Deep phenotyping of the neuroimaging and skeletal features in KBG syndrome: a study of 53 patients and review of the literature.

BACKGROUND: KBG syndrome is caused by haploinsufficiency of ANKRD11 and is characterised by macrodontia of upper central incisors, distinctive facial features, short stature, skeletal anomalies, developmental delay, brain malformations and seizures. The central nervous system (CNS) and skeletal features remain poorly defined. METHODS: CNS and/or skeletal imaging were collected from molecularly confirmed individuals with KBG syndrome through an international network. We evaluated the original imaging and compared our results with data in the literature. RESULTS: We identified 53 individuals, 44 with CNS and 40 with skeletal imaging. Common CNS findings included incomplete hippocampal inversion and posterior fossa malformations; these were significantly more common than previously reported (63.4% and 65.9% vs 1.1% and 24.7%, respectively). Additional features included patulous internal auditory canal, never described before in KBG syndrome, and the recurrence of ventriculomegaly, encephalic cysts, empty sella and low-lying conus medullaris. We found no correlation between these structural anomalies and epilepsy or intellectual disability. Prevalent skeletal findings comprised abnormalities of the spine including scoliosis, coccygeal anomalies and cervical ribs. Hand X-rays revealed frequent abnormalities of carpal bone morphology and maturation, including a greater delay in ossification compared with metacarpal/phalanx bones. CONCLUSION: This cohort enabled us to describe the prevalence of very heterogeneous neuroradiological and skeletal anomalies in KBG syndrome. Knowledge of the spectrum of such anomalies will aid diagnostic accuracy, improve patient care and provide a reference for future research on the effects of ANKRD11 variants in skeletal and brain development.

Deficits in emotion recognition and processing in children with high callous-unemotional traits: the role of the MAOA gene.

Children with high Callous-Unemotional (CU) traits show deficits in recognizing and processing facial expressions. Alterations in emotion recognition have been linked to a higher synaptic concentration of monoaminergic neurotransmitters. The current study investigated the relationship between the MAOA-Low-activity alleles and the ability to recognize and process facial expressions in 97 male children (8-12 years old) diagnosed with disruptive behavior disorder. Participants completed a computerized emotion-recognition task while an eye-tracking system recorded the number (Fixation Count, FC) and length (Fixation Duration, FD) of fixations to the eye region of the emotional stimuli. Children with high CU traits exhibited lower scores in recognition of sadness and anger, and lower FC and FD for sadness and fear than children with low CU traits. Children carrying the MAOA-Low-activity alleles displayed lower FD for sadness, and FD and FC for fear than those carrying the MAOA-High-activity alleles. These genetic effects appeared even stronger in children with CU traits. Moderation analysis revealed that CU traits were associated with lower FC and FD for fear, and lower FD for sadness, probably due to the MAOA-Low-activity alleles. Our findings, although to be replicated, suggest MAOA-Low-activity alleles as potential genetic biomarkers to identify CU children in need of training focused on emotion processing.

The "Measure of Empathy in Early Childhood": Psychometric Properties and Associations with Externalizing Problems and Callous Unemotional Traits.

Empathy is crucial to the development of socio-emotional skills in youth and empathy development is central to understanding and subtyping youth with externalizing problems. This study explored for the first time the psychometric properties of the Measure of Empathy in Early Childhood (MEEC) in a sample of 652 Italian children aged 6 to 8 years. The gender invariance of MEEC scores and their associations with other measures of empathy and prosocial behavior, and children's externalizing problems and callous-unemotional (CU) traits were also evaluated. Results indicated that with some modifications, a 5-factor structure of the Italian version of MEEC scores fitted the data and was invariant across gender. Results further supported the reliability and validity of MEEC total and subscale scores. Practical implications of these results are discussed.

Social withdrawal and gender differences: Clinical phenotypes and biological bases.

Evidence from everyday life suggests that differences in social behaviors between males and females exist, both in animal and in humans. These differences can be related to socio-cultural determinants, but also to specialized portions of the brain (the social brain), from the neurotransmitter to the neural network level. The high vulnerability of this system is expressed by the wide range of neuropsychiatric disorders associated with social dysfunctions, particularly social withdrawal. The principal psychiatric disorders with prominent social withdrawal are described, including hikikomori-like syndromes, and anxiety, depressive, autistic, schizophrenic, and personality disorders. It is hypothesized that social withdrawal can be partially independent from other symptoms and likely reflect alterations in the social brain itself, leading to a similar, transdiagnostic social dysfunction, reflecting defects in the social brain across a variety of psychopathological conditions. An overview is provided of gender effects in the biological determinants of social behavior, including: the anatomical structures of the social brain; the dimorphic brain structures, and the modulation of their development by sex steroids; gender differences in "social" neurotransmitters (vasopressin and oxytocin), and in their response to social stress. A better comprehension of gender differences in the phenotypes of social disorders and in the neural bases of social behaviors may provide new insights for timely, focused, innovative, and gender-specific treatments.

Effect of a parenting intervention on decreasing adolescents' behavioral problems via reduction in attachment insecurity: A longitudinal, multicenter, randomized controlled trial.

INTRODUCTION: Secure attachment in adolescence, related to caregiving quality, is a robust predictor of positive behavioral adjustment in early adulthood and beyond. Nevertheless, few attempts have been made to develop treatments to promote parent-adolescent attachment security. METHODS: Using a longitudinal, multicenter, randomized controlled trial design, two questionnaire-based studies were run in Italy (Study 1: n = 100 mothers of adolescents, 60% boys, Mage = 14.89, SD = 1.58; Study 2: n = 40 mothers and 40 adolescents, 60% boys, Mage = 14.90, SD = 1.91) to test the effectiveness of an attachment-based parenting intervention (i.e., Connect) in reducing adolescents' behavioral problems and attachment insecurity 2 weeks post-intervention (t2) and at a 4-month follow-up (t3). It was further investigated whether a decrease in avoidant and anxious attachment at t2 would account for changes in externalizing and internalizing problems, respectively, at t3. All adolescents belonged to two-parent intact families. RESULTS: Mothers who completed Connect reported significantly fewer adolescent behavioral problems and lower adolescent attachment insecurity, compared to mothers in the waitlist group, at both t2 and t3 (Study 1). These findings were confirmed in a second subsample (Study 2), considering both mothers' and adolescents' reports. Controlling for pre-intervention behavioral problems, reductions in internalizing and externalizing problems were observed in both studies at t3 via a decrease in anxious and avoidant attachment, respectively, at t2. CONCLUSIONS: The findings point to the malleability of attachment security in adolescence and highlight the importance of targeting parenting quality to promote adolescent behavioral adjustment.

Empathy in Youths with Conduct Disorder and Callous-Unemotional Traits.

Previous studies indicated that a lack of empathy could be considered the core feature of callous-unemotional (CU) traits in children and adolescents. The present study is aimed at exploring relationships among CU traits, cognitive and emotional dimensions of empathy, emotion recognition (basic, social, and complex emotions), and history of maltreatment in a sample of youths with conduct disorder diagnosis. The sample consisted of 60 Italian male patients (age range 11-17 years, mean age 13.27 ± 1.90 years) referred to the Department of Child and Adolescent Psychiatry (Pisa, Italy). In the whole sample, the levels of CU traits were significantly negatively associated with both cognitive and emotional dimensions of empathy; in addition, the CD patients with high levels of CU traits show significantly lower levels of empathic concern compared to those with low levels of CU traits. Clinical implications of the findings are discussed.

A Naturalistic Comparison of Methylphenidate and Risperidone Monotherapy in Drug-Naive Youth With Attention-Deficit/Hyperactivity Disorder Comorbid With Oppositional Defiant Disorder and Aggression.

BACKGROUND/PURPOSE: Attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) are frequently co-occurring in youth, but data about the pharmacological management of this comorbidity are scarce, especially when impulsive aggression is prominent. Although stimulants are the first-line medication for ADHD, second-generation antipsychotics, namely, risperidone, are frequently used. We aimed to assess effectiveness and safety of monotherapy with the stimulant methylphenidate (MPH) and risperidone in a consecutive sample of 40 drug-naive male youths diagnosed as having ADHD-combined presentation, comorbid with ODD and aggression, without psychiatric comorbidities, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria and a structured clinical interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version). METHODS: Twenty males treated with MPH (mean age, 8.95 ± 1.67 years) and 20 males treated with risperidone (mean age, 9.35 ± 2.72 years), followed up to 6 months, were assessed according to efficacy measures (Child Behavior Checklist [CBCL], Clinical Global Impression-Severity [CGI-S] and Improvement [CGI-I], Children Global Assessment Scale), and safety measures. At the end of the follow-up, both medications were similarly effective based on CBCL subscales of aggression and rule-breaking behaviors, on Diagnostic and Statistical Manual of Mental Disorders-oriented oppositional defiant problems and conduct problems, and on CGI-S, CGI-I, and Children Global Assessment Scale, but only MPH was effective on CBCL attention problems and attention-deficit/hyperactivity problems. Risperidone was associated with weight gain and elevated prolactin levels. IMPLICATIONS/CONCLUSIONS: Although the nonrandomized, nonblind design limits the conclusions of our exploratory study, our findings suggest that when ADHD is comorbid with ODD and aggression MPH and risperidone are both effective on aggressive behavior, but only stimulants are effective on ADHD symptoms.

Moral disengagement and callous-unemotional traits: A longitudinal study of Italian adolescents with a disruptive behaviour disorder.

BACKGROUND: Callous-unemotional traits have been proposed as risk factors for a poorer prognosis in young people with disruptive behaviour disorders. Identification of factors that may cause or maintain elevated levels of such traits could help in developing targeted therapeutic interventions. Some previous studies have investigated the role of moral cognitive mechanisms, such as moral disengagement, but these previous studies focused primarily on normal or 'at-risk' samples. AIM: We aimed to evaluate associations and possible interactions between moral disengagement as a cognitive dimension and callous-unemotional traits as an affective dimension in adolescents with disruptive behaviour disorders. METHOD: We recruited 55 adolescents with a disruptive behaviour disorder from a community care hospital in Pisa. They were evaluated at baseline and after one year with measures that included a moral disengagement scale, the Antisocial Process Screening Device, to assess callous traits, and the Youth Self-Report, to explore externalising behaviour problems. RESULTS: Structural equation modelling showed that higher initial moral disengagement scores were associated with later higher levels of callous-unemotional traits in adolescents and vice versa, even after, respectively, controlling for previous levels of callous traits and moral disengagement. CONCLUSION: As impairments in either cognitive or affective traits may predispose to problematic development of the other, our findings would suggest that screening at the earliest opportunity possible for both moral disengagement and callous-unemotional traits among children with disruptive behaviour disorders could help to map natural outcome pathways and thus tailor more accurate interventions for prevention of antisocial or criminal behaviour. Copyright © 2016 John Wiley & Sons, Ltd.

Evaluation of Improvement in Externalizing Behaviors and Callous-Unemotional Traits in Children with Disruptive Behavior Disorder: A 1-Year Follow Up Clinic-Based Study.

Multi-component interventions based on cognitive behavioral principles and practices have been found effective in reducing behavioral problems in children with disruptive behavior disorders (oppositional defiant disorder and conduct disorder). However, it is still unclear if these interventions can affect children's callous-unemotional traits, which are predictive of subsequent antisocial behavior. Furthermore, it could be important to identify empirically supported treatment protocols for specific disorders addressed by child mental health services. The present study aimed to test the following two hypotheses: first, the Coping Power (CP) treatment program is able to reduce externalizing behaviors in children with disruptive behavior disorders treated in a mental health care unit; second, the CP program can reduce children's callous unemotional traits. The sample included 98 Italian children, 33 treated with the CP program; 37 with a less focused multi-component intervention, and 28 with child psychotherapy. The results showed that the CP program was more effective than the other two treatments in reducing aggressive behaviors. Furthermore, only the CP program was associated with a decrease in children's callous unemotional traits. The CP program was also associated with lower rate of referrals to mental health services at one-year follow-up. These findings support the importance of disseminating manualized and focused intervention programs in mental health services.

Which dimension of parenting predicts the change of callous unemotional traits in children with disruptive behavior disorder?

OBJECTIVE: Several studies suggested that in addition to child-driven factors (i.e., temperamental style), parenting behavior can, at least in part, influence the maintenance of Callous Unemotional (CU) traits in children; however, more information is needed to distinguish which styles (negative parenting or lack of positive parenting) predict increased levels of CU traits. The aim of the present treatment study was to examine which components of parenting are longitudinally associated with levels of CU traits in children with a disruptive behavior disorder diagnosis. METHOD: The current study examined cross-lagged reciprocal effects models between positive and negative parenting practices, and the levels of child CU traits over three time points, including both positive and negative dimensions of parenting in the same model. Participants were 126 Italian children with diagnosis of disruptive behavior disorder (oppositional defiant disorder or conduct disorder), 113 boys and 13 girls, 110 Caucasian, 48 with conduct disorder, and 78 with oppositional defiant disorder, treated with a multi-component intervention, based on cognitive behavioral principles and practices. Participants were all 9-10 years of age at the beginning of the study, and were followed-up until the age of 11-12 years (24 months in total, the first 12 under treatment) using parent report (Alabama Parenting Questionnaire and Child Behavior Check List) and child report (Inventory of Callous-Unemotional Traits) measures. RESULTS: No significant cross-lagged path was found between negative parenting and CU traits; these two variables were also unrelated when positive parenting was considered in the same model. In contrast, reciprocal effects between positive parenting and CU were found: higher levels of positive parenting predicted lower levels of CU traits. CONCLUSIONS: The current findings suggest that the positive dimension of parenting may need to be targeted in the treatment of DBD children with higher CU traits.

Efficacy and Safety of Risperidone and Quetiapine in Adolescents With Bipolar II Disorder Comorbid With Conduct Disorder.

Although a frequent co-occurrence between bipolar disorder (BD) and conduct disorder (CD) in youth has been frequently reported, data about pharmacological management are scarce and focused on BD type I. Second generation antipsychotics are frequently used in clinical practice, but no comparative studies are available. The aim of this exploratory study was to compare efficacy and safety of risperidone and quetiapine in a sample of adolescents presenting a BD type II comorbid with CD. Twenty-two patients diagnosed with a structured interview according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (male/female ratio, 12/10; mean (SD) age 15.0 (1.4) years) were randomized in 2 treatment groups (quetiapine [n = 12] vs risperidone [n = 10]), treated with flexible doses, and followed up for 12 weeks. Efficacy measures assessed manic symptoms, aggression, anxiety, depression, global clinical severity, and impairment. Safety measures included body mass index, serum prolactin, extrapyramidal adverse effects, and electrocardiogram. At the end of the study, all patients improved in all efficacy measures. Both treatments showed similar efficacy in reducing manic symptoms and aggression. Quetiapine was more effective in improving anxiety and depressive symptoms. A change in body mass index was found, and in a post hoc analysis, it was significant only in the risperidone group. Prolactin significantly increased only in the risperidone group. In BD type II, CD comorbidity, quetiapine, or risperidone monotherapy may be effective and relatively safe, although the small sample size, the limited duration of the study, and the design (lack of a blind assessments and of a placebo group) make it difficult to draw definitive conclusions.

First adaptation of coping power program as a classroom-based prevention intervention on aggressive behaviors among elementary school children.

Children with high levels of aggressive behavior create a major management problem in school settings and interfere with the learning environment of their classmates. We report results from a group-randomized trial of a program aimed at preventing aggressive behaviors. The purpose of the current study, therefore, was to determine the extent to which an indicated prevention program, Coping Power Program, is capable of reducing behavioral problems and improving pro-social behavior when delivered as a universal classroom-based prevention intervention. Nine classes (five first grade and four second grade) were randomly assigned to intervention or control conditions. Findings showed a significant reduction in overall problematic behaviors and in inattention-hyperactivity problems for the intervention classes compared to the control classes. Students who received Coping Power Program intervention also showed more pro-social behaviors at postintervention. The implications of these findings for the implementation of strategies aimed at preventing aggressive behavior in school settings are discussed.

Clinical and Biological Correlates of Emotional Dysregulation in Children and Adolescents: A Transdiagnostic Approach to Developmental Psychopathology.

Emotion regulation may be defined as the ability to regulate behavioral and physiological reactivity to sensory stimuli and environmental situations [...].

Systematic Review and Meta-Analysis: Altered Autonomic Functioning in Youths With Emotional Dysregulation.

OBJECTIVE: To systematically investigate if there is a significant association between markers of autonomic functioning and emotional dysregulation (ED) in children and adolescents. METHOD: Based on a preregistered protocol (PROSPERO: CRD42021239635), PubMed, Web of Knowledge/Science, Ovid MEDLINE, Embase, and APA PsycInfo databases were searched until April 21, 2021, to identify empirical studies reporting indices of autonomic nervous system (ANS) functioning in youths meeting DSM (version III, IV, IV-TR, 5 or 5-TR) or International Classification of Diseases (ICD) (version 9 or 10) criteria for any psychopathological/neurodevelopmental condition and assessed for ED with a validated scale. Eligible outcomes included correlation coefficients between ED and ANS measures or differences in ANS measures between youths with and without ED. Study quality was assessed with the Appraisal tool for Cross-Sectional Studies (AXIS) and the Newcastle-Ottawa Scale (NOS) for cohort studies. Random-effects meta-analyses were used for data synthesis. RESULTS: There were 12 studies (1,016 participants) included in the descriptive review and 9 studies (567 participants) included in the meta-analyses. No evidence of a significant association between ED and altered cardiac or electrodermal functioning was found. However, exploratory meta-regressions suggested a possible association between reduced resting-state cardiac vagal control and increased ED. CONCLUSION: This study did not find evidence of an association between ED and autonomic dysfunction. However, preliminary evidence that reduced vagal control at rest might be a transdiagnostic marker of ED in young people was found. Additional studies comparing autonomic measures in youths with and without ED are needed and should also assess the effects of interventions for ED on ANS functioning. STUDY PREREGISTRATION INFORMATION: Systematic Review and Meta-Analysis: Is Autonomic Nervous System Functioning Atypical in Children and Adolescents With Emotional Dysregulation? https://www.crd.york.ac.uk/prospero/; CRD42021239635.

Parenting and Emotional and Behavioral Difficulties in a General Population Sample of Adolescents: The Mediating Role of Emotional Dysregulation.

Research has shown that both parenting and emotional dysregulation are associated with mental health outcomes in youth. This cross-sectional research was developed to replicate these noted findings and explore the mediating role of emotional dysregulation to explain the relationship between parenting and emotional and behavioral difficulties (internalizing and externalizing problems) in adolescents. A total of 104 adolescents (61.5% females; M = 15.62 yrs., SD = 1.38) participated in the study. Participants completed the Parental Bonding Instrument (measuring care, promotion of autonomy, and overprotection) referring to both the mother and father, the Difficulties in Emotion Regulation Scale, and the Youth Self-Report. The results showed that difficulties in emotion regulation fully mediated the relationship between overprotection (in both parents) and low maternal care with internalizing problems, on the one hand, and the relationship between maternal overprotection and low care (in both parents) with externalizing problems, on the other hand. Furthermore, emotional dysregulation partially mediated the effect of paternal care on internalizing problems. These findings help to clarify one of the mechanisms through which parenting can affect mental health in youth. Theoretical and clinical implications are discussed.

Emotional Dysregulation and Sleep Problems: A Transdiagnostic Approach in Youth.

BACKGROUND: Sleep is a complex phenomenon that affects several aspects of life, including cognitive functioning, emotional regulation, and overall well-being. Sleep disturbances, especially during adolescence, can negatively impact emotional regulation, making it a critical factor in targeting psychopathology. METHODS: This study explores the interplay between emotional dysregulation (ED) and sleep patterns in a sample of 90 adolescent patients by means of self- and parent-rated clinical measures. RESULTS: Our findings reveal a bidirectional relationship between ED and sleep problems. Adolescents with higher affective instability experience poorer sleep quality, while those with worse sleep quality exhibit higher internalizing problems. Additionally, emotional reactivity is associated with disrupted circadian rhythms. CONCLUSIONS: These results emphasize the significance of addressing sleep problems in the context of psychopathology treatment, potentially leading to improved outcomes. Further research is needed to determine the most effective treatment strategies, including nonpharmacological and pharmacological interventions. Understanding the intricate relationship between sleep problems and emotion regulation offers insights for more targeted and effective treatment approaches for youths struggling with ED.

Clozapine Treatment for Aggressive Behaviors in Youths with Neurodevelopmental Disorders.

Objectives: The aim of this study was to assess effectiveness and tolerability of Clozapine in the treatment of aggression in youth with Neurodevelopmental Disorders. Methods: Patients were consecutively admitted at our third-level university hospital with nationwide catchment from June 2018 to October 2022, and followed up to July 2023. Eligibility criteria were as follows: (1) Autism Spectrum Disorder (ASD) and/or Intellectual Disability/Borderline Cognitive Functioning, (2) behavioral dyscontrol with physical aggression; (3) age range between 8 and 18 years; (4) clinical indication for Clozapine treatment after at least two failed trials with other Second-Generation Antipsychotics (SGAs); (5) availability of an at least 6-month-long follow-up. To evaluate the response to Clozapine, we used the Clinical Global Impressions (CGI) rating scales (Clinical Global Impressions-Severity [CGI-S] and Clinical Global Impressions-Improvement [CGI-I]), the Children's Global Assessment Scale (CGAS), and the Aberrant Behavior Checklist (ABC). Results: Twenty-six children and adolescents (21 boys, age 13.47 ± 2.05 years, follow-up duration 9.77 ± 3.50 months) were included in the analysis. Clinical severity (CGI-S) and functional impairment (Clinical Global Assessment Scale) significantly improved, as well as the ABC Total Score and the scores in several subscales. Sixteen patients (61.54%) were responders (CGI-I ≤2), and 13 (50.00%) displayed remission of aberrant behaviors (ΔABC-Total >35), while response/remission condition was not affected by add-on medications and psychotherapy. Most frequent side effects were increased appetite (50.00%), sialorrhea (38.46%), and increased repetitive behaviors (26.92%). Two patients presented epileptic seizures, while no patients presented leucopoenia. Conclusions: Our results suggest that Clozapine may be helpful in ameliorating treatment-resistant aggression in youth with neurodevelopmental conditions. Possible pharmacological strategies for the management of most frequent side effects are also suggested.

Internet Gaming Disorder in Children and Adolescents with Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder.

Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have been related to an increased risk for behavioral addictions including online gaming. However, the relationship between these two conditions and Internet gaming disorder (IGD) is still debated. The aim of this study is to address this topic by exploring the prevalence of IGD in a consecutive sample of ASD youth and ADHD youth, compared with a normal control group, and by assessing selected psychopathological and neuropsychological features in ASD and ADHD patients with and without IGD. This study included 77 ASD patients (67 males, mean age 13.58 ± 2.75 years), 94 ADHD patients (79 males, mean age 11.46 ± 2.47 years), and 147 normal controls (NC) (mean age 13.9 ± 3.0 years, 114 males) that received structured measures for IGD (IAT, IGDS9-SF, and UADI). In the ADHD group, 72.34% of the sample were above the IGD cut-off, compared with 45.45% in the ASD group and 9.5% in the NC group. ASD patients with IGD presented with greater severity and more severe attention problems, with no difference in the ASD core symptoms between patients with and without IGD. In the comparison between the ASD and ADHD groups according to the presence of IGD, ASD patients with IGD were the most severe group according to the CGI (Clinical Global Impression) scale. The follow-up, conducted on 45 patients affected by ASD, showed an improvement in CGI and CGAS (Children's Global Assessment Scale) scores, but not in the IGD symptoms. These findings could place the diagnosis of ASD as a negative prognostic factor in the follow-up of aspects of video game addiction compared with ADHD.

Extended-Release Lithium Treatment for Adolescents with Bipolar Disorder with or Without Comorbid Autism Spectrum Disorder: Protocol of a Longitudinal Prospective Naturalistic Study for the Assessment of Efficacy and Tolerability.

Background: Lithium is the gold-standard treatment for Bipolar Disorder (BD) in both adults and adolescents, effectively managing mood episodes and reducing suicide risk. While its efficacy in neurotypical youth is well established, its use in adolescents with Autism Spectrum Disorder (ASD) and comorbid BD remains under-researched. Here, we present the protocol for a study aiming to evaluate the efficacy and tolerability of Extended-Release Lithium Salts in treating adolescents with BD and comorbid ASD compared to neurotypical BD patients. Methods: This longitudinal prospective naturalistic comparative study will enroll lithium-naïve adolescents aged 12-18 with BD, with or without comorbid ASD, from the Department of Child and Adolescent Psychiatry and Psychopharmacology. Participants will be followed for six months while receiving Extended-Release Lithium Salts treatment. Primary outcomes will include mood instability, suicidality, emotional dysregulation, and aggression, assessed through a range of clinical rating scales and diagnostic tools at baseline, three months, and six months. Secondary outcomes will focus on the safety and tolerability of Extended-Release Lithium Salts, with measures including side effect ratings, physical exams, and laboratory tests. Results: We hypothesize that Extended-Release Lithium Salts will demonstrate non-inferiority in treating BD symptoms in adolescents with comorbid ASD compared to those without ASD. Conclusions: This study is poised to fill a significant gap in the literature by providing critical data on the use of lithium for adolescents with BD and ASD. Findings will inform clinical practice and future research, potentially guiding more personalized treatment approaches for this complex and vulnerable population.

Reactivity of Emotions in Adolescents - Caregivers' Tool (React): Development and Validation of a Novel Parent-Rated Measure for Assessing Emotional Dysregulation in Youth.

Objective: Emotional Dysregulation (ED) is characterized by the inability to manage emotions effectively, leading to maladaptive behaviors, and often co-occurs with psychiatric conditions carrying significant long-term consequences. Early diagnosis of ED is thus essential for targeted interventions. To address this need, we developed and validated the "Reactivity of Emotions in Adolescents: Caregivers' Tool" (REACT), a novel parent-rated questionnaire designed to assess ED in adolescents. Method: The present study involved two samples, one drawn from the general population (n = 89 healthy controls from local schools) and the other composed of clinical patients (n = 76 adolescents with different psychiatric and/or neurodevelopmental conditions). Patients' diagnoses were confirmed through the clinical interview K-SADS-PL to explore the presence of any psychopathological conditions. Participants from both groups completed the RIPoSt-Y questionnaire, providing a measure of ED, while their parents filled out the ARI, measuring affective reactivity in youth. Confirmatory and exploratory factor analyses were performed to refine the questionnaire's internal structure. Results: The final REACT questionnaire consists of 55 items distributed across three subscales, namely Negative Emotionality, Irritability, and Excitability. Psychometric evaluation showed that these subscales demonstrated excellent internal consistency and strong construct validity, with clinical patients scoring higher on all subscales compared to healthy controls. The REACT questionnaire showed also high convergent validity by exhibiting significant positive correlations with established measures of ED. Conclusions: This novel tool represents a valuable improvement in the assessment of ED in adolescence as it may facilitate tailored interventions to provide emotional well-being and long-term outcomes.