Irritability: associations with real-time affect dynamics, social interactions, and daily substance use in older adolescents.

Irritability is a common and clinically significant symptom associated with a wide range of negative outcomes. Ecological Momentary Assessment (EMA) is a valuable tool for capturing experiences, such as emotions, social interactions, and substance use in real-time, and may be useful in understanding how irritability is related to everyday functioning. We investigated cross-sectional associations between a widely used self-report irritability rating scale and affect dynamics, social interactions, and substance use captured with EMA (5 surveys daily for 14 days) in 349 18-year-olds. We also examined the associations of self- and parent-reported irritability at ages 12 and 15 with the age 18 EMA variables to explore whether these relationships persist over time. Youth-reported irritability at age 18 was linked to greater intensity, variability, and inertia of irritability, sadness, and anxiety, less positive and more negative interpersonal experiences, and greater cigarette and drug use. Most effect sizes were in the medium-small range. Associations of youth- and parent-reported irritability at ages 12 and 15 with the age 18 EMA measures were generally similar, although smaller in magnitude. Findings contribute to understanding how irritability is manifested in real-time affect dynamics and interpersonal functioning, as well as daily substance use. Most effects were evident over the course of up to 6 years - that is, early adolescent irritability, reported by both youth and their parents, was associated with similar real-time affect dynamics and interpersonal experiences at age 18. This study contributes to the literature on the developmental psychopathology of irritability by extending findings to everyday functioning.

Eye-tracking measurement of attention bias to social threat among youth: A replication and extension study.

Attentional bias to social threat cues has been linked to heightened anxiety and irritability in youth. Yet, inconsistent methodology has limited replication and led to mixed findings. The current study aims to 1) replicate and extend two previous pediatric studies demonstrating a relationship between negative affectivity and attentional bias to social threat and 2) examine the test-retest reliability of an eye-tracking paradigm among a subsample of youth. Attention allocation to negative versus non-negative emotional faces was measured using a free-viewing eye-tracking task among youth (N=185 total, 60% female, M age=13.10 years, SD age=2.77) with three face-pair conditions: happy-angry, neutral-disgust, sad-happy. Replicating procedures of two previous studies, linear mixed-effects models compared attention bias between children with anxiety disorders and healthy controls. Bifactor analysis was used to parse shared versus unique facets of general negative affectivity (i.e., anxiety, irritability), which were then examined in relation to attention bias. Test-retest reliability of the bias-index was estimated among a subsample of youth (N=36). No significant differences in attention allocation or bias emerged between anxiety and healthy control groups. While general negative affectivity across the sample was not associated with attention bias, there was a positive relationship for anxiety and irritability on duration of attention allocation toward negative faces. Test-retest reliability for attention bias was moderate (r=0.50, p<.01). While anxiety-related findings from the two previous studies were not replicated, the relationship between attention bias and facets of negative affect suggests a potential target for treatment. Evidence for test-retest reliability encourages future use of the eye-tracking task for researchers.

Predictive associations of executive functions and oppositional defiant problems and obsessive-compulsive problems in preschoolers.

Oppositional defiant problems (ODP) and obsessive-compulsive problems (OCP) may co-occur in children, though the way they interact is not known. The aim of the study was to examine longitudinal associations between executive functions at age 3 and ODP, ODP dimensions, and OCP at age 6. The sample consisted of 622 preschoolers (50% were boys) from the general population. Executive functions were assessed by teachers using the Behavior Rating Inventory of Executive Functioning - Preschool version questionnaire when children were 3 years old, and ODP and OCP were informed by parents and teachers at the age of 6 years. Multiple linear regression analyses indicated that higher Inhibit and Emotional Control and lower Shift deficits were associated with higher ODP reported by teachers, while higher Shift but lower Inhibit deficits were related to higher OCP. Moreover, ODP and OCP shared difficulties on the Flexibility Index, which means that the capacity to modulate emotions and behavior according to contextual and environmental demands is compromised in both disorders. The findings inform etiology and prevention, pointing out not only the executive function specificities related to each problem, but also common cognitive challenges related to Flexibility. Young children could benefit from training and programs designed to improve executive function processes at an early age to prevent later behavioral difficulties.

An Expanded Conceptual Framework for Understanding Irritability in Childhood: The Role of Cognitive Control Processes.

Children prone to irritability experience significant functional impairments and internalising and externalising problems. Contemporary models have sought to elucidate the underlying mechanisms in irritability, such as aberrant threat and reward biases to improve interventions. However, the cognitive control processes that underlie threat (e.g., attention towards threats) and reward (e.g., attention towards reward-related cues) biases and the factors which influence the differential activation of positive and negative valence systems and thus leading to maladaptive activation of cognitive control processes (i.e., proactive and reactive control) are unclear. Thus, we aim to integrate extant theoretical and empirical research to elucidate the cognitive control processes underlying threat and reward processing that contribute to irritability in middle childhood and provide a guiding framework for future research and treatment. We propose an expanded conceptual framework of irritability that includes broad intraindividual and environmental vulnerability factors and propose proximal 'setting' factors that activate the negative valence and positive valence systems and proactive and reactive cognitive control processes which underpin the expression and progression of irritability. We consider the implications of this expanded conceptualisation of irritability and provide suggestions for future research.

Factors Associated with High Parent- and Youth-Rated Irritability Score in Early-Onset Mood Disorders: A Cross-Sectional Study with the Affective Reactivity Index (ARI).

Correct classification of irritability is extremely important to assess prognosis and treatment indications of juvenile mood disorders. We assessed factors associated with low versus high parent- and self-rated irritability using the affective reactivity index (ARI) in a sample of 289 adolescents diagnosed with a bipolar or a major depressive disorder. Bivariate analyses were followed by multilinear logistic regression model. Factors significantly and independently associated with high versus low parent-rated ARI score were: more severe emotional dysregulation and bipolar disorders diagnosis. Factors significantly and independently associated with high versus low self-rated ARI score were: lower children depression rating scale (CDRS-R) difficulty of having fun item score, greater children depression inventory (CDI-2) self-report score, more severe emotional dysregulation, and greater CDRS-R appetite disturbance item score. High parent-rated irritability was strictly related with a bipolar disorder diagnosis, whereas high youth-rated irritability was related to depressive phenotype characterized by appetite/food-intake dysregulation, mood lability, and less anhedonia and apathy.

Assessment of affective dysregulation in children: development and evaluation of a semi-structured interview for parents and for children.

BACKGROUND: Children with affective dysregulation (AD) show an excessive reactivity to emotionally positive or negative stimuli, typically manifesting in chronic irritability, severe temper tantrums, and sudden mood swings. AD shows a large overlap with externalizing and internalizing disorders. Given its transdiagnostic nature, AD cannot be reliably and validly captured only by diagnostic categories such as disruptive mood dysregulation disorder (DMDD). Therefore, this study aimed to evaluate two semi-structured clinical interviews-one for parents and one for children. METHODS: Both interviews were developed based on existing measures that capture particular aspects of AD. We analyzed internal consistencies and interrater agreement to evaluate their reliability. Furthermore, we analyzed factor loadings in an exploratory factor analysis, differences in interview scores between children with and without co-occurring internalizing and externalizing disorders, and associations with other measures of AD and of AD-related constructs. The evaluation was performed in a screened community sample of children aged 8-12 years (n = 445). Interrater reliability was additionally analyzed in an outpatient sample of children aged 8-12 years (n = 27). RESULTS: Overall, internal consistency was acceptable to good. In both samples, we found moderate to excellent interrater reliability on a dimensional level. Interrater agreement for the dichotomous diagnosis DMDD was substantial to perfect. In the exploratory factor analysis, almost all factor loadings were acceptable. Children with a diagnosis of disruptive disorder, attention-deficit/hyperactivity disorder, or any disorder (disruptive disorder, attention-deficit/hyperactivity disorder, and depressive disorder) showed higher scores on the DADYS interviews than children without these disorders. The correlation analyses revealed the strongest associations with other measures of AD and measures of AD-specific functional impairment. Moreover, we found moderate to very large associations with internalizing and externalizing symptoms and moderate to large associations with emotion regulation strategies and health-related quality of life. CONCLUSIONS: The analyses of internal consistency and interrater agreement support the reliability of both clinical interviews. Furthermore, exploratory factor analysis, discriminant analyses, and correlation analyses support the interviews' factorial, discriminant, concurrent, convergent, and divergent validity. The interviews might thus contribute to the reliable and valid identification of children with AD and the assessment of treatment responses. TRIAL REGISTRATION: ADOPT Online: German Clinical Trials Register (DRKS) DRKS00014963. Registered 27 June 2018.

Pathomechanisms of behavioral abnormalities in Huntington disease: an update.

Huntington disease (HD), a devastating autosomal-dominant neurodegenerative disease caused by an expanded CAG trinucleotide repeat, is clinically characterized by a triad of symptoms including involuntary motions, behavior problems and cognitive deficits. Behavioral symptoms with anxiety, irritability, obsessive-compulsive behaviors, apathy and other neuropsychiatric symptoms, occurring in over 50% of HD patients are important features of this disease and contribute to impairment of quality of life, but their pathophysiology is poorly understood. Behavior problems, more frequent than depression, can be manifest before obvious motor symptoms and occur across all HD stages, usually correlated with duration of illness. While specific neuropathological data are missing, the relations between gene expression and behavior have been elucidated in transgenic models of HD. Disruption of interneuronal communications, with involvement of prefronto-striato-thalamic networks and hippocampal dysfunctions produce deficits in multiple behavioral domains. These changes that have been confirmed by multistructural neuroimaging studies are due to a causal cascade linking molecular pathologies (glutamate-mediated excitotoxicity, mitochondrial dysfunctions inducing multiple biochemical and structural alterations) and deficits in multiple behavioral domains. The disruption of large-scale connectivities may explain the variability of behavior profiles and is useful in understanding the biological backgrounds of functional decline in HD. Such findings offer new avenues for targeted treatments in terms of minimizing neurobehavioral impairment in HD.

Irritability, Negative Life Events and the Course of Anxiety and Depressive Symptoms in a Clinical Sample of Youth: A Longitudinal Study.

Objective: Irritability, the tendency to react with anger, and the experience of negative life events (NLE) have independently been associated with the emergence of anxiety and depression. Here, we investigate how irritability and cumulative effects of NLE interactively predict the course of anxiety and depression in the context of common psychiatric disorders. Method: 432 youth with no psychiatric diagnosis, or a diagnosis of an anxiety disorder, Attention-Deficit/ Hyperactivity Disorder (ADHD), or Disruptive Mood Dysregulation Disorder (DMDD), participated in this study. At baseline, we assessed NLE, parent and youth reports of irritability and anxiety, and youth reports of depression. Symptoms were annually reassessed for up to four years. Results: In youth without psychiatric diagnoses but with elevated baseline irritability, the presence of NLE predicted decreasing anxiety, while the absence of NLE predicted increasing anxiety. In youth with an anxiety disorder, elevated baseline irritability predicted decreasing anxiety independent of NLE, while a large cumulative effect of NLE predicted increasing depression. NLE predicted persisting mild anxiety in ADHD and persisting mild depressive symptoms in DMDD. Conclusion: Our findings suggest that, particularly in non-referred samples, NLE might moderate the relationship between irritability and future anxiety such that irritability/ anger in the context of NLE can positively affect the course of anxiety. Future work replicating this finding while repeatedly measuring NLE and rigorously controlling for potentially confounding effects of treatment, is warranted.

Momentary Dynamics Implicate Emotional Features in the ADHD Phenotype.

Emotional dysregulation is increasingly recognized as important to the attention-deficit/hyperactivity disorder (ADHD) phenotype alongside inattention and hyperactivity-impulsivity. Studies of ADHD have relied primarily on trait-based conceptualizations that emphasize stability of symptoms across moderate developmental timescales (i.e., months to years). Trait-based conceptualizations provide a critical view but fail to account for short-term dynamic variations in the expression of ADHD symptoms and emotion. This leaves a gap in our understanding of the short-term variation in ADHD symptom expression and the dynamic relationships among ADHD symptoms and emotion. Here, we assessed caregiver report of ADHD symptoms and positive and negative emotion using ecological momentary approaches over 2 weeks in a sample of 36 children with and without ADHD between the ages of 7-12 years old. Between-person (RKF) and within-person (RC) reliability were estimated. Multilevel models tested specific covariation hypotheses between ADHD symptoms and emotion. Analyses confirmed that ADHD and emotion ratings were reliable as individual differences (i.e., between-person; RKF range 0.93-1.0) and moment-to-moment change (i.e., within-person; Rc range 0.66-0.88) measures. Multilevel models found little evidence for lagged effects between domains, but consistently identified concurrent expression of ADHD symptoms and emotions; inattention covaried most strongly with negative emotion and hyperactivity-impulsivity covaried most strongly with positive emotion. Results demonstrate the importance of complementing trait-level conceptualizations with assessment of momentary dynamics. Momentary assessment suggests important covariation of ADHD symptoms and emotion as part of the ADHD phenotype.

Associations between trauma exposure and irritability within the family unit: a network approach.

BACKGROUND: Pediatric irritability is a pervasive psychiatric symptom, yet its etiology remains elusive. While trauma exposure may contribute to the development of irritability, empirical research is limited. This study examined the prevalence of irritability among trauma-exposed children, identified factors that differentiate trauma-exposed children with and without irritability, and employed a network analysis to uncover associations between irritability and trauma exposure in the family unit. METHODS: Sample included 676 children (56.3% male, mean age = 9.67 ± 3.7 years) and their parents referred by the Connecticut Department of Children and Families to Fathers for Change - a psychotherapy intervention designed to reduce intimate partner violence (IPV) and child maltreatment. Child's trauma exposure, post-traumatic stress disorder (PTSD) symptoms, and irritability were assessed pre-intervention using self- and caregiver-report. Parents self-reported their childhood and adulthood trauma exposures, PTSD symptoms, irritability, psychopathology, and IPV. RESULTS: Across caregiver- and child-reports, 16%-17% of children exhibited irritability. Irritable children experienced greater trauma exposure, interpersonal violence, emotional abuse, and PTSD severity. They had caregivers, particularly mothers, with greater trauma histories, IPV, and psychopathology. Network analysis revealed 10 nodes directly correlated to child's irritability including child's PTSD severity, parental IPV (specifically psychological violence), and parental psychopathology. CONCLUSIONS: Results provide initial empirical evidence that pediatric irritability is linked to trauma exposure, suggesting trauma histories be considered in the diagnosis and treatment of irritability. Interventions addressing caregiver trauma, IPV, and psychopathology may ameliorate pediatric irritability. Future studies could benefit from adopting network approaches with longitudinal or time series data to elucidate causality and points of intervention.

Effects of cariprazine on reducing symptoms of irritability, hostility, and agitation in patients with manic or mixed episodes of bipolar I disorder.

BACKGROUND: Hostility, irritability, and agitation are common in patients with bipolar I disorder. Post hoc analyses evaluated the effect of cariprazine on these symptoms in patients with bipolar I mania. METHODS: Data were pooled from three randomized, double-blind, placebo-controlled phase 3 cariprazine trials in adults with bipolar I manic/mixed episodes (NCT00488618, NCT01058096, NCT01058668); pooled cariprazine doses (3-12 mg/d) were analyzed. Patients were categorized into hostility/irritability and agitation subgroups by baseline scores: Young Mania Rating Scale (YMRS) irritability and disruptive-aggressive behavior items score ≥ 2; Positive and Negative Syndrome Scale (PANSS) hostility item ≥ 2; PANSS-Excited Component (PANSS-EC) total score ≥ 14 and score ≥ 4 on ≥ 1 individual item. Changes from baseline to week 3 in hostility/irritability- and agitation-related outcomes were evaluated. Adjustments were made for the presence of other manic symptoms, sedation, and akathisia. RESULTS: Most patients met subgroup inclusion criteria (YMRS hostility = 930; PANSS hostility = 841, PANSS-EC agitation = 486). In the YMRS subgroup, least squares mean differences in change from baseline were statistically significant for cariprazine versus placebo on YMRS hostility/irritability-related items (irritability [-0.93], disruptive-aggressive behavior [-0.79], combined [-1.75]; P ≤ 0.001 each), YMRS total score (-5.92, P ≤ 0.0001), and all individual YMRS items (-0.25 to -0.93, P ≤ 0.0001); differences remained significant after adjustment for other manic symptoms, sedation, and akathisia. Differences in PANSS hostility and PANSS-EC subgroups were significant for cariprazine versus placebo (P ≤ 0.001). LIMITATIONS: Post hoc analysis. CONCLUSION: Cariprazine demonstrated specific antihostility/irritability and anti-agitation effects in patients with manic/mixed episodes of bipolar I disorder and baseline hostility, irritability, or agitation.

Neuropsychiatric symptoms with focus on apathy and irritability in sporadic and hereditary cerebral amyloid angiopathy.

BACKGROUND: Neuropsychiatric symptoms (NPS) may affect cognition, but their burden in cerebral amyloid angiopathy (CAA), one of the main causes of intracerebral hemorrhage (ICH) and dementia in the elderly, remains unclear. We investigated NPS, with emphasis on apathy and irritability in sporadic (sCAA) and Dutch-type hereditary (D-)CAA. METHODS: We included patients with sCAA and (pre)symptomatic D-CAA, and controls from four prospective cohort studies. We assessed NPS per group, stratified for history of ICH, using the informant-based Neuropsychiatric Inventory (NPI-Q), Starkstein Apathy scale (SAS), and Irritability Scale. We modeled the association of NPS with disease status, executive function, processing speed, and CAA-burden score on MRI and investigated sex-differences. RESULTS: We included 181 participants: 82 with sCAA (mean[SD] age 72[6] years, 44% women, 28% previous ICH), 56 with D-CAA (52[11] years, 54% women, n = 31[55%] presymptomatic), and 43 controls (69[9] years, 44% women). The NPI-Q NPS-count differed between patients and controls (sCAA-ICH+:adj.ß = 1.4[95%CI:0.6-2.3]; sCAA-ICH-:1.3[0.6-2.0]; symptomatic D-CAA:2.0[1.1-2.9]; presymptomatic D-CAA:1.2[0.1-2.2], control median:0[IQR:0-3]), but not between the different CAA-subgroups. Apathy and irritability were reported most frequently: n = 12[31%] sCAA, 19[37%] D-CAA had a high SAS-score; n = 12[29%] sCAA, 14[27%] D-CAA had a high Irritability Scale score. NPS-count was associated with decreased processing speed (adj.ß=-0.6[95%CI:-0.8;-0.4]) and executive function (adj.ß=-0.4[95%CI:-0.6;-0.1]), but not with radiological CAA-burden. Men had NPS more often than women. DISCUSSION: According to informants, one third to half of patients with CAA have NPS, mostly apathy, even in presymptomatic D-CAA and possibly with increased susceptibility in men. Neurologists should inform patients and caregivers of these disease consequences and treat or refer patients with NPS appropriately.

Systematic Review and Meta-Analysis: Pharmacological and Nonpharmacological Interventions for Disruptive Mood Dysregulation Disorder.

Objectives: Disruptive mood dysregulation disorder (DMDD) is a relatively new diagnosis that comprises severe, nonepisodic irritability and recurrent outbursts of emotional instability in adolescents. This meta-analysis examined the efficacy of the available pharmacological and nonpharmacological interventions for DMDD. Methods: Literature searches were conducted in July 2023. To determine relevant articles, 330 abstracts were reviewed, and 39 articles were identified for full review. A random-effects model was used for the meta-analysis, and a subgroup analysis was performed to assess the effects of study design and intervention type. Results: Eleven studies were reviewed, including six pharmacological and five nonpharmacological. Despite high heterogeneity in effects (I2 = 85%), we showed statistically significant improvements in irritability symptoms following intervention. We showed statistically significant enhancements in symptoms of irritability following the intervention. The subgroup analysis revealed that, compared with randomized controlled trials (RCTs), open trials showed significant improvements in irritability. In addition, drug intervention significantly improved irritability compared to nondrug interventions. Atomoxetine (ATX), optimized stimulants, and stimulants combined with other drugs and behavioral therapy effectively improved irritability. Conclusions: With research indicating potential benefits for irritability from a combination of pharmacological interventions and therapy, including ATX, stimulants in conjunction with antipsychotic or antidepressant medications, and cognitive-behavioral techniques such as Dialectical Behavior Therapy for Children. Future large-scale RCTs are essential to further explore and refine these treatment approaches, especially focusing on the efficacy of combining pharmacological with effective nonpharmacological to improve irritability and overall outcomes in this population.

The Prevalence of Nomophobia in Medical Undergraduate Students of Central India.

Introduction Nomophobia is an emerging phobia resulting from people's excessive interaction with mobile phones. This phobia is rapidly increasing due to significant technological innovations and widespread acceptance and usage of mobile phones worldwide. Nomophobia is often associated with complications such as panic attacks, irritability, and anxiety. Smartphone usage is particularly high among the younger population, raising concerns as it generates distress and leads to various problems. This study aims to determine the prevalence of nomophobia among undergraduates. Method  The study utilized the Nomophobia Questionnaire (NMP-Q) with a minimum sample size of 136. A total of 300 Google Forms (Google, Mountain View, California) were circulated, out of which 172 responses were received. A Google Form comprising 20 questions related to smartphone use and nomophobia was designed and distributed to all undergraduate students, who were requested to complete the form. The data based on their responses were subsequently analyzed. Results In this study, approximately 31.40% of students disagreed with experiencing panic when running out of credits or hitting monthly data limits. Additionally, 24.42% of students agreed that not having smartphones made them worried, as their family and friends could not contact them. About 16.86% of students strongly disagreed with feeling uneasy because they could not stay updated without their phones. Furthermore, 16.28% strongly agreed that they felt anxious due to the inability to contact their family and friends when not having smartphones. Conclusion It can be concluded from this study that nomophobia is present among undergraduate students. The overall usage of smartphones has increased in this population, highlighting the emergence of a serious disorder that warrants attention. Consequently, the usage of smartphones should be reduced through structured training programs, as this proves to be an effective method for enhancing undergraduates' understanding of the prevention and treatment of nomophobia.

The utility of the irritability scale in Huntington's disease patients with evidence of irritability or aggression.

INTRODUCTION: Irritability, a common neuropsychiatric symptom in Huntington's disease (HD), lacks a standardized measurement. The Irritability Scale (IS), tailored for HD, has patient and informant versions, but variable interrater agreement has been reported frequently in previous studies. To enhance the clinical utility of the IS, this study aimed to identify the most reliable components estimating the underlying construct and develop a shortened version for time-limited contexts. METHODS: Participant and informant/observer concordance and the relationship of individual items to the complete IS scale were assessed. The short-form (SF) items were selected based on interrater agreement, exploratory factor analysis (EFA), and Item Response Theory (IRT) analysis results. Pair-wise correlation and covariance models were used to examine how SF predicted total IS score in 106 participants from the STAIR (Safety, Tolerability, and Activity of SRX246 in Irritable Subjects with Huntington's Disease) trial. Item Response Theory (IRT) analysis was used to evaluate the range and function of the selected items. RESULTS: IS interrater agreement was statistically significant (r = 0.33, p = .001). In combination with EFA factors and IRT analyses, five items were identified that showed good reliability and performance in differentiating levels of irritability. CONCLUSION: The proposed 5-item SF IS provided a reliable measure of the full scale and may be less burdensome for use in a clinical setting.

Foster Care Leads to Lower Irritability Among Adolescents with a History of Early Psychosocial Deprivation.

Irritability reflects a propensity for frustration and anger, and is a transdiagnostic symptom of both externalizing and internalizing psychopathology. While early adverse experiences are associated with higher levels of irritability, experiences of early psychosocial deprivation and whether family-based placements can mitigate the impact on subsequent irritability, remain underexplored. The current study examined irritability in 107 16-year-olds with a history of institutional care from a randomized controlled trial of foster care as an alternative to institutional care and 49 community comparison children. At age 16 years, irritability was assessed using parent- and self-report forms of the Affective Reactivity Index. Compared to community adolescents, those with a history of institutional care exhibited significantly elevated irritability levels. Among those who experienced institutional care, those randomized to foster care had lower levels of irritability compared to participants randomized to the care-as-usual group, and this effect persists after controlling for baseline negative emotionality. These findings suggest a causal link between high-quality foster care and lower irritability following psychosocial deprivation. Additionally, longer duration in institutional care and non-family placement at age 16 years were associated with higher levels of irritability, highlighting the role of caregiving in explaining variation in irritability in adolescence. Policies that support long-term, high-quality family placements for children without regular caregivers should be prioritized.

Development of a self-report screening instrument for emotional dysregulation: the Reactivity, Intensity, Polarity and Stability questionnaire, screening version (RIPoSt-SV).

BACKGROUND: Emotional dysregulation (ED) refers to the inability to manage emotional experiences or expressions hindering goal-oriented behavior. Moderate impairment on at least two domains among temper control, affective lability, and emotional over-reactivity has been proposed to identify ED in adults with attention-deficit/hyperactivity disorder (ADHD). No screening measure designed for use in diverse psychiatric samples exists. We aimed to develop a self-report screening tool for ED based on the 40-item version of the Reactivity, Intensity, Polarity, and Stability questionnaire (RIPoSt-40). METHODS: 150 adult outpatients with non-psychotic conditions were enrolled between February and July 2023 at the Second Psychiatry Unit of Pisa University Hospital. Clinically significant ED (CSED) was defined based on the previously suggested approach for ADHD. Differences between patients with and without CSED were tested. To develop our screening instrument, a decision tree algorithm was trained by hyperparameter tuning through 5-fold cross-validation in 120 subjects and tested on the remaining 30. RESULTS: 75 subjects met criteria for CSED (50 %). CSED was associated with lower age and higher prevalence of psychiatric conditions, including minor mood disorders, ADHD, cannabis use disorders, and eating disorders. We identified a decision tree consisting of six items from RIPoSt-40 that effectively detected CSED, with accuracy, sensitivity, specificity, positive and negative predictive values of 80 % or higher in both the training and testing sets. LIMITATIONS: Tertiary-level; no consensus on criteria; sample size. CONCLUSION: The screening version of the Reactivity, Intensity, Polarity, and Stability questionnaire (RIPoSt-SV) demonstrates promise as a valuable tool for ED screening in clinical settings.

Evaluating Gabapentin Dosing, Efficacy and Safety in Infants.

OBJECTIVE: Gabapentin for management of neuropathic pain, irritability, neonatal abstinence syndrome, rescue sedation, feeding intolerance and visceral hyperalgesia in infants has grown over the past decade. There remains little guidance for indications, initiation, titration and maintenance dosing trends and assessment of outcomes. The primary objective was to describe gabapentin dosing, and the secondary objectives were to identify outcomes to assess efficacy and describe weaning practices. METHODS: A retrospective single-center study was performed in infants younger than 1 year who received gabapentin at Boston Children's Hospital between 2015 and 2021. The primary outcome was indication, initiation and maximum gabapentin dose. Secondary outcomes included mortality, adverse reactions and impact on feeding volumes, weight-for-age Z-scores and face, legs, activity, cry, consolability (FLACC) scores. Descriptive statistics were utilized. RESULTS: Sixty-six infants received gabapentin at a mean ± SD age of 5.5 ± 2.7 months (range of 0-11 months). The mean ± SD initiation dose of gabapentin was 8.6 ± 5.4 mg/kg/day with a median interval of 24 hours (8-24 hours). The maximum mean dose was 23.2 ± 14.4 mg/kg/day at a median interval of every 8 hours (8 hours). The most common indications for initiation were irritability, rescue sedation, and visceral hyperalgesia. There was a statistical improvement in weight-for-age Z scores from 24 hours prior to gabapentin initiation to 2 weeks after the maximum dose of gabapentin (-2.23 ± 1.78 to -1.66 ± 1.91, p < 0.001) and a reduction in FLACC scores (2.29 ± 1.64 to 1.52 ± 1.76, p = 0.007) from 24 hours prior to gabapentin initiation to 3 days after the maximum dose of gabapentin. Three patients experienced minor adverse events. CONCLUSIONS: Gabapentin was well tolerated in infants. Initial gabapentin dosing of 5 mg/kg/dose every 24 hours appears safe and consistent with other published studies in infants. The improvement in outcomes with few adverse events suggests a beneficial role for gabapentin.

Cord serum cytokines at birth and children's trajectories of mood dysregulation symptoms from 3 to 8 years: The EDEN birth cohort.

There is growing evidence that in utero imbalance immune activity plays a role in the development of neurodevelopmental and psychiatric disorders in children. Mood dysregulation (MD) is a debilitating transnosographic syndrome whose underlying pathophysiological mechanisms could be revealed by studying its biomarkers using the Research Domain Criteria (RDoC) model. Our aim was to study the association between the network of cord serum cytokines, and mood dysregulation trajectories in offsprings between 3 and 8 years of age. We used the data of a study nested in the French birth cohort EDEN that took place from 2003 to 2014 and followed mother-child dyads from the second trimester of pregnancy until the children were 8 years of age. The 2002 mother-child dyads were recruited from the general population through their pregnancy follow-up in two French university hospitals. 871 of them were included in the nested cohort and cord serum cytokine levels were measured at birth. Children's mood dysregulation symptoms were assessed with the Strengths and Difficulties Questionnaire Dysregulation Profile at the ages 3, 5 and 8 years in order to model their mood dysregulation trajectories. Out of the 871 participating dyads, 53% of the children were male. 2.1% of the children presented a high mood dysregulation trajectory whereas the others were considered as physiological variations. We found a significant negative association between TNF-α cord serum levels and a high mood dysregulation trajectory when considering confounding factors such as maternal depression during pregnancy (adjusted Odds Ratio (aOR) = 0.35, 95% Confidence Interval (CI) [0.18-0.67]). Immune imbalance at birth could play a role in the onset of mood dysregulation symptoms. Our findings throw new light on putative immune mechanisms implicated in the development of mood dysregulation and should lead to future animal and epidemiological studies.