Is irritability multidimensional: Psychometrics of The Irritability and Dysregulation of Emotion Scale (TIDES-13).

Irritability is a common, impairing, and potentially multifaceted manifestation of psychopathology. We designed The Irritability and Dysregulation of Emotion Scale (TIDES-13) to determine whether various expressions of irritability in children and youth form multiple subdimensions with distinct correlates. We administered parent-report (n = 3875, mean age = 8.9) and youth self-report (n = 579, mean age = 15.1) versions of TIDES-13 in a population and community-based sample. We conducted exploratory/confirmatory factor analyses and regression analyses to examine the dimensionality of TIDES-13 and the associations of the scale with age, gender, anxiety, depression, ODD, ADHD traits, and the Affective Reactivity Index (ARI). A higher-order model with a global irritability dimension and four subdimensions, including proneness to anger (PA), internalized negative emotional reactivity (iNER), externalized negative emotional reactivity (eNER), and reactive aggression (RA), showed good to excellent fit in both parent-report and self-report. The global irritability dimension showed excellent internal reliability (⍵Total; parent-report = 0.97, ⍵Total; self-report = 0.95), explained a majority of the item variance (⍵Hierarchical; parent-report = 0.94, ⍵Hierarchical; self-report = 0.90), and was moderately correlated with the ARI (rparent = 0.68, rself = 0.77). Subdimensions PA, eNER, and RA were negatively associated with age in males, whereas iNER was positively associated with age in females. Traits of ODD and ADHD were associated primarily with the global irritability dimension, whereas iNER was strongly associated with anxiety and depression traits over and above the global irritability dimension. Our results support a unidimensional interpretation of irritability in a population sample. However, limited evidence of specific behavioral, age, and sex correlates with particular irritability subdimensions may warrant further investigation.

Suicidality risk in children and adolescents with externalizing disorders: symptoms profiles at high risk and the moderating role of dysregulated family relationships.

Children and adolescents with externalizing disorders are at risk for suicidal ideation or behavior. Factors that put them at risk could be symptoms related or facilitated by their environment. We evaluated the links of symptoms profiles with suicidality, and the effects of family relationship characteristics on these links. Latent profile analysis was used to subgroup participants referred for ADHD assessment (n = 1249, aged 6-17) based on their externalizing and internalizing symptoms. Self- and parent-reported child suicidal ideation (S-SI, P-SI), and parent-reported self-harm behavior (P-SHB) were compared across profiles. The moderating effects of parent-reported marital conflict and parenting practices were examined. A four-profile model showed optimal fit. Participants of the Low Symptoms profile followed by the Inattentive-Hyperactive/Impulsive profile showed lower P-SI compared to those of the Irritable-Defiant and the Conduct Problems profiles. Low Symptoms participants also reported lower S-SI compared to those of the Inattentive-Hyperactive/Impulsive and the Irritable-Defiant profiles. Participants of the Irritable-Defiant and the Conduct Problems profiles had higher P-SHB compared to the Low Symptoms and the Inattentive-Hyperactive/Impulsive participants. Dysregulated marital conflict practices were associated with greater increase in P-SI in all profiles compared to the Low Symptoms profile. Aggressive marital conflict practices were associated with increased P-SHB in the Conduct Problems profile compared to the Inattentive-Hyperactive/Impulsive profile. Children and adolescents with irritability and defiance symptoms with or without conduct problems show higher risk for suicidal ideation and behavior compared to those with ADHD symptoms alone. Dysregulated and aggressive marital conflict practices might pose additional suicidality risk in children and adolescents with disruptive behavior.

COVID-19 and the impact on psychiatric and suicide-related emergency department visits of 5-18-year-Old youth in Israel.

COVID-19 has been found to take a toll on the mental health of children and adolescents worldwide. This study retrospectively evaluated the changes in the number of general and suicide-related visits to a pediatric psychiatric emergency department (ED) at Geha Mental Health Center in Israel and the distribution of sex and age of the 5-18-year-old youth who visited the ED. The study looked at visits from the pre-pandemic years to the first and second years of the pandemic. The findings showed a sharp decrease in visits at the beginning of the pandemic, followed by a significant increase in the first year and a nonsignificant decline in the second year. The proportion of girls' ED visits was higher in the pandemic years compared to the pre-pandemic years. Regarding suicide-related visits, after a sharp decline at the beginning of the pandemic, the number of visits increased at a rate similar to the pre-pandemic period. We conclude that the pattern of change was similar to that of other population-level exposures to continuous stress conditions. Further research on the vulnerability of girls in similar situations is needed.

Genetic perturbation of AMP biosynthesis extends lifespan and restores metabolic health in a naturally short-lived vertebrate.

During aging, the loss of metabolic homeostasis drives a myriad of pathologies. A central regulator of cellular energy, the AMP-activated protein kinase (AMPK), orchestrates organismal metabolism. However, direct genetic manipulations of the AMPK complex in mice have, so far, produced detrimental phenotypes. Here, as an alternative approach, we alter energy homeostasis by manipulating the upstream nucleotide pool. Using the turquoise killifish, we mutate APRT, a key enzyme in AMP biosynthesis, and extend the lifespan of heterozygous males. Next, we apply an integrated omics approach to show that metabolic functions are rejuvenated in old mutants, which also display a fasting-like metabolic profile and resistance to high-fat diet. At the cellular level, heterozygous cells exhibit enhanced nutrient sensitivity, reduced ATP levels, and AMPK activation. Finally, lifelong intermittent fasting abolishes the longevity benefits. Our findings suggest that perturbing AMP biosynthesis may modulate vertebrate lifespan and propose APRT as a promising target for promoting metabolic health.

Cognitive flexibility in inpatient children and adolescents with a history of suicide attempts.

An increase in suicide rates during adolescence has made it the second leading cause of death for this age group. While potential deficits in cognitive flexibility have been thought to contribute to suicidality, this factor has been evaluated in only a few studies among this age group. The current study sought to evaluate cognitive flexibility in 100 psychiatric inpatient children and adolescents (age X=14.39, SD=2.53), with (n=26) and without (n=74) a history of suicide attempts, using the Wisconsin Card Sorting Test (WCST). Results showed no differences between the groups in WCST scores. However, in a small sub-sample with mood disorders only, those with a history of a suicide attempt performed better than those without such history. These findings are contrary to our hypothesis that those who attempted suicide have worse cognitive flexibility, though consistent with earlier data in adults. Further research is needed to shed light on these findings.

Facial emotion recognition in children and youth with attention-deficit/hyperactivity disorder and irritability.

The ability to recognize emotions evident in people's faces contributes to social functioning and might be affected by ADHD and irritability. Given their high co-occurrence, we examined the relative contribution of ADHD and irritability to facial emotion recognition (FER). We hypothesized that irritability but not ADHD traits would predict increased likelihood of misrecognizing emotions as negative, and that FER performance would explain the association of ADHD and irritability traits with social skills. FER was measured using the Reading the Mind in the Eyes Test (RMET) in children (6-14 years old) referred for ADHD assessment (n = 304) and healthy controls (n = 128). ADHD, irritability and social skills were measured using parent ratings. We used repeated measure logistics regression, comparing the effects across emotion valence of images (i.e., neutral/positive/negative). High irritability but not ADHD diagnosis predicted lower RMET accuracy. ADHD traits predicted lower RMET accuracy in younger but not older participants, whereas irritability predicted poorer accuracy at all ages. ADHD traits predicted lower RMET accuracy across all emotion valences, whereas irritability predicted increased probability of misrecognizing neutral and positive but not negative emotions. Irritability did not increase the probability for erroneously recognizing emotions as negative. ADHD and irritability traits fully explained the association between RMET and social skills. ADHD and irritability traits might impact the ability to identify emotions portrayed in faces. However, irritability traits appear to selectively impair recognition of neutral and positive but not negative emotions. ADHD and irritability are important when examining the link between FER and social difficulties.

Callous-Unemotional Traits and Face-Emotion Recognition as Mediators in Conduct Problems of Children With ADHD.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with increased risk for conduct problems (CP), as well as with callous-unemotional traits (CUt) and lower accuracy in face emotional recognition (FER). It is unclear, however, whether CUt and low accuracy in FER contribute to the risk for CP in ADHD. The present study investigated the possibility of such contribution. METHODS: This pilot study's participants included 31 children aged 7-17 years, diagnosed with ADHD, and treated in a psychiatric outpatient clinic. The parents rated their children on the ADHD Rating Scale, Inventory of Callous-Unemotional Traits, and the Child Behavior Checklist-Conduct Problems scale. Participants completed the Hebrew version of the children's Reading the Mind in the Eyes Test (cRMET)-a Theory of Mind measure. A bootstrapped multiple mediator model was used, adjusting for age and gender. RESULTS: ADHD symptoms were associated with CP. This association was not mediated by CUt or cRMET. CUt was associated with CP independent of ADHD symptom severity. CONCLUSIONS: ADHD symptoms and CUt both should be considered when assessing risk for CP and devising a treatment plan, in children with ADHD. Current results did not confirm the hypothesis that cRMET and CUt mediate between ADHD symptoms and CP. More studies employing larger samples, longitudinal design, and other emotion recognition measures are needed.

Body mass index increase in preschoolers with heterogeneous psychiatric diagnoses treated with risperidone.

OBJECTIVE: Use of risperidone in preschool-aged children is growing, with rising concerns of adverse metabolic consequences. Longitudinal data on risperidone-related weight gain in preschoolers are scarce. We aimed to evaluate changes in body mass index (BMI) that are associated with risperidone treatment in preschoolers. METHOD: We analyzed naturalistic, longitudinal data on 141 preschool children (112 boys, 29 girls) receiving psychiatric care. Mean patient age at baseline was 5.0 years (SD=0.8) and average follow-up period was 1.3 years (SD=0.8), with >8 mean BMI measurements per patient. We studied the effect of risperidone exposure (n=78) on age-and-sex-standardized BMI (BMI Z-score) implementing mixed models with random subject intercepts to account for repeated measures, covarying for multiple confounders including demographics, stimulant treatment and psychiatric diagnoses. We employed similar models to study dose and duration effects. RESULTS: Risperidone treatment was significantly associated with an increase in BMI (effect size of exposure=0.45 SD (SE=0.06), t (949)=7.7, p<0.001) covarying for stimulant exposure and other confounders, independent of treatment indication. Females exhibited stronger effects (risperidone treatment × sex interaction t=2.32, p=0.02)). Risperidone daily dose was associated with increase in BMI (for each additional 1 mg, effect size=0.28 SD (SE=0.07), t(419)=3.76, p<0.001). CONCLUSION: Similar to older populations, risperidone treatment in preschoolers is associated with significant weight gain, with evidence for dose effects. Findings provide critical data that can inform clinicians.

Concurrent Validity of the ABAS-II Questionnaire with the Vineland II Interview for Adaptive Behavior in a Pediatric ASD Sample: High Correspondence Despite Systematically Lower Scores.

We examined the correlation between interviewer-administered Vineland Adaptive Behavior Scale II (VABS-II) and the parent-rated Adaptive Behavior Assessment System II (ABAS-II) questionnaire in 352 participants (ages 1.5-20.8 years) with autism spectrum disorder (ASD) to determine if ABAS could be used as a screen to reduce the number of VABS interviews. Corresponding domain scores between the two measures were highly correlated but scores were significantly lower on the ABAS-II. Screening with ABAS-II significantly reduced the number of VABS-II interviews required with little cost to overall accuracy. The ABAS-II provides a cost- and time-saving alternative to the VABS-II to rule out functional impairment; however, scores are not strictly comparable between the two measures.

The association of non-suicidal self-injurious and suicidal behaviors with religiosity in hospitalized Jewish adolescents.

Religiosity may be a potent protective factor against self-injurious and suicidal behaviors. However, no previous study has addressed this relationship in adolescent psychiatric population. This study aimed to examine the association between religiosity and non-suicidal self-injurious (NSSI) and suicidal behaviors, among hospitalized Jewish adolescents. This is a cross-sectional study of 60 hospitalized Jewish adolescents in two mental health centers. They were evaluated for religiosity, NSSI, and suicidal behaviors. The following religiosity measures were found to be protective against NSSI: a higher degree of adherence to religious practices (extrinsic measure) (beta = -0.083, p = .006), a higher level of belief in religious principles (intrinsic measure) (beta = -0.063, p = .008) and a self-reported higher religious affinity (χ2 = 7.64, p = .022). The severity of suicidal ideation inversely correlated with the extrinsic measure (standardized beta = -0.2, t = -2.5, p = .015) and with self-reported degree of religious affinity (analysis of variance, F = 3.5, p = .035). History of transition in religious affinity was associated with worse suicidal ideation (3.77 ± 1.8 vs. 2.26 ± 1.99, t = -3.25, p = .004) and with suicide attempts (OR = 3.89 (95% CI: 1.08 - 14.03), p = .004); however, these relationships were mediated by history of abuse. This study provides first evidence of a protective effect of some religiosity measures on NSSI and suicidal behaviors in hospitalized Jewish adolescents.

Attention-deficit/hyperactivity disorder (ADHD) symptoms and suicidality in children: The mediating role of depression, irritability and anxiety symptoms.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with increased suicidality risk. Yet, potential mechanisms transmitting the effect of ADHD to suicidality remain unclear. We investigated whether depression, irritability and anxiety symptoms mediate between ADHD symptoms and suicidality. METHODS: ADHD, depression, irritability and anxiety symptoms as well as suicidality (composited of suicidal ideation, attempts or self-harm) were measured in an outpatient clinic for ADHD (N = 1,516, 6-17 years old, 61.1% diagnosed with ADHD) using parent and teacher questionnaires. Multiple mediator models adjusted for age, sex and psychosocial adversities were constructed separately for parent- and teacher-report. RESULTS: Parents reported higher rates of suicidality than did teachers (12.1% and 3.8%, p < .001). Suicidality was associated with parent (OR = 1.10, 95%CI: 1.07-1.14) and teacher (OR = 1.08, 95%CI: 1.03-1.15) reported ADHD symptoms. The association between ADHD symptoms and suicidality was mediated by both parent- and teacher-reported depression (39.1% and 45.3% of total effect, respectively) and irritability symptoms (36.8% and 38.4% of total effect, respectively). Anxiety symptoms mediated between ADHD and suicidality for parent- but not teacher-report (19.0% of total effect). No direct effect of ADHD symptoms was found once depression, irritability and anxiety were controlled. LIMITATIONS: The cross-sectional design limits the ability to determine causal order between mediators and outcome. CONCLUSIONS: Our results confirmed the association between ADHD symptoms and suicidality. However, this association was indirect and fully mediated by symptoms of depression, irritability and anxiety. Assessing these symptoms may enable an estimate of suicidality and help managing suicidal risk in ADHD.

The effect of methylphenidate treatment on psychopathic behavior of patients having attention-deficit hyperactivity disorder with and without oppositional defiant disorder.

To evaluate the effect of 3 months of methylphenidate (MPH) treatment on psychopathic behavior in children having attention-deficit hyperactivity disorder (ADHD) with and without comorbid oppositional defiant disorder (ODD). Twenty-seven children with Diagnostic and Statistical Manual of Mental Disorders, fifth ed., ADHD (13 female/14 male; aged 13.3±2.2 years old) were compared to an age/sex matched ADHD/ODD group (N=27, eight female/19 male; aged 11.8±1.9 years). The attention-deficit hyperactivity disorder rating scale (ADHD-RS) and the California Child Q-Set (CCQ) were used in both groups before MPH treatment (0.8-1.2 mg/kg/day) and 3 months thereafter. Significant reduction in the ADHD-RS scores was detected following MPH treatment in both the ADHD/ODD group and in the ADHD group (P<0.0011 and P=0.0012, respectively). Reduction in the CCQ scores was obtained in the ADHD/ODD group (P=0.0001) but not in in the ADHD group (P=0.18). A correlation was found between the reductions in the ADHD-RS and CCQ scores following MPH treatment in the ADHD/ODD group (Spearman's r=0.43, P=0.024). MPH treatment in children with ADHD/ODD was associated with reduction in psychopathic scores, and the reduction correlated with a corresponding improvement in their ADHD severity.

The reliability, concurrent validity and association with salivary oxytocin of the self-report version of the Inventory of Callous-Unemotional Traits in adolescents with conduct disorder.

The present study evaluated the self-report version of the Inventory of Callous-Unemotional Traits (ICU-SR) in terms of reliability, concurrent validity, and correlation with salivary oxytocin levels, a potential biomarker of CU traits. 67 socially at-risk male adolescents (mean 16.2 years) completed the ICU-SR, ICU teacher-version (ICU-TR), Strengths and Difficulties Questionnaire, and their medical files were coded for previous antisocial acts using Brown-Goodwin Lifetime Aggression Scale. Salivary samples were assayed for oxytocin. The reliability of ICU-SR was lower (α = 0.71) than ICU-TR (α = 0.86). ICU-SR mean score was significantly lower than ICU-TR (M = 25.29, SD = 8.02; M = 33.14, SD = 9.47). ICU-TR but not ICU-SR, significantly correlated with history of antisocial acts (r = 0.40). Two-way analysis of variance showed a significant effect of conduct disorder and oxytocin on ICU-TR but not ICU-SR [F(1,59) = 6.53; F(1,59) = 6.08], and a significant interaction only for ICU-TR [F(1,59) = 2.89]. Subjective self-reports of CU traits may be less reliable and valid than teachers' reports.

Salivary oxytocin in adolescents with conduct problems and callous-unemotional traits.

Callous-unemotional (CU) traits correlate with the severity and prognosis of conduct disorder in youth. The neuropeptide oxytocin (OT) has been linked to prosocial behaviors, including empathy and collaboration with others. This study discusses a possible role for OT in the biology of delinquent behavior. We hypothesized that in delinquent youth OT secretion will correlate with the severity of conduct problems and specifically with the level of CU traits. The study group included 67 male adolescents (mean age 16.2 years) undergoing residential treatment, previously assessed by an open clinical interview and history for the psychiatric diagnosis. Staff based Inventory of Callous-Unemotional traits for psychopathy and Strength and Difficulties Questionnaire were administered, and patients' medical and social personal files were systematically coded for previous history of antisocial acts using the Brown-Goodwin Questionnaire. Salivary OT was assayed by ELISA. Salivary OT levels were inversely correlated with conduct problems severity on Strength and Difficulties Questionnaire (r = -0.27; p ≤ 0.01). Recorded history of antisocial acts did not correlate with current OT levels. Odds ratio (OR) for significant CU traits among subjects with conduct problems was increased in low-OT (OR = 14, p ≤ 0.05) but not in high-OT subjects (OR = 6, p ≥ 0.05). Children with conduct problems and low levels of salivary OT are at risk for significant CU traits. These results suggest a possible role for salivary OT as a biomarker for CU traits and conduct problems severity.

[Pharmacotherapy for conduct disorder in children and adolescents].

RATIONALE: Conduct disorder (CD) is a common disorder which is typified by a variety of behavioral problems and aggression. Treating CD is a challenge in the field of child and adolescent psychiatry. The use of drugs for this indication is broad despite the lack of systematic knowledge on this subject. OBJECTIVES: This paper aims to review research data available on the efficacy of the different medication classes and agents for CD and to specify the considerations that should be taken accordingly. MATERIALS AND METHODS: Trials on the pharmacotherapy of CD in children and adolescents are reviewed from the PubMed database (dated from 1980 until today). RESULTS: Trials of antipsychotics, lithium, anti-epileptics, stimulants, alfa-2 agonists and beta-blockers were found. The use of typical antipsychotics is accompanied by major side-effects. Research on risperidone, the most investigated agent, shows it to be effective. Limited research with positive results is also available on quetiapine, olanzapine and aripiprazole. Trials of lithium yield contradictory results. Few trials with valproate suggest it to be effective for this indication. There is evidence showing the efficacy of stimulants but substance abuse is a potential risk in this population. The results for other agents are very few. CONCLUSIONS: There are few well controlled studies of the pharmacotherapy of conduct disorder in children and adolescents. The most proven efficacy is for the atypical antipsychotics. Valproate or lithium may be possible second or third alternatives, based on some supporting evidence. When Attention-Deficit/Hyperactivity Disorder is diagnosed, stimulant use should be considered. Given the adverse effects profile of these agents on the one hand, and the developmental risks of avoiding medication on the other hand, a risk-benefit analysis should be conducted for each patient and adverse effects should be monitored carefully. More research is needed to broaden and deepen the knowledge on this subject.

Interaction of child and family psychopathology leading to suicidal behavior.

According to the Centers for Disease Control and Prevention, suicide is the third leading cause of death in adolescence in the United States. Nonfatal forms of suicidal behavior are the most common reasons for the psychiatric hospitalization of adolescents in many countries. The risk for suicide attempt among offspring of suicide completers is multifactorial, challenging experts to develop a strategy that includes assessment and management that consider these factors. Although treatment of depression is necessary, antisuicide treatment strategies that solely target depression may not be sufficient to reduce suicidal risk. Other factors, such as impulsive aggression and parental history of sexual abuse, also contribute to suicidal risk.