International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators.

Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar depression; post-traumatic stress disorder), included one or more control arms, did not provide any other study-administered treatment in conjunction with ketamine (although clinically prescribed concurrent treatments were allowable), and assessed outcome using either the Montgomery-Åsberg Depression Rating Scale or the Hamilton Rating Scale for Depression (HRSD-17). Individual patient-level data for at least one outcome was obtained from 17 of 25 eligible trials [pooled n = 809]. Rates of participant-level data availability across 33 moderators that were solicited from these 17 studies ranged from 10.8% to 100% (median = 55.6%). After data harmonization, moderators available in at least 40% of the dataset were tested sequentially, as well as with a data-driven, combined moderator approach. Robust main effects of ketamine on acute [~24-hours; ß*(95% CI) = 0.58 (0.44, 0.72); p < 0.0001] and post-acute [~7 days; ß*(95% CI) = 0.38 (0.23, 0.54); p < 0.0001] depression severity were observed. Two study-level moderators emerged as significant: ketamine effects (relative to placebo) were larger in studies that required a higher degree of previous treatment resistance to federal regulatory agency-approved antidepressant medications (≥2 failed trials) for study entry; and in studies that used a crossover design. A comprehensive data-driven search for combined moderators identified statistically significant, but modest and clinically uninformative, effects (effect size r ≤ 0.29, a small-medium effect). Ketamine robustly reduces depressive symptoms in a heterogeneous range of patients, with benefit relative to placebo even greater in patients more resistant to prior medications. In this largest effort to date to apply precision medicine approaches to ketamine treatment, no clinical or demographic patient-level features were detected that could be used to guide ketamine treatment decisions.Review Registration: PROSPERO Identifier: CRD42021235630.

Displays of negative facial affect during parent-adolescent conflict and the bidirectional transmission of social anxiety.

BACKGROUND: Symptoms of social anxiety rise rapidly during adolescence, particularly for girls. Pervasive displays of parental negative affect may increase adolescents' fear of negative evaluation (FNE), thereby increasing risk for social anxiety symptoms. Adolescent displays of negative affect may also exacerbate parents' social anxiety symptoms (via FNE of their child or their parenting skills), yet little research has tested transactional pathways of transmission in families. By early adolescence, rates of parent-child conflict rise, and offspring become increasingly independent in their own displays of negative affect, increasing opportunities for hypothesized transactional pathways between parent-adolescent displays of negative affect and social anxiety symptoms. METHODS: This study included 129 parents and daughters (11-13; no baseline social anxiety disorder), two-thirds of whom were at high risk for social anxiety due to a shy/fearful temperament. We used actor-partner interdependence models (APIM) to test whether displays of negative facial affect, assessed individually for each parent and daughter during a conflict discussion, would predict their partner's social anxiety symptoms two years later. Automated facial affect coding assessed the frequency of negative affect during the discussion. Clinician ratings of social anxiety symptoms were completed at baseline and two-year follow-up. RESULTS: Both parents and daughters who displayed more frequent negative facial affect at baseline had partners with higher follow-up social anxiety symptoms, an effect that was maintained after accounting for actors' and partners' baseline symptoms. CONCLUSIONS: Findings are consistent with intergenerational models positing that parental negative affective behaviors increase risk for adolescent social anxiety symptoms but also suggest that adolescent negative facial affect may exacerbate parental social anxiety symptoms. These bidirectional effects improve understanding of how social anxiety is maintained within a transactional family structure and highlight that displays of negative affect during parent-adolescent interaction may warrant future examination as a potential treatment target for adolescent social anxiety.

Development of Overgeneral Autobiographical Memory in Offspring of Depressed Mothers.

Maternal depression increases the risk for offspring cognitive vulnerabilities, which may be a mechanism underlying the intergenerational transmission of depression. Little is known about how cognitive vulnerabilities, particularly memory biases, develop in the offspring of depressed mothers. Understanding the etiology of memory biases may lead to novel intervention targets. Therefore, the current study examined the prospective impact of maternal depression on the development of offspring overgeneral autobiographical memory (OGM; i.e., the tendency to recall less specific memories), a cognitive vulnerability implicated in the intergenerational transmission of depression. Participants were offspring (ages 8-14; 51% daughters, 81% Caucasian) of mothers with (n= 129) or without (n= 122) a history of major depressive disorder (MDD) during the offspring's life. Mothers and offspring completed assessments every 6 months for 2 years. Compared to offspring of never-depressed mothers, offspring of mothers with a history of MDD recalled less specific memories in response to negative, but not positive, cue words at the initial assessment, and this bias was maintained across the 2-year follow-up. For offspring of depressed, but not never-depressed, mothers, higher levels of maternal depressive symptoms at a given assessment predicted prospective decreases in the children's autobiographical memory specificity. Again, this finding was specific to negative, but not positive, cue words. These results suggest that maternal depression has both short- and long-term effects on the development of offspring OGM to negative cues, which may represent a malleable cognitive vulnerability for the intergenerational transmission of MDD that could be targeted for intervention.

Children's history of suicidal ideation and synchrony of facial displays of affect during mother-child interactions.

BACKGROUND: Suicidal thoughts and behavior can begin early in childhood and are a leading cause of death in youth. Although specific mechanisms of risk remain largely unknown, theorists and researchers highlight the importance of the parent-child relationship. The current study focused on one aspect of this relationship: the dynamic exchange of facial affect during interactions. Specifically, we examined the relation between children's history of suicidal ideation (SI) and synchrony of facial expressions during positive and negative mother-child interactions. METHODS: Participants were 353 mother-child dyads. Of these, 44 dyads included a child with an SI history. Dyads engaged in positive and negative discussions during which their facial electromyography was recorded from mothers and children to index second-to-second changes in positive (zygomaticus) and negative (corrugator) facial affect. RESULTS: Child SI dyads were characterized specifically by reduced synchrony of positive facial affect during the positive discussion compared to dyads without child SI. CONCLUSIONS: These findings suggest child SI dyads exhibit reduced synchrony of normative positive expressions during mother-child interactions. If replicated and extended in longitudinal research, these results may help to explain one mechanism of risk among children with SI.

Adolescent girls' physiological reactivity to real-world peer feedback: A pilot study to validate a Peer Expressed Emotion task.

Peer feedback becomes highly salient during adolescence, especially for girls. The way in which adolescents react to social feedback is associated with psychosocial adjustment and mental health. Consequently, researchers are increasingly interested in understanding the physiological and neural underpinnings of adolescent response to feedback by simulating the experience of rejection and acceptance using computer-based paradigms. However, these paradigms typically use nonfamiliar peers and the facade of internet chatrooms or games to present artificial peer feedback. The current study piloted the use of a novel and potentially more ecologically valid peer expressed emotion paradigm in which participants listen to prerecorded clips of ostensible personalized feedback made by their close friend. Physiological data measuring autonomic nervous system response were collected as an index of emotional reactivity/arousal and cognitive-affective processing. Results show promising preliminary evidence validating the task for future use. Participants (N = 18 girls, aged 11-17 years) reported feeling more positive following praise, relative to critical and neutral feedback, and reported feeling more upset following criticism, relative to praise and neutral feedback. Girls exhibited greater pupillary dilation, skin conductance levels (N = 17), and/or heart rate (N = 17) while listening to affectively charged, peer feedback compared with neutral yet personally relevant statements. Girls also exhibited variable physiological response when listening to praising versus critical feedback. Findings from this pilot study validate the use of this novel Peer Expressed Emotion task for the investigation of adolescents' emotional and physiological reactivity in response to real-world peer evaluation. However, it is important to recognize that this study provides only preliminary findings and that future research is needed to replicate the results in larger samples.

Using mobile eye-tracking technology to examine adolescent daughters' attention to maternal affect during a conflict discussion.

Attention to socio-emotional stimuli (i.e., affect-biased attention) is an integral component of emotion regulation and human communication. Given the strong link between maternal affect and adolescent behavior, maternal affect may be a critical influence on adolescent affect-biased attention during mother-child interaction. However, prior methodological constraints have precluded fine-grained examinations of factors such as maternal affect on adolescent attention during real-world social interaction. Therefore, this pilot study capitalized on previously validated technological advances by using mobile eye-tracking and facial affect coding software to quantify the influence of maternal affect on adolescents' attention to the mother during a conflict discussion. Results from 7,500 to 9,000 time points sampled for each mother-daughter dyad (n = 28) indicated that both negative and positive maternal affect, relative to neutral, elicited more adolescent attentional avoidance of the mother (ORs = 2.68-9.20), suggesting that typically developing adolescents may seek to avoid focusing on maternal affect of either valence during a conflict discussion. By examining the moment-to-moment association between in vivo displays of maternal affect and subsequent adolescent attention toward the mother's face, these results provide preliminary evidence that maternal affect moderates adolescent attention. Our findings are consistent with cross-species approach-avoidance models suggesting that offspring respond to affectively charged conversations with greater behavioral avoidance or deference.

Adolescents' perceptions of maternal response to negative affect predict emotional reactivity during mother-daughter interaction: A multi-modal assessment.

Parental socialization of emotion consists of parental behaviors that scaffold child emotional reactivity and regulation. The current study examined whether adolescents' perceptions of their mothers' supportive versus non-supportive responses to negative emotions could predict adolescent emotional reactivity. Thirty adolescent girls (Mage  = 14.41 [1.55]) reported on how their mothers typically respond to their negative emotions and then completed a laboratory-based mother-adolescent interaction task. A multi-modal assessment of adolescent emotional reactivity during the interaction included adolescents' skin conductance levels (SCLs) and state anxiety, and mother-daughter interactions were behaviorally coded to assess how often dyads engaged in both negative and positive escalation (i.e., a pattern of negative or positive behavior of one partner being reciprocated by the other). Adolescents who reported that their mothers used more non-supportive responses to their negative emotion tended to exhibit higher SCL and engage in more negative escalation with their mothers during the interaction task. Furthermore, adolescents' SCL was positively correlated with both their state anxiety levels and negative escalation during the task. Together, these findings suggest that adolescents who perceive their mothers as less supportive of negative emotions are more likely to exhibit greater negative emotionality during parent-adolescent interaction, which may relate to risk for emotional disorders.

Neighborhood crime risk and resting respiratory sinus arrhythmia in middle childhood: Evidence of gender differences.

Although there is a robust link between resting respiratory sinus arrhythmia (RSA), a biological marker of emotion regulation, and risk for psychopathology, the factors that may be associated with aberrant RSA development remain unclear. The goal of the current study was to examine the relation between children's resting levels of RSA and neighborhood crime, a macro-level environmental stressor associated with increased risk for multiple forms of psychopathology in youth. The levels of neighborhood crime were obtained using a geocoded neighborhood crime exposure database, allowing for the objective assessment of the likelihood of crime occurring in the child's community. The results indicated that the relation between neighborhood crime and resting RSA differed for girls and boys such that living in a neighborhood with higher risk of exposure to violent crimes was associated with lower RSA for girls, but not boys. These results suggest that living in a higher crime neighborhood is associated with an objective, biologically-based marker of emotion regulation and highlight how neighborhood crime may be specifically associated with risk for girls.

Looking for the negative: Depressive symptoms in adolescent girls are associated with sustained attention to a potentially critical judge during in vivo social evaluation.

Attention biases toward negative stimuli are implicated in the development and maintenance of depression. However, research is needed to understand how depression affects attention biases as they unfold in a dynamic social environment, particularly during adolescence when depression rates significantly increase due to enhanced reactivity to social stress. To examine attention biases in a live, socially evaluative environment, 26 adolescent girls from the community gave a speech in front of a potentially critical judge and a positive judge while wearing mobile eye tracking glasses. Girls' depressive symptoms were measured using the Moods and Feelings Questionnaire. Across the sample, girls looked at the positive judge more frequently and for longer periods of time compared with the potentially critical judge. In contrast, higher depressive symptoms were associated with looking at the potentially critical judge for longer periods of time. When directly comparing attention to the potentially critical judge relative to the positive judge, dysphoric girls looked at the potentially critical judge more frequently and for longer periods of time compared with the positive judge. Findings suggest that adolescent depressive symptoms are related to sustained attention toward potentially critical evaluation at the exclusion of positive evaluation. This novel approach allowed for an in vivo examination of attention biases as they unfold during social evaluation, which begins to illuminate the interpersonal significance of attention biases. If replicated and extended longitudinally, this research could be used to identify adolescents at high risk for future depression and potentially be leveraged clinically in attention bias modification treatment.

Parental Expressed Emotion-Criticism and Neural Markers of Sustained Attention to Emotional Faces in Children.

There is growing evidence for the role of environmental influences on children's information-processing biases for affectively salient stimuli. The goal of this study was to extend this research by examining the relation between parental criticism (expressed emotion-criticism, or EE-Crit) and children's processing of facial displays of emotion. Specifically, we examined the relation between EE-Crit and children's sensitivity in detecting facial displays of emotion. We also examined a neural marker of sustained attention, the late positive potential (LPP) event-related potential component (ERP). Participants were 87 children (ages 7-11 years; 53.3% female, 77.8% Caucasian) and their parents (ages 24-71; 90% female, 88.9% Caucasian). Parents completed the Five-Minute Speech Sample to determine levels of EE-Crit toward their child. Children completed a morphed faces task during which behavioral and ERP responses were assessed. Although there were no group differences in sensitivity in detecting facial displays of emotion, we found that children of parents exhibiting high, compared to low, EE-Crit displayed less attention (smaller LPP magnitudes) to all facial displays of emotion (fearful, happy, sad). These results suggest that children of critical parents may exhibit an avoidant pattern of attention to affectively-salient interpersonal stimuli.

Synchrony of physiological activity during mother-child interaction: moderation by maternal history of major depressive disorder.

BACKGROUND: Family environment plays an important role in the intergenerational transmission of major depressive disorder (MDD), but less is known about how day-to-day mother-child interactions may be disrupted in families with a history of MDD. Disruptions in mother-child synchrony, the dynamic and convergent exchange of physiological and behavioral cues during interactions, may be one important risk factor. Although maternal MDD is associated with a lack of mother-child synchrony at the behavioral level, no studies have examined the impact of maternal MDD on physiological synchrony. Therefore, this study examined whether maternal history of MDD moderates mother-child physiological synchrony [measured via respiratory sinus arrhythmia (RSA)] during positive and negative discussions. METHOD: Children aged 7-11 years and mothers with either a history of MDD during the child's lifetime (n = 44) or no lifetime diagnosis of any mood disorder (n = 50) completed positive and negative discussion tasks while RSA was continuously recorded for both child and mother. RESULTS: Results indicated significant between-dyad and within-dyad group differences in physiological synchrony during positive and negative discussions. Between-dyad analyses revealed evidence of synchrony only among never depressed dyads, among whom higher average mother RSA during both discussions was associated with higher average child RSA. Within-dyad analyses revealed that never depressed dyads displayed positive synchrony (RSA concordance), whereas dyads with a history of maternal MDD displayed negative synchrony (RSA discordance) during the negative discussion and that the degree of negative synchrony exhibited during the negative discussion was associated with mothers' and children's levels of sadness. CONCLUSIONS: These results provide preliminary evidence that physiological synchrony is disrupted in families with a history of maternal MDD and may be a potential risk factor for the intergenerational transmission of depression.

Brief report: Overgeneral autobiographical memory in adolescent major depressive disorder.

The current study examined whether overgeneral autobiographical memory (OGM) bias serves as a state-like marker of major depressive disorder (MDD) in adolescence or whether it would also be observed in currently nondepressed adolescents with a history of MDD. We examined differences in OGM to positive and negative cue words between adolescents (aged 11-18 years) with current MDD (n = 15), remitted MDD (n = 25), and no history of any depressive disorder (n = 25). Youth and their parents were administered a structured diagnostic interview and adolescents completed the autobiographical memory test. Compared to never depressed adolescents, adolescents with current or remitted MDD recalled less specific memories in response to positive and negative cue words. The difference between the two MDD groups was small and nonsignificant. These findings suggest that OGM is not simply a state-like marker in currently depressed adolescents, but is also evident in adolescents with remitted MDD, indicating that it may represent a trait-like vulnerability that increases risk for relapse.

Sensitivity in detecting facial displays of emotion: Impact of maternal depression and oxytocin receptor genotype.

The current study examined sensitivity in detecting emotional faces among children of depressed and non-depressed mothers. A second goal was to examine the potential moderating role of the oxytocin receptor gene (OXTR rs53576), which has been linked to emotion recognition in the past. Participants included 247 children (ages 8-14). Children completed a forced choice emotion identification task. Maternal history of major depressive disorder during children's lives was associated with children's sensitivity in detecting emotional faces among children homozygous for the OXTR rs53576 G allele, but not among carriers of the A allele. Among G homozygotes, children of depressed mothers exhibited increased sensitivity in detecting sad faces, and reduced sensitivity in detecting happiness, compared to children of non-depressed mothers.

Influence of maternal depression on children's brooding rumination: Moderation by CRHR1 TAT haplotype.

There is growing evidence that brooding rumination plays a key role in the intergenerational transmission of major depressive disorder (MDD) and may be an endophenotype for depression risk. However, less is known about the mechanisms underlying this role. Therefore, the goal of the current study was to examine levels of brooding in children of mothers with a history of MDD (n = 129) compared to children of never depressed mothers (n = 126) and to determine whether the variation in a gene known to influence hypothalamic-pituitary-adrenal axis functioning--corticotropin-releasing hormone receptor 1 (CRHR1)--would moderate the link between maternal MDD and children's levels of brooding. We predicted children of mothers with a history of MDD would exhibit higher levels of brooding than children of mothers with no lifetime depression history but that this link would be stronger among children carrying no copies of the protective CRHR1 TAT haplotype. Our results supported these hypotheses and suggest that the development of brooding among children of depressed mothers, particularly children without the protective CRHR1 haplotype, may serve as an important mechanism of risk for the intergenerational transmission of depression.

Overgeneral autobiographical memory in children of depressed mothers.

The goal of this study was to examine overgeneral autobiographical memory in a population at-risk for depression (i.e., children of depressed mothers). We predicted that children of depressed mothers would display less-specific memories than children of non-depressed mothers and that these results would be observed among children with no prior history of depression themselves. Participants in this study were children (age 8-14; 50% girls, 83% Caucasian) of mothers with (n = 103) or without (n = 120) a history of major depressive disorder during the child's life. Mothers' and children's diagnoses were confirmed with a diagnostic interview, and children completed the Autobiographical Memory Test and a measure of depressive symptoms. We found that children of depressed mothers, compared to children of non-depressed mothers, recalled less-specific memories in response to negative cue words but not positive cue words. Importantly, these results were maintained even when we statistically controlled for the influence of children's current depressive symptom levels and excluded children with currently depressed mothers. These results suggest that overgeneral autobiographical memory for negative events may serve as a marker of depression risk among high-risk children with no prior depression history.

AttentionCARE: replicability of a BCI for the clinical application of augmented reality-guided EEG-based attention modification for adolescents at high risk for depression.

Affect-biased attention is the phenomenon of prioritizing attention to emotionally salient stimuli and away from goal-directed stimuli. It is thought that affect-biased attention to emotional stimuli is a driving factor in the development of depression. This effect has been well-studied in adults, but research shows that this is also true during adolescence, when the severity of depressive symptoms are correlated with the magnitude of affect-biased attention to negative emotional stimuli. Prior studies have shown that trainings to modify affect-biased attention may ameliorate depression in adults, but this research has also been stymied by concerns about reliability and replicability. This study describes a clinical application of augmented reality-guided EEG-based attention modification ("AttentionCARE") for adolescents who are at highest risk for future depressive disorders (i.e., daughters of depressed mothers). Our results (n = 10) indicated that the AttentionCARE protocol can reliably and accurately provide neurofeedback about adolescent attention to negative emotional distractors that detract from attention to a primary task. Through several within and cross-study replications, our work addresses concerns about the lack of reliability and reproducibility in brain-computer interface applications, offering insights for future interventions to modify affect-biased attention in high-risk adolescents.

Attentional capture by angry faces in girls who self-injure: Evidence from steady state visual evoked potentials.

BACKGROUND: Non-suicidal self-injury (NSSI) is a significant public health concern, not only because of the personal and social cost of the behavior itself, but also because it increases risk for future self-injurious behaviors, including suicide attempts. NSSI is increasingly prevalent during adolescence, which highlights the need for research aimed at identifying modifiable risk factors that can be targeted to reduce future risk. Building from theoretical models that highlight interpersonal processes, this study examined whether adolescents with an NSSI history exhibit greater difficulty inhibiting attention to emotionally salient interpersonal stimuli (face), indexed via steady state visual evoked potentials (SSVEPs), which provide a direct neural index of the ability to inhibit attention to task-irrelevant stimuli. METHODS: Adolescent girls aged 13-17 with (n = 26) and without (n = 28) an NSSI history completed a change-detection computer task during which frequency-tagged SSVEPs were used to assess adolescents' ability to inhibit attention to affectively salient stimuli from spatially superimposed targets. RESULTS: Compared with adolescents with no NSSI history, adolescents with NSSI demonstrated difficulty inhibiting attention to angry adult faces. CONCLUSIONS: These findings underscore specific deficits in attentional filtering among girls with an NSSI history, which, if replicated and extended, could be a promising intervention target for reducing risk for future NSSI.

Avoidance Bias to Angry Faces Predicts the Development of Depressive Symptoms among Adolescent Girls.

Interpersonal-motivational models posit that heightened avoidance of aversive social stimuli and diminished approach of appetitive social stimuli increases social withdrawal and reduces positive social interactions, thereby increasing risk for future social anxiety and depression. The current study examined if approach-avoidance biases toward angry and happy faces, measured during the Approach Avoidance Task (AAT), would be associated with the development of adolescent depressive and social anxiety symptoms. At baseline, participants included 129 never-depressed adolescent girls (ages 11-13), two-thirds of whom were at high-risk for internalizing problems due to shy/fearful temperament. Girls reported their depressive and social anxiety symptoms every 6 months for 24 months and completed the AAT at baseline and 24-mo follow-up. Heightened avoidance bias toward angry faces at baseline predicted increases in depressive symptoms across the follow-up, even after accounting for temperament and pubertal status. In contrast, girls with greater depression and social anxiety symptoms at 24-mo follow-up exhibited less avoidance bias for angry faces at the same time point. Findings suggest that avoidance behaviors (i.e., avoiding people or settings associated with angry faces, which are often perceived as hostile, critical, or rejecting) may be a risk factor for depression, above and beyond risk imparted by temperament or advances in puberty. However, with increasing internalizing symptoms, it may become more difficult for adolescents to maintain avoidance for aversive social stimuli, and without the introduction of more adaptive emotion regulation strategies, these biases may continue to increase and maintain risk for internalizing problems.

Using Neurofeedback from Steady-State Visual Evoked Potentials to Target Affect-Biased Attention in Augmented Reality.

Biases in attention to emotional stimuli (i.e., affect-biased attention) contribute to the development and mainte-nance of depression and anxiety and may be a promising target for intervention. Past attempts to therapeutically modify affect-biased attention have been unsatisfactory due to issues with reliability and precision. Electroencephalogram (EEG)-derived steady-state visual evoked potentials (SSVEPS) provide a temporally-sensitive biological index of attention to competing visual stimuli at the level of neuronal populations in the visual cortex. SSVEPS can potentially be used to quantify whether affective distractors vs. task-relevant stimuli have "won" the competition for attention at a trial-by-trial level during neuro-feedback sessions. This study piloted a protocol for a SSVEP-based neurofeedback training to modify affect-biased attention using a portable augmented-reality (AR) EEG interface. During neurofeedback sessions with five healthy participants, signifi-cantly greater attention was given to the task-relevant stimulus (a Gabor patch) than to affective distractors (negative emotional expressions) across SSVEP indices (p<0.000l). SSVEP indices exhibited excellent internal consistency as evidenced by a maximum Guttman split-half coefficient of 0.97 when comparing even to odd trials. Further testing is required, but findings suggest several SSVEP neurofeedback calculation methods most deserving of additional investigation and support ongoing efforts to develop and implement a SSVEP-guided AR-based neurofeedback training to modify affect-biased attention in adolescent girls at high risk for depression.

Racial Stress and Trauma and the Development of Adolescent Depression: A Review of the Role of Vigilance Evoked by Racism-Related Threat.

There are known disparities in the burden of illness and access/quality of care for African, Latino/a, Asian, and Native American (ALANA) patients diagnosed with depressive disorders, which may occur because of health inequities. Racial stress and trauma (RST), or the significant fear and distress that can be imparted from exposure to racism, is one such inequity linked to the development of depression. The current review summarizes past research examining the association between racism, RST, and depression, as well as avenues in which RST becomes biologically embedded in ALANA individuals. We describe multimodal research that supports vigilance as a potential mediator of the association between RST and depression and consider the nuanced role that vigilance plays during experiences with racism. Finally, we describe methodological advances in the assessment of vigilance evoked by RST and the clinical implications that may be generated by future improvements. In each of these areas, we present examples of how ongoing and future research can be leveraged to provide support for psychosocial programs that facilitate autonomous community healing and resilience, increase calls for public policy changes, and support clinical interventions that lessen the burden of racism on ALANA communities.