In 2010, the Research Domain Criteria (RDoC) were developed to advance our understanding of the pathophysiology of mental illness across multiple levels of analysis, ranging from cells to circuits to self-report instruments. Several conceptual RDoC-informed manuscripts have highlighted the importance of studying how developmental processes give rise to psychopathology. However, there are few empirical studies that integrate the RDoC framework with development and psychopathology principles. This special issue was developed to fill this empirical gap. In this introduction to the special issue, we describe how the developmental psychopathology field predates and informs the RDoC framework. We highlight three important ways in which developmental psychopathology and the RDoC framework can mutually inform one another, leading to novel discoveries to identify, prevent, and treat mental health problems across the life span.

The prenatal period represents a critical time for brain growth and development. These rapid neurological advances render the fetus susceptible to various influences with life-long implications for mental health. Maternal distress signals are a dominant early life influence, contributing to birth outcomes and risk for offspring psychopathology. This prospective longitudinal study evaluated the association between prenatal maternal distress and infant white matter microstructure. Participants included a racially and socioeconomically diverse sample of 85 mother–infant dyads. Prenatal distress was assessed at 17 and 29 weeks’ gestational age (GA). Infant structural data were collected via diffusion tensor imaging (DTI) at 42–45 weeks’ postconceptional age. Findings demonstrated that higher prenatal maternal distress at 29 weeks’ GA was associated with increased fractional anisotropy, b = .283, t(64) = 2.319, p = .024, and with increased axial diffusivity, b = .254, t(64) = 2.067, p = .043, within the right anterior cingulate white matter tract. No other significant associations were found with prenatal distress exposure and tract fractional anisotropy or axial diffusivity at 29 weeks’ GA, or earlier in gestation.

Transformation of the maternal–fetal relationship into the mother–infant relationship remains an enigmatic process. This progression is considered using a Research Domain Criteria (RDoC) informed approach centered on domains of Arousal/Regulation, Positive/Negative Valence, and Social Processes. One hundred and fifty-eight maternal–fetal dyads began participation during pregnancy, maternal–infant dyads were followed at 6 months postpartum. Women exhibited stability in feelings of attachment to the fetus and infant, and in positive/negative appraisal of pregnancy and motherhood. Elicited maternal physiological arousal to emotionally evocative videos generated fetal heart rate variability and motor activity responses. Parasympathetic (i.e., heart rate variability) suppression in the fetus was associated with more positive and regulated infant social communication in the Face-to-Face Still Face protocol; suppression of maternal respiratory sinus arrhythmia was related to infant affect but in the opposite direction. Maternal ratings of infant temperament aligned with maternal antenatal affective valence. Attachment trajectories characterized by stability from antenatal to postnatal periods were most associated with maternal affective appraisal of pregnancy; shifts were influenced by infant characteristics and maternal sympathetic responsivity. Results illustrate how variation in arousal and regulatory systems of the pregnant woman and fetus operate within the context of maternal positive and negative valence systems to separately and jointly shape affiliation and temperament in early infancy.

We examined whether Research Domain Criteria (RDoC)-informed measures of prenatal stress predicted newborn neurobehavior and whether these effects differed by newborn sex. Multilevel, prenatal markers of prenatal stress were obtained from 162 pregnant women. Markers of the Negative Valence System included physiological functioning (respiratory sinus arrhythmia [RSA] and electrodermal [EDA] reactivity to a speech task, hair cortisol), self-reported stress (state anxiety, pregnancy-specific anxiety, daily stress, childhood trauma, economic hardship, and family resources), and interviewer-rated stress (episodic stress, chronic stress). Markers of the Arousal/Regulatory System included physiological functioning (baseline RSA, RSA, and EDA responses to infant cries) and self-reported affect intensity, urgency, emotion regulation strategies, and dispositional mindfulness. Newborns’ arousal and attention were assessed via the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale. Path analyses showed that high maternal episodic and daily stress, low economic hardship, few emotion regulation strategies, and high baseline RSA predicted female newborns’ low attention; maternal mindfulness predicted female newborns’ high arousal. As for male newborns, high episodic stress predicted low arousal, and high pregnancy-specific anxiety predicted high attention. Findings suggest that RDoC-informed markers of prenatal stress could aid detection of variance in newborn neurobehavioral outcomes within hours after birth. Implications for intergenerational transmission of risk for psychopathology are discussed.

We investigated whether infant temperament was predicted by level of and change in maternal hostility, a putative transdiagnostic vulnerability for psychopathology, substance use, and insensitive parenting. A sample of women (N = 247) who were primarily young, low-income, and had varying levels of substance use prenatally (69 nonsmokers, 81 tobacco-only smokers, and 97 tobacco and marijuana smokers) reported their hostility in the third trimester of pregnancy and at 2, 9, and 16 months postpartum, and their toddler's temperament and behavior problems at 16 months. Maternal hostility decreased from late pregnancy to 16 months postpartum. Relative to pregnant women who did not use substances, women who used both marijuana and tobacco prenatally reported higher levels of hostility while pregnant and exhibited less change in hostility over time. Toddlers who were exposed to higher levels of prenatal maternal hostility were more likely to be classified in temperament profiles that resemble either irritability or inhibition, identified via latent profile analysis. These two profiles were each associated with more behavior problems concurrently, though differed in their association with competence. Our results underscore the utility of transdiagnostic vulnerabilities in understanding the intergenerational transmission of psychopathology risk and are discussed in regards to the Research Domain Criteria (RDoC) framework.

The research domain criteria (RDoC) is an innovative approach designed to explore dimensions of human behavior. The aim of this approach is to move beyond the limits of psychiatric categories in the hope of aligning the identification of psychological health and dysfunction with clinical neuroscience. Despite its contributions to adult psychopathology research, RDoC undervalues ontogenetic development, which circumscribes our understanding of the etiologies, trajectories, and maintaining mechanisms of psychopathology risk. In this paper, we argue that integrating temperament research into the RDoC framework will advance our understanding of the mechanistic origins of psychopathology beginning in infancy. In illustrating this approach, we propose the incorporation of core principles of temperament theories into a new “life span considerations” subsection as one option for infusing development into the RDoC matrix. In doing so, researchers and clinicians may ultimately have the tools necessary to support emotional development and reduce a young child's likelihood of psychological dysfunction beginning in the first years of life.

In the last decade, an abundance of research has utilized the National Institute of Mental Health (NIMH) research domain criteria (RDoC) framework to examine mechanisms underlying anxiety and depression in youth. However, relatively little work has examined how these mechanistic intrapersonal processes intersect with context during childhood and adolescence. The current paper covers reviews and meta-analyses that have linked RDoC-relevant constructs to ecological systems in internalizing problems in youth. Specifically, cognitive, biological, and affective factors within the RDoC framework were examined. Based on these reviews and some of the original empirical research they cover, we highlight the integral role of ecological factors to the RDoC framework in predicting onset and maintenance of internalizing problems in youth. Specific recommendations are provided for researchers using the RDoC framework to inform future research integrating ecological systems and development. We advocate for future research and research funding to focus on better integration of the environment and development into the RDoC framework.

Despite nonoverlapping diagnostic criteria, internalizing and externalizing disorders show substantial comorbidity. This comorbidity is attributable, at least in part, to transdiagnostic neuroaffective mechanisms. Both unipolar depression and externalizing disorders are characterized by structural and functional compromises in the striatum and its projections to the anterior cingulate cortex (ACC) and other frontal regions. Smaller volumes and dampened reward responding in these regions are associated with anhedonia and irritability – mood states that cut across the internalizing and externalizing spectra. In contrast, smaller amygdala volumes and dampened amygdala function differentiate externalizing disorders from internalizing disorders. Little is known, however, about associations between internalizing–externalizing comorbidity and brain volumes in these regions, or whether such patterns differ by sex. Using a transdiagnostic, research domain criteria (RDoC)-informed approach, we evaluate associations between heterotypic (Internalizing × Externalizing) symptom interactions and striatal, amygdalar, and ACC volumes among participants in the Adolescent Brain Cognitive Development study (N = 6,971, mean age 9.9 years, 51.6% female). Heterotypic symptoms were associated with ACC volumes for both sexes, over and above the main effects of internalizing and externalizing alone. However, heterotypic comorbidity was associated with larger ACC volumes for girls, but with smaller ACC volumes for boys. These findings suggest a need for further studies and transdiagnostic assessment by sex.

Discrimination has been associated with adverse mental health outcomes, though it is unclear how early in life this association becomes apparent. Implicit emotion regulation, developing during childhood, is a foundational skill tied to a range of outcomes. Implicit emotion regulation has yet to be tested as an associated process for mental illness symptoms that can often emerge during this sensitive developmental period. Youth aged 9–11 were recruited for the Adolescent Brain Cognitive Development (ABCD) study. Associations between psychotic-like experiences, depressive symptoms, and total discrimination (due to race, ethnicity, nationality, weight, or sexual minority status) were tested, as well as associations with implicit emotion regulation measures (emotional updating working memory and inhibitory control). Analyses examined whether associations with symptoms were mediated by implicit emotion regulation. Discrimination related to decreased implicit emotion regulation performance, and increased endorsement of depressive symptoms and psychotic-like experiences. Emotional updating working memory performance partially mediated the association between discrimination and psychotic-like experiences, while emotional inhibitory control did not. Discrimination and implicit emotion regulation could serve as putative transdiagnostic markers of vulnerability. Results support the utility of using multiple units of analysis to improve understanding of complex emerging neurocognitive functions and developmentally sensitive periods.

The relationships infants and young children have with their caregivers are fundamental to their survival and well-being. Theorists and researchers across disciplines have attempted to describe and assess the variation in these relationships, leading to a general acceptance that caregiving is critical to understanding child functioning, including developmental psychopathology. At the same time, we lack consensus on how to assess these fundamental relationships. In the present paper, we first review research documenting the importance of the caregiver–child relationship in understanding environmental risk for psychopathology. Second, we propose that the National Institute of Mental Health's Research Domain Criteria (RDoC) initiative provides a useful framework for extending the study of children's risk for psychopathology by assessing their caregivers’ social processes. Third, we describe the units of analysis for caregiver social processes, documenting how the specific subconstructs in the domain of social processes are relevant to the goal of enhancing knowledge of developmental psychopathology. Lastly, we highlight how past research can inform new directions in the study of caregiving and the parent–child relationship through this innovative extension of the RDoC initiative.

The National Institute of Mental Health's Research Domain Criteria (RDoC) framework has prompted a paradigm shift from categorical psychiatric disorders to considering multiple levels of vulnerability for probabilistic risk of disorder. However, the lack of neurodevelopmentally based tools for clinical decision making has limited the real-world impact of the RDoC. Integration with developmental psychopathology principles and statistical methods actualize the clinical implementation of RDoC to inform neurodevelopmental risk. In this conceptual paper, we introduce the probabilistic mental health risk calculator as an innovation for such translation and lay out a research agenda for generating an RDoC- and developmentally informed paradigm that could be applied to predict a range of developmental psychopathologies from early childhood to young adulthood. We discuss methods that weigh the incremental utility for prediction based on intensity and burden of assessment, the addition of developmental change patterns, considerations for assessing outcomes, and integrative data approaches. Throughout, we illustrate the risk calculator approach with different neurodevelopmental pathways and phenotypes. Finally, we discuss real-world implementation of these methods for improving early identification and prevention of developmental psychopathology. We propose that mental health risk calculators can build a needed bridge between the RDoC multiple units of analysis and developmental science.

Informed by the National Institute of Mental Health's Research Domain Criteria (RDoC) and developmental psychopathology frameworks, the current study used cortisol area under the curve with respect to ground (AUCg) as an index of differential sensitivity to context, which was expected to predispose young children with elevated vulnerability to adverse caregiving experiences and adaptive sensitivity to intervention effects. Particularly, the study aimed to determine whether improving caregivers’ responsive parenting through the Filming Interactions to Nurture Development (FIND) intervention would buffer children's biologically embedded vulnerability to caregivers’ depressive symptoms. Data were derived from a randomized controlled trial using pretest–posttest design with low-income families of children aged 4 to 36 months (N = 91). Young children's differential sensitivity was measured using cortisol AUCg during a structured stress paradigm. As hypothesized, children whose cortisol AUCg indicated greater sensitivity to social context exhibited more internalizing and externalizing behaviors in relation to caregivers’ elevated depressive symptoms. Critically, the intervention program was effective in attenuating psychopathology symptoms among the more biologically sensitive children. As proven by rigorous statistical tests, the findings of this study partially supported the differential susceptibility hypotheses, indicating both greater vulnerability to adverse conditions and responsiveness to intervention among children with high levels of cortisol AUCg.

Suicidal thoughts and behaviors (STBs) are major public health concerns among adolescents, and research is needed to identify how risk is conferred over the short term (hours and days). Sleep problems may be associated with elevated risk for STBs, but less is known about this link in youth over short time periods. The current study utilized a multimodal real-time monitoring approach to examine the association between sleep problems (via daily sleep diary and actigraphy) and next-day suicidal thinking in 48 adolescents with a history of STBs during the month following discharge from acute psychiatric care. Results indicated that specific indices of sleep problems assessed via sleep diary (i.e., greater sleep onset latency, nightmares, ruminative thoughts before sleep) predicted next-day suicidal thinking. These effects were significant even when daily sadness and baseline depression were included in the models. Moreover, several associations between daily-level sleep problems and next-day suicidal thinking were moderated by person-level measures of the construct. In contrast, sleep indices assessed objectively (via actigraphy) were either not related to suicidal thinking or were related in the opposite direction from hypothesized. Together, these findings provide some support for sleep problems as a short-term risk factor for suicidal thinking in high-risk adolescents.

Emotion dysregulation is cross-diagnostic and impairing. Most research has focused on dysregulated expressions of negative affect, often measured as irritability, which is associated with multiple forms of psychopathology and predicts negative outcomes. However, the Research Domain Criteria (RDoC) include both negative and positive valence systems. Emerging evidence suggests that dysregulated expressions of positive affect, or excitability, in early childhood predict later psychopathology and impairment above and beyond irritability. Typically, irritability declines from early through middle childhood; however, the developmental trajectory of excitability is unknown. The impact of excitability across childhood on later emotion dysregulation is also yet unknown. In a well-characterized, longitudinal sample of 129 children studied from ages 3 to 5.11 years through 14 to 19 years, enriched for early depression and disruptive symptoms, we assessed the trajectory of irritability and excitability using multilevel modeling and how components of these trajectories impact later emotion dysregulation. While irritability declines across childhood, excitability remains remarkably stable both within and across the group. Overall levels of excitability (excitability intercept) predict later emotion dysregulation as measured by parent and self-report and predict decreased functional magnetic resonance imaging activity in cognitive emotion regulation regions during an emotion regulation task. Irritability was not related to any dysregulation outcome above and beyond excitability.

Irritability is a transdiagnostic symptom dimension in developmental psychopathology, closely related to the Research Domain Criteria (RDoC) construct of frustrative nonreward. Consistent with the RDoC framework and calls for transdiagnostic, developmentally-sensitive assessment methods, we report data from a smartphone-based, naturalistic ecological momentary assessment (EMA) study of irritability. We assessed 109 children and adolescents (Mage = 12.55 years; 75.20% male) encompassing several diagnostic groups – disruptive mood dysregulation disorder (DMDD), attention-deficit/hyperactivity disorder (ADHD), anxiety disorders (ANX), healthy volunteers (HV). The participants rated symptoms three times per day for 1 week. Compliance with the EMA protocol was high. As tested using multilevel modeling, EMA ratings of irritability were strongly and consistently associated with in-clinic, gold-standard measures of irritability. Further, EMA ratings of irritability were significantly related to subjective frustration during a laboratory task eliciting frustrative nonreward. Irritability levels exhibited an expected graduated pattern across diagnostic groups, and the different EMA items measuring irritability were significantly associated with one another within all groups, supporting the transdiagnostic phenomenology of irritability. Additional analyses utilized EMA ratings of anxiety as a comparison with respect to convergent validity and transdiagnostic phenomenology. The results support new measurement tools that can be used in future studies of irritability and frustrative nonreward.

Regulatory processes underlie mother-infant interactions and may be disrupted in adverse caregiving environments. Child maltreatment and sleep variability may reflect high-risk caregiving, but it is unknown whether they confer vulnerability for poorer mother–infant parasympathetic coordination. The aim of this study was to examine mother–infant coregulation of respiratory sinus arrhythmia (RSA) in relation to child maltreatment severity and night-to-night sleep variability in 47 low-income mother–infant dyads. Maternal and infant sleep was assessed with actigraphy and daily diaries for 7 nights followed by a mother–infant still-face procedure during which RSA was measured. Higher maltreatment severity was associated with weakened concordance in RSA coregulation related to the coupling of higher mother RSA with lower infant RSA, suggesting greater infant distress and lower maternal support. In addition, higher infant sleep variability was associated with infants’ lower mean RSA and concordance in lagged RSA coregulation such that lower maternal RSA predicted lower infant RSA across the still-face procedure, suggesting interrelated distress. The findings indicate that adverse caregiving environments differentially impact regulatory patterns in mother–infant dyads, which may inform modifiable health-risk behaviors as targets for future intervention.

The etiology of psychopathology is multifaceted and warrants consideration of factors at multiple levels and across developmental time. Although experiences of adversity in early life have been associated with increased risk of developing psychopathology, pathways toward maladaptation or resilience are complex and depend upon a variety of factors, including individuals’ physiological regulation and cognitive functioning. Therefore, in a longitudinal cohort of 113 mother–child dyads, we explored associations from early adverse experiences to physiological coregulation across multiple systems and subsequent variations in executive functioning. Latent profile analysis derived multisystem profiles based on children's heart rate, respiratory sinus arrhythmia, pre-ejection period, and cortisol measured during periods of rest and reactivity throughout a developmentally challenging protocol. Three distinct profiles of multisystem regulation emerged: heightened multisystem baseline activity (anticipatory arousal/ autonomic nervous system [ANS] responder), typically adaptive patterns across all systems (active copers/mobilizers), and heightened hypothalamic–pituitary–adrenal (HPA) axis activity (HPA axis responders). Path models revealed that children exposed to adversity before 18 months were more likely to evidence an anticipatory arousal/ANS responders response at 36 months, and children in this profile had lower executive functioning scores than the active copers/mobilizers. In sum, these findings provide important information about potential physiological associations linking early adversity to variations in children's task-based executive functioning.

Nonsuicidal self-injury (NSSI) is a common but poorly understood phenomenon in adolescents. This study examined the Sustained Threat domain in female adolescents with a continuum of NSSI severity (N = 142). Across NSSI lifetime frequency and NSSI severity groups (No + Mild NSSI, Moderate NSSI, Severe NSSI), we examined physiological, self-reported and observed stress during the Trier Social Stress Test; amygdala volume; amygdala responses to threat stimuli; and resting-state functional connectivity (RSFC) between amygdala and medial prefrontal cortex (mPFC). Severe NSSI showed a blunted pattern of cortisol response, despite elevated reported and observed stress during TSST. Severe NSSI showed lower amygdala–mPFC RSFC; follow-up analyses suggested that this was more pronounced in those with a history of suicide attempt for both moderate and severe NSSI. Moderate NSSI showed elevated right amygdala activation to threat; multiple regressions showed that, when considered together with low amygdala–mPFC RSFC, higher right but lower left amygdala activation predicted NSSI severity. Patterns of interrelationships among Sustained Threat measures varied substantially across NSSI severity groups, and further by suicide attempt history. Study limitations include the cross-sectional design, missing data, and sampling biases. Our findings highlight the value of multilevel approaches in understanding the complexity of neurobiological mechanisms in adolescent NSSI.

Traditional categorical approaches to classifying personality disorders are limited in important ways, leading to a shift in the field to dimensional approaches to conceptualizing personality pathology. Different areas of psychology – personality, developmental, and psychopathology – can be leveraged to understand personality pathology by examining its structure, development, and underlying mechanisms. However, an integrative model that encompasses these distinct lines of inquiry has not yet been proposed. In order to address this gap, we review the latest evidence for dimensional classification of personality disorders based on structural models of maladaptive personality traits, provide an overview of developmental theories of pathological personality, and summarize the Research Domain Criteria (RDoC) initiative, which seeks to understand underlying mechanisms of psychopathology. We conclude by proposing an integrative model of personality pathology development that aims to elucidate the developmental pathways of personality pathology and its underlying mechanisms.

Attention-deficit hyperactivity disorder (ADHD) is a common, chronic, and impairing disorder, yet presentations of ADHD and clinical course are highly heterogeneous. Despite substantial research efforts, both (a) the secondary co-occurrence of ADHD and complicating additional clinical problems and (b) the developmental pathways leading toward or away from recovery through adolescence remain poorly understood. Resolving these requires accounting for transactional influences of a large number of features across development. Here, we applied a longitudinal cross-lagged panel network model to a multimodal, multilevel dataset in a well-characterized sample of 488 children (nADHD = 296) to test Research Domain Criteria initiative-inspired hypotheses about transdiagnostic risk. Network features included Diagnostic and Statistical Manual of Mental Disorders symptoms, trait-based ratings of emotional functioning (temperament), and performance-based measures of cognition. Results confirmed that ADHD symptom domains, temperamental irritability, and working memory are independent transdiagnostic risk factors for psychopathology based on their direct associations with other features across time. ADHD symptoms and working memory each had direct, independent associations with depression. Results also demonstrated tightly linked co-development of ADHD symptoms and temperamental irritability, consistent with the possibility that this type of anger dysregulation is a core feature that is co-expressed as part of the ADHD phenotype for some children.