Irritability and Temperament: Concurrent and Prospective Relationships in Childhood and Adolescence.

OBJECTIVE: Irritability symptoms are closely associated with, and may reflect, temperament traits, particularly negative affectivity (NA). However, there are few empirical data on the relationships between child temperament and irritability symptoms. METHOD: We investigated cross-sectional and longitudinal relationships between irritability symptoms and temperament traits from age 3-15 in a community sample of 609 children and their parents. Irritability symptoms were assessed through structured interviews with parents at ages 3/6, and inventories completed by parents and youth at ages 12/15. Temperament traits were assessed using parent reports at ages 3/6, and parent and child reports at ages 12/15. Path analysis and structural equation modeling were used to explore longitudinal associations from ages 3-6 and 12-15, respectively. RESULTS: Higher levels of irritability symptoms at ages 3/6 were concurrently associated with higher levels of NA and lower levels of effortful control (EC). In adolescence, higher irritability symptoms were concurrently associated with higher negative temperament and disinhibition. In longitudinal analyses from age 3-6 and 12-15, irritability symptoms showed modest but significant stability after adjusting for the stability of temperament traits. However, there were significant differences in the stability paths at age 3-6, reflecting lower stability of irritability symptoms. Finally, EC at age 3 predicted increased irritability symptoms at age 6, while irritability symptoms at age 3 predicted increased NA at age 6. CONCLUSION: Irritability symptoms are robustly associated with both temperamental NA and difficulty regulating attention and behavior. These findings help situate irritability symptoms within widely accepted temperament/personality taxonomies.

Causal effects of psychostimulants on neural connectivity: a mechanistic, randomized clinical trial.

BACKGROUND: Psychostimulants are frequently used to treat attention-deficit/hyperactivity disorder (ADHD), but side effects are common leading to many patients discontinuing treatment. Identifying neural mechanisms by which psychostimulants attenuate symptoms may guide the development of more refined and tolerable therapeutics. METHODS: We conducted a 12-week, randomized, placebo-controlled trial (RCT) of a long-acting amphetamine, lisdexamfetamine (LDEX), in patients with ADHD, ages 6-25 years old. Of the 58 participants who participated in the RCT, 49 completed pre- and post-RCT magnetic resonance imaging scanning with adequate data quality. Healthy controls (HCs; n = 46) were included for comparison. Treatment effects on striatal and thalamic functional connectivity (FC) were identified using static (time-averaged) and dynamic (time-varying) measures and then correlated with symptom improvement. Analyses were repeated in independent samples from the Adolescent Brain Cognitive Development study (n = 103) and the ADHD-200 Consortium (n = 213). RESULTS: In 49 participants (25 LDEX; 24 Placebo), LDEX increased static and decreased dynamic FC (DFC). However, only DFC was associated with the therapeutic effects of LDEX. Additionally, at baseline, DFC was elevated in unmedicated-ADHD participants relative to HCs. Independent samples yielded similar findings - ADHD was associated with increased DFC, and psychostimulants with reduced DFC. Static FC findings were inconsistent across samples. CONCLUSIONS: Changes in dynamic, but not static, FC were associated with the therapeutic effects of psychostimulants. While prior research has focused on static FC, DFC may offer a more reliable target for new ADHD interventions aimed at stabilizing network dynamics, though this needs confirmation with subsequent investigations.

Developmental pathways from preschool irritability to multifinality in early adolescence: the role of diurnal cortisol.

BACKGROUND: Early irritability predicts a broad spectrum of psychopathology spanning both internalizing and externalizing disorders, rather than any particular disorder or group of disorders (i.e. multifinality). Very few studies, however, have examined the developmental mechanisms by which it leads to such phenotypically diverse outcomes. We examined whether variation in the diurnal pattern of cortisol moderates developmental pathways between preschool irritability and the subsequent emergence of internalizing and externalizing symptoms 9 years later. METHOD: When children were 3 years old, mothers were interviewed about children's irritability and completed questionnaires about their children's psychopathology. Six years later, children collected saliva samples at wake-up and bedtime on three consecutive days. Diurnal cortisol patterns were modeled as latent difference scores between evening and morning samples. When children were approximately 12 years old, mothers again completed questionnaires about their children's psychopathology. RESULTS: Among children with higher levels of irritability at age 3, a steeper diurnal cortisol slope at age 9 predicted greater internalizing symptoms and irritability at age 12, whereas a blunted slope at age 9 predicted greater externalizing symptoms at age 12, adjusting for baseline and concurrent symptoms. CONCLUSION: Our results suggest that variation in stress system functioning can predict and differentiate developmental trajectories of early irritability that are relatively more internalizing v. those in which externalizing symptoms dominate in pre-adolescence.

Stressful life events moderate the effect of neural reward responsiveness in childhood on depressive symptoms in adolescence.

BACKGROUND: Reward processing deficits have been implicated in the etiology of depression. A blunted reward positivity (RewP), an event-related potential elicited by feedback to monetary gain relative to loss, predicts new onsets and increases in depression symptoms. Etiological models of depression also highlight stressful life events. However, no studies have examined whether stressful life events moderate the effect of the RewP on subsequent depression symptoms. We examined this question during the key developmental transition from childhood to adolescence. METHODS: A community sample of 369 children (mean age of 9) completed a self-report measure of depression symptoms. The RewP to winning v. losing was elicited using a monetary reward task. Three years later, we assessed stressful life events occurring in the year prior to the follow-up. Youth depressive symptoms were rated by the children and their parents at baseline and follow-up. RESULTS: Stressful life events moderated the effect of the RewP on depression symptoms at follow-up such that a blunted RewP predicted higher depression symptoms in individuals with higher levels of stressful life events. This effect was also evident when events that were independent of the youth's behavior were examined separately. CONCLUSIONS: These results suggest that the RewP reflects a vulnerability for depression that is activated by stress.

Early Childhood Psychopathology Prospectively Predicts Social Functioning in Early Adolescence.

Psychopathology in school-age children predicts impairment later in development. However, the long-term psychosocial consequences of early childhood psychopathology are less well known. The current study is the first to prospectively examine how a range of diagnoses and symptoms in early childhood predict psychosocial functioning across specific domains during early adolescence 6-9 years later. A community sample (N = 595; 44.9% female; 88.7% White, 12.6% Hispanic) was assessed for psychopathology at ages 3 and 6 using the Preschool Age Psychiatric Assessment. Diagnoses and dimensional scores for depressive, anxiety, attention-deficit/hyperactivity (ADHD), and oppositional defiant disorders (ODD) were examined. When children were 12 years old, children and parents completed the UCLA Life Stress Interview for Children, a semistructured interview assessing functioning in multiple domains (academic, behavior, close friends, broader peers, maternal relationship, paternal relationship). Having a diagnosis in early childhood predicted greater impairment in all domains in early adolescence, except paternal relationship. Externalizing disorders predicted impairment in more domains than internalizing disorders. Most of the associations between early childhood psychopathology and poorer functioning in adolescence persisted after taking into account adolescent psychopathology. Moreover, the majority of bivariate associations with depressive, ODD, and ADHD symptoms, but not anxiety symptoms, persisted in a subsample of children who did not meet criteria for a diagnosis in early childhood. Early childhood psychopathology has long-lasting deleterious effects on several domains of psychosocial functioning, often beyond the effects of continuing or recurring adolescent psychopathology. Findings thereby highlight the validity and clinical significance of early psychopathology.

Homotypic and heterotypic continuity of internalizing and externalizing symptoms from ages 3 to 12: The moderating role of diurnal cortisol.

Psychological symptoms that arise in early childhood can follow a multitude of patterns into adolescence, including homotypic continuity (i.e., similar symptoms over time) and heterotypic continuity (i.e., a shift in symptoms over time). However, we know very little about the factors that distinguish homotypic vs. heterotypic continuity of early internalizing and externalizing symptoms over development. In a separate line of research, diurnal cortisol has been shown to predict later internalizing and externalizing problems. In the current study, we tested whether diurnal cortisol patterns moderated the course of internalizing and externalizing symptoms from preschool to early adolescence. 554 children (54% male) and parents participated in a longitudinal study. Parents reported on their children's internalizing and externalizing symptoms at ages 3 and 12, and children collected diurnal saliva samples at age 9. Results showed that a steeper cortisol decline at age 9 combined with high internalizing or externalizing problems at age 3 predicted higher internalizing problems at age 12. A more blunted cortisol decline combined with early internalizing or externalizing problems predicted higher externalizing problems in early adolescence. These results illustrate the moderating role of stress system functioning in homotypic and heterotypic patterns of psychopathology from preschool to early adolescence.

Parenting style moderates the effects of exposure to natural disaster-related stress on the neural development of reactivity to threat and reward in children.

Little is known about the effect of natural disasters on children's neural development. Additionally, despite evidence that stress and parenting may both influence the development of neural systems underlying reward and threat processing, few studies have brought together these areas of research. The current investigation examined the effect of parenting styles and hurricane-related stress on the development of neural reactivity to reward and threat in children. Approximately 8 months before and 9 months after Hurricane Sandy, 74 children experiencing high and low levels of hurricane-related stress completed tasks that elicited the reward positivity and error-related negativity, event-related potentials indexing sensitivity to reward and threat, respectively. At the post-Hurricane assessment, children completed a self-report questionnaire to measure promotion- and prevention-focused parenting styles. Among children exposed to high levels of hurricane-related stress, lower levels of promotion-focused, but not prevention-focused, parenting were associated with a reduced post-Sandy reward positivity. In addition, in children with high stress exposure, greater prevention-focused, but not promotion-focused, parenting was associated with a larger error-related negativity after Hurricane Sandy. These findings highlight the need to consider contextual variables such as parenting when examining how exposure to stress alters the development of neural reactivity to reward and threat in children.

Hurricane Sandy Exposure Alters the Development of Neural Reactivity to Negative Stimuli in Children.

This study examined whether exposure to Hurricane Sandy-related stressors altered children's brain response to emotional information. An average of 8 months (Mage  = 9.19) before and 9 months after (Mage  = 10.95) Hurricane Sandy, 77 children experiencing high (n = 37) and low (n = 40) levels of hurricane-related stress exposure completed a task in which the late positive potential, a neural index of emotional reactivity, was measured in response to pleasant and unpleasant, compared to neutral, images. From pre- to post-Hurricane Sandy, children with high stress exposure failed to show the same decrease in emotional reactivity to unpleasant versus neutral stimuli as those with low stress exposure. Results provide compelling evidence that exposure to natural disaster-related stressors alters neural emotional reactivity to negatively valenced information.

Parental depressive history, parenting styles, and child psychopathology over 6 years: The contribution of each parent's depressive history to the other's parenting styles.

The link between parental depressive history and parenting styles is well established, as is the association of parenting with child psychopathology. However, little research has examined whether a depressive history in one parent predicts the parenting style of the other parent. As well, relatively little research has tested transactional models of the parenting-child psychopathology relationship in the context of parents' depressive histories. In this study, mothers and fathers of 392 children were assessed for a lifetime history of major depression when their children were 3 years old. They then completed measures of permissiveness and authoritarianism and their child's internalizing and externalizing symptoms when children were 3, 6, and 9 years old. The results showed that a depressive history in one parent predicted the other parent's permissiveness. Analyses then showed that child externalizing symptoms at age 3 predicted maternal permissiveness and authoritarianism and paternal permissiveness at age 6. Maternal permissiveness at age 6 predicted child externalizing symptoms at age 9. No relationships in either direction were found between parenting styles and child internalizing symptoms. The results highlight the importance of considering both parents' depressive histories when understanding parenting styles, and support transactional models of parenting styles and child externalizing symptoms.

The impact of an unpredictable context and intolerance of uncertainty on the electrocortical response to monetary gains and losses.

There is growing evidence that unpredictability and uncertainty can alter reward system functioning. The present study examined the impact of (1) a task-irrelevant unpredictable relative to predictable context and (2) individual differences in intolerance of uncertainty (IU) on the reward-related positivity (RewP), an event-related potential (ERP) response to monetary gains relative to losses. Specifically, 64 participants listened to predictable and unpredictable tone sequences while electroencephalography was recorded during a monetary gambling task. Participants also completed the Intolerance of Uncertainty Scale, which measures both cognitive distress (prospective IU) and behavioral inhibition (inhibitory IU) elicited by uncertainty, in addition to the Depression Anxiety Stress Scale-21 and Penn State Worry Questionnaire. Results indicated that the RewP was reduced during the unpredictable relative to the predictable context. Greater self-reported anxiety elicited by the unpredictable context was associated with a decreased RewP, and a decreased RewP was associated with poorer lose-shift behavioral adjustment. Furthermore, the RewP mediated the relationship between self-reported anxiety elicited by the unpredictable context and lose-shift behavioral adjustment. The IU subscales demonstrated the opposite relationship with the RewP across both contexts-inhibitory IU was associated with an attenuated RewP and prospective IU was associated with an enhanced RewP. In contrast, anxiety, depression, stress, and worry symptomatology were not associated with the RewP. This is the first study to demonstrate that an unpredictable context and individual differences in the degree to which people cannot tolerate uncertainty impact an ERP measure of reward system functioning.

Transdiagnostic factors and pathways to multifinality: The error-related negativity predicts whether preschool irritability is associated with internalizing versus externalizing symptoms at age 9.

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.

Neural reactivity to monetary rewards and losses differentiates social from generalized anxiety in children.

BACKGROUND: The relationship between reward sensitivity and pediatric anxiety is poorly understood. Evidence suggests that alterations in reward processing are more characteristic of depressive than anxiety disorders. However, some studies have reported that anxiety disorders are also associated with perturbations in reward processing. Heterogeneity in the forms of anxiety studied may account for the differences between studies. We used the feedback-negativity, an event-related potential sensitive to monetary gains versus losses (ΔFN), to examine whether different forms of youth anxiety symptoms were uniquely associated with reward sensitivity as indexed by neural reactivity to the receipt of positive and negative monetary outcomes. METHOD: Participants were 390, eight- to ten-year-old children (175 females) from a large community sample. The ΔFN was measured during a monetary reward task. Self-reports of child anxiety and depression symptoms and temperamental positive emotionality (PE) were obtained. RESULTS: Multiple regression analysis revealed that social anxiety and generalized anxiety symptoms were unique predictors of reward sensitivity after accounting for concurrent depressive symptoms and PE. While social anxiety was associated with a greater ΔFN, generalized anxiety was associated with a reduced ΔFN. CONCLUSIONS: Different symptom dimensions of child anxiety are differentially related to alterations in reward sensitivity. This may, in part, explain inconsistent findings in the literature regarding reward processing in anxiety.

Preschool irritability predicts child psychopathology, functional impairment, and service use at age nine.

BACKGROUND: Little is known about the predictive validity and clinical significance of chronic irritability during early childhood. This prospective, longitudinal study examined associations of preschool chronic irritability with psychiatric disorders, functional impairment, and service use at age nine in a large community sample. METHODS: Four hundred and forty-six children were assessed at age three and again at age nine. Child psychopathology and functional impairment were assessed at age three with the Preschool Age Psychiatric Assessment (PAPA) with parents and at age nine with the Kiddie-Schedule of Affective Disorders and Schizophrenia (K-SADS) with parents and children. Items from the PAPA were used to create a dimensional measure of chronic irritability at age three. At age nine, mothers, fathers, and youth completed the Child Depression Inventory (CDI) and the Screen for Anxiety Related Disorders (SCARED). RESULTS: Chronic irritability at age three predicted any current and lifetime anxiety disorders at age nine, current and lifetime generalized anxiety disorder, and current separation anxiety, after controlling for baseline anxiety disorders. In addition, preschool irritability predicted increases in anxiety and disruptive behavior disorder symptoms on the K-SADS, and maternal and paternal reports of depressive and anxiety symptoms on the CDI and SCARED. Lastly, preschool irritability predicted greater functional impairment and outpatient treatment use, even after controlling for all psychiatric disorders at baseline. CONCLUSIONS: Findings underscore the central role of irritability in developmental psychopathology and support the importance of early detection and interventions targeting preschool irritability.

Longitudinal Associations Between Reward Responsiveness and Depression Across Adolescence.

OBJECTIVE: Lower neural response to reward predicts subsequent depression during adolescence. Both pubertal development and biological sex have important effects on reward system development and depression during this period. However, relations among these variables across the transition from childhood to adolescence are not well characterized. METHOD: Depressive symptoms, pubertal status, and the reward positivity (RewP) event-related potential component, a neural indicator of reward responsivity, were assessed in 609 community-recruited youth at 9, 12, and 15 years of age. Structural equation modeling was used to examine concurrent and prospective relations within and between depression and reward responsiveness as well as the influence of pubertal status and biological sex on these variables across assessments. RESULTS: Stability paths for depression, the RewP, and pubertal status were significant across assessments. Compared with male participants, female participants reported more advanced pubertal status at all assessments, a smaller RewP at age 9, and higher levels of depression at age 15. More advanced pubertal status was associated with a larger RewP at age 15. Most importantly, there were bidirectional prospective effects between the RewP and depression from ages 12 to 15; a lower RewP at age 12 predicted increases in depression at age 15, whereas increased depression at age 12 predicted a lower RewP at age 15. CONCLUSION: These findings indicate that there are bidirectional prospective effects between reward responsiveness and depression that emerge between ages 12 and 15. This may be a crucial time for studying bidirectional reward responsiveness-depression associations across time.

A Transdiagnostic Perspective on Youth Irritability.

Irritability is increasingly recognized as a significant clinical problem in youth. It is a criterion for multiple diagnoses and predicts the development of a wide range of disorders. Research on etiopathogenesis suggests that genetic and family environmental factors play a role, as do abnormalities in reward and cognitive control circuitry. However, many of these effects are age dependent. Threat-responsive self-regulatory systems and the degree to which irritability manifests as tonic or phasic influence whether irritable youth exhibit more internalizing versus externalizing outcomes.

Early Predictors of Adolescent Irritability.

Limited research has examined precursors/risk factors for adolescent irritability. This study examines continuity of irritability from early childhood to adolescence and identifies antecedents of adolescent irritability. Across self-reports and mother-reports, evidence was found for continuity of irritability. A range of variables assessed at age 3 predicted irritability at age 15. These findings suggest that adolescent irritability is characterized by distinct developmental pathways from age 3 that have potential to result in an irritable phenotype at age 15. Adolescent-reported and mother-reported irritability may be capturing distinct underlying constructs of irritability; both should be considered in assessments of adolescent irritability.

Effects of Maternal Depression and Mother-Child Relationship Quality in Early Childhood on Neural Reactivity to Rejection and Peer Stress in Adolescence: A 9-Year Longitudinal Study.

Problems in mother-child relationships are thought to be key to intergenerational transmission of depression. To evaluate neural and behavioral processes involved in these pathways, we tested effects of maternal depression and maternal-child relationship quality in early childhood on neural and interviewer-based indicators of social processes in adolescence. At age 3, children and mothers (N=332) completed an observational parenting measure and diagnostic interviews with mothers. At age 12, adolescents completed a task in which event-related potentials (ERPs) were recorded to peer acceptance and rejection feedback and interviews to assess peer stress. Lower mother-child relationship quality at age 3 was associated with enhanced reactivity to rejection, as measured by N1, and greater peer stress at age 12. Indirect effects of maternal depression through mother-child relationship quality were observed for N1 and peer stress. Findings inform understanding of disruptions in social functioning that are likely relevant to the intergenerational transmission of depression.

Stability and change in emotional processing across development: A 6-year longitudinal investigation using event-related potentials.

ERPs reveal the temporal dynamics of emotional processing and are easily assessed in children. Yet, little longitudinal research has examined ERPs sensitive to emotion across development. We aimed to systematically identify timing and spatial distributions of ERPs sensitive to emotion in a longitudinal sample of youth (N = 62) using principal component analysis (PCA) and evaluate stability and change in emotional responses across development. Participants completed an emotional interrupt paradigm in childhood (Mage  = 9.38, SD = 0.42), early adolescence (Mage  = 13.03, SD = 0.24), and midadolescence (Mage  = 15.16, SD = 0.17). ERPs were recorded to unpleasant, pleasant, and neutral images. Participants were instructed to respond to a target while viewing images. Two components sensitive to emotion emerged across development: P300/early late positive potential (LPP) and late LPP. The P300/early LPP component was characterized by an enhanced positivity for unpleasant compared to pleasant and neutral images. The late LPP was enhanced for both unpleasant and pleasant compared to neutral images, and more positive for unpleasant compared to pleasant images. The components showed moderate to strong stability. Overall LPP magnitude decreased from childhood into adolescence. There was a developmental shift in distributions from occipital sites in childhood to centroparietal sites in midadolescence. Results support use of PCA to inform scoring windows and electrode selection. The shift in distribution may reflect developmental focalization in underlying neural circuitry. Future work is needed using multimodal approaches to further understand the relationship between ERPs and changes in neural circuitry across development.

Sensitivity to Peer Feedback in Young Adolescents with Symptoms of ADHD: Examination of Neurophysiological and Self-Report Measures.

Many youth with ADHD experience peer difficulties, but the mechanisms underlying this dysfunction remain unknown. Very little work has examined neurophysiological measures of social feedback processing in relation to ADHD symptoms. The goal of this study was to examine associations of ADHD symptoms with indicators of sensitivity to social feedback in a laboratory task and self-report of rejection sensitivity. A large community sample of 10- to 15-year-old adolescents (N = 391; Mage = 12.64, 48.6% girls) participated in the study. Mothers rated youth ADHD symptoms. Youth completed the Island Getaway task, which elicits neurophysiological (i.e., event-related potentials [ERP]) measures of sensitivity to peer rejection and acceptance feedback, and also completed self-ratings of rejection sensitivity. Greater ADHD symptoms were associated with an enhanced N1 ERP component, which correlated with higher levels of self-reported rejection sensitivity. In addition, greater ADHD symptoms were associated with reduced reactivity to social acceptance, as measured by the later reward positivity ERP component. Youth with elevated ADHD symptoms exhibited enhanced sensitivity to peer rejection at the neurophysiological and self-report level, as well as reduced neurophysiological reactivity to peer acceptance. Future work including neural measures of social functioning may serve to elucidate mechanisms underlying the social dysfunction characteristic of ADHD.

Depression symptom dimensions and asymmetrical frontal cortical activity while anticipating reward.

Unipolar depression has been characterized as involving diminished approach motivation and reward sensitivity. A psychophysiological indicator of approach motivation involves an asymmetry in frontal EEG activity, such that greater left relative to right frontal cortical activity indicates increased approach motivation. Consistent with the perspective of reduced approach motivation tendencies, depression has been associated with decreased relative left frontal cortical activity. To date, supporting research has primarily relied on categorical diagnoses or composite symptom counts. However, given the heterogeneity in depression, it is unclear what specific symptom dimensions relate to decreased relative left frontal cortical activity. The present study examined the association between multiple depression symptom dimensions and asymmetrical frontal cortical activity while anticipating reward in separate undergraduate (n = 75) and clinical samples (current major depressive disorder [n = 68] and never depressed controls [n = 67]). All participants completed the Inventory of Depression and Anxiety Symptoms, a self-report measure of factor-analytically derived symptom dimensions. Frontal cortical activity was assessed during a computerized slot machine task while participants anticipated potential monetary reward or no incentive. In undergraduates with low depression symptoms and never depressed controls, reward trials relative to no-incentive trials elicited greater relative left frontal cortical activity. Furthermore, in both samples across all participants, increased dysphoria and lassitude symptoms were associated with decreased relative left frontal cortical activity while anticipating reward. The present study suggests that depression symptoms consistent with motivational disengagement are associated with decreased relative left frontal cortical activity.