The Relation of Callous-Unemotional Traits and Bullying in Early Adolescence Is Independent from Sex and Age and Moderated by Conduct Problems.

In youths, callous-unemotional (CU) traits and conduct problems (CP) are independently associated with bullying perpetration and these effects are also observed when controlling for sex. Moreover, research indicates that the co-existence of high levels of both CU and CP further increase the risk. Although several studies have examined the relationship between CU traits and traditional bullying, few have also included a measure of cyberbullying and very few of them have focused the early adolescence. The aim of this study was to replicate and extend these findings in a large sample of Italian early adolescents considering both traditional and cyberbullying behaviors. Data were extracted from the Bullying and Youth Mental Health Naples study (BYMHNS) which included 2959 students of 10-15 years of age. CP, CU traits, traditional bullying behaviors, and cyberbullying behaviors were assessed by multi-item self-report scales. As expected, we replicated the significant and specific association between CU traits and traditional bullying, extending the findings to cyberbullying. In addition, in the latter case the effect was moderated by CP. The theoretical and clinical implications of these results were discussed.

Phantom Phone Signals in youths: Prevalence, correlates and relation to psychopathology.

The term Phantom Phone Signals (PPS) refers to the perception of a mobile phone ringing, vibrating and blinking when in fact it did not. Data in youth are lacking, and controversies exist on whether PPS is related to psychopathology. In the present study, we showed data on the prevalence of PPS in a population (N = 2959) of students aged 10 to 14 years. We also explored the possible association between PPS and emotional or behavioural problems. Our results showed that PPS is a relatively common phenomenon with a prevalence rate of 58.9%, being more frequent in females. In univariate and multivariate analyses, we also found an association between the presence of PPS and emotional problems and temper tantrums, after accounting for relevant covariates. PPS is a relevant phenomenon to be considered in youth. It is common and may be a signal for emotional problems.

Epidemiological pattern of bullying using a multi-assessment approach: Results from the Bullying and Youth Mental Health Naples Study (BYMHNS).

BACKGROUND: Bullying is a widespread phenomenon that has captured attention from mental health researchers. Several studies have assessed bullying prevalence with some methodological concerns. OBJECTIVES: Preliminary, we analyzed the psychometric properties of two bullying scales for victimization (the multidimensional peer victimization scale - MPVS) and for perpetration (the bully subscale of the Illinois bully scale - IBS-B); then, we estimated bullying prevalence; finally, we evaluated the effect of gender and classroom on the phenomenon. PARTICIPANTS AND SETTING: 2959 students from the metropolitan city of Naples constituted the sample. METHODS: Data collection was obtained using a multi-assessment approach that included both single-item questions and intensity scales in order to compare the two methods. RESULTS: The two scales resulted valid and showed good reliability. The MPVS displayed a 1-factor second order model. The IBS-B had a mono-factorial structure. Both showed full invariance for gender and classroom. Prevalence of victimization was 37% whereas that for perpetration was 21%. As expected we obtained several bullying prevalence results depending on the specificity of questions and in particular repetitiveness of episodes. There was a good correspondence between results of single-item questions and multi-item scales. Finally results demonstrated several differences for gender and classroom attended. CONCLUSION: In this epidemiological study the multi-assessment approach identified different but complementary features of bullying phenomena. The use of the two measurement approaches allowed us to obtain more precise and exhaustive information on bullying prevalence and compare it with previous findings.

Psychotic-like experiences in help-seeking adolescents: Dimensional exploration and association with different forms of bullying victimization - A developmental social psychiatry perspective.

BACKGROUND: Psychotic-like experiences (PLEs) are common in the general population and increase the risk of psychotic disorders. Adolescents are a high-risk group of this condition. Stressful events, such as bullying, have a role in the onset of PLEs. This study has several aims: (1) to assess PLEs in adolescents seeking help from a Child and Adolescent Mental Health Service, (2) to assess the association of PLEs with specific bullying victimization and (3) to assess difference in PLEs and victimizations by sex and age. METHODS: Participants were help-seeking (HS) adolescents initially screened for PLEs. They completed an assessment including characteristics of PLEs and bullying victimization. We paid particular attention to different kinds of PLEs and victimization. RESULTS: In total, 50 PLE-positive adolescents screened from 324 HS adolescents (15.4%) constituted the sample. Paranoia and verbal bullying were the PLEs and form of victimization most represented, respectively. Verbal bullying was strongly associated with paranoia (odds ratio (OR): 4.40, confidence interval (CI): 2.8-5.9, p < .001). Results remained significant after controlling for confounder (socio-demographic, anxiety, depression and for the latter analysis also other forms of victimization). Furthermore, social manipulation showed a strong association of paranoia and physical bullying with grandiosity. Verbal bullying was also associated with psychotic negative symptoms, but controlling for emotional symptoms and other victimization led to a reduction in the effect. Men were more involved in physical victimization and experienced grandiosity; on the contrary, late adolescents were most involved in social victimization and negative psychotic symptoms Conclusion: PLEs are relevant in HS adolescents. Bullying victimization interacts with the onset of these phenomena. In particular, verbal bullying predicted paranoia onset significantly.

Second generation antipsychotics in 'real-life' paediatric patients. Adverse drug reactions and clinical outcomes of drug switch.

OBJECTIVE: Gap in knowledge on benefit/risk ratio of second generation antipsychotics (SGA) in the paediatric population represents a challenge for the scientific community. This study aims to analyse all suspected adverse drug reactions (ADRs) to SGA observed during the study period; compare the safety profiles of risperidone and aripiprazole; evaluate the effect of switching from risperidone to aripiprazole or to a first generation antipsychotic (FGA). METHODS: Prospective analysis of spontaneously reported ADRs concerning 184 paediatric outpatients between 2012 and 2014.; clinical outcomes of drug switch were evaluated. RESULTS: Out of the 184 patients, 130 experienced at least one ADR; ADRs were usually not serious and more frequently associated with aripiprazole. Switching to aripiprazole was associated with better results than switching to FGAs in the Clinical Global Impression scale- Efficacy (CGI-E) scores (p = 0.018), Disturbed behaviour checklist-parents (DBC-P) self-absorption subscale (p = 0.010); only a trend for difference between changing to aripiprazole vs FGAs in the DBC-P total score (p = 0.054) and social relating subscale (p = 0.053) was observed. CONCLUSIONS: SGAs safety data were consistent with the ones already known; however, there is still a need to improve the knowledge in pharmacovigilance field among clinicians. Switching to aripiprazole may be a valid alternative to risperidone.

Persistence in Therapy With Risperidone and Aripiprazole in Pediatric Outpatients: A 2-Year Naturalistic Comparison.

OBJECTIVE: The practical effectiveness of second-generation antipsychotics in children and adolescents is an understudied issue. It is a crucial area of study, though, because such patients are often treated for long-lasting disorders. METHODS: We carried out a 24-month (March 2012-March 2014) observational study on an unselected population of pediatric outpatients treated with risperidone, aripiprazole, olanzapine, or quetiapine aiming to (1) describe drug use, (2) compare post hoc the discontinuation rates due to specific causes and dose adjustments by Kaplan-Meier analyses between drugs, and (3) analyze predictors influencing these outcomes by Cox multivariate models. RESULTS: Among 184 pediatric patients, 77% patients were prescribed risperidone, and 18% were prescribed aripiprazole. Olanzapine or quetiapine were scantly used; therefore, they were excluded from analyses. Risperidone was prevalent in younger, male patients with disruptive behavioral disorders; aripiprazole, in patients with tic disorders. Overall, discontinuations occurred mostly in the first 6 months, and, at 24 months, the discontinuation numbers were similar between users of risperidone and aripiprazole (41.5% vs 39.4%). In univariate analyses, dose reduction was higher for aripiprazole (P = .033). Multivariate analyses yielded the following predictors: for all-cause discontinuation, baseline severity (hazard ratio [HR] = 1.48, P = .001) and dose increase (HR = 3.55, P = .001); for patient-decided discontinuation, dose change (increase: HR = 6.43, P = .004; reduction: HR = 7.89, P = .049) and the presence of concomitant drugs (HR = 4.03, P = .034), while autistic patients discontinued less (HR = 0.23, P = .050); for clinician-decided discontinuation due to adverse drug reactions, baseline severity (HR = 1.96, P = .005) and dose increase (HR = 5.09, P = .016); for clinician-decided discontinuation due to inefficacy, baseline severity (HR = 2.88, P = .014) and the use of aripiprazole (HR = 5.55, P = .013); for dose increase, none; for dose reduction, the occurrence of adverse drug reactions (HR = 4.74, P = .046), while dose reduction was less probable in autistic patients (HR = 0.22, P = .042). CONCLUSIONS: The findings of this study show a similarity between the overall effectiveness of risperidone and aripiprazole in a real-life pediatric outpatient setting.

Therapeutic drug monitoring of second-generation antipsychotics in pediatric patients: an observational study in real-life settings.

PURPOSE: Available guidelines on therapeutic drug monitoring of second-generation antipsychotics were designed for adults; therefore, they cannot be transferred as such in pediatric patients, who may have different drug absorption, distribution, metabolism, and elimination. Moreover, available tools that guide dosing in neuropsychiatric pediatric patients are scant, leading to the possibility of reduced efficacy and/or increased risks of toxicity. Here we describe the results of observational therapeutic drug monitoring conducted in three pediatric neuropsychiatry units across Italy in 2012-2014, with the following aims: (1) to describe the distribution of plasma concentrations of second-generation antipsychotics in our pediatric patients and (2) to identify clinical covariates associated with plasma drug levels. METHODS: Five hundred fifty-six plasma trough concentrations of the second-generation antipsychotics risperidone (plus 9-hydroxy-risperidone), aripiprazole, olanzapine, and quetiapine were measured from 172 pediatric outpatients overall. The distribution of drug concentrations was described and correlated with drug doses and clinical variables. RESULTS: Risperidone plasma levels were lower than in adults (median 13.6 ng/ml), with a high inter-patient (78.9%) but lower intra-patient (34.2%) variability. In multiple regression analyses, risperidone plasma levels depended only on drug dose (p < 0.001). Aripiprazole plasma levels were similar to those described in adults (median 165.8 ng/ml) and were widely distributed, with an inter-patient variability of 81.1%, while the intra-patient variability was much lower (29.3%). Multiple regression analyses indicated that aripiprazole plasma levels were influenced by the daily doses (p < 0.001) and by the number of concomitant drugs (p < 0.01). CONCLUSION: Our study described the distribution of plasma levels of SGAs in a real-life setting involving pediatric patients, significantly increasing the amount of available data for this fragile population. If confirmed in larger dataset, these data may contribute to the definition of optimal therapeutic window for risperidone and aripiprazole plasma levels in pediatric patients.

Transcranial direct current stimulation for hyperactivity and noncompliance in autistic disorder.

OBJECTIVES: To evaluate the safety, efficacy, and feasibility of inhibitory transcranial direct current stimulation (tDCS) for the treatment of behavioural abnormalities of autistic patients. METHODS: Twelve young adult patients with autistic disorder were enrolled. All subjects presented intellectual disability and most of them had speech impairment. The Aberrant Behavior Checklist (ABC) was administered as the primary outcome measure before and after a 2-week tDCS course. All subjects received 10 daily applications of 20 min/1.5 mA/cathodal (inhibitory) tDCS over the left dorso-lateral pre-frontal cortex. RESULTS: Eight out of 10 study completers improved in their abnormal behaviours, reaching an average reduction of 26.7% of the total ABC score. The remaining two patients showed no changes. In the whole group of completers, among the five subscales contributing to the significant reduction of the total score, the most remarkable and statistically significant change was seen in the subscale assessing hyperactivity and non-compliance (-35.9%, P = 0.002). No adverse effects were reported. CONCLUSIONS: Inhibitory tDCS improved the ABC rating scores for autistic behaviours. Owing to its ease of use, cost-effectiveness and the limited availability of specific treatment strategies, tDCS might be a valid therapeutic option to be tested in autistic patients.

Prevalence and titre of antibodies to cytomegalovirus and epstein-barr virus in patients with autism spectrum disorder.

BACKGROUND/AIM: The etiology of autism spectrum disorders (ASD) is currently unknown. Few studies have explored the role of Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) as potential etiological factors of ASD. The aim of the present study was to evaluate the seropositivity rate and antibody titre to CMV and EBV in children with ASD compared to same-aged healthy controls. PATIENTS AND METHODS: We compared the seropositivity rate and titre of antibodies to CMV and EBV in 54 children with ASD (19 with autistic disorder and 35 with non-autistic disorder ASD) and in 46 controls. RESULTS: Seropositivity rate and titre of the two antibodies were not dissimilar between cases and controls. However, considering only patients with ASD, those seropositive for CMV tended to test worse to the major severity scales than the seronegative ones. CONCLUSION: Titre and seropositivity rate of antibodies to CMV and EBV are similar between children with ASD and healthy controls.

Exposure to Varicella Zoster Virus is higher in children with autism spectrum disorder than in healthy controls. Results from a case-control study.

BACKGROUND/AIM: Autism spectrum disorder (ASD) is a group of central nervous system disorders lacking a definite etiology. The aim of the present study was to compare the exposure rate and titer of antibodies to Varicella Zoster Virus (VZV) in children with ASD and in healthy controls. PATIENTS AND METHODS: We enrolled 54 children with ASD and 46 control individuals. RESULTS: The exposure rate and titer of anti-VZV antibodies were significantly higher in children with ASD compared to controls (59% vs. 39% and 694 mIU/ml vs. 94 mIU/ml, respectively). CONCLUSION: In the present case-control study, exposure to VZV was found to be independently associated with ASD.

Prevalence of herpes simplex virus 1 and 2 antibodies in patients with autism spectrum disorders.

BACKGROUND/AIM: The etiology of autism spectrum disorder (ASD) is unknown, even though it is hypothesized that a viral infection could trigger this disorder. The aim of this study was to evaluate the seropositivity rate and antibody level of Herpes Simplex Virus 1 (HSV1) and Herpes Simplex Virus 2 (HSV2) in children with ASD compared to same-aged healthy controls. PATIENTS AND METHODS: We compared seropositivity rate and levels of antibodies to HSV1/2 in 54 children with ASD (19 with autistic disorder and 35 with non-autistic ASD) and in 46 controls. RESULTS: Seropositivity rate and levels of anti-HSV1/2 were not dissimilar between cases and controls. Exposure to HSV2 was minimal. CONCLUSION: Rate of contact with HSV1 and HSV2 assessed by the mean of detection of specific antibodies was similar between children with ASD and healthy controls.

Epidemiological study on behavioural and emotional problems in developmental age: prevalence in a sample of Italian children, based on parent and teacher reports.

BACKGROUND: The aim of this study is to examine the prevalence of behavioural and emotional problems in a sample of school children living in Campania, a region of South Italy. METHODS: The Child Behavior Checklist (CBCL) Parent Report Form (PRF) and the CBCL Teacher Rating Form (TRF) were administered to parents and teachers of a sample of school children aged 8-9 yr. RESULTS: The subjects (SS) eligible for the study were 3072. In 2137 (69.5%) cases parents returned the envelopes back. 1228 (57.4%) subjects were excluded because of lack of signed consensus, unfilled or incomplete forms. Parents reported children's behavioural or emotional Total Problems in 14.7% of the SS. (5.2% borderline, 9.5% clinical), Internalizing Problems in 18.5% (8.0% borderline, 10.5% clinical), and Externalizing Problems in 8.5% (3.8% borderline, 4.7% clinical) respectively. At the Competence Scale of CBCL more than 2/3 of the sample show high rate for Total Competence Problem (24.3% borderline, 47.3% clinical.) Teachers reported 8.7% of SS having Total Problems, (4.3% borderline, 4.4% clinical), Internalizing problems were detected in 13.3% of the sample (4.9% borderline and 8.4% clinical), while Externalizing problems were reported for 9.6% of SS (4.1% borderline and 5.5% clinical). In the sub-scale of Academic Performances teachers report a high number of subjects with problems, 18.7%, whose 4.3% had a "borderline" score, and 14.4% had a "clinical" score. CONCLUSION: Concerning Total Problems (clinical and borderline SS, 14.7% as reported by parents, 8.7% as reported by teachers) we obtained a prevalence similar to that reported in the rest of the country, with differences in gender (males 13.2%, females 16.0% as reported by parents; males 7.4%, females 9.7% as reported by teachers). The difficulties in social and relationship competencies area were higher (4/10 children). This datum should be cautiously evaluated because the possible inadequacy of CBCL competences scale.

Prevalence of HHV-6 and HHV-8 antibodies in patients with autism spectrum disorders.

BACKGROUND/AIM: The etiology of autism spectrum disorders (ASD) still eludes investigators. Several viral infections have been associated with ASD etiopathogenesis but few studies have ever focused on the role of HHV-6 and HHV-8, two members of the herpesviridae family. The aim of the present study was to evaluate seropositivity rate and levels of antibodies to HHV6 and HHV-8 in children with ASD compared to controls. PATIENTS AND METHODS: We measured and compared seropositivity rate and levels of antibodies to HHV-6 and HHV-8 in 30 children with ASD (14 with autistic disorder and 16 with non-autistic disorder ASD) and in 28 healthy controls of the same age. RESULTS: Seropositivity rate and levels of the two antibodies were similar in cases and controls. Seropositivity rate and levels of antibodies were not correlated with disease severity in children with ASD. CONCLUSION: Levels and seropositivity rate of antibodies to HHV-6 and HHV-8 do not differ between children with ASD and controls.

Antibodies against food antigens in patients with autistic spectrum disorders.

PURPOSE: Immune system of some autistic patients could be abnormally triggered by gluten/casein assumption. The prevalence of antibodies to gliadin and milk proteins in autistic children with paired/impaired intestinal permeability and under dietary regimen either regular or restricted is reported. METHODS: 162 ASDs and 44 healthy children were investigated for intestinal permeability, tissue-transglutaminase (tTG), anti-endomysium antibodies (EMA)-IgA, and total mucosal IgA to exclude celiac disease; HLA-DQ2/-DQ8 haplotypes; total systemic antibodies (IgA, IgG, and IgE); specific systemic antibodies: α-gliadin (AGA-IgA and IgG), deamidated-gliadin-peptide (DGP-IgA and IgG), total specific gliadin IgG (all fractions: α, ß, γ, and ω), ß-lactoglobulin IgG, α-lactalbumin IgG, casein IgG; and milk IgE, casein IgE, gluten IgE,-lactoglobulin IgE, and α-lactalbumin IgE. RESULTS: AGA-IgG and DPG-IgG titers resulted to be higher in ASDs compared to controls and are only partially influenced by diet regimen. Casein IgG titers resulted to be more frequently and significantly higher in ASDs than in controls. Intestinal permeability was increased in 25.6% of ASDs compared to 2.3% of healthy children. Systemic antibodies production was not influenced by paired/impaired intestinal permeability. CONCLUSIONS: Immune system of a subgroup of ASDs is triggered by gluten and casein; this could be related either to AGA, DPG, and Casein IgG elevated production or to impaired intestinal barrier function.

Response to measles-mumps-rubella vaccine in children with autism spectrum disorders.

BACKGROUND/AIM: The etiology of autism spectrum disorders (ASD) is unknown. The measles-mumps-rubella (MMR) vaccination has been in the past implicated in ASD pathogenesis. The aim of our study was to evaluate the rate of seropositivity and the levels of antibodies against MMR antigens in a cohort of children with ASD compared to control children. PATIENTS AND METHODS: In a cohort of children with ASD and same-age healthy controls, we measured levels and seropositivity of antibodies against MMR. RESULTS: A total of 60 children, 31 with ASD and 29 controls were enrolled. The seropositivity rate and levels of all the three antibodies were similar in cases and controls. CONCLUSION: Children with ASD have a similar level and seropositivity rate of antibodies against the MMR vaccine to same-age controls. As persistent infections are typically associated with high antibody levels, our results support the arguments against a role of MMR vaccination as a causal factor or co-factor in development of ASD.

Etiopathogenesis of autism spectrum disorders: fitting the pieces of the puzzle together.

Autism spectrum disorders (ASD) are disorders of the central nervous system characterized by impairments in communication and social reciprocity. Despite thousands of studies on this topic, the etiopathogenesis of these disorders remains unclear, apart from a general belief that they derive from an interaction between several genes and the environment. Given the mystery surrounding the etiopathogenesis of ASD it is impossible to plan effective preventive and treatment measures. This is of particular concern due to the progressive increase in the prevalence of ASD, which has reached a figure as high as 1:88 children in the USA. Here we present data corroborating a novel unifying hypothesis of the etiopathogenesis of ASD. We suggest that ASD are disorders of the immune system that occur in a very early phase of embryonic development. In a background of genetic predisposition and environmental predisposition (probably vitamin D deficiency), an infection (notably a viral infection) could trigger a deranged immune response which, in turn, results in damage to specific areas of the central nervous system. If proven, this hypothesis would have dramatic consequences for strategies aimed at preventing and treating ASD. To confirm or refute this hypothesis, we need a novel research approach, which unlike former approaches in this field, examine the major factors implicated in ASD (genetic, infections, vitamin D deficiency, immune system deregulation) not separately, but collectively and simultaneously.

Polysomnographic findings in Rett syndrome: a case-control study.

PURPOSE: Rett syndrome is a severe neurodevelopmental disorder mainly affecting females and usually linked to mutations in the methyl-CpG-binding protein 2 gene, with an estimated prevalence of 1 in 10,000 live female births. Clinical features which usually become more apparent over time include breathing dysfunction, seizures, spasticity, peripheral vasomotor disturbance, scoliosis, growth retardation, and hypotrophic feet, with a great variety of presentations. The clear immaturity in brainstem mechanisms is expressed by the presence of early sleep disorders such as nocturnal awakenings, bruxism, and difficulty falling asleep, and no conclusive findings were derived from the few polysomnographic studies about the sleep macrostructural aspects. The aim of this study is to analyze the sleep macrostructural parameters, the nocturnal respiratory characteristic, and the presence of periodic limb movements in a sample of children affected by Rett syndrome. MATERIALS: Thirteen Rett subjects underwent a polysomnographic study, and the findings were compared with those obtained by a group of 40 healthy children. RESULTS: The Rett group shows a great impairment in sleep macrostructural and respiratory parameters, with a higher percentage of pathological periodic limb movements than the controls. CONCLUSIONS: This study may be considered a report about the ventilatory impairment during sleep in Rett syndrome and the first approach to the macrostructural aspects of sleep supported by the PSG data that could be considered mandatory for a better comprehension of this very complex syndrome.