Dante Cicchetti propelled forward the field of developmental psychopathology by advancing this framework and championing new methods, including emphasizing the central role that multilevel analysis holds for explicating pathways of risk and resilience. His work continues to change the face of existing science. It has also paved the way for the formation of new projects, like the Research Domain Criteria initiative. This paper uses our laboratory’s work on multilevel approaches to studying adolescent depression, non-suicidal self-injury, and suicidal thoughts and behaviors to shine a spotlight on Dr Cicchetti’s contributions. In addition, we review recent developments, ongoing challenges, and promising future directions within developmental psychopathology as we endeavor to carry on the tradition of growth in the field.

Resilience promotes positive adaptation to challenges and may facilitate recovery for adolescents experiencing psychopathology. This work examined concordance across the experience, expression, and physiological response to stress as a protective factor that may predict longitudinal patterns of psychopathology and well-being that mark resilience. Adolescents aged 14–17 at recruitment (oversampled for histories of non-suicidal self-injury; NSSI) were part of a three-wave (T1, T2, T3) longitudinal study. Multi-trajectory modeling produced four distinct profiles of stress experience, expression, and physiology at T1 (High-High-High, Low-Low-Low, High-Low-Moderate, and High-High-Low, respectively). Linear mixed-effect regressions modeled whether the profiles predicted depressive symptoms, suicide ideation, NSSI engagement, positive affect, satisfaction with life, and self-worth over time. Broadly, concordant stress response profiles (Low-Low-Low, High-High-High) were associated with resilient-like patterns of psychopathology and well-being over time. Adolescents with a concordant High-High-High stress response profile showed a trend of greater reduction in depressive symptoms (B = 0.71, p = 0.052), as well as increased global self-worth (B = –0.88, p = 0.055), from T2 to T3 compared to the discordant High-High-Low profile. Concordance across multi-level stress responses may be protective and promote future resilience, whereas blunted physiological responses in the presence of high perceived and expressed stress may indicate poorer outcomes over time.

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.

Growing evidence suggests that emotion socialization may be disrupted by maternal depression. However, little is known about emotion-related parenting by mothers with bipolar disorder or whether affective modeling in early childhood is linked to young adults’ recollections of emotion socialization practices. The current study investigates emotion socialization by mothers with histories of major depression, bipolar disorder, or no mood disorder. Affective modeling was coded from parent–child interactions in early childhood and maternal responses to negative emotions were recollected by young adult offspring (n = 131, 59.5% female, M age = 22.16, SD = 2.58). Multilevel models revealed that maternal bipolar disorder was associated with more neglecting, punishing, and magnifying responses to children's emotions, whereas maternal major depression was associated with more magnifying responses; links between maternal diagnosis and magnifying responses were robust to covariates. Young adult recollections of maternal responses to emotion were predicted by affective modeling in early childhood, providing preliminary validity evidence for the Emotions as a Child Scale. Findings provide novel evidence that major depression and bipolar disorder are associated with altered emotion socialization and that maternal affective modeling in early childhood prospectively predicts young adults’ recollections of emotion socialization in families with and without mood disorder.

We observed gendered coping strategies and conflict resolution outcomes used by adolescents and parents during a conflict discussion task to evaluate associations with current and later adolescent psychopathology. We studied 137 middle- to upper-middle-class, predominantly Caucasian families of adolescents (aged 11–16 years, 65 males) who represented a range of psychological functioning, including normative, subclinical, and clinical levels of problems. Adolescent coping strategies played key roles both in the extent to which parent–adolescent dyads resolved conflict and in the trajectory of psychopathology symptom severity over a 2-year period. Gender-prototypic adaptive coping strategies were observed in parents but not youth, (i.e., more problem solving by fathers than mothers and more regulated emotion-focused coping by mothers than fathers). Youth–mother dyads more often achieved full resolution of conflict than youth–father dyads. There were generally not bidirectional effects among youth and parents’ coping across the discussion except boys’ initial use of angry/hostile coping predicted fathers’ angry/hostile coping. The child was more influential than the parent on conflict resolution. This extended to exacerbation/alleviation of psychopathology over 2 years: higher conflict resolution mediated the association of adolescents’ use of problem-focused coping with decreases in symptom severity over time. Lower conflict resolution mediated the association of adolescents’ use of angry/hostile emotion coping with increases in symptom severity over time. Implications of findings are considered within a broadened context of the nature of coping and conflict resolution in youth–parent interactions, as well as on how these processes impact youth well-being and dysfunction over time.

Integrative, multilevel approaches investigating neurobiological systems relevant to threat detection promise to advance understanding of the pathophysiology of major depressive disorder (MDD). In this study we considered key neuronal and hormonal systems in adolescents with MDD and healthy controls (HC). The goals of this study were to identify group differences and to examine the association of neuronal and hormonal systems. MDD and HC adolescents (N = 79) aged 12–19 years were enrolled. Key brain measures included amygdala volume and amygdala activation to an emotion face-viewing task. Key hormone measures included cortisol levels during a social stress task and during the brain scan. MDD and HC adolescents showed group differences on amygdala functioning and patterns of cortisol levels. Amygdala activation in response to emotional stimuli was positively associated with cortisol responses. In addition, amygdala volume was correlated with cortisol responses, but the pattern differed in depressed versus healthy adolescents, most notably for unmedicated MDD adolescents. The findings highlight the value of using multilevel assessment strategies to enhance understanding of pathophysiology of adolescent MDD, particularly regarding how closely related biological threat systems function together while undergoing significant developmental shifts.

Multilevel models of developmental psychopathology implicate both characteristics of the individual and their rearing environment in the etiology of internalizing problems and disorders. Maladaptive regulation of fear and sadness, the core of anxiety and depression, arises from the conjoint influences of ineffective parasympathetic regulation of emotion and ineffective emotion socialization experiences. In 171 youths (84 female, M = 13.69 years, SD = 1.84), we measured changes of respiratory sinus arrhythmia (RSA) in response to sadness- and fear-inducing film clips and maternal supportive and punitive responses to youths' internalizing emotions. Youths and mothers reported on youths' internalizing problems and anxiety and depression symptoms concurrently and 2 years later at Time 2. Maternal supportive emotion socialization predicted fewer, and punitive socialization predicted more, mother-reported internalizing problems at Time 2 only for youths who showed RSA suppression to fear-inducing films. More RSA suppression to sadness-inducing films predicted more youth-reported internalizing problems at Time 2 in girls only. In addition, less supportive emotion socialization predicted more youth-reported depression symptoms at Time 2 only for girls who showed more RSA suppression to sadness. RSA suppression to sadness versus fear might reflect different patterns of atypical parasympathetic regulation of emotional arousal, both of which increase the risk for internalizing difficulties in youths, and especially girls, who lack maternal support for regulating emotions.

Although there is considerable evidence that relational victimization is associated with depressive symptoms in youth, our understanding about the mechanisms by which victimization and depressive symptoms are linked is limited. The current study explored ruminating about victimization experiences as a potential mechanism that might contribute to an understanding of the association between relational victimization and depressive symptoms. We also tested the specificity of the proposed models by controlling for and testing parallel models of a highly related behavior: relational aggression. A sample of 499 adolescents from sixth through eighth grades participated. Teacher reports were used to assess relational victimization and relational aggression. Self-reports were used to assess depressive symptoms and rumination. The results showed that rumination partially mediated the association between relational victimization and depressive symptoms. No moderation effect was found. In contrast, rumination moderated the association between relational aggression and depressive symptoms. Specifically, relational aggression was associated with depressive symptoms for those adolescents who were also ruminators. Thus, ruminating about victimization experiences appears to be an important mechanism that functions differently for relational aggression and relational victimization in conferring risk for depressive symptoms. The findings offer important practical implications for those working with adolescents and also lay the groundwork for future research.

There is growing evidence that many offspring of parents with bipolar disorder (BD) will develop moderate to severe forms of psychopathology during childhood and adolescence, including thought problems. The purpose of this study was to evaluate the developmental progression of thought problems within the context of a family risk study. Repeated assessments of thought problems, spanning approximately 15 years, were conducted in offspring (N = 192 from 98 families) of parents diagnosed with BD (O-BD), unipolar depression (O-UNI), or no significant psychiatric or medical problems (O-WELL). Survival analysis showed that the O-BD group had the greatest estimated probability of developing thought problems over time, followed by O-UNI, and then O-WELL and O-BD exhibiting higher levels of persistence than O-WELL. Parent-reported thought problems in childhood and adolescence predicted a range of problems in young adulthood. Disturbances in reality testing and other atypical behaviors are likely to disrupt progression through important developmental periods and to associate with poor outcomes. These findings are likely relevant to preventing the occurrence or progression of problems in offspring of bipolar parents. The study of thought problems across development represents an important area of continued research in children at risk for development of affective disorders.

Allostasis, or the maintenance of stability through physiological change, refers to the process by which individuals adjust to the continually changing demands that are put upon somatic activity by salient events. Bauer and colleagues proposed that allostasis could be detected through patterns of the joint reactivity of the autonomic nervous system (ANS) and hypothalamic–pituitary–adrenal (HPA) axis system under stressful conditions. We examined the associations between ANS and HPA reactivity and the development of externalizing and internalizing problems over 2 years in a sample of 215 adolescents. The interactions of ANS and HPA reactivity were contemporaneously associated with, and longitudinally predictive of, adolescents' emotional and behavioral problems. Adolescents with symmetrical high reactivity across systems had more internalizing and fewer externalizing problems initially. Over time, both symmetrical and asymmetrical reactivity predicted increasing internalizing problems in girls, depending on the measure of ANS activity that was examined, heart rate, or blood pressure reactivity. Implications for the understanding of allostasis and the dynamic nature of the relations between multiple physiological regulatory systems and adolescents' developing psychopathology are discussed.

There is growing evidence that many offspring of bipolar parents will develop moderate to severe forms of psychopathology during childhood and adolescence. The purpose of this study was to apply growth curve models to evaluate developmental progression with regard to continuity and cascades representative within the context of a family risk study of bipolar disorder (BD). Repeated assessments of externalizing, internalizing, and thought problems, spanning more than a decade, were examined in a total of 94 offspring of parents with BD (O-BD), major depressive disorder (O-UNI), or no significant psychiatric or medical problems (O-WELL). Continuity was defined by the growth curve of the O-WELL group who exhibited low levels of problems from early childhood through late adolescence. Discontinuity, as evidenced by greater complexity of growth curves relative to the O-WELL group, was exhibited in the at- risk offspring groups for internalizing problems. Different patterns of developmental cascades were supported for the at-risk group with O-UNI showing a robust cascade from self-regulatory deficits (externalizing problems) to internalizing problems. There was also support for a cascade from self-regulatory deficits to thought problems across the entire group (with some support that this pattern was accounted for primarily by O-BD). This study not only serves to advance our understanding of the risks associated with a family history of BD, but also provides a novel approach to examining developmental cascades.

In a previous paper, the authors found that impairment on the Wisconsin Card Sorting Test (WCST) in adolescence was predictive of bipolar disorder in young adulthood among offspring of mothers with bipolar illness. In the present study, the authors explore the contribution of maternal characteristics, beyond maternal mood disorder, to the prediction of offspring dysfunction on the WCST. Results showed that maternal bipolar disorder and maternal negativity were both predictive of impaired performance on the WCST during adolescence. The contribution of maternal negativity to offspring WCST impairment was not better explained by maternal personality disorder, mother's functional impairment, family loading for bipolar disorder, or offspring disruptive behavioral disturbance. Findings did not support a moderator model. However, support was found for a mediation model in which maternal negativity contributed to risk for offspring bipolar disorder through its negative association with apparent frontal lobe functioning, as measured by the WCST. Findings are discussed from the perspective of a vulnerability–stress model. In addition, the authors consider the possibility that maternal negativity and offspring impairment on the WCST may be reflective of a common heritable trait.The findings presented in this paper come from the doctoral dissertation of the first author, which was funded by an NIMH Intramural Research Training Award. The authors are enormously grateful to Anne Mayfield, without whom this project would not have been possible. We are deeply indebted to Ann S. Masten, W. Andrew Collins, L. Alan Sroufe, Monica Luciana, and Carrie Borchardt, who provided support and guidance throughout all stages of this project. We are also thankful to Robert Asarnow for his advice and encouragement, and to Roger E. Meyer and Daniel N. Klein for their comments on earlier drafts of this paper. In addition, we acknowledge the contributions of Gail Inoff-Germain, who administered diagnostic interviews and neuropsychological measures at adolescent follow-up; Rula B. Garside, who undertook the painstaking job of establishing interrater reliability; Erika Sundstrom, who devoted many hours to data organization and quality assurance; and Sara Avery Torvik and Patricia Kasdan, whose combined gifts of organization and warmth created a comfortable atmosphere for study participants. Finally, we thank the extraordinary research participants of the NIMH Childrearing Study, who have shown enormous bravery and dedication by sharing with us 23 years of their lives.

Studies of adults who have been diagnosed with, and treated for, bipolar disorder have shown that these patients exhibit impairment on measures of executive functioning. However, it is unclear whether executive dysfunction precedes the diagnosis of bipolar illness, or develops subsequent to its onset. Moreover, investigators have failed to control for the effects of premorbid attentional problems on cognitive performance in these patients. The present authors explored these questions using data from a longitudinal prospective study of individuals at risk for major mood disorder. Results revealed that 67% of participants who met criteria for bipolar disorder in young adulthood showed impairment on the Wisconsin Card Sorting Test (WCST) when they were assessed during adolescence, as compared with 17% of individuals with no major mood diagnosis, and 19% with unipolar depression. This association between performance on the WCST and bipolar illness was not accounted for by high rates of premorbid attentional disturbance. In fact, among participants with early attentional problems, only those who ultimately developed bipolar disorder exhibited impairment on the WCST. Early attentional problems that preceded unipolar depression or no mood disorder were not associated with executive dysfunction.The findings presented in this paper come from the doctoral dissertation of the first author, which was funded by an NIMH Intramural Research Training Award. The authors are enormously grateful to Roger E. Meyer for his comments on earlier drafts of this paper and to Anne Mayfield, without whom this project would not have been possible. We are deeply indebted to Ann S. Masten, W. Andrew Collins, L. Alan Sroufe, Monica Luciana, and Carrie Borchardt, who provided invaluable guidance throughout all stages of this project, as well as Robert Asarnow, who was an important mentor during the review process. In addition, we acknowledge the contributions of Gail Inoff–Germain, who administered diagnostic interviews and neuropsychological measures at adolescent follow-up; Rula B. Garside, who undertook the painstaking job of establishing interrater reliability; Erika Sundstrom, who devoted many hours to data organization and quality assurance; and Sara Avery Torvik and Patricia Kasdan, whose combined gifts of organization and warmth created a comfortable atmosphere for study participants. Finally, we thank the extraordinary research participants of the NIMH Childrearing Study, who have shown enormous bravery and dedication by sharing with us 23 years of their lives.

Individual differences in salivary testosterone were examined in 213 adolescents (106 boys, 107 girls; mean age = 13.66 years) in relation to externalizing and internalizing psychopathology. Self- and parent-report measures of behavior problems and psychiatric symptoms were obtained. Latent anxiety–depression, disruptive behavior, and attention problem constructs were developed using multitrait, multimethod procedures. Saliva samples were collected in the morning, midday, and late afternoon on multiple days and were later assayed for testosterone. Latent constructs were derived for testosterone level and diurnal variation across the six sampling occasions. Structural equations modeled relationships between problem behavior and intra- and interindividual differences in testosterone separately by gender. For boys, lower levels of testosterone and testosterone levels that decreased more slowly across the day were related to higher levels of anxiety–depression and attention problems. These associations were not moderated by pubertal development. For girls, steep declines in testosterone production across the day related to higher levels of disruptive behavior problems, but this association was only evident after including pubertal development as a moderator in the model. These findings raise novel questions regarding the nature and magnitude of links between testosterone and problem behavior in youth.

The purpose of this study was to examine adrenocortical activity (basal, diurnal variation, and responses to social stressors) in adolescents at risk for psychopathology. Salivary cortisol levels were examined in normally developing and at-risk youth with internalizing and externalizing symptoms ranging from subclinical to clinical levels. Adolescents showed expected patterns of diurnal variation, with high early morning cortisol levels and a pattern of decline throughout the day. Females showed higher midday and late afternoon levels than males, and these patterns interacted with risk status. Internalizing problems sometimes were associated with gradual rather than steep declines in basal cortisol production. Both immediate and delayed cortisol reactivity to a social performance stressor were associated with internalizing symptoms. There was no evidence of relations between externalizing problems and underarousal of the hypothalamic–pituitary–adrenal (HPA) system. These and other results suggest that gender is an important moderating factor linking psychopathology, development, and context with HPA axis functioning in adolescence.

The focus of this article is on internalizing problems that are experienced by children and adolescents. We provide an historical perspective, selectively examine the current state of knowledge, consider advances and gaps in what is known, and identify new research directions. Diagnosis, epidemiology, theory, and research first are considered separately for anxiety and depressive disorders. These internalizing problems, however, whether clinical or subclinical, share many common features and show high comorbidity rates. We emphasize the importance of systematic analysis of comorbid anxiety and depression, including their comorbidity with externalizing problems. This could lead to more valid classification of subtypes of internalizing problems and further an understanding of the diverse conditions that constitute internalized distress. We highlight the need to study anxiety and depression within a developmental psychopathology framework, as well as to include both categorical and dimensional assessments of these problems in the same research designs. This will be essential for understanding the complex interplay of biological and environmental processes that contribute to the emergence, progression, and amelioration of internalizing problems over time.