Alterations in neural circuits underlying emotion regulation following child maltreatment: a mechanism underlying trauma-related psychopathology.

BACKGROUND: Disruptions in neural circuits underlying emotion regulation (ER) may be a mechanism linking child maltreatment with psychopathology. We examined the associations of maltreatment with neural responses during passive viewing of negative emotional stimuli and attempts to modulate emotional responses. We investigated whether the influence of maltreatment on neural activation during ER differed across development and whether alterations in brain function mediated the association between maltreatment and a latent general psychopathology ('p') factor. METHODS: Youth aged 8-16 years with (n = 79) and without (n = 72) exposure to maltreatment completed an ER task assessing neural responses during passive viewing of negative and neutral images and effortful attempts to regulate emotional responses to negative stimuli. P-factor scores were defined by a bi-factor model encompassing internalizing and externalizing psychopathology. RESULTS: Maltreated youth had greater activation in left amygdala and salience processing regions and reduced activation in multiple regions involved in cognitive control (bilateral superior frontal gyrus, middle frontal gyrus, and dorsal anterior cingulate cortex) when viewing negative v. neutral images than youth without maltreatment exposure. Reduced neural recruitment in cognitive control regions mediated the association of maltreatment with p-factor in whole-brain analysis. Maltreated youth exhibited increasing recruitment with age in ventrolateral prefrontal cortex during reappraisal while control participants exhibited decreasing recruitment with age. Findings were similar after adjusting for co-occurring neglect. CONCLUSIONS: Child maltreatment influences the development of regions associated with salience processing and cognitive control during ER in ways that contribute to psychopathology.

Differential Associations of Distinct Forms of Childhood Adversity With Neurobehavioral Measures of Reward Processing: A Developmental Pathway to Depression.

Childhood adversity is associated with altered reward processing, but little is known about whether this varies across distinct types of adversity. In a sample of 94 children (6-19 years), we investigated whether experiences of material deprivation, emotional deprivation, and trauma have differential associations with reward-related behavior and white matter microstructure in tracts involved in reward processing. Material deprivation (food insecurity), but not emotional deprivation or trauma, was associated with poor reward performance. Adversity-related influences on the integrity of white matter microstructure in frontostriatal tracts varied across childhood adversity types, and reductions in frontostriatal white matter integrity mediated the association of food insecurity with depressive symptoms. These findings document distinct behavioral and neurodevelopmental consequences of specific forms of adversity that have implications for psychopathology risk.

Emotion regulation processes linking peer victimization to anxiety and depression symptoms in adolescence.

Difficulties with emotion regulation can take many forms, including increased sensitivity to emotional cues and habitual use of maladaptive cognitive or behavioral regulation strategies. Despite extensive research on emotion regulation and youth adjustment, few studies integrate multiple measures of emotion regulation. The present study evaluated the underlying structure of emotion regulation processes in adolescence using both task- and survey-based measures and determined whether differences in these emotion regulation latent factors mediated the association between peer victimization and internalizing psychopathology. Adolescents aged 16-17 years (n = 287; 55% female; 42% White) recruited in three urban centers in the United States completed baseline and follow-up assessments 4 months apart. Three models of emotion regulation were evaluated with confirmatory factor analysis. A three-factor model fit the data best, including cognitive regulation, behavioral regulation, and emotional reactivity latent factors. Task-based measures did not load onto these latent factors. Difficulties with behavioral regulation mediated the association between peer victimization and depression symptoms, whereas cognitive regulation difficulties mediated the association with anxiety symptoms. Findings point to potential targets for intervention efforts to reduce risk for internalizing problems in adolescents following experiences of peer victimization.

Salience network response to changes in emotional expressions of others is heightened during early adolescence: relevance for social functioning.

Adolescence is a unique developmental period when the salience of social and emotional information becomes particularly pronounced. Although this increased sensitivity to social and emotional information has frequently been considered with respect to risk behaviors and psychopathology, evidence suggests that increased adolescent sensitivity to social and emotional cues may confer advantages. For example, greater sensitivity to shifts in the emotions of others is likely to promote flexible and adaptive social behavior. In this study, a sample of 54 children and adolescents (age 8-19 years) performed a delayed match-to-sample task for emotional faces while undergoing fMRI scanning. Recruitment of the anterior cingulate and anterior insula when the emotion of the probe face did not match the emotion held in memory followed a quadratic developmental pattern that peaked during early adolescence. These findings indicate meaningful developmental variation in the neural mechanisms underlying sensitivity to changes in the emotional expressions. Across all participants, greater activation of this network for changes in emotional expression was associated with less social anxiety and fewer social problems. These results suggest that the heightened salience of social and emotional information during adolescence may confer important advantages for social behavior, providing sensitivity to others' emotions that facilitates flexible social responding.

Violence exposure and neural systems underlying working memory for emotional stimuli in youth.

Violence exposure during childhood is common and associated with poor cognitive and academic functioning. However, little is known about how violence exposure influences cognitive processes that might contribute to these disparities, such as working memory, or their neural underpinnings, particularly for cognitive processes that occur in emotionally salient contexts. We address this gap in a sample of 54 participants aged 8 to 19 years (50% female), half with exposure to interpersonal violence. Participants completed a delayed match to sample task for emotional faces while undergoing functional magnetic resonance imaging scanning. Violence-exposed youth performed worse than controls on happy and neutral, but not angry, trials. In whole-brain analysis, violence-exposed youth had reduced activation in the left middle frontal gyrus and right intraparietal sulcus during encoding and the left superior temporal sulcus and temporal-parietal junction during retrieval compared to control youth. Reduced activation in the left middle frontal gyrus during encoding and the left superior temporal sulcus during retrieval mediated the association between violence exposure and task performance. Violence exposure influences the frontoparietal network that supports working memory as well as regions involved in facial processing during working memory for emotional stimuli. Reduced neural recruitment in these regions may explain atypical patterns of cognitive processing seen among violence-exposed youth, particularly within emotional contexts.

Catastrophizing, rumination, and reappraisal prospectively predict adolescent PTSD symptom onset following a terrorist attack.

BACKGROUND: Disruptions in emotion regulation are a transdiagnostic risk factor for psychopathology. However, scant research has examined whether emotion regulation strategies are related to the onset of posttraumatic stress disorder (PTSD) symptoms among youths exposed to trauma. We investigated whether pretrauma emotion regulation strategies prospectively predicted PTSD symptom onset after the 2013 Boston Marathon terrorist attack among adolescents and whether these associations were moderated by the degree of exposure to media coverage of the attack. METHODS: A sample of 78 Boston-area adolescents (mean age = 16.72 years, 65% female) who previously participated in studies assessing emotion regulation and psychopathology were recruited following the terrorist attack. Within 4 weeks of the attack, we assessed self-reported PTSD symptoms and attack-related media exposure via an online survey. We examined the association of pretrauma emotion regulation strategies with PTSD symptom onset after adjustment for pretrauma internalizing symptoms and violence exposure. RESULTS: Greater pretrauma engagement in rumination predicted onset of PTSD symptoms following the attack. Adolescents who engaged in catastrophizing also had greater PTSD symptoms postattack, but only when exposed to high levels of media coverage of the attacks; the same pattern was observed for adolescents who engaged in low levels of cognitive reappraisal. CONCLUSIONS: Engagement in specific emotion regulation strategies prior to a traumatic event predicts the onset of PTSD symptoms among youths exposed to trauma, extending transdiagnostic models of emotion regulation to encompass trauma-related psychopathology in children and adolescents.

Misclassification and identification of emotional facial expressions in depressed youth: a preliminary study.

Accurate processing of social and affective cues, especially facial cues, is important for human adaptation. Previous studies have examined depressed adults' sensitivity to identify emotional facial expressions, yet only one study has investigated this in depressed youth. In addition, very little is known about whether depressed individuals exhibit biases when incorrectly labeling, or misclassifying, emotional expressions. Therefore, this preliminary study explored whether sensitivity to, or misclassification of, emotional facial expressions differed among currently depressed youth, those with a history of depression, and never-depressed control participants. A community sample of 280 youth (7-16 years; M = 11.51, SD = 2.44; 56% girls) completed a forced-choice emotion identification task consisting of a series of randomly presented facial images that morphed an emotional expression (angry, happy, and sad) with a neutral expression in 10% increments (e.g., 10% sad/90% neutral; 20% sad/80% neutral). Findings demonstrated that currently depressed were more likely than remitted and never-depressed youth to misclassify happy and sad facial expressions as angry. No depression group differences were found in sensitivity to identify emotional expressions. Results suggest that currently depressed youth show biased perceptions of threat, which may contribute to the maintenance of their depressive symptoms.

Observed positive parenting behaviors and youth genotype: evidence for gene-environment correlations and moderation by parent personality traits.

Gene-environment correlations (rGE) have been demonstrated in behavioral genetic studies, but rGE have proven elusive in molecular genetic research. Significant gene-environment correlations may be difficult to detect because potential moderators could reduce correlations between measured genetic variants and the environment. Molecular genetic studies investigating moderated rGE are lacking. This study examined associations between child catechol-O-methyltransferase genotype and aspects of positive parenting (responsiveness and warmth), and whether these associations were moderated by parental personality traits (neuroticism and extraversion) among a general community sample of third, sixth, and ninth graders (N = 263) and their parents. Results showed that parent personality traits moderated the rGE association between youths' genotype and coded observations of positive parenting. Parents with low levels of neuroticism and high levels of extraversion exhibited greater sensitive responsiveness and warmth, respectively, to youth with the valine/valine genotype. Moreover, youth with this genotype exhibited lower levels of observed anger. There was no association between the catechol-O-methyltransferase genotype and parenting behaviors for parents high on neuroticism and low on extraversion. Findings highlight the importance of considering moderating variables that may influence child genetic effects on the rearing environment. Implications for developmental models of maladaptive and adaptive child outcomes, and interventions for psychopathology, are discussed within a developmental psychopathology framework.

Association of Demographic and Socioeconomic Indicators With the Use of Wearable Devices Among Children.

Importance: The use of consumer-grade wearable devices for collecting data for biomedical research may be associated with social determinants of health (SDoHs) linked to people's understanding of and willingness to join and remain engaged in remote health studies. Objective: To examine whether demographic and socioeconomic indicators are associated with willingness to join a wearable device study and adherence to wearable data collection in children. Design, Setting, and Participants: This cohort study used wearable device usage data collected from 10 414 participants (aged 11-13 years) at the year-2 follow-up (2018-2020) of the ongoing Adolescent Brain and Cognitive Development (ABCD) Study, performed at 21 sites across the United States. Data were analyzed from November 2021 to July 2022. Main Outcomes and Measures: The 2 primary outcomes were (1) participant retention in the wearable device substudy and (2) total device wear time during the 21-day observation period. Associations between the primary end points and sociodemographic and economic indicators were examined. Results: The mean (SD) age of the 10 414 participants was 12.00 (0.72) years, with 5444 (52.3%) male participants. Overall, 1424 participants (13.7%) were Black; 2048 (19.7%), Hispanic; and 5615 (53.9%) White. Substantial differences were observed between the cohort that participated and shared wearable device data (wearable device cohort [WDC]; 7424 participants [71.3%]) compared with those who did not participate or share data (no wearable device cohort [NWDC]; 2900 participants [28.7%]). Black children were significantly underrepresented (-59%) in the WDC (847 [11.4%]) compared with the NWDC (577 [19.3%]; P < .001). In contrast, White children were overrepresented (+132%) in the WDC (4301 [57.9%]) vs the NWDC (1314 [43.9%]; P < .001). Children from low-income households (<$24 999) were significantly underrepresented in WDC (638 [8.6%]) compared with NWDC (492 [16.5%]; P < .001). Overall, Black children were retained for a substantially shorter duration (16 days; 95% CI, 14-17 days) compared with White children (21 days; 95% CI, 21-21 days; P < .001) in the wearable device substudy. In addition, total device wear time during the observation was notably different between Black vs White children (ß = -43.00 hours; 95% CI, -55.11 to -30.88 hours; P < .001). Conclusions and Relevance: In this cohort study, large-scale wearable device data collected from children showed considerable differences between White and Black children in terms of enrollment and daily wear time. While wearable devices provide an opportunity for real-time, high-frequency contextual monitoring of individuals' health, future studies should account for and address considerable representational bias in wearable data collection associated with demographic and SDoH factors.

Neural Markers of Emotion Reactivity and Regulation Before and After a Targeted Social Rejection: Differences Among Girls With and Without Suicidal Ideation and Behavior Histories.

BACKGROUND: Suicidal thoughts and behaviors (STBs) are common among adolescent girls and increase risk for suicide death. Emotion regulation difficulties are linked with STBs, particularly in response to targeted social rejection. However, neural correlates of this link have not been investigated and may identify novel targets for interventions. Here, we examined neural correlates of emotion regulation before and after an experimentally delivered targeted social rejection in adolescent girls with STBs and girls without STBs (i.e., control participants). METHODS: Girls (N = 138; age range, 9-15 years; mean [SD] age = 11.6 [1.79] years) completed a functional neuroimaging emotion regulation task. In the middle of the task, participants were socially rejected by an unfamiliar confederate whom the participants had elected to meet. Participants also completed a multimethod STB assessment. RESULTS: Before rejection, girls with a history of STBs, compared with control participants, showed greater activation in the right superior frontal gyrus when passively viewing negative stimuli, and girls with suicidal behavior (SB) versus those without SB showed less activation in the right frontal pole during emotion regulation attempts. Following the rejection, girls with STBs, compared with control participants, showed greater activation in the right inferior frontal gyrus during emotion regulation. CONCLUSIONS: Before social rejection, girls with SB versus without SB may not activate brain regions implicated in emotion regulation, suggesting a vulnerability to poor regulation at their baseline emotional state. After social rejection, girls with any history of STBs showed altered activation in a brain region strongly associated with inhibition and emotion regulation success, possibly reflecting increased effort at inhibiting emotional responses during regulation following stress exposure.

Lessons learned from designing an asynchronous remote community approach for behavioral activation intervention for teens.

Adolescent depression is common; however, over 60% of depressed adolescents do not receive mental health care. Digitally-delivered evidence-based psychosocial interventions (EBPIs) may provide an opportunity to improve access and engagement in mental health care. We present a case study that reviews lessons learned from using the Discover - Design - Build - Test (DDBT) model to create, develop, and evaluate a high-fidelity prototype of an app to deliver an EBPI for depression, behavioral activation (BA), on an Asynchronous Remote Communities (ARC) platform (referred to as ActivaTeen). We review work at each stage of the DDBT framework, including initial formative work, iterative design and development work, and an initial feasibility study. We engaged teens with depression, mental health clinicians, and expert evaluators through the process. We found that the DDBT model supported the research team in understanding the requirements for our prototype system, ActivaTeen, and conceiving of and developing specific ideas for implementation. Our work contributes a case study of how the DDBT framework can be applied to adapting an EBPI to a new, scalable and digital format. We provide lessons learned from engaging teens and clinicians with an asynchronous approach to EBPIs and human centered design considerations for teen mental health.

Chronic family stress interacts with 5-HTTLPR to predict prospective depressive symptoms among youth.

BACKGROUND: Previous research, predominantly with adults, has shown that the serotonin transporter gene (5-HTTLPR) interacts with stress (G × E) to predict depressive symptoms; however, few G × E studies have been conducted with youth using rigorous methods, particularly a prospective design and contextual interview to assess stress. This study examined the interaction between 5-HTTLPR and stress, both chronic and episodic, to predict longitudinal change in depressive symptoms among children and adolescents. METHODS: A general community sample of youth (N = 200; 57% girls; mean age: 12.09 years old) was genotyped for 5-HTTLPR (rs 25531) at baseline. They were interviewed via contextual stress procedures to ascertain chronic family stress and episodic stressors and completed depressive symptoms questionnaires at baseline and 6 months later. RESULTS: A significant G × E showed that chronic family stress predicted prospective increases in depressive symptoms over 6 months among youth possessing the high-risk S allele. This G × E was not found for episodic stressors occurring in the last 6 months. There was no moderation by sex or pubertal status. CONCLUSIONS: These findings advance knowledge on G × E effects in depression among youth. This is the first study to show that chronic family stress, but not episodic stressors, when ascertained by rigorous stress interview, interacts with 5-HTTLPR to prospectively predict depressive symptoms among children and adolescents.

Developmental Variation in the Associations of Attention Bias to Emotion with Internalizing and Externalizing Psychopathology.

Attention biases to emotion are associated with symptoms of internalizing and externalizing psychopathology in children and adolescents. It is unknown whether attention biases to emotion and their associations with different symptoms of psychopathology vary across development from early childhood through young adulthood. We examine this age-related variation in the current study. Participants (N = 190; ages: 4-25) completed survey-based psychopathology symptom measures and a dot-probe task to assess attention bias to happy, sad, and angry relative to neutral faces. We tested whether linear or non-linear (e.g., spline-based models) associations best characterized age-related variation in attention to emotion. We additionally examined whether attention biases were associated with depression, anxiety, and externalizing symptoms and whether these associations varied by age. No age-related differences in attention biases were found for any of the emotional faces. Attention biases were associated with psychopathology symptoms, but only when examining moderation by age. Biased attention to angry faces was associated with greater symptoms of anxiety and depression in adolescents and young adults, but not children. Similarly, biased attention to happy faces was associated with externalizing symptoms in adolescents and young adults, but not in children. In contrast, biased attention to happy faces was associated with greater anxiety symptoms in children, but not in adolescents or young adults. Biased attention toward social threat and reward becomes more strongly coupled with internalizing and externalizing symptoms, respectively, during the transition to adolescence. These findings could inform when interventions such as attention bias modification training may be most effective.

Reward processing modulates the association between trauma exposure and externalizing psychopathology.

Childhood adversity is common and strongly associated with risk for psychopathology. Identifying factors that buffer children from experiencing psychopathology following adversity is critical for developing more effective intervention approaches. The present study examined several behavioral metrics of reward processing reflecting global approach motivation for reward and the degree to which reward responses scaled with reward value (i.e., behavioral sensitivity to reward value) as potential moderators of the association of multiple dimensions of adversity-including trauma, caregiver neglect, and food insecurity-with depression and externalizing psychopathology in a sample of youth aged 8-16 years (n = 132). Trauma exposure and externalizing problems were positively associated at low and moderate levels of reward reactivity, but this association became non-significant at high levels of reward reactivity. Our findings extend prior work, suggesting that high behavioral sensitivity to reward value may buffer against externalizing problems following exposure to trauma.

Altered Neural Processing of Threat-Related Information in Children and Adolescents Exposed to Violence: A Transdiagnostic Mechanism Contributing to the Emergence of Psychopathology.

OBJECTIVE: Exposure to violence in childhood is associated with increased risk for multiple forms of internalizing and externalizing psychopathology. We evaluated how exposure to violence in early life influences neural responses to neutral and threat-related stimuli in childhood and adolescence, developmental variation in these associations, and whether these neural response patterns convey transdiagnostic risk for psychopathology over time. METHOD: Participants were 149 youths (75 female and 74 male), aged 8 to 17 years (mean = 12.8, SD = 2.63), who had experienced physical abuse, sexual abuse, or domestic violence (n = 76) or had never experienced violence (n = 73). Participants underwent functional magnetic resonance imaging scanning while passively viewing fearful, neutral, and scrambled faces presented rapidly in a block design without specific attentional demands. Internalizing and externalizing psychopathology were assessed concurrently with the scan and 2 years later and were used to compute a transdiagnostic general psychopathology factor (p factor). RESULTS: Exposure to violence was associated with reduced activation in the dorsal anterior cingulate cortex (dACC) and frontal pole (1,985 voxels, peak x, y, z = 6, 4, 40) when viewing fearful (versus scrambled) faces, and reduced activation in dorsomedial prefrontal cortex and superior frontal gyrus (1,970 voxels, peak x, y, z = 16, 64, 10) when viewing neutral faces, but not amygdala activation or connectivity. Lower dACC response to fearful faces predicted increase in the p factor 2 years later (B = -0.186, p = .031) and mediated the association of violence exposure with longitudinal increases in the p factor. CONCLUSION: Reduced recruitment of the dACC-a region involved in salience processing, conflict monitoring, and cognitive control-in response to threat-related cues may convey increased transdiagnostic psychopathology risk in youths exposed to violence.

Dynamic associations between stressful life events and adolescent internalizing psychopathology in a multiwave longitudinal study.

Associations between stressful life events (SLEs) and internalizing psychopathology are complex and bidirectional, involving interactions among stressors across development to predict psychopathology (i.e., stress sensitization) and psychopathology predicting greater exposure to SLEs (i.e., stress generation). Although stress sensitization and generation theoretical models inherently focus on within-person effects, most previous research has compared average levels of stress and psychopathology across individuals in a sample (i.e., between-person effects). The present study addressed this gap by investigating stress sensitization and stress generation effects in a multiwave, prospective study of SLEs and adolescent depression and anxiety symptoms. Depression, anxiety, and SLE exposure were assessed every 3 months for 2 years (8 waves of data) in a sample of adolescents (n = 382, aged 11 to 15 at baseline). Multilevel modeling revealed within-person stress sensitization effects such that the association between within-person increases in SLEs and depression, but not anxiety, symptoms were stronger among adolescents who experienced higher average levels of SLEs across 2 years. We also observed within-person stress generation effects, such that adolescents reported a greater number of dependent-interpersonal SLEs during time periods after experiencing higher levels of depression at the previous wave than was typical for them. Although no within-person stress generation effects emerged for anxiety, higher overall levels of anxiety predicted greater exposure to dependent-interpersonal SLEs. Our findings extend prior work by demonstrating stress sensitization in predicting depression following normative forms of SLEs and stress generation effects for both depression and anxiety using a multilevel modeling approach. Clinical implications include an individualized approach to interventions. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Extinction Learning as a Potential Mechanism Linking High Vagal Tone with Lower PTSD Symptoms among Abused Youth.

Childhood abuse is a potent risk factor for psychopathology, including posttraumatic stress disorder (PTSD). Research has shown high resting vagal tone, a measure of parasympathetic nervous system function, protects abused youth from developing internalizing psychopathology, but potential mechanisms explaining this effect are unknown. We explored fear extinction learning as a possible mechanism underlying the protective effect of vagal tone on PTSD symptoms among abused youth. We measured resting respiratory sinus arrhythmia (RSA) and skin conductance responses (SCR) during a fear conditioning and extinction task in youth with variability in abuse exposure (N = 94; aged 6-18 years). High RSA predicted lower PTSD symptoms and enhanced extinction learning among abused youths. In a moderated-mediation model, extinction learning mediated the association of abuse with PTSD symptoms only among youth with high RSA. These findings highlight extinction learning as a possible mechanism linking high vagal tone to decreased risk for PTSD symptoms among abused youth.

Neurobiological Markers of Resilience to Depression Following Childhood Maltreatment: The Role of Neural Circuits Supporting the Cognitive Control of Emotion.

BACKGROUND: Childhood adversity is strongly linked to negative mental health outcomes, including depression and anxiety. Leveraging cognitive neuroscience to identify mechanisms that contribute to resilience in children with a history of maltreatment may provide viable intervention targets for the treatment or prevention of psychopathology. We present a conceptual model of a potential neurobiological mechanism of resilience to depression and anxiety following childhood adversity. Specifically, we argue that neural circuits underlying the cognitive control of emotion may promote resilience, wherein a child's ability to recruit the frontoparietal control network to modulate amygdala reactivity to negative emotional cues-such as during cognitive reappraisal-buffers risk for internalizing symptoms following exposure to adversity. METHODS: We provide preliminary support for this model of resilience in a longitudinal sample of 151 participants 8 to 17 years of age with (n = 79) and without (n = 72) a history of childhood maltreatment who completed a cognitive reappraisal task while undergoing functional magnetic resonance imaging. RESULTS: Among maltreated youths, those who were better able to recruit prefrontal control regions and modulate amygdala reactivity during reappraisal exhibited lower risk for depression over time. By contrast, no association was observed between neural functioning during reappraisal and depression among youths without a history of maltreatment. CONCLUSIONS: These preliminary findings support the hypothesis that children who are better able to regulate emotion through recruitment of the frontoparietal network exhibit greater resilience to depression following childhood maltreatment. Interventions targeting cognitive reappraisal and other cognitive emotion regulation strategies may have potential for reducing vulnerability to depression among children exposed to adversity.

5-HTTLPR moderates the association between attention away from angry faces and prospective depression among youth.

Attention bias to emotion has been studied as a risk factor associated with depression. No study has examined whether attention bias within the context of measured genetic risk leads to increased risk for clinical depressive episodes over time. The current study investigated whether genetic risk, as indexed by the serotonin-transporter-linked polymorphic region (5-HTTLPR), moderated the relationship between attention bias to emotional faces and clinical depression onset prospectively across 18-months in a community sample of youth (n = 428; mean age = 11.97, SD = 2.28; 59% girls). Youth who attended away from angry emotional faces and were homozygous for the S allele of the 5-HTTLPR polymorphism were at greater risk for prospective depressive episode onset. The current study's findings highlight the importance of examining risk for depression across multiple levels of analysis and demonstrate attention away from threat as a possible point of intervention related to attention bias modification and depression treatment among youth.