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.

Omega-3/6 supplementation for mild to moderate inattentive ADHD: a randomised, double-blind, placebo-controlled efficacy study in Italian children.

Recently there has been a growing interest in non-pharmacological treatments for ADHD. We evaluated the efficacy of a specific Omega-3/6 dietary supplement (two capsules containing 279 mg eicosapentaenoic acid [EPA], 87 mg Docosahexaenoic Acid [DHA], 30 mg gamma linolenic acid [GLA] each) in ameliorating inattentive symptoms in inattentive-ADHD children (6-12 years) with a baseline ADHD-RS-Inattention score ≥ 12. Secondary objectives included changes in global functioning, severity of illness, depression, and anxiety symptoms, learning disorders and in the fatty acids blood levels. The study was a randomised, double-blind, placebo-controlled efficacy and safety trial with a 6-month double-blind evaluation of Omega-3/6 vs placebo (Phase-I) and a further 6-month-open-label treatment with Omega-3/6 on all patients (Phase-II). In total 160 subjects were enrolled. No superiority of Omega-3/6 supplement to placebo was observed on the primary outcome (ADHD-RS-inattention score) after the first 6-months, with 46.3% of responders in the Omega-3/6 group and 45.6% in the placebo group; a slight (not statistically significant) reduction in Omega-6/3 ratio blood levels was measured in the active treatment group. Twelve months after enrolment, percentages of responders were similar between groups. A mild statistical, although not clinically significant, improvement was observed on the ADHD-RS-total score in the Omega-3/6 group but not on the ADHD-RS-Inattention score; a slight (not-statistically significant) reduction in Omega-6/3 ratio was observed in the group taking active treatment only during Phase II. In conclusion, no clinical beneficial effects of Omega-3/6 were detected on inattentive symptoms, suggesting a limited role of Omega-3/6 dietary products in children with mild ADHD-I.Trial registration: At the time of the Ethical submission, according to the clinical trial Italian law, registration was not mandatory for food additive as Omega 3/6 were then classified. The trial was approved by the Ethical Committee of the Cagliari University Hospital (resolution n. 662; September 22nd, 2011).

Psychopathological features in referred adolescents with psychogenic nonepileptic seizures with or without epilepsy.

Psychogenic nonepileptic seizures (PNES) are episodic manifestations that mimic epileptic seizures (ES) although not associated with electroencephalogram (EEG) abnormalities. Psychogenic nonepileptic seizures and ES, however, can often cooccur. Emotional distress in adolescents can trigger PNES, but the psychopathological and personality features are still unknown. The aim of this study was to explore psychopathological features in a sample of referred youth with PNES, with or without ES, compared with a control group with ES. Thirty-four patients aged 12 to 21 years, 19 females and 15 males, were included in the study, 15 patients with PNES, 7 with PNES and ES, and 12 with ES. The three groups were compared according to psychiatric categorical diagnoses, psychopathological dimensions, life stressors, and personality traits, including alexithymia, interpersonal reactivity, and resilience, all assessed with structured measures. Patients with PNES, with or without ES, were more severely impaired, had a higher incidence of mood disorders, more frequent lifetime traumatic experiences, and lower resilience. All the three groups presented alexythimic traits and emotional dysregulation. Major limitations are the small sample size and the lack of a control group of healthy subjects. Disentagling psychopathological characteristics in PNES can help clinicians to focus diagnostic approaches and therapeutic interventions.

Emotional dysregulation and callous unemotional traits as possible predictors of short-term response to methylphenidate monotherapy in drug-naïve youth with ADHD.

BACKGROUND: Emotional dysregulation (ED) and callous unemotional (CU) traits can be associated with ADHD in youth, influencing its natural history and outcome, but their effect on medication efficacy is unexplored. We examined whether two measures of baseline ED and CU traits, the Child Behavior Checklist-Dysregulation Profile (CBCL-DP) and the Antisocial Process Screening Device (APSD), respectively, were predictors of change of ADHD-Rating Scale (ADHD-RS) after a 4-week methylphenidate (MPH) monotherapy. METHODS: 43 patients (37 males, 8-16 years, mean 9.9 ± 2.7 years) were included. Hierarchical linear regression models were used to explore whether CBCL-DP and APSD might predict ADHD-RS score, controlling for baseline severity. RESULTS: Baseline CBCL-DP predicted higher post-treatment ADHD-RS scores in total and hyperactivity-impulsivity, but not in inattention subscale. Baseline APSD was not significantly related to ADHD-RS scores at the follow-up. LIMITATIONS: Small sample size, lack of gender diversity, non-blind design and short period of observation. CONCLUSION: ED, assessed with that CBCL-DP, might be a negative predictor of change of hyperactive-impulsive symptoms after MPH treatment and should be systematically assessed at baseline.

Clinical and electroencephalographic correlates of psychiatric features in children with frontal lobe epilepsy.

BACKGROUND AND OBJECTIVE: Frontal lobe epilepsy (FLE) is often associated with psychiatric features, although the factors predisposing to the concurrence of these conditions have yet to be determined, especially in younger children. We aimed at defining possible clinical and electroencephalography (EEG) features that may enhance the psychiatric risk in pediatric FLE. METHOD: We performed a structured psychiatric assessment of 59 children with FLE, using both categorical and dimensional approaches, correlated psychopathology with epilepsy data, and cognitive development. RESULTS: About 1/3 of patients with FLE displayed intellectual disability (ID), and more than 2/3 displayed psychiatric disorders, including depression, disruptive behaviors, anxiety, and bipolar/psychotic disorders. Psychiatric dimensions such as impulse control problems, attentional deficits, social problems, and aggressive behaviors were frequent features of FLE. Intellectual disability was associated with an earlier onset of psychiatric disorders and more frequent disruptive behavior disorders and aggressiveness. Long-standing epilepsy and bilateral or anterior frontal EEG abnormalities also increased the risk of psychopathology. Finally, right-hemisphere lesions were associated with disruptive behavior disorders, fast EEG rhythms with attention/memory problems, and phases of seizure remission with impulse control problems. CONCLUSIONS: Clinical and EEG markers of increased psychopathological risk may help in defining consistent at-risk subgroups within FLE and improving early diagnosis, prognosis, and treatment. Categorical and dimensional approaches to psychiatric diagnosis may generate new research hypotheses and support the investigation of the complex pathophysiological bases shared by different neurodevelopmental disturbances.

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.

Internalizing and externalizing symptoms in preschool and school-aged children with epilepsy: Focus on clinical and EEG features.

INTRODUCTION: Psychiatric and behavioral problems are frequent comorbidities of epilepsy, although their clinical and electroencephalographic (EEG) correlates remain uncertain. In this study, we have assessed the frequency of psychopathological problems in a cohort of children with epilepsy, and established their main clinical and EEG-associated features. METHODS: One hundred fifty-nine young patients with epilepsy were recruited and assessed through the Child Behavior Checklist for preschool-aged children (CBCL 1 1/2-5) or for school-aged children (CBCL 6-18). Child Behavior Checklist (CBCL) results were then correlated to the main clinical and EEG data. RESULTS: We found emotional and behavioral problems in about half of the children in our sample. Internalizing, social, and attention problems were more common than externalizing features. Moderate intellectual disability, a nonidiopathic etiology of epilepsy, a poor control of seizures, and antiepileptic polytherapies, as well as an early age at seizure-onset and a longer duration of the disorder, were all associated with specific behavioral and emotional problems. A temporal site of interictal EEG abnormalities also enhanced the risk for psychiatric comorbidities, especially in the externalizing domain. CONCLUSIONS: Several clinical and EEG features are associated with an increased risk for emotional and behavioral comorbidities in children with epilepsy. Their identification may foster an early diagnosis and appropriate care, limiting the worsening of psychiatric symptoms and their impact on quality of life and health status. A better understanding of the underlying clinical and molecular mechanisms is needed to further improve prevention and treatment interventions.

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.

Clinical features, developmental course, and psychiatric comorbidity of adult autism spectrum disorders.

Autism spectrum disorders (ASDs) include a heterogeneous group of neurodevelopmental disorders with early onset in childhood. ASDs should be considered lifelong clinical entities, although there is a certain variability in developmental trajectories, and therefore should be considered of great interest also for adulthood psychiatrists. A few studies have been carried out to explore the clinical picture and course development of these disorders during adulthood, or their relationship with other mental disorders. Indeed, ASDs often share overlapping features with other disorders, such as schizophrenia and obsessive-compulsive, mood, and personality disorders, and as a result misdiagnoses often occur. The aim of this review is to summarize the available literature on ASDs in adulthood with a specific focus on the clinical picture, course, and psychiatric comorbidity. It is proposed that a careful diagnostic screening for ASDs in adults would contribute to clarifying the relationship with comorbid psychiatric disorders, while improving the possibility of treatment and outcome of such conditions.

Relationship between seasonal weather changes, risk of dehydration, and incidence of severe bradyarrhythmias requiring urgent temporary transvenous cardiac pacing in an elderly population.

There is little information on any seasonal variations or meteorological factors associated with symptomatic bradyarrhythmias requiring cardiac pacing. The aim of this single-center study was to investigate the seasonal distribution of the incidence of severe, life-threatening bradyarrhythmias requiring urgent temporary transvenous cardiac pacing in an elderly population. Consecutive patients who underwent urgent temporary transvenous cardiac pacing between 2007 and 2012 were enrolled. The baseline characteristics of the patients and some meteorological parameters, including the calculation the daily heat index (HI), were recorded. During the study period, 79 consecutive patients (mean age 82 ± 8 years, 41% male) underwent urgent temporary transvenous cardiac pacing, mainly for third-degree atrioventricular block (79%). The incidence of bradyarrhythmias was significantly higher in summer than in the other seasons (P < 0.001). Moreover, the highest incidence was observed in months with HI > 90 °F for >3 h per day for at least 10 days (P < 0.001). A direct correlation was found between the average monthly temperature and the monthly number of patients undergoing temporary cardiac pacing (r = 0.54, P < 0.001). Compared with other patients, those observed during the hottest months were significantly older and more frequently affected by chronic disabling neurological diseases (all P < 0.05). In addition, they more frequently showed biochemical indices of dehydration, renal function impairment and hyperkalemia (all P < 0.05). This study showed an increased incidence of severe bradyarrhythmias in an elderly population during the hottest months of the year. In these months, in subjects characterized by increased susceptibility to dehydration, the risk of developing bradyarrhythmias was increased significantly.

Paediatric European Risperidone Studies (PERS): context, rationale, objectives, strategy, and challenges.

In children and adolescents with conduct disorder (CD), pharmacotherapy is considered when non-pharmacological interventions do not improve symptoms and functional impairment. Risperidone, a second-generation antipsychotic is increasingly prescribed off-label in this indication, but its efficacy and tolerability is poorly studied in CD, especially in young people with normal intelligence. The Paediatric European Risperidone Studies (PERS) include a series of trials to assess short-term efficacy, tolerability and maintenance effects of risperidone in children and adolescents with CD and normal intelligence as well as long-term tolerability in a 2-year pharmacovigilance. In addition to its core studies, secondary PERS analyses will examine moderators of drug effects. As PERS is a large-scale academic project involving a collaborative network of expert centres from different countries, it is expected that results will lead to strengthen the evidence base for the use of risperidone in CD and improve standards of care. Challenging issues faced by the PERS consortium are described to facilitate future developments in paediatric neuropsychopharmacology.

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.

Efficacy of Methylphenidate for Internet Gaming Disorder and Internet Addiction in Patients with Attention-Deficit/Hyperactivity Disorder.

BACKGROUND: Internet Gaming Disorder (IGD) and Internet Addiction (IA) are related clinical conditions often comorbid with Attention-Deficit/Hyperactivity Disorder (ADHD). OBJECTIVE: We evaluated the efficacy of MPH for IGD/IA symptoms in ADHD patients. METHODS: We enrolled 38 drug-naive patients diagnosed with ADHD (Attention-Deficit/Hyperactivity Disorder) and IGD/IA. At baseline, all patients underwent a clinical assessment for IGD/IA symptoms and then received the most appropriate therapy according to their clinical profile. Twenty-one patients received MPH (methylphenidate) treatment, and 17 patients did not. Patients were re-evaluated after three months of treatment. RESULTS: Findings revealed significant reductions in IGD/IA symptoms over time, while no significant effect of MPH on symptom reduction was found. Clinical predictors of symptom reduction were identified, including IQ (Intelligence Quotient) and comorbid anxiety. CONCLUSION: This longitudinal prospective study contributes to the understanding of IGD/IA treatment in ADHD patients and highlights the importance of considering individual clinical characteristics when predicting treatment response. However, MPH may not directly impact IGD/IA symptom reduction.

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.