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.

Editors' Note: Third Annual Report Regarding JAACAP's Antiracist Journey.

In 2020, we wrote to you of our dedication and vision for JAACAP "to be antiracist at every level."1 Over the last 3 years, we have pursued initiatives "to reshape the Journal to pursue this vision."2,3 In this article, we provide an update on these goals and initiatives (Figure 1). With the launching of our new open access journal, JAACAP Open,4 in late 2022, we now extend these initiatives to both scientific journals in the JAACAP family and aspire to be a leader among mental health journals in our intentional pursuit of antiracist policies and practices.

10 Lessons Learned in Launching a Division-Wide Measurement-Based Care Initiative.

Mental health problems are a major source of morbidity and mortality for children and adolescents, affecting 15% to 20% of those under 18 years of age in the US.1 Half of all mental health conditions start by age 14 years, although most cases remain undetected and untreated.2 Despite knowing much about mental health conditions affecting children, many speculate that the lack of standardized approaches to patient care contribute to poor outcomes, including substantial diagnostic variation, few remissions, risk for relapse or recidivism, and, ultimately, greater mortality due to an inability to accurately predict who will make a suicide attempt.3-5 Studies support this over-reliance on the "art of medicine" (ie, subjective judgment without use of standardized measures), finding that only 17.9% of psychiatrists and 11.1% of psychologists in the US routinely administer symptom rating scales to their patients, despite studies suggesting that when using clinical judgment alone, mental health providers detect deterioration for only 21.4% of patients.4.

Neural activation to peer acceptance and rejection in relation to concurrent and prospective depression risk in adolescent and pre-adolescent girls.

Neurobiological sensitivity to peer interactions is a proposed marker of risk for adolescent depression. We investigated neural response to peer rejection and acceptance in relation to concurrent and prospective depression risk in adolescent and pre-adolescent girls. Participants were 76 girls (Mage=13, 45% racial/ethnic minorities) varying in depression risk: 22 with current major depressive disorder (MDD), 30 at High Risk for MDD based on parental history, and 24 at Low Risk with no psychiatric history. Girls participated in the Chatroom-Interact task-involving rejection and acceptance feedback from fictitious peers-while undergoing functional magnetic resonance neuroimaging. Activation in response to peer rejection and acceptance was extracted from regions of interest. Depressive symptoms were assessed at 6- and 12-month follow-up. Girls with MDD showed blunted left subgenual anterior cingulate response to acceptance versus girls in High and Low Risk groups. Girls in the High Risk group showed greater right temporo-parietal junction (rTPJ) and right anterior insula (AI) activation to both acceptance and rejection versus girls in the MDD (rTPJ) and Low Risk (rTPJ, AI) groups. Greater rTPJ response to rejection was associated with fewer depressive symptoms at 12-months and mediated the association between High Risk group status and 12-month depressive symptoms; greater rTPJ response to acceptance mediated the association between High Risk and increased 12-month depressive symptoms. Our finding of associations between altered neural response to peer interactions and concurrent and prospective depression risk/resilience highlights the importance of neural underpinnings of social cognition as risk and compensatory adaptations along the pathway to depression.

Sensation Seeking in Children and Adults with Pediatric-Onset Bipolar Disorder.

Bipolar disorder (BD) is one of the most impairing psychiatric illnesses. Those with pediatric-onset BD tend to have worse outcomes; therefore, accurate conceptualization is important for aspects of care, such as tailored treatment interventions. Sensation seeking behaviors may be a window into the psychopathology of pediatric-onset BD. Participants with BD and healthy controls (HC) ages 7-27 completed self-report assessments, including the Sensation Seeking Scale- V (SSS-V). Among the BD group, there was a significant positive correlation between the Disinhibition subscale and age. Analyses indicated that the BD group scored lower on the Thrill and Adventure Seeking subscale but higher on the Disinhibition scale when compared to the HC group. We found that individuals with pediatric-onset BD are more likely to engage in socially risky behaviors. These results are an important step in understanding sensation seeking characteristics in BD youth and improving treatment, ultimately helping individuals live a more stable life.

Systematic Review: White Matter Microstructural Organization in Adolescents With Depression.

Objective: A growing body of literature has focused on the neural mechanisms of depression. Our goal was to conduct a systematic review on the white matter microstructural differences in adolescents with depressive disorders vs adolescents without depressive disorders. Method: We searched PubMed and PsycINFO for publications on August 3, 2022 (original search conducted in July 2021). The review was registered on PROSPERO (registration number: CRD42021268200), and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Eligible studies were original research papers comparing diffusion tensor/spectrum imaging findings in adolescents with vs without depression (originally ages 12-19 years, later expanded to 11-21 years). Studies were excluded if they focused on depression exclusively in the context of another condition, used only dimensional depressive symptom assessment(s), or used the same dataset as another included publication. Results: The search yielded 575 unique records, of which 14 full-text papers were included (824 adolescents with depression and 686 without depression). The following white matter regions showed significant differences in fractional anisotropy in at least 3 studies: uncinate fasciculus, cingulum, anterior corona radiata, inferior fronto-occipital fasciculus, and corpus callosum (genu and body). Most studies reported decreased, rather than increased, fractional anisotropy in adolescents with depression. Limitations include the possibility for selective reporting bias and risk of imprecision, given the small sample sizes in some studies. Conclusion: Our systematic review suggests aberrant white matter microstructure in limbic-cortical-striatal-thalamic circuits, and the corpus callosum, in adolescents with depression. Future research should focus on developmental trajectories in depression, identifying sources of heterogeneity and integrating findings across imaging modalities.

Cognitive Flexibility and Impulsivity Deficits in Suicidal Adolescents.

Although neurocognitive deficits have been documented in adolescents with suicidal ideation (SI) and suicide attempts (SA), it is unclear whether certain impairments differentiate these groups, potentially suggesting heightened risk for SA. Focus on specific facets of impulsivity and cognitive control may indicate distinctions between adolescents with SA vs. SI. The current study examined dimensions of impulsivity and cognitive control in 141 adolescents with SA (n = 41) vs. SI without SA (n = 49) vs. typically-developing controls (TDCs; n = 51). Adolescents completed cross-sectional neurocognitive tasks via the Cambridge Neuropsychological Testing Automated Battery, in addition to demographic and clinical measures. Analyses involved ANOVAs and ANCOVAs. Results indicated that adolescents with SA demonstrated less set shifting/cognitive flexibility (reduced ability to adapt to/disengage from stimuli) and greater impulsive decision making (reduced ability to collect/evaluate information before making decisions) compared to TDCs. In addition, both TDCs and adolescents with SA had greater response inhibition (increased ability to stop motor responses that have begun/become prepotent) than those with SI. Similar results were found when analyzing female adolescents separately. There were no significant differences for male adolescents, potentially due to the small subsample (n = 40). There were no significant findings for spatial planning/problem solving or visuospatial working memory. Findings suggest: 1) less set shifting/cognitive flexibility and greater impulsive decision making for adolescents with SA vs. TDCs; and 2) greater response inhibition for TDCs and adolescents with SA vs. SI. Such information may be useful for improving risk assessments (adding neurocognitive tasks) and targeted treatments (incorporating cognitive remediation) for this impaired population.

Maltreatment history and reasons for self-injurious behavior among adolescents engaged in non-suicidal self-injury versus adolescents who attempted suicide.

OBJECTIVE: Self-injurious behavior (SIB) is a significant public health concern in the United States, especially among adolescents with histories of maltreatment. This study compared maltreatment characteristics and reasons for SIB between three homogenous samples of adolescents with either: (1) non-suicidal self-injury (NSSI); (2) suicide attempt/s (SA), and (3) typically developing controls (TDC). METHOD: Participants (N = 124) aged 13-17 years completed questionnaires about their maltreatment and SIB histories. RESULTS: Maltreatment rates were as follows: 90% NSSI group, 76% SA group, and 40% TDC group. Adolescents in the NSSI group reported significantly higher rates of emotional neglect compared to the SA group. Maltreated adolescents in the NSSI and SA groups reported the same top three SIB reasons: (1) get rid of bad feelings, (2) mental state at the time, and (3) problems with family. However, maltreated NSSI participants were significantly more likely to engage in SIB for emotion regulation reasons than maltreated SA participants, who were more likely to engage in SIB for interpersonal reasons. Physical neglect and physical abuse also arose as significant predictors of specific SIB reasons. CONCLUSIONS: Our findings help elucidate the maltreatment profiles and reasons for SIB among adolescents engaged in NSSI or SA. Specific maltreatment experiences may also influence the reasons why adolescents engaged in SIB.

Sleep and mental health in childhood: a multi-method study in the general pediatric population.

BACKGROUND: Sleep problems, altered sleep patterns and mental health difficulties often co-occur in the pediatric population. Different assessment methods for sleep exist, however, many studies only use one measure of sleep or focus on one specific mental health problem. In this population-based study, we assessed different aspects of sleep and mother-reported mental health to provide a broad overview of the associations between reported and actigraphic sleep characteristics and mental health. METHODS: This cross-sectional study included 788 children 10-11-year-old children (52.5% girls) and 344 13-14-year-old children (55.2% girls). Mothers and children reported on the sleep of the child and wrist actigraphy was used to assess the child's sleep patterns and 24 h activity rhythm. Mental health was assessed via mother-report and covered internalizing, externalizing and a combined phenotype of internalizing and externalizing symptoms, the dysregulation profile. RESULTS: Higher reported sleep problems were related to more symptoms of mental health problems in 10-11- and 13-14-year-old adolescents, with standardized ß-estimates ranging between 0.11 and 0.35. There was no association between actigraphy-estimated sleep and most mental health problems, but earlier sleep onset was associated with more internalizing problems (ß = - 0.09, SE = 0.03, p-value = 0.002), and higher intra-daily variability of the 24 h activity rhythm was associated with more dysregulation profile symptoms at age 10-11 (ß = 0.11, SE = 0.04, p-value = 0.002). DISCUSSION: Reported sleep problems across informants were related to all domains of mental health problems, providing evidence that sleep can be an important topic to discuss for clinicians seeing children with mental health problems. Actigraphy-estimated sleep characteristics were not associated with most mental health problems. The discrepancy between reported and actigraphic sleep measures strengthens the idea that these two measures tap into distinct constructs of sleep.

Relationship between cognitive flexibility and subsequent course of mood symptoms and suicidal ideation in young adults with childhood-onset bipolar disorder.

Neurocognitive deficits, such as cognitive flexibility impairments, are common in bipolar disorder (BD) and predict poor academic, occupational, and functional outcomes. However, the association between neurocognition and illness trajectory is not well understood, especially across developmental transitions. This study examined cognitive flexibility and subsequent mood symptom and suicidal ideation (SI) course in young adults with childhood-onset BD-I (with distinct mood episodes) vs. BD-not otherwise specified (BD-NOS) vs. typically-developing controls (TDCs). Sample included 93 young adults (ages 18-30) with prospectively verified childhood-onset DSM-IV BD-I (n = 34) or BD-NOS (n = 15) and TDCs (n = 44). Participants completed cross-sectional neuropsychological tasks and clinical measures. Then participants with BD completed longitudinal assessments of mood symptoms and SI at 6-month intervals (M = 39.18 ± 16.57 months of follow-up data). Analyses included ANOVAs, independent-samples t tests, chi-square analyses, and multiple linear regressions. Participants with BD-I had significant deficits in cognitive flexibility and executive functioning vs. BD-NOS and TDCs, and impaired spatial working memory vs. TDCs only. Two significant BD subtype-by-cognitive flexibility interactions revealed that cognitive flexibility deficits were associated with subsequent percentage of time depressed and with SI in BD-I but not BD-NOS, regardless of other neurocognitive factors (full-scale IQ, executive functioning, spatial working memory) and clinical factors (current and prior mood and SI symptoms, age of BD onset, global functioning, psychiatric medications, comorbidity). Thus, cognitive flexibility may be an important etiological brain/behavior mechanism, prognostic indicator, and intervention target for childhood-onset BD-I, as this deficit appears to endure into young adulthood and is associated with worse prognosis for subsequent depression and SI.

Lower pro- to anti-inflammatory ratios associated with reduced neurocognitive flexibility in symptomatic adolescents with bipolar disorder.

INTRODUCTION: Peripheral inflammatory markers, such as C-reactive protein (CRP), are elevated among adolescents and adults with bipolar disorder (BD), particularly during symptomatic episodes. Neurocognition, predominantly in the domain of executive function, is also impaired among adults and youth with BD. In adults with BD, CRP is negatively associated with neurocognitive functioning. We aim to investigate this relationship in BD adolescents. METHODS: Serum levels of CRP and five other inflammatory markers (interleukin (IL)-1ß, IL-6, IL-10, IL-4 and tumor necrosis factor α (TNF)) were examined in 60 adolescents with BD (34 symptomatic, 26 asymptomatic) age- and sex-matched to 51 healthy controls (HC). Diagnoses were confirmed using semi-structured interviews. Pro- to anti-inflammatory marker ratios were also examined. Neurocognitive flexibility was assessed via the intra/extradimensional shift (IED) task from the CANTAB battery. Multivariate linear regression controlled for age, sex and race. RESULTS: Within symptomatic BD adolescents, but not asymptomatic BD or HC adolescents, lower IL-6/IL-10 and lower CRP/IL-10 ratios were significantly associated with worse performance on the neurocognitive flexibility task (p = 0.03 and p = 0.04, respectively). Both models accounted for 13.3% of variance in neurocognitive flexibility. No significant CRP by diagnosis interaction effects were observed on neurocognitive flexibility. LIMITATIONS: Limited sample-size restricted ability to separate the symptomatic BD adolescents into varying mood states. CONCLUSION: More balanced pro- to anti-inflammatory ratios were associated with better neurocognitive flexibility in symptomatic BD adolescents. Prospective studies are warranted to assess the direction of these findings.

This Is Your Brain on Irritability: A Clinician's Guide to Understanding How We Know What We Know Now, and What We Need to Know in the Future, About Irritability in Children and Adolescents.

Irritability is a common reason why children and adolescents are brought for psychiatric care. Although research is advancing what is known about the underlying brain and behavior mechanisms of irritability, clinicians often are shut out of that research. This article explains some of these research methods, providing brief summaries of what is known about brain/behavior mechanisms in disorders involving irritability, including bipolar disorder, disruptive mood dysregulation disorder, attention-deficit/hyperactivity disorder, and autism spectrum disorder. Greater access to these methods may help clinicians now and in the future, with such mechanisms translated into improved care, as occurs in the treatment of childhood leukemia.

Facial emotion recognition and mood symptom course in young adults with childhood-onset bipolar disorder.

Facial emotion recognition deficits are common in bipolar disorder (BD) and associated with impairment. However, the relationship between facial emotion recognition and mood course is not well understood. This study examined facial emotion recognition and subsequent mood symptoms in young adults with childhood-onset BD versus typically developing controls (TDCs). The sample included 116 young adults (ages 18-30, 58% male, 78% White) with prospectively verified childhood-onset BD (n = 52) and TDCs (n = 64). At baseline, participants completed a facial emotion recognition task (Diagnostic Analysis of Non-Verbal Accuracy-2) and clinical measures. Then, participants with BD completed mood symptom assessments every 6 months (M = 8.7 ± 5.2 months) over two years. Analyses included independent-samples t tests and mixed-effects regression models. Participants with BD made significantly more recognition errors for child expressions than TDCs. There were no significant between-group differences for recognition errors for adult expressions, or errors for specific child or adult emotional expressions. Participants had moderate baseline mood symptoms. Significant time-by-facial emotion recognition interactions revealed more recognition errors for child emotional expressions predicted lower baseline mania and stable/consistent trajectory; fewer recognition errors for child expressions predicted higher baseline mania and decreasing trajectory. In addition, more recognition errors for adult sad expressions predicted stable/consistent depression trajectory and decreasing mania; fewer recognition errors for adult sad expressions predicted decreasing depression trajectory and stable/consistent mania. Effects remained when controlling for baseline demographics and clinical variables. Facial emotion recognition may be an important brain/behavior mechanism, prognostic indicator, and intervention target for childhood-onset BD, which endures into young adulthood and is associated with mood trajectory.

Longitudinal course of depressive symptom severity among youths with bipolar disorders: Moderating influences of sustained attention and history of child maltreatment.

BACKGROUND: Pediatric bipolar disorders are often characterized by disruptions in cognitive functioning, and exposure to child maltreatment (e.g., physical and sexual abuse) is associated with a significantly poorer course of illness. Although clinical and developmental research has shown maltreatment to be robustly associated with poorer cognitive functioning, it is unclear whether maltreatment and cognitive function jointly influence the clinical course of bipolar symptoms. METHODS: This secondary analysis examined moderating effects of lifetime childhood physical and sexual abuse, and cognitive disruptions (sustained attention, affective information processing), on longitudinal ratings of depression symptom severity in youths from the Course and Outcome of Bipolar Youth (COBY) study, examined from intake (M = 12.24 years) through age 22 (N = 198; 43.9% female; Mean age of bipolar onset = 8.85 years). RESULTS: A significant moderating effect was detected for sustained attention and maltreatment history. In the context of lower sustained attention, maltreatment exposure was associated with higher depression symptom severity during childhood, but not late adolescence. There was no association between maltreatment and symptom severity in the context of higher sustained attention, and no association between attention and depression symptom severity for non-maltreated youths. LIMITATIONS: Depression symptom ratings at each assessment were subject to retrospective recall bias despite the longitudinal design. Cognitive assessments were administered at different ages across youths. CONCLUSIONS: Depressive symptoms in pediatric bipolar may be jointly moderated by impairments in attention and exposure to maltreatment. Assessment of these risks, particularly in childhood, may be beneficial for considering risk of recurrence or chronicity of depressive symptoms.

Editorial: It's Difficult To Make Predictions, Especially About the Future: Risk Calculators Come of Age in Child Psychiatry.

A quote attributed to many people, from the Nobel prize-winning Quantum physicist Niels Bohr to legendary baseball player (and philosopher) Yogi Berra states: "It is difficult to make predictions, especially about the future." As though any other prediction would matter; but this is exactly what parents want when they bring their child to the doctor for any concern, ranging from a bump or bruise to whether the child has bipolar disorder. They want the doctor to use both the science and art of medicine to answer key questions: What is wrong with my child? What tests or workup is needed to figure this out? What is the best treatment for this problem? Will my child get better?

Maladaptive personality traits and the course of suicidal ideation in young adults with bipolar disorder: Cross-sectional and prospective approaches.

BACKGROUND: Childhood-onset bipolar disorder (BD) has considerable morbidity and mortality, including suicide. Many risk factors have been identified for suicidality, but the potential role of personality traits as assessed by a computer-assisted self-report measure remains unclear. AIMS: To address this gap in knowledge, we tested relations between pathological-range personality traits and suicidal ideation among young adults whose childhood-onset BD was prospectively confirmed by enrollment in the Course and Outcome of Bipolar Youth study (COBY) as children (n = 45) and a newly enrolled group of typically developing controls (TDCs; n = 52) both cross-sectionally and longitudinally after 1.5 years of follow up. MATERIALS & METHODS: Personality traits were assessed with the computerized Schedule for Nonadaptive and Adaptive Personality-2 (SNAP-2). RESULTS: Cross-sectionally, we found that participants with BD had elevated Suicide Proneness and Low Self-esteem versus TDCs at baseline. Furthermore, longitudinal analyses in the BD participants for whom we had 1.5 years of prospectively collected illness-course data showed that greater Suicide Proneness and Low Self-esteem prospectively predicted greater levels, shorter time until occurrence, and greater frequency of suicidal ideation during the follow-up. CONCLUSION: Our findings suggest the role of specific personality-related vulnerabilities in the course of BD that, pending replication, could contribute to development of interventions focused on personality traits among individuals with BD.

White matter correlates of cognitive flexibility in youth with bipolar disorder and typically developing children and adolescents.

Prior studies using behavioral tasks and neuroimaging have shown that children and adolescents with bipolar disorder (BD) have deficits in cognitive flexibility (CF)-defined as adaptation to changing rewards and punishments. However, no study, to our knowledge, has examined the white matter microstructural correlates of CF in youth with BD. To address this gap, we examined the relationship between CF assessed with the Cambridge Neuropsychological Testing Automated Battery (CANTAB)'s Intra-Extra Dimensional Set Shift task (ID/ED) and diffusion tensor imaging analyzed with FSL's preprocessing tools and Tract-Based Spatial Statistics (TBSS). We found a significantly different relationship between microstructural integrity of multiple white matter regions and CF performance in BD (n=28) and age-matched typically developing control (TDC) youths (n=26). Evaluation of the slopes of linear regressions in BD vs. TDC (ID/ED Simple Reversal error rate vs. fractional anisotropy) revealed significantly different slopes across the groups, indicating an aberrant relationship between CF and underlying white matter microstructure in youth with BD. These results underscore the importance of examining specific CF-neuroimaging relationships in BD youth. Future longitudinal studies could seek to define the white matter microstructural trajectories in BD vs. TDC, and relative to CF deficits and BD illness course.

Sex Differences in the Longitudinal Course and Outcome of Bipolar Disorder in Youth.

OBJECTIVE: Despite substantial literature on sex differences in adults with bipolar disorder (BD), little is known about this topic in youth; this study examines sex differences in mood symptomatology and psychiatric comorbidity in prospectively followed youth with BD. METHODS: A subsample of the Course and Outcome of Bipolar Youth study (N = 370; female n = 199, male n = 171) enrolled October 2000-July 2006 (age at intake = 7-17.11 years) who met DSM-IV criteria for bipolar I disorder (BD-I; n = 221), bipolar II disorder (BD-II; n = 26), or operationalized BD not otherwise specified (BD-NOS; n = 123) with ≥ 4 years follow-up was included. Analyses examined sex differences at intake and, prospectively, in mood symptomatology and psychiatric comorbidity for a mean ± SD follow-up of 10.5 ± 1.72 years. RESULTS: Females were older than males at intake (mean ± SD age = 13.33 ± 3.32 vs 12.04 ± 3.16 years; P = .0002) and at age at mood onset (9.33 ± 4.22 vs 7.53 ± 3.74 years; P < .0001). After adjustment for confounders, males spent more time with syndromal ADHD (Padjusted = .001) and females spent more time with syndromal anxiety (Padjusted = .02). There were trends toward males spending more time with substance use disorder and females having more non-suicidal self-injurious behavior (Padjusted = .07 and .09, respectively). There were no sex differences on outcome variables, including rate of or time to recovery and recurrence. CONCLUSIONS: Contrasting with adult literature, this study identified minimal sex differences in the course of youth with BD. Longer-term studies are needed to clarify if youth-onset BD remains a "sex neutral" subtype of BD or diverges according to sex in adulthood.