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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 functions 1 – 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 mapping 4 (the median neuroimaging study sample size is about 25), but potentially too small for capturing reproducible brain–behavioural phenotype associations 5 , 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. Combined data from three large studies, with a total sample size of around 50,000 individuals, indicate that many previous studies linking the brain to complex phenotypes have been statistically underpowered, producing inflated and irreproducible effects.

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.

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.

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. Summary 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.

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.

Difficulty using reparative behaviors (i.e., prosocial behaviors that individuals use after they have transgressed to cause another’s distress) has been concurrently associated with poorer social functioning and both internalizing and externalizing disorders in children and adults. Despite these associations, no study has examined social and psychological outcomes of children who display consistently low levels of reparative behaviors across childhood. This study used established developmental trajectories of reparative behaviors that span preschool through early adolescence (low-stable, moderate-stable, and high-stable) to predict social and psychological outcomes in adolescence (N = 129). Membership in trajectories characterized by lower levels of reparative behaviors predicted greater social rejection, social withdrawal, aggression, and symptoms of depression in adolescence, even when controlling for baseline levels of each outcome. Membership in the low-stable reparative trajectory also significantly mediated the relationship between high levels of guilt in preschool and greater depression severity in adolescence. Findings suggest that children who display persistently low levels of reparative behaviors may be at-risk for a variety of poorer social and emotional outcomes. Further, preschoolers who display both high levels of guilt and low levels of reparative behaviors may be at particularly high risk for depression recurrence in adolescence. Thus, interventions that teach young children reparative skills and/or promote approach rather than avoidance after transgressions may have important implications for preventing a wide range of poorer social and emotional outcomes in adolescence.

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.

Despite research exploring preadolescent mood disorders, the ability to predict increases in depression severity and risk for self-injurious thoughts and behaviors (SITBs) remains poor, leaving clinicians few markers to predict increases in individual risk. One promising area of research has focused on sleep disturbances as an acute and proximal risk factor for depression and SITBs. However, little of this research has focused on children prior to adolescence or incorporated designs that enable us to disentangle the directionality of the associations between these constructs. The current study explored the temporal dynamics and directionality of the association between sleep disturbances and psychological symptoms, including depression, suicidal thoughts, and self-harm behaviors in a sample of preadolescents enriched for a history of early childhood mood disorders. Participants completed weekly electronic assessments for one year to examine week-by-week associations between sleep disturbances (i.e., trouble sleeping and fatigue) and depression, suicidal thoughts, and self-harm behaviors. Both trouble sleeping and fatigue were found to predict and precede increased depression severity, and trouble sleeping predicted endorsement of self-harm behaviors the following week, even when controlling for prior depression severity and self-harm behaviors, respectively. There was no evidence for the reverse association (i.e., depression severity or self-harm behaviors predicting subsequent sleep disturbances). Our findings provide the first evidence for a temporal and directional association between sleep disturbances and subsequent depression severity and self-harm behaviors in preadolescents. These findings highlight the potential utility targeting sleep within existing treatments for depression and self-harm behaviors in preadolescents.

Depression is often a relapsing disorder that can start as early as preschool. In adults and adolescents, family and peer criticism/conflict and rejection sensitivity are associated with recurrence. However, it is not yet clear whether similar factors are associated with relapse among early adolescent youth who experience depression starting in preschool. The current study used data from a unique longitudinal study, which began at preschool age and included 161 youth. It oversampled for those with preschool‐onset major depressive disorder (PO‐MDD) and included community controls (CCs). When the youth were 7–12 years old, we administered diagnostic interviews and weekly surveys over 1 year. These measures were repeated at ages 8–15, along with ecological momentary assessment (EMA) three to four times a day for 8 days, and an event‐related potential (ERP) task assessing neural reactivity to social feedback. We assessed whether youth with a history of PO‐MDD who were experiencing depression in adolescence (i.e., non‐remitted youth [NRY]) versus those who were not (i.e., remitted youth [RY]) and/or CCs experienced greater family/peer criticism/conflict and sensitivity to interpersonal stress. Across multiple time scales (weekly and daily), NRY experienced greater parent and peer criticism/conflict and were more reactive to such criticism/conflict than RY and CCs. Further, in weekly surveys, NRY displayed a stronger association between experiencing interpersonal criticism/conflict and depression compared to CCs, with a similar trend compared to RY. In momentary assessments, NRY showed a longer‐lasting association between family conflict and both negative affect (NA) and connectedness than RY. In addition, neural measures indicated a stronger response to negative social feedback among NRY. Taken together, these data identify potential interpersonal treatment targets for youth with early‐onset depression who continue to experience depression into adolescence. Trial Registration: ClinicalTrials.gov identifier: NCT02076425

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; χ2 = 6.45; p = .01) and the interaction of children’s relatively more positive than negative maternal representations and treatment group (Estimate = .30; SE = .13; χ2 = 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.