral prefrontal activation to exclusion was related to externalizing problems, particularly in the foster care sample. CONCLUSIONS: Findings highlight greater neural sensitivity to exclusionary, and lesser sensitivity to inclusionary, peer interactions in adolescents in foster care. Engagement of prefrontal clusters may reflect greater salience and emotion regulatory processes during exclusion, while parietal and temporal clusters may reflect reduced attention and behavioural engagement during inclusion. Thus foster care involvement is associated with broad changes in neural responses during peer interactions, and further these potentially relate to externalizing problems that have been identified in this vulnerable population.

Rapid assessment of psychological and epidemiological correlates of COVID-19 concern, financial strain, and health-related behavior change in a large online sample.

COVID-19 emerged in November 2019 leading to a global pandemic that has not only resulted in widespread medical complications and loss of life, but has also impacted global economies and transformed daily life. The current rapid response study in a convenience online sample quickly recruited 2,065 participants across the United States, Canada, and Europe in late March and early April 2020. Cross-sectional findings indicated elevated anxiety and depressive symptoms compared to historical norms, which were positively associated with COVID-19 concern more strongly than epidemiological data signifying risk (e.g., world and country confirmed cases). Employment loss was positively associated with greater depressive symptoms and COVID-19 concern, and depressive symptoms and COVID-19 concern were significantly associated with more stringent self-quarantine behavior. The rapid collection of data during the early phase of this pandemic is limited by under-representation of non-White and middle age and older adults. Nevertheless, these findings have implications for interventions to slow the spread of COVID-19 infection.

Improving practices and inferences in developmental cognitive neuroscience.

The past decade has seen growing concern about research practices in cognitive neuroscience, and psychology more broadly, that shake our confidence in many inferences in these fields. We consider how these issues affect developmental cognitive neuroscience, with the goal of progressing our field to support strong and defensible inferences from our neurobiological data. This manuscript focuses on the importance of distinguishing between confirmatory versus exploratory data analysis approaches in developmental cognitive neuroscience. Regarding confirmatory research, we discuss problems with analytic flexibility, appropriately instantiating hypotheses, and controlling the error rate given how we threshold data and correct for multiple comparisons. To counterbalance these concerns with confirmatory analyses, we present two complementary strategies. First, we discuss the advantages of working within an exploratory analysis framework, including estimating and reporting effect sizes, using parcellations, and conducting specification curve analyses. Second, we summarize defensible approaches for null hypothesis significance testing in confirmatory analyses, focusing on transparent and reproducible practices in our field. Specific recommendations are given, and templates, scripts, or other resources are hyperlinked, whenever possible.

Getting to know me better: An fMRI study of intimate and superficial self-disclosure to friends during adolescence.

Adolescence is often defined as a period of social reorientation, characterized by increased engagement with, and reliance on, same-aged peers. Consistent with these shifting motivations, we hypothesized that communicating information about oneself to friends would be intrinsically valued during adolescence. We specifically examined behavioral and neural differences when sharing information of varying depth in intimacy. These questions were investigated in a sample of early adolescent girls (N = 125, ages 10.0-13.0 years) who completed a self-disclosure monetary choice task while undergoing fMRI. Behaviorally, adolescents gave up more money to share superficial self-referential information than intimate self-referential information with a (real-life) close friend. Neural analyses identified extensive engagement of regions that support social cognition and emotion regulation when engaging in intimate self-disclosure. Behavioral and neural valuation of sharing superficial information were related to individual differences in self-worth and friendship quality. Comparatively, across all levels of analyses, adolescents were less likely to share intimate information. Findings highlight both the value and costs associated with self-disclosure during this time of increased peer sensitivity. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Gut Feelings Begin in Childhood: the Gut Metagenome Correlates with Early Environment, Caregiving, and Behavior.

Psychosocial environments impact normative behavioral development in children, increasing the risk of problem behaviors and psychiatric disorders across the life span. Converging evidence demonstrates that early normative development is affected by the gut microbiome, which itself can be altered by early psychosocial environments. However, much of our understanding of the gut microbiome's role in early development stems from nonhuman animal models and predominately focuses on the first years of life, during peri- and postnatal microbial colonization. As a first step to identify if these findings translate to humans and the extent to which these relationships are maintained after initial microbial colonization, we conducted a metagenomic investigation among a cross-sectional sample of early school-aged children with a range of adverse experiences and caregiver stressors and relationships. Our results indicate that the taxonomic and functional composition of the gut microbiome correlates with behavior during a critical period of child development. Furthermore, our analysis reveals that both socioeconomic risk exposure and child behaviors associate with the relative abundances of specific taxa (e.g., Bacteroides and Bifidobacterium species) as well as functional modules encoded in their genomes (e.g., monoamine metabolism) that have been linked to cognition and health. While we cannot infer causality within this study, these findings suggest that caregivers may moderate the gut microbiome's link to environment and behaviors beyond the first few years of life.IMPORTANCE Childhood is a formative period of behavioral and biological development that can be modified, for better or worse, by the psychosocial environment that is in part determined by caregivers. Not only do our own genes and the external environment influence such developmental trajectories, but the community of microbes living in, on, and around our bodies-the microbiome-plays an important role as well. By surveying the gut microbiomes of a cross-sectional cohort of early school-aged children with a range of psychosocial environments and subclinical mental health symptoms, we demonstrated that caregiving behaviors modified the child gut microbiome's association to socioeconomic risk and behavioral dysregulation.

Study Protocol: Transitions in Adolescent Girls (TAG).

BACKGROUND: Despite recent studies linking pubertal processes to brain development, as well as research demonstrating the importance of both pubertal and neurodevelopmental processes for adolescent mental health, there is limited knowledge of the full pathways and mechanisms behind the emergence of mental illnesses such as depression and anxiety disorders in adolescence. The Transitions in Adolescent Girls (TAG) study aims to understand the complex relationships between pubertal development, brain structure and connectivity, the behavioral and neural correlates of social and self-perception processes, and adolescent mental health in female adolescents. METHODS: The TAG study includes 174 female adolescents aged 10.0 to 13.0 years, recruited from the local community in Lane County, Oregon, USA. The participants, along with a parent/guardian, will complete three waves of assessment over the course of 3 years; the third wave is currently underway. Each wave includes collection of four saliva samples (one per week) and one hair sample for the assessment of hormone levels and immune factors; an MRI session including structural, diffusion, resting-state functional and task-based functional scans; the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS), a diagnostic interview on current and lifetime mental health; production of a short self-narrative video; and measurement of height, weight, and waist circumference. The functional MRI tasks include a self-evaluation paradigm and a self-disclosure paradigm. In addition, adolescents and their parents/guardians complete a number of surveys to report on the adolescent's pubertal development, mental health, social environment and life events; adolescents also report on various indices of self-perception and social-emotional functioning. DISCUSSION: The knowledge gained from this study will include developmental trajectories of pubertal, neurological, and social processes and their roles as mechanisms in predicting emergence of mental illness in female adolescents. This knowledge will help identify modifiable, developmentally specific risk factors as targets for early intervention and prevention efforts.