Reproducible brain-wide association studies require thousands of individuals.

Magnetic resonance imaging (MRI) has transformed our understanding of the human brain through well-replicated mapping of abilities to specific structures (for example, lesion studies) and functions1-3 (for example, task functional MRI (fMRI)). Mental health research and care have yet to realize similar advances from MRI. A primary challenge has been replicating associations between inter-individual differences in brain structure or function and complex cognitive or mental health phenotypes (brain-wide association studies (BWAS)). Such BWAS have typically relied on sample sizes appropriate for classical brain mapping4 (the median neuroimaging study sample size is about 25), but potentially too small for capturing reproducible brain-behavioural phenotype associations5,6. Here we used three of the largest neuroimaging datasets currently available-with a total sample size of around 50,000 individuals-to quantify BWAS effect sizes and reproducibility as a function of sample size. BWAS associations were smaller than previously thought, resulting in statistically underpowered studies, inflated effect sizes and replication failures at typical sample sizes. As sample sizes grew into the thousands, replication rates began to improve and effect size inflation decreased. More robust BWAS effects were detected for functional MRI (versus structural), cognitive tests (versus mental health questionnaires) and multivariate methods (versus univariate). Smaller than expected brain-phenotype associations and variability across population subsamples can explain widespread BWAS replication failures. In contrast to non-BWAS approaches with larger effects (for example, lesions, interventions and within-person), BWAS reproducibility requires samples with thousands of individuals.

Activity increases in empathy-related brain regions when children contribute to peers' sadness and happiness.

Responding empathically when causing peers' emotions is critical to children's interpersonal functioning, yet there are surprising gaps in the literature. Previous research has focused on empathy when witnessing others' emotions instead of causing others' emotions, on negative emotions instead of positive emotions, and on behavioral correlates instead of neural correlates. In this study, children (N = 38; Mage = 9.28 years; 50% female) completed a functional magnetic resonance imaging block design task in which they played a rigged game where they won and lost coins for themselves or peers and viewed their peers' happiness and sadness. We used a region of interest approach to test whether activity in brain regions associated with positive and negative empathy in adults showed significantly greater activity in each condition (i.e., when children won and lost tokens for themselves and peers) compared with a fixation baseline. We predicted that experiencing self-conscious emotions, such as pride and guilt, would heighten the experience of empathy. Activity in the amygdala, which is associated with visceral arousal, and in the anterior insula and dorsal anterior cingulate cortex, which are associated with integrated arousal, increased significantly when winning and losing for oneself and peers and observing their resulting happy and sad facial expressions. Activity did not differ when playing for oneself versus peers, indicating that self-conscious emotions do not heighten empathy and instead support similar neural processes underlying firsthand and secondhand (empathic) emotions. These findings support that empathy during middle childhood involves the same brain regions as empathy during adulthood and that children experience firsthand and secondhand positive and negative emotions in similar ways.

Less attention to emotional faces is associated with low empathy and prosociality in 12-to 20-month old infants.

The development of empathy and prosocial behavior begins in infancy and is likely supported by emotion processing skills. The current study explored whether early emerging deficits in emotion processing are associated with disruptions in the development of empathy and prosociality. We investigated this question in a large, diverse sample of 147, 11- to 20-month-old infants (42% female; 61% Black; 67% low socioeconomic status). Infants completed two observational tasks assessing prosocial helping and one task assessing empathy and prosocial comforting behavior. Infants also completed an eye-tracking task assessing engagement and disengagement with negative emotional faces. Infants who attended less to angry, sad, and fearful faces (i.e., by being slower to look at and/or quicker to look away from negative compared to neutral faces) engaged in fewer helping behaviors, and effect sizes were larger when examining infants' attention toward the eye regions of faces. Additionally, infants who were quicker to look away from the eye regions of angry faces, but not the whole face, displayed less empathy and comforting behaviors. Results suggest that as early as 12 months of age, infants' decreased attention toward negative emotional faces, particularly the eye regions, is associated with less empathy and prosociality during a developmental period in which these abilities are rapidly maturing.

Early Emotion Development Intervention Improves Mental Health Outcomes in Low-Income, High-Risk Community Children.

Children living in poverty and facing related forms of adversity are at higher risk for experiencing concurrent and later psychopathology. Although negative psychological outcomes can be improved by enhancing sensitive and responsive caregiving early in development, interventions targeting the caregiver-child dyad are not readily accessible. The present study investigated the feasibility and effectiveness of delivering a shortened eight-session form of Parent-Child Interaction Therapy-Emotion Development (PCIT-ED) in-person or remotely as an early intervention for 3-6-year-old children (N = 62) at elevated risk for psychopathology who were growing up in low-income communities. Caregiver-child dyads were randomized to eight-sessions of PCIT-ED or online parenting education. Relative to parenting education, children receiving PCIT-ED exhibited lower externalizing symptoms and functional impairment and more positive peer relationships following the intervention. Findings support the effectiveness of this shortened form of PCIT-ED, delivered in-person or remotely, as an early intervention to improve symptoms of psychopathology and functioning in high-risk children living in poverty.Trial registration Clinicaltrials.gov; NCT04399629.

Associations of observed callous-unemotional behaviors in early childhood with conduct problems and substance use over 14 years.

Callous-unemotional (CU) behaviors (i.e., low concern and active disregard for others) uniquely predict severe conduct problems and substance use when present by late childhood. Less is known about the predictive utility of CU behaviors displayed in early childhood, when morality is developing and interventions may be more effective. Children aged 4-7 years (N = 246; 47.6% girls) completed an observational task wherein they were encouraged to tear an experimenter's valued photograph, and blind raters coded children's displayed CU behaviors. During the next 14 years, children's conduct problems (i.e., oppositional defiant and conduct symptoms) and age of onset of substance use were assessed. Compared to children displaying fewer CU behaviors, children displaying greater CU behaviors were 7.61 times more likely to meet criteria for a conduct disorder (n = 52) into early adulthood (95% CI, 2.96-19.59; p = <.0001), and their conduct problems were significantly more severe. Greater CU behaviors were associated with earlier onset of substance use (B = -.69, SE = .32, t = -2.14, p = .036). An ecologically valid observed indicator of early CU behavior was associated with substantially heightened risk for conduct problems and earlier onset substance use into adulthood. Early CU behavior is a powerful risk marker identifiable using a simple behavioral task which could be used to target children for early intervention.

Maternal emotional intelligence and negative parenting affect are independently associated with callous-unemotional traits in preschoolers.

Deficits in emotion intelligence (EI) are a key component of early-childhood callous-unemotional (CU) traits. Children's EI may be influenced by their mother's EI through both familial genetic and environmental mechanisms; however, no study has directly tested the role of maternal EI in the development of CU traits. This study investigated whether maternal EI had a direct relationship with children's CU traits when controlling for the potential influence of parenting affect and other psychiatric diagnoses. Mothers and their 3- to 5-year-old preschoolers (N = 200) were recruited as part of a parent-child interaction-emotion development therapy treatment trial for preschool clinical depression and comorbid psychopathology. Using data collected prior to treatment, regression models tested whether maternal EI was related to children's CU traits, which specific aspects of maternal EI were most strongly associated with CU traits, and whether associations held after accounting for observed parenting affect. Maternal EI (p < 0.005), specifically the ability to understand others' emotions (p < 0.01), was significantly associated with children's CU traits. This relationship was specific, as maternal EI did not predict depression or oppositional defiant disorder. Both maternal EI and observed negative parenting affect were independently and significantly related to CU traits (p < 0.05) in a combined model. Given that maternal EI and observed negative parenting affect were independent predictors of CU traits in preschoolers with comorbid depression, findings suggest that current treatments for CU traits that focus solely on improving parenting could be made more effective by targeting maternal EI and helping mothers better model emotional competence.

Reported autism diagnosis is associated with psychotic-like symptoms in the Adolescent Brain Cognitive Development cohort.

Although the schizophrenia (SCZ) rate is increased in autism spectrum disorder (ASD), it is difficult to identify which ASD youth will develop psychosis. We explored the relationship between ASD and emerging psychotic-like experiences (PLS) in a sample of 9127 youth aged 9-11 from the Adolescent Brain Cognitive Development (ABCD) cohort. We predicted that parent-reported ASD would be associated with PLS severity, and that ASD youth with PLS (ASD+/PLS+) would differ from ASD youth without PLS (ASD+/PLS-) and youth with PLS but not ASD (ASD-/PLS+) in cognitive function. We fit regression models that included parent-reported ASD, family history of psychosis, lifetime trauma, executive function, processing speed, working memory, age, sex, race, ethnicity, and income-to-needs ratio as predictors of Prodromal Questionnaire-Brief Child (PQ-BC) distress score, a continuous index of PLS severity. We assessed cognitive differences using regression models with ASD/PLS status and relevant covariates as predictors of NIH Toolbox measures. ASD increased raw PQ-BC distress scores by 2.47 points (95% CI 1.33-3.61), an effect at least as large as Black race (1.27 points, 95% CI 0.75-1.78), family history of psychosis (1.05 points, 95% CI 0.56-1.54), and Latinx ethnicity (0.99 points, 95% CI 0.53-1.45. We did not identify differences in cognition for ASD+/PLS+ youth relative to other groups. Our finding of association between ASD and PLS in youth is consistent with previous literature and adds new information in suggesting that ASD may be a strong risk factor for PLS even compared to established SCZ risk factors.

Sustained remission of child depression despite drift in parent emotion management skills 18 weeks following Parent Child Interaction Therapy: emotion development.

Whether effects of psychotherapies for depression are sustained after treatment is an important clinical issue. In older depressed children and adolescents such treatments have been shown to be sustained for several months. Rates of remission ranged from 62-69% at 3 months-1 year in one large scale study. To date there has been no data to inform whether the effects of earlier interventions for depression in the preschool period are sustained. To address this, we used data from a randomized controlled trial of a novel early intervention for depression called "Parent Child Interaction Therapy Emotion Development" (PCIT-ED) that has shown efficacy for depression, parenting stress and parenting practices. Participants and their caregivers were re-assessed 18 weeks after treatment completion. All study procedures were approved by the Washington University School of Medicine Internal Review Board prior to data collection. Study findings demonstrated a high rate of sustained gains in remission from depression, decreased parenting stress and parental depression 18 weeks after completion of a trial of PCIT-ED in a population of young children. Parental response to the child expression of emotion, a key treatment target drifted back towards baseline after 3 months. Relapse rates were 17% and predictors of relapse were the presence of an externalizing disorder, a higher number of co-morbid disorders and poorer guilt reparation and emotion regulation measured at treatment completion. This extends the body of literature demonstrating parent-child interaction therapy (PCIT) to have sustained effects on targeted disruptive symptom profiles to early childhood depression. This relatively low relapse rate after 18 weeks is comparable or better than many empirically proven treatments for depression in older children.

Early socioemotional competence, psychopathology, and latent class profiles of reparative prosocial behaviors from preschool through early adolescence.

Children who have difficulty using reparative behaviors following transgressions display a wide range of poorer social and emotional outcomes. Despite the importance of reparative skills, no study has charted the developmental trajectory of these behaviors or pinpointed predictors of poorer reparative abilities. To address these gaps in the literature, this study applied growth mixture modeling to parent reports of children's reparative behaviors (N = 230) in a 9-year longitudinal data set spanning from preschool to early adolescence. Three distinct trajectories of reparative behaviors were found: a low-stable, moderate-stable, and high-stable latent class. Poorer emotion understanding, social withdrawal, social rejection, and maladaptive guilt in the preschool period predicted membership in a low-stable reparative trajectory. Externalizing diagnoses, particularly conduct disorder and oppositional defiant disorder, also predicted membership in a low-stable reparative trajectory. Preschool-onset depression predicted membership in a low-stable reparative trajectory through high levels of maladaptive guilt. The findings from this study suggest that socioemotional deficits in the preschool period set children on longstanding trajectories of impaired reparative responding. Thus, emotion understanding, social functioning, maladaptive guilt, and early psychiatric symptoms should be targeted in early preventive interventions.

Toddlers imitate prosocial demonstrations in bystander but not transgressor contexts.

Although prosocial abilities are associated with a wide range of healthy outcomes, few studies have experimentally examined socialization practices that may cause increased prosocial responding. The purpose of this study was to investigate conditions under which 2- and 3-year-old children can acquire prosocial behaviors through imitation. In Study 1 (N = 53), toddlers in the experimental condition watched a video of an adult comfort a woman in distress by performing a novel prosocial action without depicting how the woman was hurt. Parents then pretended they hurt their own finger and feigned distress. Children in the experimental condition were more likely to imitate the novel action relative to two control groups: (a) children who did not watch the video but witnessed a distressed parent, and (b) children who watched the video but witnessed parents engage in a neutral interaction. Thus, in a bystander context where children witnessed parent distress, toddlers imitated a general demonstration of how to respond prosocially to distress and applied this information to a specific distress scenario. In Study 2 (N = 54), the procedures were identical to those in the first study except that children were led to believe that they had transgressed to cause parent distress. In a transgressor context, children in the experimental condition were not more likely to imitate the prosocial behavior relative to children in either control group. These studies demonstrate that whether or not children have caused a victim's distress greatly affects their ability to apply a socially learned prosocial behavior, possibly due to self-conscious emotions such as guilt and shame.

Preschool Depression: a Diagnostic Reality.

PURPOSE OF REVIEW: We review findings related to predictors, correlates, outcomes, and treatment of preschool depression that have been published in the last 3 years. RECENT FINDINGS: Preschool depression displays a chronic course through late adolescence and is associated with temperamental and personality traits, poorer physical health, and negative parenting practices. Preschool depression predicts deficits into adolescence, including social difficulties and blunted neural response to rewards. Depressed preschoolers can experience suicidal ideation and behaviors and display an accurate understanding of the finality of death. A treatment for preschool depression has now been validated that uses the parent-child relationship to enhance emotion development and reduce depressive symptoms. Preschool depression is homotypic with depression that occurs later in life. Future work elucidating mechanisms through which preschool depression develops and informs the sub-groups for which particular treatments may be most effective will have considerable implications for prevention and early intervention.

Empathic Responses to Mother's Emotions Predict Internalizing Problems in Children of Depressed Mothers.

Recent theories posit that empathy, typically an adaptive characteristic, may be associated with internalizing problems when children are chronically exposed to mother's depression. We tested this postulation in a sample of children (N = 82, M age = 5 years). Children witnessed their mothers express sadness, anger, and happiness during a simulated phone conversation, and researchers rated children's negative affective empathy, positive affective empathy, and information-seeking (cognitive empathy) in response to their mother's emotions. The chronicity of mother's depression during the child's lifetime moderated associations between children's empathy and internalizing problems. As predicted, all three empathy measures were related to greater mother-rated internalizing problems in children of chronically (i.e., 2-3 years) depressed mothers. Greater positive empathy was related to lower internalizing problems in children of nondepressed mothers. Positive empathy may contribute to adaptive processes when mothers are not depressed, and positive, negative, and cognitive empathy may contribute to maladaptive processes when mothers are chronically depressed.

Positively Biased Processing of Mother's Emotions Predicts Children's Social and Emotional Functioning.

Risk for internalizing problems and social skills deficits likely emerges in early childhood when emotion processing and social competencies are developing. Positively biased processing of social information is typical during early childhood and may be protective against poorer psychosocial outcomes. We tested the hypothesis that young children with relatively less positively biased attention to, interpretations of, and attributions for their mother's emotions would exhibit poorer prosocial skills and more internalizing problems. A sample of 4- to 6-year-old children (N=82) observed their mothers express happiness, sadness and anger during a simulated emotional phone conversation. Children's attention to their mother when she expressed each emotion was rated from video. Immediately following the phone conversation, children were asked questions about the conversation to assess their interpretations of the intensity of mother's emotions and misattributions of personal responsibility for her emotions. Children's prosocial skills and internalizing problems were assessed using mother-report rating scales. Interpretations of mother's positive emotions as relatively less intense than her negative emotions, misattributions of personal responsibility for her negative emotions, and lack of misattributions of personal responsibility for her positive emotions were associated with poorer prosocial skills. Children who attended relatively less to mother's positive than her negative emotions had higher levels of internalizing problems. These findings suggest that children's attention to, interpretations of, and attributions for their mother's emotions may be important targets of early interventions for preventing prosocial skills deficits and internalizing problems.

Children's empathy responses and their understanding of mother's emotions.

This study investigated children's empathic responses to their mother's distress to provide insight about child factors that contribute to parental socialisation of emotions. Four- to six-year-old children (N = 82) observed their mother's sadness and anger during a simulated emotional phone conversation. Children's facial negative affect was rated and their heart rate variability (HRV) was recorded during the conversation, and their emotion understanding of the conversation was measured through their use of negative emotion words and perspective-taking themes (i.e., discussing the causes or resolution of mother's emotions) in narrative accounts of the conversation. There were positive quadratic relationships between HRV and ratings of facial affect, narrative references to mother's negative emotions and perspective-taking themes. High and low HRV was associated with high facial negative affect, suggesting well-regulated sympathy and poorly regulated personal distress empathic responses, respectively. Moderate HRV was associated with low facial negative affect, suggesting minimal empathic engagement. High and low HRV were associated with the highest probabilities of both emotion understanding indicators, suggesting both sympathy and personal distress responses to mother's distress facilitate understanding of mother's emotions. Personal distress may motivate attempts to understand mother's emotions as a self-soothing strategy, whereas sympathy-related attempts to understand may be motivated by altruism.

Preadolescent Suicidal Thoughts and Behaviors: An Intensive Longitudinal Study of Risk Factors.

OBJECTIVE: Dramatic increases in rates of suicidal thoughts and behaviors (STBs) among youth highlight the need to pinpoint early risk factors. This study used intensive longitudinal sampling to assess what the concurrent associations were between risk factors and STB status, how proximal changes in risk factors were related to STB status, and how risk factors prospectively predicted changes in STB status in a preadolescent sample enriched for early childhood psychopathology. METHOD: A total of 192 participants were included from the Parent-Child Interaction Therapy-Emotional Development (PCIT-ED) Study, a longitudinal study of children with and without preschool depression. Participants 7 to 12 years of age completed a diagnostic interview, followed by 12 months of intensive longitudinal sampling, assessing experiences of suicidal ideation and 11 psychosocial variables with known links to STBs in adolescents and adults. Preadolescents with STB history (high-risk) received surveys weekly, and those without STB history (lower-risk) received surveys monthly. RESULTS: Female sex, elevated depressive symptoms, greater use of expressive suppression and rumination, emotional clarity, and perceived burdensomeness were uniquely concurrently associated with the likelihood of STB endorsement. Within the high-risk group, (1) increases in depression, expressive suppression, rumination, and perceived burdensomeness, and decreases in positive affect from weekt to weekt+1 were associated with a higher likelihood of a positive STB status at weekt+1; and (2) higher expressive suppression, perceived burdensomeness, and caregiver criticism and conflict at weekt compared to participants' mean levels prospectively predicted increases in the likelihood of a positive STB report from weekt to weekt+1. CONCLUSION: Psychosocial factors influencing STBs in adolescents and adults also affect preadolescents in day-to-day life. Expressive suppression and perceived burdensomeness consistently emerged as novel risk indicators and potential targets for treatment. In addition, increases in depression, rumination, and caregiver criticism and conflict, as well as decreases in positive affect, might prompt heightened STB screening and assessments for preadolescents with a history of STBs.

Learning how to help others: two-year-olds' social learning of a prosocial act.

Engaging in prosocial behaviors (acts that benefit others) is associated with many positive outcomes in children, including the development of positive peer relationships, academic achievement, and good psychological functioning. This study examined the social learning mechanisms toddlers use to acquire prosocial behaviors. This brief report presents a new experimental procedure in which 2-year-olds (28-32 months, N=30) saw a video of an adult performing a novel prosocial behavior in response to another person's distress. Children then had the opportunity to imitate and implement the behavior in response to their own parent's physical distress. Children who saw the video were more likely to perform the novel action and to display non-demonstrated prosocial behaviors relative to (a) children who did not view the video but saw a parent in distress and (b) children who saw the video but witnessed their mother engage in a neutral activity. These results suggest that toddlers imitate and emulate prosocial behaviors for social interaction and that children can apply such behaviors in appropriate situations.

Children's Maternal Representations Moderate the Efficacy of Parent-Child Interaction Therapy-Emotion Development (PCIT-ED) Treatment For Preschool Depression.

A randomized controlled trial (RCT) demonstrated that a novel psychotherapy, Parent-Child Interaction Therapy-Emotion Development (PCIT-ED), effectively treats preschool-onset depression. However, little is known about which children benefit most from PCIT-ED. As positive parent-level factors are associated with lesser depressive symptoms, this study explored the potential moderating role of positive parenting relationships on PCIT-ED efficacy. This study examined mothers and their children aged 3-6 (N = 185) who participated in the PCIT-ED RCT. Children were randomized to immediate PCIT-ED treatment (n = 94) or a waitlist control condition (n = 91) that received treatment after 18 weeks. Prior to treatment, children completed a narrative story completion task that was videotaped and coded for children's positive and negative representations of their mothers. Parent-child interaction tasks were also completed pre-treatment and videotaped and coded to measure observed parenting. Odds of MDD diagnosis post-treatment were predicted by the interaction of children's negative maternal representations and treatment group (Estimate = -.68; SE = .27; [Formula: see text] = 6.45; p = .01) and the interaction of children's relatively more positive than negative maternal representations and treatment group (Estimate = .30; SE = .13; [Formula: see text] = 5.27; p = .02). Observed parenting measures did not significantly predict odds of MDD diagnosis. Thus, PCIT-ED predicted loss of MDD diagnosis for children who displayed maternal representations that were less negative, and relatively more positive than negative. Results suggest that children with relatively more positive maternal representations may be more likely to benefit from PCIT-ED, whereas children with more negative maternal representations may need targeted work to decrease negative maternal perceptions before initiating PCIT-ED in order for treatment to be most effective.

Early Childhood Socioeconomic Status and Cognitive and Adaptive Outcomes at the Transition to Adulthood: The Mediating Role of Gray Matter Development Across Five Scan Waves.

BACKGROUND: Early low socioeconomic status (SES) is associated with poor outcomes in childhood, many of which endure into adulthood. It is critical to determine how early low SES relates to trajectories of brain development and whether these mediate relationships to poor outcomes. We use data from a unique 17-year longitudinal study with five waves of structural brain imaging to prospectively examine relationships between preschool SES and cognitive, social, academic, and psychiatric outcomes in early adulthood. METHODS: Children (n = 216, 50% female, 47.2% non-White) were recruited from a study of early onset depression and followed approximately annually. Family income-to-needs ratios (SES) were assessed when children were ages 3 to 5 years. Volumes of cortical gray and white matter and subcortical gray matter collected across five scan waves were processed using the FreeSurfer Longitudinal pipeline. When youth were ages 16+ years, cognitive function was assessed using the NIH Toolbox, and psychiatric diagnoses, high-risk behaviors, educational function, and social function were assessed using clinician administered and parent/youth report measures. RESULTS: Lower preschool SES related to worse cognitive, high-risk, educational, and social outcomes (|standardized B| = 0.20-0.31, p values < .003). Lower SES was associated with overall lower cortical (standardized B = 0.12, p < .0001) and subcortical gray matter (standardized B = 0.17, p < .0001) volumes, as well as a shallower slope of subcortical gray matter growth over time (standardized B = 0.04, p = .012). Subcortical gray matter mediated the relationship of preschool SES to cognition and high-risk behaviors. CONCLUSIONS: These novel longitudinal data underscore the key role of brain development in understanding the long-lasting relations of early low SES to outcomes in children.

Callous-Unemotional Traits as an Intervention Target and Moderator of Parent-Child Interaction Therapy-Emotion Development Treatment for Preschool Depression and Conduct Problems.

OBJECTIVE: Callous-unemotional (CU) traits-characterized by low empathy, prosociality, and guilt-predict severe and persistent conduct problems. Although some interventions for conduct problems have been less effective in children with high levels of CU traits, studies have not examined whether CU traits interfere with treatment for other childhood disorders. Moreover, few treatments have demonstrated efficacy in decreasing CU traits themselves in early childhood. This study examined whether Parent-Child Interaction Therapy-Emotion Development (PCIT-ED), a novel PCIT adaptation that promotes emotional competence with demonstrated efficacy in treating preschool-onset major depressive disorder and oppositional defiant disorder, was also effective in treating these disorders in children displaying higher levels of CU traits. The study also examined whether PCIT-ED treatment produced significant and sustained decreases in CU traits. METHOD: This study examined 3- to 5-year-olds (N = 114) with preschool-onset major depressive disorder who completed the PCIT-ED trial. Children were randomly assigned to either immediate PCIT-ED treatment (n = 64) or a waitlist control condition (n = 50) in which they received the active treatment after 18 weeks. Psychiatric diagnoses and severity and CU traits in children were assessed at baseline, immediately after treatment, and 18 weeks after treatment completion. RESULTS: Compared with the waitlist, PCIT-ED effectively reduced major depressive disorder and oppositional defiant disorder in preschoolers, regardless of initial levels of CU traits. Moreover, CU traits decreased from before to after treatment, and this treatment effect was sustained 18 weeks after treatment. CONCLUSION: Results support that novel interventions that enhance emotional development display significant promise in treating CU traits-behaviors that left untreated predict severe conduct problems, criminality, and substance use. CLINICAL TRIAL REGISTRATION INFORMATION: A Randomized Controlled Trial of PCIT-ED for Preschool Depression; https://clinicaltrials.gov; NCT02076425.