Associations between infants' frontal EEG asymmetry and temperamental negative affectivity (NA) across infants' first year of life and the potential moderating role of maternal prenatal depressive symptoms were examined prospectively in infants (n = 242) of mothers at elevated risk for perinatal depression. In predicting EEG, in the context of high prenatal depressive symptoms, infant NA and frontal EEG asymmetry were negatively associated at 3 months of age and positively associated by 12 months of age. By contrast, for low depression mothers, infant NA and EEG were not significantly associated at any age. Postnatal depressive symptoms did not add significantly to the models. Dose of infants' exposure to maternal depression mattered: infants exposed either pre- or postnatally shifted from a positive association at 3 months to a negative association at 12 months; those exposed both pre- and postnatally shifted from a negative association at 3 months to a positive association at 12 months. Prenatal relative to postnatal exposure did not matter for patterns of association between NA and EEG. The findings highlight the importance of exploring how vulnerabilities at two levels of analysis, behavioral and psychophysiological, co-occur over the course of infancy and in the context of mothers' depressive symptomatology.

There is increasing interest among developmental psychopathologists in broad transdiagnostic factors that give rise to a wide array of clinical presentations (multifinality), but little is known about how these processes lead to particular psychopathological manifestations over the course of development. We examined whether individual differences in the error-related negativity (ΔERN), a neural indicator of error monitoring, predicts whether early persistent irritability, a prototypical transdiagnostic construct, is associated with later internalizing versus externalizing outcomes. When children were 3 years old, mothers were interviewed about children's persistent irritability and completed questionnaires about their children's psychopathology. Three years later, EEG was recorded while children performed a go/no-go task to measure the ΔERN. When children were approximately 9 years old, mothers again completed questionnaires about their children's psychopathology. The results indicated that among children who were persistently irritable at age 3, an enhanced or more negative ΔERN at age 6 predicted the development of internalizing symptoms at age 9, whereas a blunted or smaller ΔERN at age 6 predicted the development of externalizing symptoms. Our results suggest that variation in error monitoring predicts, and may even shape, the expression of persistent irritability and differentiates developmental trajectories from preschool persistent irritability to internalizing versus externalizing outcomes in middle to late childhood.

In response to rapidly growing rates of comorbidity among psychiatric disorders, clinical scientists have become interested in identifying transdiagnostic processes that can help explain dysfunction across diagnostic categories (e.g., Kring & Sloan, 2009). One factor that has received a great deal of attention is that of emotion regulation, namely, the ability to modulate the intensity and/or duration of emotional states (e.g., Cicchetti, Ackerman, & Izard, 1995; Gross, 1998). Recent theoretical and empirical work has begun to emphasize the role that emotion regulation plays in the temporal comorbidity between internalizing and externalizing conditions (e.g., Aldao & De Los Reyes, 2015; De Los Reyes & Aldao, 2015; Drabick & Kendall, 2010; Jarrett & Ollendick, 2008; Patrick & Hajcak, 2016). However, close inspection of this work reveals two very pertinent areas of growth: (a) this literature is characterized by mixed findings that are likely explained, in part, by methodological heterogeneity; and (b) emotion regulation tends to be studied in relatively narrow terms. To address these issues, we provide a series of recommendations for facilitating cross-study comparisons and leveraging multifaceted approaches to studying emotion regulation processes within a developmental psychopathology framework. We hope that our perspective can enhance the organization and growth of this very important area of inquiry, and ultimately result in more effective prevention and treatment programs.

Transactional cascades among child internalizing and externalizing symptoms, and fathers’ and mothers’ posttraumatic stress disorder (PTSD) symptoms were examined in a sample of families with a male parent who had been deployed to recent military conflicts in the Middle East. The role of parents’ positive engagement and coercive interaction with their child, and family members’ emotion regulation were tested as processes linking cascades of parent and child symptoms. A subsample of 183 families with deployed fathers and nondeployed mothers and their 4- to 13-year-old children who participated in a randomized control trial intervention (After Deployment: Adaptive Parenting Tools) were assessed at baseline prior to intervention, and at 12 and 24 months after baseline, using parent reports of their own and their child's symptoms. Parents’ observed behavior during interaction with their children was coded using a multimethod approach at each assessment point. Reciprocal cascades among fathers’ and mothers’ PTSD symptoms, and child internalizing and externalizing symptoms, were observed. Fathers’ and mothers’ positive engagement during parent–child interaction linked their PTSD symptoms and their child's internalizing symptoms. Fathers’ and mothers’ coercive behavior toward their child linked their PTSD symptoms and their child's externalizing symptoms. Each family member's capacity for emotion regulation was associated with his or her adjustment problems at baseline. Implications for intervention, and for research using longitudinal models and a family-systems perspective of co-occurrence and cascades of symptoms across family members are described.

We propose a novel developmentally informed framework to push research beyond a focus on comorbidity between discrete diagnostic categories and to move toward research based on the well-validated dimensional and hierarchical structure of psychopathology. For example, a large body of research speaks to the validity and utility of the internalizing and externalizing spectra as organizing constructs for research on common forms of psychopathology. The internalizing and externalizing spectra act as powerful explanatory variables that channel the psychopathological effects of genetic and environmental risk factors, predict adaptive functioning, and account for the likelihood of disorder-level manifestations of psychopathology. As such, our proposed theoretical framework uses the internalizing and externalizing spectra as central constructs to guide future psychopathology research across the life span. The framework is particularly flexible, because any of the facets or factors from the dimensional and hierarchical structure of psychopathology can form the focus of research. We describe the utility and strengths of this framework for developmental psychopathology in particular and explore avenues for future research.

It is well known that comorbidity is the rule, not the exception, for categorically defined psychiatric disorders, and this is also the case for internalizing disorders of depression and anxiety. This theoretical review paper addresses the ubiquity of comorbidity among internalizing disorders. Our central thesis is that progress in understanding this co-occurrence can be made by employing latent dimensional structural models that organize psychopathology as well as vulnerabilities and risk mechanisms and by connecting the multiple levels of risk and psychopathology outcomes together. Different vulnerabilities and risk mechanisms are hypothesized to predict different levels of the structural model of psychopathology. We review the present state of knowledge based on concurrent and developmental sequential comorbidity patterns among common discrete psychiatric disorders in youth, and then we advocate for the use of more recent bifactor dimensional models of psychopathology (e.g., p factor; Caspi et al., 2014) that can help to explain the co-occurrence among internalizing symptoms. In support of this relatively novel conceptual perspective, we review six exemplar vulnerabilities and risk mechanisms, including executive function, information processing biases, cognitive vulnerabilities, positive and negative affectivity aspects of temperament, and autonomic dysregulation, along with the developmental occurrence of stressors in different domains, to show how these vulnerabilities can predict the general latent psychopathology factor, a unique latent internalizing dimension, as well as specific symptom syndrome manifestations.

Using a sample of 228 females with and without childhood attention-deficit/hyperactivity disorder followed prospectively across 16 years, we measured childhood neurocognitive vulnerability via executive dysfunction using teacher-reported cognitive and learning problems. We then ascertained relations between dimensionally measured internalizing and externalizing psychopathology during adulthood and showed that childhood neurocognitive vulnerability reliably predicted such associated psychopathology. We identified six serial mediation pathways from childhood neurocognitive vulnerability to adult psychopathology through three early- and late-adolescent domains: individual (self-control and delay of gratification), peer (rejection/conflict and acceptance/friendship), and school (academic performance and school failure). The serial indirect effects occurred for the pathways from childhood neurocognitive vulnerability through early-adolescent academic performance, to late-adolescent school failure, to adult associated psychopathology, and from neurocognitive vulnerability through adolescent self-control and then the ability to delay gratification, to adult psychopathology. Furthermore, these indirect effects, plus two others, were moderated by parental distress during childhood and early adolescence, such that under conditions of high distress, the serial indirect effects were weaker than when parental distress was low. We discuss the potential importance of behavioral self-regulation and educational success for later psychological functioning, especially among girls, as well as implications for ontogenic process models of psychopathology.

High rates of comorbidity are observed between internalizing and externalizing problems, yet the developmental dynamics of comorbid symptom presentations are not yet well understood. This study explored the developmental course of latent profiles of internalizing and externalizing symptoms across kindergarten, first grade, and second grade. The sample consisted of 336 children from an urban, low-income community, selected based on relatively high (61%) or low (39%) aggressive/oppositional behavior problems at school entry (64% male; 70% African American, 20% Hispanic). Teachers reported on children's symptoms in each year. An exploratory latent profile analysis of children's scores on aggression/oppositionality, hyperactivity/inattention, anxiety, and social withdrawal symptom factors revealed four latent symptom profiles: comorbid (48% of the sample in each year), internalizing (19%–23%), externalizing (21%–22%), and well-adjusted (7%–11%). The developmental course of these symptom profiles was examined using a latent transition analysis, which revealed remarkably high continuity in the comorbid symptom profile (89% from one year to the next) and moderately high continuity in both the internalizing and externalizing profiles (80% and 71%, respectively). Internalizing children had a 20% probability of remitting to the well-adjusted profile by the following year, whereas externalizing children had a 25% probability of transitioning to the comorbid profile. These results are consistent with the hypothesis that a common vulnerability factor contributes to developmentally stable internalizing–externalizing comorbidity, while also suggesting that some children with externalizing symptoms are at risk for subsequently accumulating internalizing symptoms.

We discuss comorbidity, continuity, and discontinuity of anxiety-related disorders from the perspective of a two-dimensional neuropsychology of fear (threat avoidance) and anxiety (threat approach). Pharmacological dissection of the “neurotic” disorders justifies both a categorical division between fear and anxiety and a subdivision of each mapped to a hierarchy of neural modules that process different immediacies of threat. It is critical that each module can generate normal responses, symptoms of another syndrome, or syndromal responses. We discuss the resultant possibilities for comorbid dysfunction of these modules both with each other and with some disorders not usually classified as anxiety related. The simplest case is symptomatic fear/anxiety comorbidity, where dysfunction in one module results in excess activity in a second, otherwise normal, module to generate symptoms and apparent comorbidity. More complex is syndromal fear/anxiety comorbidity, where more than one module is concurrently dysfunctional. Yet more complex are syndromal comorbidities of anxiety that go beyond the two dimensional fear/anxiety systems: depression, substance use disorder, and attention-deficit/hyperactivity disorder. Our account of attention-deficit/hyperactivity disorder–anxiety comorbidity entails discussion of the neuropsychology of externalizing disorders to account for the lack of anxiety comorbidity in some of these. Finally, we link the neuropsychology of disorder to personality variation, and to the development of a biomarker of variation in the anxiety system among individuals that, if extreme, may provide a means of unambiguously identifying the first of a range of anxiety syndromes.

Self-inflicted injury (SII) is a continuum of intentionally self-destructive behaviors, including nonsuicidal self-injuries, suicide attempts, and death by suicide. These behaviors are among the most pressing yet perplexing clinical problems, affecting males and females of every race, ethnicity, culture, socioeconomic status, and nearly every age. The complexity of these behaviors has spurred an immense literature documenting risk and vulnerability factors ranging from individual to societal levels of analysis. However, there have been relatively few attempts to articulate a life span developmental model that integrates ontogenenic processes across these diverse systems. The objective of this review is to outline such a model with a focus on how observed patterns of comorbidity and continuity can inform developmental theories, early prevention efforts, and intervention across traditional diagnostic boundaries. Specifically, when SII is viewed through the developmental psychopathology lens, it becomes apparent that early temperamental risk factors are associated with risk for SII and a range of highly comorbid conditions, such as borderline and antisocial personality disorders. Prevention efforts focused on early-emerging biological and temperamental contributors to psychopathology have great potential to reduce risk for many presumably distinct clinical problems. Such work requires identification of early biological vulnerabilities, behaviorally conditioned social mechanisms, as well as societal inequities that contribute to self-injury and underlie intergenerational transmission of risk.

Epidemiologic studies demonstrating high rates of co-occurrence among psychiatric disorders at the population level have contributed to large literatures focused on identifying the causal mechanisms underlying the patterns of co-occurrence among these disorders. Such efforts have long represented a core focus of developmental psychopathologists and have more recently been supported by the Research Domain Criteria initiative developed by the NIMH, which provides a further framework for how the hypothesized mechanisms can be studied at different levels of analysis. The present overview focuses on molecular genetic approaches that are being used currently to study the etiology of psychiatric disorders, and how these approaches have been applied in efforts to understand the biological mechanisms that give rise to comorbid conditions. The present report begins with a review of molecular genetic approaches used to identify individual variants that confer risk for multiple disorders and the intervening biological mechanisms that contribute to their comorbidity. This is followed by a review of molecular genetic approaches that use genetic data in aggregate to examine these questions, and concludes with a discussion of how developmental psychopathologists are uniquely positioned to apply these methods in a way that will further our understanding of the causal factors that contribute to the development of comorbid conditions.

Persistently elevated behavioral inhibition (BI) in children is a marker of vulnerability to psychopathology. However, little research has considered the joint influences of caregiver and child factors that may moderate the continuity of BI in early childhood, particularly genetic variants that may serve as markers of biological plasticity, such as the serotonin transporter linked polymorphic region (5-HTTLPR). We explored this issue in 371 preschoolers and their caregivers, examining whether parent characteristics (i.e., overinvolvement or anxiety disorder) and child 5-HTTLPR influenced the continuity of BI between ages 3 and 5. Measures were observational ratings of child BI, observational and questionnaire measures of parenting, and parent interviews for anxiety disorder history, and children were genotyped for the 5-HTTLPR. Parent factors did not moderate the association between age 3 and age 5 BI; however, child BI at age 3 interacted with children's 5-HTTLPR variants to predict age 5 BI, such that children with at least one copy of the short allele exhibited less continuity of BI over time relative to children without this putative plasticity variant. Findings are consistent with previous work indicating the 5-HTTLPR short variant increases plasticity to contextual influences, thereby serving to decrease the continuity of BI in early childhood.

Stress-related pathophysiology drives comorbid trajectories that elude precise prediction. Allostatic load algorithms that quantify biological “wear and tear” represent a comprehensive approach to detect multisystemic disease processes of the mind and body. However, the multiple morbidities directly or indirectly related to stress physiology remain enigmatic. Our aim in this article is to propose that biological comorbidities represent discrete pathophysiological processes captured by measuring allostatic load. This has applications in research and clinical settings to predict physical and psychiatric comorbidities alike. The reader will be introduced to the concepts of allostasis, allostasic states, allostatic load, and allostatic overload as they relate to stress-related diseases and the proposed prediction of biological comorbidities that extend rather to understanding psychopathologies. In our transdisciplinary discussion, we will integrate perspectives related to (a) mitochondrial biology as a key player in the allostatic load time course toward diseases that “get under the skin and skull”; (b) epigenetics related to child maltreatment and biological embedding that shapes stress perception throughout lifespan development; and (c) evolutionary drivers of distinct personality profiles and biobehavioral patterns that are linked to dimensions of psychopathology.

Accumulating behavioral and genetic research suggests that most forms of psychopathology share common genetic and neural vulnerabilities and are manifestations of a relatively few core underlying processes. These findings support the view that comorbidity mostly arises, not from true co-occurrence of distinct disorders, but from the behavioral expression of shared vulnerability processes across the life span. The purpose of this review is to examine the role of the prefrontal cortex (PFC) in the shared vulnerability mechanisms underlying the clinical phenomena of comorbidity from a transdiagnostic and ontogenic perspective. In adopting this perspective, we suggest complex transactions between neurobiologically rooted vulnerabilities inherent in PFC circuitry and environmental factors (e.g., parenting, peers, stress, and substance use) across development converge on three key PFC-mediated processes: executive functioning, emotion regulation, and reward processing. We propose that individual differences and impairments in these PFC-mediated functions provide intermediate mechanisms for transdiagnostic symptoms and underlie behavioral tendencies that evoke and interact with environmental risk factors to further potentiate vulnerability.

Trait impulsivity, which is often defined as a strong preference for immediate over delayed rewards and results in behaviors that are socially inappropriate, maladaptive, and short-sighted, is a predisposing vulnerability to all externalizing spectrum disorders. In contrast, anhedonia is characterized by chronically low motivation and reduced capacity to experience pleasure, and is common to depressive disorders. Although externalizing and depressive disorders have virtually nonoverlapping diagnostic criteria in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, heterotypic comorbidity between them is common. Here, we review common neural substrates of trait impulsivity, anhedonia, and irritability, which include both low tonic mesolimbic dopamine activity and low phasic mesolimbic dopamine responding to incentives during reward anticipation and associative learning. We also consider how other neural networks, including bottom-up emotion generation systems and top-down emotion regulation systems, interact with mesolimbic dysfunction to result in alternative manifestations of psychiatric illness. Finally, we present a model that emphasizes a translational, transdiagnostic approach to understanding externalizing/depression comorbidity. This model should refine ways in which internalizing and externalizing disorders are studied, classified, and treated.

Adolescence is a period marked by increases in risk taking, sensation seeking, and emotion dysregulation. Neurobiological models of adolescent development propose that lagging development in brain regions associated with affect and behavior control compared to regions associated with reward and emotion processing may underlie these behavioral manifestations. Cross-sectional studies have identified several functional brain networks that may contribute to risk for substance use and psychopathology in adolescents. Determining brain structure measures that prospectively predict substance use and psychopathology could refine our understanding of the mechanisms that contribute to these problems, and lead to improved prevention efforts. Participants (N = 265) were healthy substance-naïve adolescents (ages 12–14) who underwent magnetic resonance imaging and then were followed annually for up to 13 years. Cortical thickness and surface area measures for three prefrontal regions (dorsolateral prefrontal cortex, inferior frontal gyrus, and orbitofrontal cortex) and three cortical regions from identified functional networks (anterior cingulate cortex, insular cortex, and parietal cortex) were used to predict subsequent binge drinking, externalizing symptoms, and internalizing symptoms. Thinner dorsolateral prefrontal cortex and inferior frontal cortex in early adolescence predicted more binge drinking and externalizing symptoms, respectively, in late adolescence (ps < .05). Having a family history of alcohol use disorder predicted more subsequent binge drinking and externalizing symptoms. Thinner parietal cortex, but not family history, predicted more subsequent internalizing symptoms (p < .05). This study emphasizes the temporal association between maturation of the salience, inhibition, and executive control networks in early adolescence and late adolescent behavior outcomes. Our findings indicate that developmental variations in these brain regions predate behavioral outcomes of substance use and psychopathology, and may therefore serve as prospective biomarkers of vulnerability.