Importance of investing in adolescence from a developmental science perspective.

This review summarizes the case for investing in adolescence as a period of rapid growth, learning, adaptation, and formational neurobiological development. Adolescence is a dynamic maturational period during which young lives can pivot rapidly-in both negative and positive directions. Scientific progress in understanding adolescent development provides actionable insights into windows of opportunity during which policies can have a positive impact on developmental trajectories relating to health, education, and social and economic success. Given current global changes and challenges that affect adolescents, there is a compelling need to leverage these advances in developmental science to inform strategic investments in adolescent health.

More time awake after sleep onset is linked to reduced ventral striatum response to rewards in youth with anxiety.

BACKGROUND: Poor sleep and anxiety disorders are highly comorbid in youth, and each predicts altered ventral striatum (VS) response to rewards, which may impact mental health risk. Contrasting evidence suggests previously reported negative associations between sleep health and VS response may be stronger or weaker in youth with anxiety, indicating sensitivity to win/loss information or blunted reward processing, respectively. We cross-sectionally examined the role of sleep in VS response to rewards among youth with anxiety versus a no-psychiatric-diagnosis comparison (ND) group. We expected a group*sleep interaction on VS response to rewards but did not hypothesize directionality. METHODS: As part of the pretreatment battery for a randomized clinical trial, 74 youth with anxiety and 31 ND youth (ages 9-14 years; n = 55 female) completed a monetary reward task during fMRI. During the same pretreatment window, actigraphy and diary-estimated sleep were collected over 5 days, and participants and their parents each reported participants' total sleep problems. We examined group*sleep interactions on VS response to monetary rewards versus losses via three mixed linear models corresponding to actigraphy, diary, and questionnaires, respectively. RESULTS: Each model indicated group*sleep interactions on VS response to rewards. Actigraphy and diary-estimated time awake after sleep onset predicted reduced VS response in youth with anxiety but not ND youth. Parent-reported sleep problems similarly interacted with group, but simple slopes were nonsignificant. CONCLUSIONS: Wake after sleep onset was associated with blunted reward response in youth with anxiety. These data suggest a potential pathway through which sleep could contribute to perturbed reward function and reward-related psychopathology (e.g., depression) in youth with anxiety.

Subgenual Anterior Cingulate Cortex Reactivity to Rejection Vs. Acceptance Predicts Depressive Symptoms among Adolescents with an Anxiety History.

OBJECTIVE: The goal of this study was to examine whether neural sensitivity to negative peer evaluation conveys risk for depression among youth with a history of anxiety. We hypothesized that brain activation in regions that process affective salience in response to rejection, relative to acceptance, from virtual peers would predict depressive symptoms 1 year later and would be associated with ecological momentary assessment (EMA) reports of peer connectedness. METHOD: Participants were 38 adolescents ages 11-16 (50% female) with a history of anxiety, recruited from a previous clinical trial. The study was a prospective naturalistic follow-up of depressive symptoms assessed 2 years (Wave 2) and 3 years (Wave 3) following treatment. At Wave 2, participants completed the Chatroom Interact Task during neuroimaging and 16 days of EMA. RESULTS: Controlling for depressive and anxiety symptoms at Wave 2, subgenual anterior cingulate (sgACC; ß = .39, p = .010) activation to peer rejection (vs. acceptance) predicted depressive symptoms at Wave 3. SgACC activation to rejection (vs. acceptance) was highly negatively correlated with EMA reports of connectedness with peers in daily life (r = - .71, p < .001). CONCLUSION: Findings suggest that elevated sgACC activation to negative, relative to positive, peer evaluation may serve as a risk factor for depressive symptoms among youth with a history of anxiety, perhaps by promoting vigilance or reactivity to social evaluative threats. SgACC activation to simulated peer evaluation appears to have implications for understanding how adolescents experience their daily social environments in ways that could contribute to depressive symptoms.

Therapeutic Alliance, Attendance, and Outcomes in Youths Receiving CBT or Client-Centered Therapy for Anxiety.

OBJECTIVE: Positive associations between therapeutic alliance and outcome (e.g. youth symptom severity) have been documented in the youth anxiety literature; however, little is known about the conditions under which early alliance contributes to positive outcomes in youth. The present study examined the relations between therapeutic alliance, session attendance, and outcomes in youths (N = 135; 55.6% female) who participated in a randomized clinical trial testing the efficacy of cognitive-behavioral therapy or client-centered therapy for anxiety. METHOD: We evaluated a conceptual model wherein: (1) early alliance indirectly contributes to positive outcomes by improving session attendance; (2) alliance-outcome associations differ by intervention type, with stronger associations in cognitive-behavioral therapy compared to client-centered therapy; and (3) alliance-outcome associations vary across outcome measurement timepoints, with the effect of early alliance on outcomes decaying over time. RESULTS: Contrary to hypotheses, provider ratings of early alliance predicted greater youth-rated anxiety symptom severity post-treatment (i.e. worse treatment outcomes). Session attendance predicted positive youth-rated outcomes, though there was no indirect effect of early alliance on outcomes through session attendance. CONCLUSIONS: Results show that increasing session attendance is important for enhancing outcomes and do not support early alliance as a predictor of outcomes.

Longitudinal Change in Adolescent Depression and Anxiety Symptoms from before to during the COVID-19 Pandemic.

This study aimed to examine changes in depression and anxiety symptoms from before to during the first 6 months of the COVID-19 pandemic in a sample of 1,339 adolescents (9-18 years old, 59% female) from three countries. We also examined if age, race/ethnicity, disease burden, or strictness of government restrictions moderated change in symptoms. Data from 12 longitudinal studies (10 U.S., 1 Netherlands, 1 Peru) were combined. Linear mixed effect models showed that depression, but not anxiety, symptoms increased significantly (median increase = 28%). The most negative mental health impacts were reported by multiracial adolescents and those under 'lockdown' restrictions. Policy makers need to consider these impacts by investing in ways to support adolescents' mental health during the pandemic.

Short Research Article: Promoting digital citizenship through a school-based intervention in early adolescence in Perú (a pilot quasi-experimental study).

OBJECTIVE: Evaluate the preliminary effectiveness of a school-based intervention to promote digital citizenship (DC) in Perú. METHODS: We piloted a translation and cultural adaptation of a DC curriculum originally designed for the U.S. with students in Perú. Students were assigned to either the Intervention group (n = 136, 52% female; mean age = 13.3) or Control group (n = 130, 55% female; mean age = 13.4). Students in the Control group continued with "business-as-usual" during their advisory period while the Intervention group received the DC curriculum. RESULTS: We found limited evidence that the DC curriculum can promote positive online experience and online conflict resolution skills, as well as increase knowledge regarding DC terms and concepts. However, the lack of strong effects suggests the need to revise materials, improve implementation and consider further adaptations. Nonetheless, results from this proof-of-concept study provide building blocks for future implementations of DC interventions for youth in Latin America.

Modeling changes in probabilistic reinforcement learning during adolescence.

In the real world, many relationships between events are uncertain and probabilistic. Uncertainty is also likely to be a more common feature of daily experience for youth because they have less experience to draw from than adults. Some studies suggest probabilistic learning may be inefficient in youths compared to adults, while others suggest it may be more efficient in youths in mid adolescence. Here we used a probabilistic reinforcement learning task to test how youth age 8-17 (N = 187) and adults age 18-30 (N = 110) learn about stable probabilistic contingencies. Performance increased with age through early-twenties, then stabilized. Using hierarchical Bayesian methods to fit computational reinforcement learning models, we show that all participants' performance was better explained by models in which negative outcomes had minimal to no impact on learning. The performance increase over age was driven by 1) an increase in learning rate (i.e. decrease in integration time scale); 2) a decrease in noisy/exploratory choices. In mid-adolescence age 13-15, salivary testosterone and learning rate were positively related. We discuss our findings in the context of other studies and hypotheses about adolescent brain development.

Basophil sensitivity reflects long-term clinical outcome of subcutaneous immunotherapy in grass pollen-allergic patients.

BACKGROUND: Allergic rhinoconjunctivitis is a public health problem. Allergen Immunotherapy is an effective and safe treatment, that modifies the natural course of allergic disease and induces long-term tolerance. OBJECTIVE: To correlate basophil and antibody biomarkers of subcutaneous immunotherapy to clinical outcomes and cellular changes in target tissue. METHODS: Adults suffering from allergic rhinoconjunctivitis due to grass pollen allergy were randomized to receive subcutaneous immunotherapy (n = 18) or to an open control group (n = 6). Patients reported daily symptom and medication scores and weekly rhinitis related quality of life scores during four pollen seasons. Biomarkers were measured every 3 months for three years treatment and every 6 months in the follow-up year. Nasal and cutaneous allergen challenge tests were performed annually. Leukocyte subsets were assessed in nasal mucosa biopsies at baseline and after treatment. RESULTS: Subcutaneous immunotherapy led to a 447-fold decrease in basophil sensitivity during the first treatment year. This remained 100-fold lower than baseline during the 3 year-treatment period and 10-fold lower during the follow-up year (n = 18, P = .03). Decrease in basophil sensitivity after three weeks of treatment predicted long-term improvement in seasonal combined symptom and medication scores (á¿¥=-0.69, P = .0027) during three years of treatment. AUC of IgE-blocking factor correlated to nasal allergen challenge (á¿¥ = 0.63, P = .0012) and SPT (á¿¥ = 0.45, P = .03). Plasma cell numbers in the nasal mucosa increased during treatment (P = .02). CONCLUSION: Decrease in basophil sensitivity after three weeks of subcutaneous allergen immunotherapy predicted the clinical outcome of this treatment.

Adolescent, caregiver and community experiences with a gender transformative, social emotional learning intervention.

BACKGROUND: Inequitable gender norms, beliefs and behaviors, are shaped by learning experiences during key developmental stages in an individual's life course, and can have negative impacts on health and well-being outcomes. Very early adolescence represents one stage when formative learning experiences about gender inequity can have the potential to support or hinder more equitable gender norms, beliefs and behaviors. The aim of this qualitative study was to evaluate the effect of a gender transformative, social emotional learning intervention for very young adolescents (VYAs) that included experiential learning with peers, parents/caregivers and community members. METHODS: This study examined the effects of an intervention designed to provide social emotional learning opportunities for adolescents ages 10-11 in Dar es Salaam, Tanzania. The qualitative sample included 279 participants. Qualitative methods included 102 in-depth interviews with VYAs, 22 focus groups with 117 VYAs, 60 in-depth interviews with parents/caregivers and 54 participant observations. A grounded theory approach was used to identify emergent themes. RESULTS: Participants reported growth in targeted areas of social emotional mindsets and skills, including a shift in gender norms, beliefs and behaviors. VYAs reported that experiential learning in mixed gender teams provided opportunities to actively practice and reflect on gender norms, beliefs and behaviors. VYAs also reported active practice of social emotional mindsets and skills with peers, parents/caregivers and the community. Parents/caregivers reported changes in VYAs' social emotional mindsets and skills within the home, with the community and with siblings and peers. Both adolescents and parent/caregivers reported positive change towards more equitable gender norms, beliefs and behaviors through participation in experiential learning activities and reflective discussions. CONCLUSIONS: These findings suggest that an intervention providing social and emotional experiential learning opportunities during the developmental window of very young adolescence can be effective in transforming gender norms, beliefs and behaviors. Involvement of peers, parents/caregivers and community members was effective at supporting learning social emotional mindsets and skills in VYAs. Findings encourage local and global adolescent programming to include gender transformative content paired with social emotional experiential learning with peers, family and the community and can stimulate positive change in gender norms, beliefs and behaviors to promote gender equity.

Parents still matter! Parental warmth predicts adolescent brain function and anxiety and depressive symptoms 2 years later.

Anxiety is the most prevalent psychological disorder among youth, and even following treatment, it confers risk for anxiety relapse and the development of depression. Anxiety disorders are associated with heightened response to negative affective stimuli in the brain networks that underlie emotion processing. One factor that can attenuate the symptoms of anxiety and depression in high-risk youth is parental warmth. The current study investigates whether parental warmth helps to protect against future anxiety and depressive symptoms in adolescents with histories of anxiety and whether neural functioning in the brain regions that are implicated in emotion processing and regulation can account for this link. Following treatment for anxiety disorder (Time 1), 30 adolescents (M age = 11.58, SD = 1.26) reported on maternal warmth, and 2 years later (Time 2) they participated in a functional neuroimaging task where they listened to prerecorded criticism and neutral statements from a parent. Higher maternal warmth predicted lower neural activation during criticism, compared with the response during neutral statements, in the left amygdala, bilateral insula, subgenual anterior cingulate (sgACC), right ventrolateral prefrontal cortex, and anterior cingulate cortex. Maternal warmth was associated with adolescents' anxiety and depressive symptoms due to the indirect effects of sgACC activation, suggesting that parenting may attenuate risk for internalizing through its effects on brain function.

Promoting gender equity in very young adolescents: targeting a window of opportunity for social emotional learning and identity development.

BACKGROUND: The transition from childhood to adolescence is a uniquely sensitive period for social and emotional learning in the trajectory of human development. This transition is characterized by rapid physical growth, sexual maturation, cognitive and behavioral changes and dynamic changes in social relationships. This pivotal transition provides a window of opportunity for social emotional learning that can shape early adolescent identity formation and gender norms, beliefs and behaviors. The objective of this study is to evaluate the potential of a social emotional learning intervention for very young adolescents (VYAs) to improve social emotional mindsets and skills. METHODS: Discover Learning is a social emotional learning intervention designed for VYAs (10-11 years of age) to support development of social emotional mindsets and skills from four primary schools in Dar es Salaam, Tanzania. The intervention delivered three different packages of learning experiences to three arms of the study. 528 VYAs were randomized to each of the three study arms (A-Content learning, B-Content learning and reflection, and C-Content learning, reflection and experiential practice). A quantitative survey was administered to all participants before and after the intervention to capture changes in social emotional mindsets and skills. A discrete choice experiment measured changes in gender norms, beliefs and behaviors. RESULTS: 528 VYAs were included in the analysis. Participants in all three arms of the study demonstrated significant improvements in social emotional mindsets and skills outcomes (generosity, curiosity, growth mindset, persistence, purpose and teamwork). However, Group C (who received experiential social learning opportunities in small, mixed-gender groups and a parent and community learning components demonstrated larger treatment effects on key outcomes in comparison to Groups A and B. Results indicate Group C participants had greater change in gender equity outcomes (OR = 1.69, p = <0.001) compared to Group A (OR = 1.30, p = <0.001) and Group B (OR = 1.23, p = 0.004). CONCLUSION: These findings provide evidence that social emotional learning interventions targeting VYAs can improve social emotional mindsets and skills and gender equity outcomes. The findings indicate the importance of experiential learning activities in mixed-gender groups during the unique developmental window of early adolescence. The study also provides support for the inclusion of parental/caregiver and community engagement in programs designed for VYAs. TRIAL REGISTRATION: Retrospectively registered on July 7th, 2020. NCT0445807.

Positive and Negative Online Experiences and Loneliness in Peruvian Adolescents During the COVID-19 Lockdown.

Global COVID-19 lockdowns have disrupted adolescents' in-person social networks, increasing likelihood of loneliness. Social media can help adolescents maintain and develop peer relationships across distance. In this short longitudinal study with 735 Peruvian adolescents (ages: 11-17) from low-to-middle-income urban settings, we investigated whether online experiences relate to loneliness during initial stages of lockdown. Loneliness remained constant between week 6 and 11 of lockdown, was higher for females and similar across school-grades. Positive and negative online experiences were more frequent for older students, and females experienced more negative online experiences than males. Greater positive online experiences related to lower loneliness, with the reverse pattern for negative online experiences. Our results suggest that positive online experiences may mitigate loneliness during physical isolation.

A phase IIb, randomised, parallel-group study: the efficacy, safety and tolerability of once-daily umeclidinium in patients with asthma receiving inhaled corticosteroids.

BACKGROUND: Patients with asthma uncontrolled on inhaled corticosteroids may benefit from umeclidinium (UMEC), a long-acting muscarinic antagonist. METHODS: This Phase IIb, double-blind study included patients with reversible, uncontrolled/partially-controlled asthma for ≥6 months, receiving ≥100 mcg/day fluticasone propionate (or equivalent) for ≥12 weeks. Following a 2-week run-in on open-label fluticasone furoate (FF) 100 mcg, patients were randomised (1:1:1) to receive UMEC 31.25 mcg, UMEC 62.5 mcg or placebo on top of FF 100 mcg once-daily for 24 weeks. As-needed salbutamol was provided. Primary and secondary endpoints were change from baseline in clinic trough forced expiratory volume in 1 s (FEV1) and clinic FEV1 3 h post-dose, respectively, at Week 24. Other endpoints included change from baseline in home daily spirometry (trough FEV1, evening FEV1, morning [pre-dose] and evening peak expiratory flow) over 24 weeks. Safety was assessed throughout the study. RESULTS: The intent-to-treat population comprised 421 patients (UMEC 31.25 mcg: n =139, UMEC 62.5 mcg: n =139, placebo: n =143). UMEC 31.25 mcg and 62.5 mcg demonstrated significantly greater improvements from baseline in clinic trough FEV1 at Week 24 (difference [95% CI]: 0.176 L [0.092, 0.260; p<0.001] and 0.184 L [0.101, 0.268; p<0.001], respectively), clinic FEV1 3 h post-dose at Week 24 (0.190 L [0.100, 0.279; p<0.001] and 0.198 L [0.109, 0.287; p<0.001], respectively) and mean change from baseline in daily home spirometry over 24 weeks versus placebo. No new safety signals were identified. CONCLUSIONS: UMEC is a highly effective bronchodilator that leads to improved lung function when administered as a single bronchodilator on top of FF in subjects with fully reversible, uncontrolled/partially-controlled moderate asthma. These data support a favourable benefit/risk profile for UMEC (31.25 mcg and 62.5 mcg). TRIAL REGISTRATION: GSK study ID: 205832; Clinicaltrials.gov ID: NCT03012061.

Sleep problems in adolescence are prospectively linked to later depressive symptoms via the cortisol awakening response.

Sleep disturbance is a symptom of and a well-known risk factor for depression. Further, atypical functioning of the HPA axis has been linked to the pathogenesis of depression. The purpose of this study was to examine the role of adolescent HPA axis functioning in the link between adolescent sleep problems and later depressive symptoms. Methods: A sample of 157 17-18 year old adolescents (61.8% female) completed the Pittsburgh Sleep Quality Inventory (PSQI) and provided salivary cortisol samples throughout the day for three consecutive days. Two years later, adolescents reported their depressive symptoms via the Center for Epidemiological Studies Depression Scale (CES-D). Results: Individuals (age 17-18) with greater sleep disturbance reported greater depressive symptoms two years later (age 19-20). This association occurred through the indirect effect of sleep disturbance on the cortisol awakening response (CAR) (indirect effect = 0.14, 95%CI [.02 -.39]). Conclusions: One pathway through which sleep problems may lead to depressive symptoms is by up-regulating components of the body's physiological stress response system that can be measured through the cortisol awakening response. Behavioral interventions that target sleep disturbance in adolescents may mitigate this neurobiological pathway to depression during this high-risk developmental phase.

Changes in cognitive flexibility and hypothesis search across human life history from childhood to adolescence to adulthood.

How was the evolution of our unique biological life history related to distinctive human developments in cognition and culture? We suggest that the extended human childhood and adolescence allows a balance between exploration and exploitation, between wider and narrower hypothesis search, and between innovation and imitation in cultural learning. In particular, different developmental periods may be associated with different learning strategies. This relation between biology and culture was probably coevolutionary and bidirectional: life-history changes allowed changes in learning, which in turn both allowed and rewarded extended life histories. In two studies, we test how easily people learn an unusual physical or social causal relation from a pattern of evidence. We track the development of this ability from early childhood through adolescence and adulthood. In the physical domain, preschoolers, counterintuitively, perform better than school-aged children, who in turn perform better than adolescents and adults. As they grow older learners are less flexible: they are less likely to adopt an initially unfamiliar hypothesis that is consistent with new evidence. Instead, learners prefer a familiar hypothesis that is less consistent with the evidence. In the social domain, both preschoolers and adolescents are actually the most flexible learners, adopting an unusual hypothesis more easily than either 6-y-olds or adults. There may be important developmental transitions in flexibility at the entry into middle childhood and in adolescence, which differ across domains.

Suicidal Ideation Among Anxious Youth: A Preliminary Investigation of the Role of Neural Processing of Social Rejection in Interaction with Real World Negative Social Experiences.

Suicidal ideation increases in adolescence, especially for anxious youth, and is a frequent precursor to suicide. This study examined whether neural processing of social rejection interacted with negative social experiences to predict suicidal ideation. Thus, to our knowledge this is the first study to examine how brain function may interact with the environment to contribute to suicidal ideation in youth, consistent with a developmental psychopathology perspective. Thirty-six anxious youth (ages 11 to 16) completed diagnostic interviews and questionnaires, an ecological momentary assessment (EMA) protocol, and a functional magnetic resonance imaging paradigm. Results showed that youth experienced greater severity of suicidal ideation when they exhibited heightened activation to social rejection in the right anterior insula and also experienced high levels of peer victimization or EMA-measured daily negative social experiences. Findings provide preliminary evidence that alterations in neural processing of social rejection interacts with exposure to negative social experiences to contribute to suicidal ideation.

Parental coping socialization is associated with healthy and anxious early-adolescents' neural and real-world response to threat.

The ways parents socialize their adolescents to cope with anxiety (i.e., coping socialization) may be instrumental in the development of threat processing and coping responses. Coping socialization may be important for anxious adolescents, as they show altered neural threat processing and over reliance on disengaged coping (e.g., avoidance and distraction), which can maintain anxiety. We investigated whether coping socialization was associated with anxious and healthy adolescents' neural response to threat, and whether neural activation was associated with disengaged coping. Healthy and clinically anxious early adolescents (N = 120; M = 11.46 years; 71 girls) and a parent engaged in interactions designed to elicit adolescents' anxiety and parents' response to adolescents' anxiety. Parents' use of reframing and problem solving statements was coded to measure coping socialization. In a subsequent visit, we assessed adolescents' neural response to threat words during a neuroimaging task. Adolescents' disengaged coping was measured using ecological momentary assessment. Greater coping socialization was associated with lower anterior insula and perigenual cingulate activation in healthy adolescents and higher activation in anxious adolescents. Coping socialization was indirectly associated with less disengaged coping for anxious adolescents through neural activation. Findings suggest that associations between coping socialization and early adolescents' neural response to threat differ depending on clinical status and have implications for anxious adolescents' coping.

Anxiety Treatment and Targeted Sleep Enhancement to Address Sleep Disturbance in Pre/Early Adolescents with Anxiety.

Sleep disturbance is prevalent in anxious youth and prospectively predicts poor emotional adjustment in adolescence. Study 1 examined whether anxiety treatment improves subjective and objective sleep disturbance in anxious youth. Study 2 examined whether a sleep intervention called Sleeping TIGERS can further improve sleep following anxiety treatment. Study 1 examined 133 youth (ages 9-14; 56% female; 11% ethnic/racial minority) with generalized, social, or separation anxiety over the course of anxiety treatment (cognitive behavioral treatment or client-centered treatment). Sleep-related problems (parent-, child-report) and subjective (diary) and objective (actigraphy) sleep patterns were assessed across treatment in an open trial design. Study 2 included 50 youth (ages 9-14; 68% female; 10% ethnic/racial minority) who continued to report sleep-related problems after anxiety treatment and enrolled in an open trial of Sleeping TIGERS. Pre- and postassessments duplicated Study 1 and included the Focal Interview of Sleep to assess sleep disturbance. Study 1 demonstrated small reductions in sleep problems and improvements in subjective sleep patterns (diary) across anxiety treatment, but outcomes were not deemed clinically significant, and 75% of youth stayed above clinical cutoff. Study 2 showed clinically significant, large reductions in sleep problems and small changes in some subjective sleep patterns (diary). Anxiety treatment improves, but does not resolve, sleep disturbance in peri-pubertal youth, which may portend risk for poor emotional adjustment and mental health. The open trial provides preliminary support that Sleeping TIGERS can improve sleep in anxious youth to a clinically significant degree.

Attention to Peer Feedback Through the Eyes of Adolescents with a History of Anxiety and Healthy Adolescents.

During adolescence, youth may experience heightened attention bias to socially relevant stimuli; however, it is unclear if attention bias toward social threat may be exacerbated for adolescents with a history of anxiety. This study evaluated attentional bias during the Chatroom-Interact task with 25 adolescents with a history of anxiety (18F, Mage = 13.6) and 22 healthy adolescents (13F, Mage = 13.8). In this task, participants received feedback from fictional, virtual peers who either chose them (acceptance) or rejected them (rejection). Overall, participants were faster to orient toward and spent longer time dwelling on their own picture after both rejection and acceptance compared to non-feedback cues. Social feedback was associated with greater pupillary reactivity, an index of cognitive and emotional neural processing, compared to non-feedback cues. During acceptance feedback (but not during rejection feedback), anxious youth displayed greater pupil response compared to healthy youth, suggesting that positive feedback from peers may differentially influence youth with a history of an anxiety disorder.

Development of the Cerebral Cortex across Adolescence: A Multisample Study of Inter-Related Longitudinal Changes in Cortical Volume, Surface Area, and Thickness.

Before we can assess and interpret how developmental changes in human brain structure relate to cognition, affect, and motivation, and how these processes are perturbed in clinical or at-risk populations, we must first precisely understand typical brain development and how changes in different structural components relate to each other. We conducted a multisample magnetic resonance imaging study to investigate the development of cortical volume, surface area, and thickness, as well as their inter-relationships, from late childhood to early adulthood (7-29 years) using four separate longitudinal samples including 388 participants and 854 total scans. These independent datasets were processed and quality-controlled using the same methods, but analyzed separately to study the replicability of the results across sample and image-acquisition characteristics. The results consistently showed widespread and regionally variable nonlinear decreases in cortical volume and thickness and comparably smaller steady decreases in surface area. Further, the dominant contributor to cortical volume reductions during adolescence was thinning. Finally, complex regional and topological patterns of associations between changes in surface area and thickness were observed. Positive relationships were seen in sulcal regions in prefrontal and temporal cortices, while negative relationships were seen mainly in gyral regions in more posterior cortices. Collectively, these results help resolve previous inconsistencies regarding the structural development of the cerebral cortex from childhood to adulthood, and provide novel insight into how changes in the different dimensions of the cortex in this period of life are inter-related.SIGNIFICANCE STATEMENT Different measures of brain anatomy develop differently across adolescence. Their precise trajectories and how they relate to each other throughout development are important to know if we are to fully understand both typical development and disorders involving aberrant brain development. However, our understanding of such trajectories and relationships is still incomplete. To provide accurate characterizations of how different measures of cortical structure develop, we performed an MRI investigation across four independent datasets. The most profound anatomical change in the cortex during adolescence was thinning, with the largest decreases observed in the parietal lobe. There were complex regional patterns of associations between changes in surface area and thickness, with positive relationships seen in sulcal regions in prefrontal and temporal cortices, and negative relationships seen mainly in gyral regions in more posterior cortices.