Irritability in Youths: A Critical Integrative Review.

Irritability, defined as proneness to anger that may impair an individual's functioning, is common in youths. There has been a recent upsurge in relevant research. The authors combine systematic and narrative review approaches to integrate the latest clinical and translational findings and provide suggestions for addressing research gaps. Clinicians and researchers should assess irritability routinely, and specific assessment tools are now available. Informant effects are prominent, are stable, and vary by age and gender. The prevalence of irritability is particularly high among individuals with attention deficit hyperactivity disorder, autism spectrum disorder, and mood and anxiety disorders. Irritability is associated with impairment and suicidality risk independent of co-occurring diagnoses. Developmental trajectories of irritability (which may begin early in life) have been identified and are differentially associated with clinical outcomes. Youth irritability is associated with increased risk of anxiety, depression, behavioral problems, and suicidality later in life. Irritability is moderately heritable, and genetic associations differ based on age and comorbid illnesses. Parent management training is effective for treating psychological problems related to irritability, but its efficacy in treating irritability should be tested rigorously, as should novel mechanism-informed interventions (e.g., those targeting exposure to frustration). Associations between irritability and suicidality and the impact of cultural context are important, underresearched topics. Analyses of large, diverse longitudinal samples that extend into adulthood are needed. Data from both animal and human research indicate that aberrant responses to frustration and threat are central to the pathophysiology of irritability, revealing important translational opportunities.

Adolescent Substance Use Patterns and Risk for Suicidal Thoughts and Behaviors in Young Adulthood.

OBJECTIVE: There is strong evidence that substance use is a risk factor for suicidality. Prior studies have focused on the suicide risk associated with using individual substances, even though substance users often use more than one substance. This study investigates the association between patterns of adolescent substance use and suicidality in young adulthood. METHOD: Participants were U.S. adolescents (n = 2,111, 58.9% female, mean age = 16.31 years) from the NEXT Generation Health Study, which followed tenth graders for 7 years (2009/2010-2016) and collected data via yearly surveys. Longitudinal latent class analysis was used to identify high school patterns of substance use, and logistic regression was used to relate these patterns to risk of suicidality in young adulthood. RESULTS: We identified two groups of adolescents: "non-/infrequent users" (71%) and "multiple substance users" (29%). Multiple substance users had higher odds of making a suicide plan or attempt in young adulthood (odds ratio [OR] = 2.41, 95% CI [1.05, 5.53]), but not suicidal ideation (OR = 1.55, 95% CI [0.80, 2.99]), than non-/infrequent users, adjusting for sociodemographic factors and depressive symptoms. Multiple substance users with suicidal ideation were not more likely to progress to a later plan or attempt (OR = 1.41, 95% CI [0.41, 4.84]) than non-/infrequent users. CONCLUSIONS: Adolescents who use substances in high school are at higher risk for making a suicide plan or attempt in young adulthood. Early identification of these adolescents may help inform interventions to mitigate risk for suicidal behaviors in young adulthood.

Children's cognitive performance and suicide risk through middle adulthood.

BACKGROUND: Longitudinal studies show that lower cognitive performance in adolescence and early adulthood is associated with higher risk of suicide death throughout adulthood. However, it is unclear whether this cognitive vulnerability originates earlier in childhood since studies conducted in children are scarce and have inconsistent results. METHODS: Vital status of 49,853 individuals born between 1959 and 1966 to participants in the Collaborative Perinatal Project cohort was determined by a probabilistic linkage to the National Death Index, covering all US deaths occurring from 1979 through 2016. Cox proportional hazard models were used to examine associations of general, verbal, and non-verbal intelligence at ages 4 and 7, and academic skills at age 7 with suicide death coded according to ICD-9/10 criteria, while accounting for sociodemographic and pregnancy factors previously associated with suicide in this sample. RESULTS: By the end of 2016, 288 cohort members had died by suicide. Cognitive performance at 7 years on tests with verbal components was associated with suicide risk (average vs. high verbal intelligence, HR = 1.97, 95% CI 1.05-3.71; low vs. high spelling skills, HR = 2.02, 95% CI 1.16-3.51; low vs. high reading skills, HR = 2.01, 95% CI 1.27-3.17). Associations were still evident, especially for verbal intelligence and reading skills, but hazard ratios were attenuated after adjusting for prenatal and sociodemographic factors at birth (verbal intelligence, HR = 1.97, 95% CI 1.03-3.78; spelling, HR = 1.61, 95% CI 0.90-2.88; reading, HR = 1.67, 95% CI 1.02-2.72). CONCLUSIONS: Childhood neurocognitive performance is associated with vulnerability to suicide mortality through middle-adulthood, suggesting that there might be a cognitive diathesis for suicide originating in early childhood. Future studies should examine how multiple domains of childhood cognitive performance contribute to vulnerability to suicide risk, including by increasing risk for social and environmental factors that are associated not only with suicide but also with many types of psychiatric disorders.

Editorial: The Paradox of Reward Processing in the Association Between Irritability and Depression.

Irritability as part of depression has been studied for a long time; it was a cardinal symptom in Burton's concept of melancholia and an underlying mechanism toward oneself in Freud's description of melancholia. Today, irritability is considered a cardinal symptom of depression in children and adolescents by DSM-5, along with depressed mood and anhedonia, and is present in about 40% of youth with depression. Longitudinally, irritability has been shown to be a specific predictor of depression across development in several studies.1 The mechanisms underlying the close relationship between irritability and depression are unclear, but most evidence points to shared risk factors, including genetic risk, family history of depression, early temperament and personality, and parenting styles.2 However, other plausible shared mechanisms, especially those involving neural circuits, have been undertested.

Longitudinal associations between positive attributes and psychopathology and their interactive effects on educational outcomes.

Psychopathology is associated with impaired learning and early termination of schooling, whereas positive attributes are associated with better educational outcomes. However, it is important to understand if and how psychopathology and positive attributes longitudinally impact each other so we could shed light on where to intervene to promote educational outcomes through these constructs. A large prospective school-based community cohort of youths (5-15 years of age, 45% female) were assessed and followed up for 3 years (n = 2010; 80% retention). We assessed the longitudinal impact of positive attributes (Youth Strength Inventory) and psychopathology (bifactor model of Strengths and Difficulties Questionnaire) using a cross-lagged panel model. We also used generalized mixed effects models to investigate how these both constructs predict school dropout and literacy, adjusting for confounders and testing their interaction. Positive attributes negatively predicted, and were negatively predicted by, the general factor of psychopathology and conduct problems in the cross-lagged panel model. Positive attributes (OR = 0.57, 95% CI [0.44, 0.73], p < 0.001) and specific conduct symptoms (OR = 2.33, 95% CI [1.64, 3.33], p < 0.001) predicted school dropout, whereas the general factor of psychopathology predicted lower literacy ability (ß = - 0.08, 95% CI [- 0.11, - 0.05], p < 0.001). However, the protective association of positive attributes on school dropout decreases as the general factor of psychopathology increases. These findings provide new evidence that positive attributes and psychopathology mutually influence each other over development and have interactive effects on educational outcomes.

Adverse childhood experiences and premature mortality through mid-adulthood: A five-decade prospective study.

Background: Adverse childhood experiences (ACEs) can have lasting effects on adult health and survival. In this study, we aimed to examine how the cumulative number and clustering patterns of ACEs were related to premature mortality. Methods: Participants (N=46 129; 45% White, 48% Black; 49·5% females) were offspring (born in 1959-1966) of participants enrolled in the Collaborative Perinatal Project (CPP). We conducted latent class analysis to examine the clustering patterns of ACEs assessed between children's birth and age seven. We also calculated the cumulative ACE scores of 13 individual ACEs. Cox regression models were used to examine the associations of ACE clusters and scores with risk of premature mortality from adolescence to mid-adulthood. Findings: At the start of the follow-up for mortality in 1979, participants were 12-20 years old (Mean=15·99 years), and within the 38-year follow-up through 2016, 3 344 deaths were observed among the 46 129 CPP offspring. Five latent classes of ACEs were identified. Compared to children with Low Adversity (48% of the sample), children in Family Instability (9%, HR=1·28, 95%CI 1·07-1·53), Poverty & Crowded Housing (21%, HR=1·41, 95%CI 1·24-1·62), and Poverty & Parental Separation (19%, HR=1·50, 95%CI 1·33-1·68) classes had higher hazards of premature mortality. In addition, children with 2 (HR=1·27, 95%CI 1·14-1·41), 3 (HR=1·29, 95%CI 1·15-1·45), and 4+ (HR=1·45, 95%CI 1·30-1·61) ACEs had higher hazards of mortality than those with no ACE. The clusters of Poverty & Crowded Housing (HR=1·28, 95%CI 1·10-1·49) and Poverty & Parental Separation (HR=1·23, 95%CI 1·02-1·48) remained associated with higher risk of premature mortality, beyond the cumulative risk of higher number of ACEs (HR=1·05, 95%CI 1·01-1·08). Interpretation: About half of the CPP cohort experienced early life adversities that clustered into four distinct patterns, which were associated with different risk of premature mortality. It is important to deepen our understanding of how specific clusters of childhood adversities affect health and premature mortality to better inform approaches to prevention and interventions.

The developmental origins of suicide mortality: a systematic review of longitudinal studies.

Suicide prevention efforts generally target acute precipitants of suicide, though accumulating evidence suggests that vulnerability to suicide is partly established early in life before acute precipitants can be identified. The aim of this systematic review was to synthesize evidence on early life vulnerability to suicide beginning in the prenatal period and extending through age 12. We searched PubMed, Embase, PsycNet, Web of Science, Scopus, Social Services Abstracts, and Sociological Abstracts for prospective studies published through January 2021 that investigated early life risk factors for suicide mortality. The search yielded 13,237 studies; 54 of these studies met our inclusion criteria. Evidence consistently supported the link between sociodemographic (e.g., young maternal age at birth, low parental education, and higher birth order), obstetric (e.g., low birth weight), parental (e.g., exposure to parental death by external causes), and child developmental factors (e.g., exposure to emotional adversity) and higher risk of suicide death. Among studies that also examined suicide attempt, there was a similar profile of risk factors. We discuss a range of potential pathways implicated in these associations and suggest that additional research be conducted to better understand how early life factors could interact with acute precipitants and increase vulnerability to suicide.

Prenatal origins of suicide mortality: A prospective cohort study in the United States.

Most suicide research focuses on acute precipitants and is conducted in high-risk populations. Yet, vulnerability to suicide is likely established years prior to its occurrence. In this study, we aimed to investigate the risk of suicide mortality conferred by prenatal sociodemographic and pregnancy-related factors. Offspring of participants (N = 49,853) of the Collaborative Perinatal Project, a U.S. population-based cohort of pregnancies enrolled between 1959 and 1966, were linked to the U.S. National Death Index to determine their vital status by the end 2016. We examined associations between sociodemographic factors during pregnancy, pregnancy complications, labor and delivery complications, and neonatal complications with suicide death coded according to ICD-9/10 criteria. By the end of 2016, 3,555 participants had died. Of these, 288 (214 males, 74 females) died by suicide (incidence rate = 15.6 per 100,000 person-years, 95% Confidence Interval [CI] = 13.9-17.5). In adjusted models, male sex (Hazard Ratio [HR] = 2.98, CI: 2.26-3.93), White race (HR = 2.14, CI = 1.63-2.83), low parental education (HR = 2.23, CI = 1.38-3.62), manual parental occupation (HR = 1.38, CI = 1.05-1.82), being a younger sibling (HR = 1.52, CI = 1.10-2.11), higher rates of pregnancy complications (HR = 2.36, CI = 1.08-5.16), and smoking during pregnancy (HR = 1,28, CI = 0.99-1.66) were independently associated with suicide risk, whereas birth and neonatal complications were not. Consistent with the developmental origins of psychiatric disorders, vulnerability to suicide mortality is established early in development. Both sociodemographic and pregnancy factors play a role in this risk, which underscores the importance of considering life course approaches to suicide prevention, possibly including provision of high-quality prenatal care, and alleviating the socioeconomic burdens of mothers and families.

How and Why Are Irritability and Depression Linked?

Based on its course over time, irritability is linked to depression cross-sectionally and longitudinally. Cross-sectionally, irritability takes an episodic form as a symptom in pediatric depression; yet, irritability in the absence of depressed mood or anhedonia is rare. Longitudinally, chronic irritability has been shown to predict depression rather than bipolar disorder or externalizing disorders. Evidence suggests that the link between irritability and depression is explained mostly by shared genetic risk. Both conditions are also associated with higher rates of family history of depression, childhood temperaments and personality styles, and negative parenting styles. The treatment implications are discussed.

Editorial: Moving From Concept to Proof in the Distinction Between Phasic and Tonic Irritability.

In child and adolescent psychiatry, irritability is listed as a cardinal or associated symptom in nearly every emotional, behavioral, and neurodevelopmental disorder in the DSM-5. Despite the omnipresence of irritability in distinct psychiatric disorders, its manifestation is highly heterogeneous, across and within individuals. Part of that heterogeneity has to do with its temporal dynamics. Specifically, irritability has been conceptualized as having 2 components, termed phasic and tonic irritability.1 Phasic irritability has been defined as relatively short-lived temper outbursts of intense anger that can be accompanied by verbal or physical aggression, whereas tonic irritability has been defined as persistently angry or grumpy mood. Despite this conceptual distinction, it is still unclear whether phasic and tonic irritability might differ in their clinical correlates, underlying mechanisms, longitudinal course, and/or treatment response.

Resilience Factors in the Association Between Depressive Symptoms and Suicidality.

PURPOSE: To investigate whether life satisfaction and optimism might reduce the risk of suicidal thoughts and behaviors among adolescents with depressive symptoms. METHODS: Participants were 1,904 youth from the NEXT Generation Health Study, a national sample of U.S. adolescents, followed over 7 years from 2009/2010 to 2015/2016. Longitudinal latent profile analysis and logistic regressions were conducted. RESULTS: We identified three subgroups of adolescents with different patterns of depressive symptoms across the first six waves: "Low" (40%), "Mild" (42%), and "Moderate to Severe" (18%). The Moderate to Severe (OR = 14.47, 95% CI [6.61, 31.66]) and Mild (OR = 3.90, 95% CI [2.22, 6.86]) depression profiles had significantly higher odds of developing suicidality than the Low depression profile. Both life satisfaction and optimism moderated the association between depressive symptom profile and suicidality. The difference in suicidality risk between the Mild and Low depression profiles was significantly attenuated at high versus low levels of life satisfaction, with a difference of -.08, 95% CI [-.14, -.03]. In addition, the difference in suicidality risk between the Moderate to Severe and Low depression profiles was attenuated at high versus low levels of optimism, with a difference of -.11, 95% CI [-.21, -.01]. CONCLUSIONS: For adolescents transitioning to young adulthood, resilience factors such as life satisfaction and optimism may buffer against suicidality risk in the face of mild or moderate to severe depressive symptoms.

Multimodal Neuroimaging of Suicidal Thoughts and Behaviors in a U.S. Population-Based Sample of School-Age Children.

OBJECTIVE: Suicide deaths and suicidal thoughts and behaviors are considered a public health emergency, yet their underpinnings in the brain remain elusive. The authors examined the classification accuracy of individual, environmental, and clinical characteristics, as well as multimodal brain imaging correlates, of suicidal thoughts and behaviors in a U.S. population-based sample of school-age children. METHODS: Children ages 9-10 years (N=7,994) from a population-based sample from the Adolescent Brain Cognitive Development study were assessed for lifetime suicidal thoughts and behaviors. After quality control procedures, structural MRI (N=6,238), resting-state functional MRI (N=4,134), and task-based functional MRI (range, N=4,075-4,608) were examined. Differences with Welch's t test and equivalence tests, with observed effect sizes (Cohen's d) and their 90% confidence intervals <|0.15|, were examined. Classification accuracy was examined with area under precision-recall curves (AUPRCs). RESULTS: Among the 7,994 unrelated children (females, N=3,757, 47.0%), those with lifetime suicidal thoughts and behaviors based on child (N=684, 8.6%), caregiver (N=654, 8.2%), and concordant (N=198, 2.5%) reports had higher levels of social adversity and psychopathology, among themselves and their caregivers, compared with never-suicidal children (N=6,854, 85.7%). Only one imaging test survived statistical correction: caregiver-reported suicidal thoughts and behaviors were associated with a thinner left bank of the superior temporal sulcus. On the basis of the prespecified bounds of |0.15|, approximately 48% of the group mean differences for child-reported suicidal thoughts and behaviors comparisons and approximately 22% for caregiver-reported suicidal thoughts and behaviors comparisons were considered equivalent. All observed effect sizes were relatively small (d≤|0.30|), and both non-imaging and imaging correlates had low classification accuracy (AUPRC ≤0.10). CONCLUSIONS: Commonly applied neuroimaging measures did not reveal a discrete brain signature related to suicidal thoughts and behaviors in youths. Improved approaches to the neurobiology of suicide are critically needed.

Great Expectations: A Critical Review of and Suggestions for the Study of Reward Processing as a Cause and Predictor of Depression.

Both human and animal studies support the relationship between depression and reward processing abnormalities, giving rise to the expectation that neural signals of these processes may serve as biomarkers or mechanistic treatment targets. Given the great promise of this research line, we scrutinized those findings and the theoretical claims that underlie them. To achieve this, we applied the framework provided by classical work on causality as well as contemporary approaches to prediction. We identified a number of conceptual, practical, and analytical challenges to this line of research and used a preregistered meta-analysis to quantify the longitudinal associations between reward processing abnormalities and depression. We also investigated the impact of measurement error on reported data. We found that reward processing abnormalities do not reach levels that would be useful for clinical prediction, yet the available evidence does not preclude a possible causal role in depression.

The Role of Paternal Accommodation of Paediatric OCD Symptoms: Patterns and Implications for Treatment Outcomes.

Family accommodation (FA) refers to the participation of family members in obsessive-compulsive disorder (OCD) rituals. Most studies have focused on maternal accommodation; consequently, little is known about fathers' accommodation of OCD. The current study aims to extend the existing literature by examining maternal versus paternal accommodation of OCD symptoms.The sample consisted of 209 children with OCD (Mean [M] age = 14.1 years) and their parents (NMothers = 209, NFathers = 209) who had completed the Family Accommodation Scale- Parent Report (FAS-PR). Paired t-test and chi-square analyses were used to compare FA of OCD symptoms between mothers and fathers. Linear regression was used to examine correlates of maternal and paternal FA and its impact on treatment outcomes.Mothers reported significantly higher levels of daily FA than fathers. Correlates of maternal and paternal accommodation included OCD symptom severity, emotional and behavioral difficulties, and parent psychopathology. Both maternal and paternal FA significantly predicted worse treatment outcomes.Both mothers and fathers accommodate child OCD symptoms with high frequency, and in similar ways. Although mothers accommodate to a greater extent than fathers, both maternal and paternal involvement in rituals are a significant predictor of the child's treatment response. Results emphasise the need to consider the whole family system, including fathers, in understanding and treating OCD in children.

Associations between brain activity and endogenous and exogenous cortisol - A systematic review.

To arrive at a coherent understanding of the relation between glucocorticoids and the human brain, we systematically reviewed the literature for studies examining the associations between endogenous or exogenous cortisol and human brain function. Higher levels of endogenous cortisol during psychological stress were related to increased activity in the middle temporal gyrus and perigenual anterior cingulate cortex (ACC), decreased activity in the ventromedial prefrontal cortex, and altered function (i.e., mixed findings, increased or decreased) in the amygdala, hippocampus and inferior frontal gyrus. Moreover, endogenous cortisol response to psychological stress was related to increased activity in the inferior temporal gyrus and altered function in the amygdala during emotional tasks that followed psychological stress. Exogenous cortisol administration was related to increased activity in the postcentral gyrus, superior frontal gyrus and ACC, and altered function in the amygdala and hippocampus during conditioning, emotional and reward-processing tasks after cortisol administration. These findings were in line with those from animal studies on amygdala activity during and after stress.

A Double-Blind Randomized Placebo-Controlled Trial of Citalopram Adjunctive to Stimulant Medication in Youth With Chronic Severe Irritability.

OBJECTIVE: Despite the clinical importance of chronic and severe irritability, there is a paucity of controlled trials for its pharmacological treatment. Here, we examine the effects of adding citalopram (CTP) to methylphenidate (MPH) in the treatment of chronic severe irritability in youth using a double-blind randomized placebo-controlled design. METHOD: After a lead-in phase of open treatment with stimulant, 53 youth meeting criteria for severe mood dysregulation (SMD) were randomly assigned to receive CTP or placebo (PBO) for 8 weeks. A total of 49 participants, 48 of them (98%) meeting disruptive mood dysregulation disorder (DMDD) criteria, were included in the intent-to-treat analysis. The primary outcome measure was the proportion of response based on improvements of irritability at the week 8 of the trial. RESULTS: At the end of the trial, a significantly higher proportion of response was seen in those participants randomly assigned to CTP+MPH compared to PBO+MPH (35% CTP+MPH versus 6% PBO+MPH; odds ratio = 11.70, 95% CI = 2.00-68.16, p = 0.006). However, there were no differences in functional impairment between groups at the end of the trial. No differences were found in any adverse effect between treatment groups, and no trial participant exhibited hypomanic or manic symptoms. CONCLUSION: Adjunctive CTP might be efficacious in the treatment of chronic severe irritability in youth resistant to stimulant treatment alone. CLINICAL TRIAL REGISTRATION INFORMATION: A Controlled Trial of Serotonin Reuptake Inhibitors Added to Stimulant Medication in Youth With Severe Mood Dysregulation; https://clinicaltrials.gov; NCT00794040.

Bidirectional Associations Between Stress and Reward Processing in Children and Adolescents: A Longitudinal Neuroimaging Study.

BACKGROUND: Aberrations in both neural reward processing and stress reactivity are associated with increased risk for mental illness; yet, how these two factors relate to each other remains unclear. Several studies suggest that stress exposure impacts reward function, thus increasing risk for psychopathology. However, the alternative hypothesis, in which reward dysfunction impacts stress reactivity, has been rarely examined. The current study aimed to test both hypotheses using a longitudinal design. METHODS: Participants were 38 children (23 girls; 61%) from a prospective cohort study. A standard stress-exposure measure was collected at 7 years of age. Children performed a well-validated imaging reward paradigm at age 10, and a standardized acute psychological stress laboratory protocol was administered both at age 10 and at age 13. Structural equation modeling was used to examine bidirectional associations between stress and neural response to reward anticipation. RESULTS: Higher exposure to stressful life events at age 7 predicted lower neural response to reward anticipation in regions of the basal ganglia at age 10, which included ventral caudate, nucleus accumbens, putamen, and globus pallidus. Lower response to reward anticipation in medial prefrontal and anterior cingulate cortex predicted higher stress reactivity at age 13. CONCLUSIONS: Our findings provide support for bidirectional associations between stress and reward processing, in that stress may impact reward anticipation, but also in that reduced reward anticipation may increase susceptibility to stress.

Probing the Irritability-Suicidality Nexus.

Suicide is a major public health concern.1 Although still rare in absolute numbers, suicide is the second cause of death in adolescents and seems to be on the rise.2 One of the strongest risk factors for suicide is suicidality (ie, suicide ideation and attempts) alongside depression, substance abuse and, of course, access to lethal means.3-5 Identifying modifiable early predictors of suicidality and suicide should therefore be a priority for mental health researchers. In this issue of the Journal, Orri et al. examine whether distinct childhood trajectories of irritability, one of the most common symptoms across psychiatric disorders in youth, are associated with suicidality in adolescence.6.

Deficits in emotion recognition are associated with depressive symptoms in youth with disruptive mood dysregulation disorder.

BACKGROUND: Although severe irritability is a predictor of future depression according to recent meta-analytic evidence, other mechanisms for this developmental transition remain unclear. In this study, we test whether deficits in emotion recognition may partially explain this specific association in youth with severe irritability, defined as disruptive mood dysregulation disorder (DMDD). METHODS: Participants aged 8-20 years (M = 13.3, SD = 2.8) included youth with DMDD, split by low depressive (DMDD/LD; n = 52) and high depressive (DMDD/HD; n = 25) symptoms, and healthy controls (HC; n = 39). A standardized computer task assessed emotion recognition of faces and voices of adults and children expressing happiness, fear, sadness, and anger. A Group (3) × Emotion (4) × Actor (2) × Modality (2) repeated measures analysis of covariance examined the number of errors and misidentification of emotions. Linear regression was then used to assess whether deficits in emotion recognition were predictive of depressive symptoms at a 1 year follow-up. RESULTS: DMDD/HD youth were more likely to interpret happy stimuli as angry and fearful compared to DMDD/LD (happy as angry: p = 0.018; happy as fearful: p = 0.008) and HC (happy as angry: p = 0.014; happy as fearful: p = 0.024). In youth with DMDD, the misidentification of happy stimuli as fearful was associated with higher depressive symptoms at follow-up (ß = 0.43, p = 0.017), independent of baseline depressive and irritability symptoms. CONCLUSIONS: Deficits in emotion recognition are associated, cross-sectionally and longitudinally, with depressive symptoms in youth with severe irritability. Future studies should examine the neural correlates that contribute to these associations.

Reward Processing in Depression: A Conceptual and Meta-Analytic Review Across fMRI and EEG Studies.

OBJECTIVE: A role for aberrant reward processing in the pathogenesis of depression has long been proposed. However, no review has yet examined its role in depression by integrating conceptual and quantitative findings across functional MRI (fMRI) and EEG methodologies. The authors quantified these effects, with an emphasis on development. METHOD: A total of 38 fMRI and 12 EEG studies were entered into fMRI and EEG meta-analyses. fMRI studies primarily examined reward anticipation and reward feedback. These were analyzed using the activation likelihood estimation method. EEG studies involved mainly the feedback-related negativity (FRN) event-related potential, and these studies were analyzed using random-effects meta-analysis of the association between FRN and depression. RESULTS: Analysis of fMRI studies revealed significantly reduced striatal activation in depressed compared with healthy individuals during reward feedback. When region-of-interest analyses were included, reduced activation was also observed in reward anticipation, an effect that was stronger in individuals under age 18. FRN was also significantly reduced in depression, with pronounced effects in individuals under age 18. In longitudinal studies, reduced striatal activation in fMRI and blunted FRN in EEG were found to precede the onset of depression in adolescents. CONCLUSIONS: Taken together, the findings show consistent neural aberrations during reward processing in depression, namely, reduced striatal signal during feedback and blunted FRN. These aberrations may underlie the pathogenesis of depression and have important implications for development of new treatments.