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Background Childhood trauma (CT) is a major yet elusive psychiatric risk factor, whose multidimensional conceptualization and heterogeneous effects on brain morphology might demand advanced mathematical modeling. Therefore, we present an unsupervised machine learning approach to characterize the clinical and neuroanatomical complexity of CT in a larger, transdiagnostic context. Methods We used a multicenter European cohort of 1076 female and male individuals (discovery: n = 649; replication: n = 427) comprising young, minimally medicated patients with clinical high-risk states for psychosis; patients with recent-onset depression or psychosis; and healthy volunteers. We employed multivariate sparse partial least squares analysis to detect parsimonious associations between combinations of items from the Childhood Trauma Questionnaire and gray matter volume and tested their generalizability via nested cross-validation as well as via external validation. We investigated the associations of these CT signatures with state (functioning, depressivity, quality of life), trait (personality), and sociodemographic levels. Results We discovered signatures of age-dependent sexual abuse and sex-dependent physical and sexual abuse, as well as emotional trauma, which projected onto gray matter volume patterns in prefronto-cerebellar, limbic, and sensory networks. These signatures were associated with predominantly impaired clinical state- and trait-level phenotypes, while pointing toward an interaction between sexual abuse, age, urbanicity, and education. We validated the clinical profiles for all three CT signatures in the replication sample. Conclusions Our results suggest distinct multilayered associations between partially age- and sex-dependent patterns of CT, distributed neuroanatomical networks, and clinical profiles. Hence, our study highlights how machine learning approaches can shape future, more fine-grained CT research.

Highlights • Panic-prone individuals often exhibit reduced tolerance when wearing RPDs. • Studies found that wearing RPDs may induce a real burden of respiratory effects. • Panic-prone individuals may be at higher risk of RPD-related respiratory discomfort. • Various strategies to decrease discomfort may overcome the risk of poor compliance., Background The wearing of respiratory protective devices (RPDs) correctly and continually in situations where people are at risk of respiratory infections is crucial for infection prevention. Certain people are poorly compliant with RPDs due to RPD-related annoyance, including respiratory discomfort. We hypothesized that individuals vulnerable to panic attacks are included in this group. No published studies on this topic are available. The evidence for our hypothesis was reviewed in this study as a starting point for future research. Methods We selected a set of experimental studies that measured the respiratory physiological burden in RPD wearers through objective and validated methods. We conducted a bibliographic search of publications in the PubMed database (January 2000–May 2020) to identify representative studies that may be of interest for panic respiratory pathophysiology. Results Five studies were included. Wearing RPDs exerted significant respiratory effects, including increased breathing resistance, CO2 rebreathing due to CO2 accumulation in the RPD cavity, and decreased inhaled O2 concentration. We discussed the implications of these effects on the respiratory pathophysiology of panic. Limitations Most studies had a small sample size, with a preponderance of young participants. Different methodologies were used across the studies. Furthermore, differences in physical responses between wearing RPDs in experimental settings or daily life cannot be excluded. Conclusions This research supports the idea that panic-prone individuals may be at higher risk of respiratory discomfort when wearing RPDs, thereby reducing their tolerance for these devices. Strategies to decrease discomfort should be identified to overcome the risk of poor compliance.

This single-arm, open-label study aimed to investigate the efficacy of a cognitive-behavioural group training based on acceptance and commitment therapy (ACT) on cognition in drug-naïve children with attention deficit hyperactivity disorder (ADHD). Thirty-six children with ADHD aged 8–13 were invited to participate in the 9-month ACT training programme, which consisted of 26 weekly sessions of group therapy lasting 90 min each. Their parents also received 12 sessions of ACT-based parent training, every 2 weeks. The outcome measure for the present study was the change in the cognitive performance assessed by a battery of computerised task. The cognitive outcome of children receiving ACT-group intervention was compared to that of an external untreated control group of children with ADHD. No significant improvements were observed in any of the cognitive measures. This preliminary study suggests that the 9-month ACT-group training programme might not have positive effects on cognitive difficulties usually occurring in ADHD. Future randomised controlled trials with larger sample sizes are required to shed more light on this issue.

Individual responses to methylphenidate (MPH) can significantly differ in children with attention-deficit/hyperactivity disorder (ADHD) in terms of the extent of clinical amelioration, optimal dosage needed, possible side effects, and short- and long-term duration of the benefits. In the present repeated-measures observational study, we undertook a proof-of-concept study to determine whether clustering analysis could be useful to characterize different clusters of responses to MPH in children with ADHD. We recruited 33 children with ADHD who underwent a comprehensive clinical, cognitive, and neurophysiological assessment before and after one month of MPH treatment. Symptomatology changes were assessed by parents and clinicians. The neuropsychological measures used comprised pen-and-paper and computerized tasks. Functional near-infrared spectroscopy was used to measure cortical hemodynamic activation during an attentional task. We developed an unsupervised machine learning algorithm to characterize the possible clusters of responses to MPH in our multimodal data. A symptomatology improvement was observed for both clinical and neuropsychological measures. Our model identified distinct clusters of amelioration that were related to symptom severity and visual-attentional performances. The present findings provide preliminary evidence that clustering analysis can potentially be useful in identifying different responses to MPH in children with ADHD, highlighting the importance of a personalized medicine approach within the clinical framework.

Objective The aim of the present study is evaluate the effectiveness of an Acceptance and Commitment Therapy (ACT)-based training protocol, in adjunct to token economy and previous parent training, in a sample of children with Attention-Deficit/Hyperactivity Disorder (ADHD). By promoting the reduction of immediate responses to thoughts and feelings, we aimed to reduce the impulsive behaviour of children and to improve their self-regulation. Methods The protocol was centred on awareness of the present moment, defusion and acceptance of feelings and emotions. Behavioural (Conners’ Parent Rating Scale -Revised: Long version, CPRS-R:L) and severity measures (Clinical Global Impression -Severity, CGI-S) were assessed before and after treatment in a clinical sample of 31 children aged 8–13 years. Results At the end of the ACT protocol, children showed significant improvement in global functioning and behavioural symptoms. There were significant improvements in the CPRS subscales Cognitive Problems (p = 0.005), Hyperactivity (p = 0.006), Perfectionism (p = 0.017), ADHD Index (p = 0.023), Global Index: Restless–Impulsive (p = 0.023), Global Index: Total (p = 0.036), DSM IV Inattentive (p = 0.029), DSM IV Hyperactive–Impulsive (p = 0.016), and DSM IV Total (p = 0.003). When controlling for the confounding effect of pharmacological therapy, comorbidities and socio-economic status, treatment maintained a significant effect on the CPRS subscales Perfectionism (partial η2 = 0.31, p η2 = 0.29, p η2 = 0.31, p η2 = 0.20, p = 0.02). Symptom severity as rated by CGI-S scores decreased in 74.2% of the children. Conclusions This preliminary work on an Acceptance and Commitment Therapy-based child training in children affected by ADHD resulted in significant improvements, measured by a rating scale specific for ADHD.

Background Attention deficit/hyperactivity disorder (ADHD) can be comorbid with frequent anxiety and mood disorders, as well as emotional symptoms (anxiety, irritability, mood lability). These may also be triggered by drugs and appear as adverse drug reactions (ADRs). Methods We mined data from the US Food and Drug Administration Adverse Event Reporting System pharmacovigilance database, focused on methylphenidate, atomoxetine, amphetamine, lisdexamfetamine, and their derivatives. We collected reports of ADRs connected with mood or emotional symptoms in pediatric patients, excluding drug abuse/accidents. Reporting odds ratios (RORs) were calculated and compared between drug classes and children/adolescents. Results We collected 6176 ADRs of interest of which 59% occurred in children. Atomoxetine accounted for 50.7% of reports, methylphenidate for 32.5%, lisdexamfetamine for 14.2%, and amphetamine for 2.6%. Irritability, anxiety, obsessive thoughts, depressed mood, and euphoria scored significant RORs for all drugs, overall with an increasing risk from methylphenidate to atomoxetine, lisdexamfetamine, and amphetamine. Apathy regarded mostly atomoxetine, and crying regarded all drugs except methylphenidate. Several age-based differences were found. Notably, affect lability hit only adolescents. All drugs scored significant self-injury RORs, except lisdexamfetamine in adolescents, with an increasing risk from methylphenidate to lisdexamfetamine, atomoxetine, and amphetamine. For suicidality, all drugs had significant RORs in children, and methylphenidate was better than atomoxetine and lisdexamfetamine. In adolescents, only methylphenidate and atomoxetine scored significant RORs. Conclusions We conclude that real-world data from the US Food and Drug Administration Adverse Event Reporting System are consistent with previous evidence from meta-analyses. They support a hierarchy of drug safety for several ADRs (except self-injury/suicidality) with methylphenidate as safest, followed by atomoxetine, lisdexamfetamine, and amphetamine last. Self-injury and suicidality RORs were overall higher in children.

Objectives: Second-generation antipsychotics (SGAs) increase appetite and weight, leading toward a metabolic syndrome. Risperidone and aripiprazole, the most widely used pediatric SGAs, have been studied predominantly in short-term clinical trials, where risperidone leads to a rapid weight increase and aripiprazole to a slower one, while long-term effects are not yet elucidated. Factors that may influence weight gain are likewise not clarified, although baseline weight, previous SGA exposure, pubertal status, and type of SGA have been suggested as moderators. We analyzed weight gain induced by risperidone and aripiprazole in a sample of pediatric outpatients enrolled into a 2-year observational study. Methods: We assessed at several time points their body mass index (BMI)-Z scores (age and sex-corrected and referred to national norms). We used hierarchical mixed-effects modeling to design BMI-Z trajectories and observed the effects of several variables on determining them. Results: The study group comprised of 127 patients, predominantly males (79%), of 12.6 years on average, treated with risperidone (81%) and aripiprazole (19%) for disruptive behavioral symptoms in patients with and without neurodevelopmental disorders. Overall, BMI-Z was 1.2 at first and 1.4 at last visit (no significant change). We could design four weight-change trajectories, determined by the factors: drug (risperidone/aripiprazole) and age status (children/adolescent). Additional factors not retained in the model but possibly explanatory include the previous duration of SGA treatment and a progressive patient-selection effect due to dropouts in this observational study. Risperidone treatment was associated with trends of BMI-Z increase in children and decrease in adolescents. Aripiprazole treatment was associated with significant BMI-Z increase, higher in children than in adolescents. Results are probably due to longer previous drug exposure in adolescents. Conclusions: Children were at risk of weight gain more than adolescents, for both risperidone and, of note, aripiprazole. Adolescents and patients with long previous drug exposure tend to reach stable BMI-Z, although in the range between excessive weight and obesity.

Background Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by deficits in self-controlling attention, behavior, and emotions. In recent years, noninvasive optical techniques, such as near infrared spectroscopy (NIRS), have been used to measure the neural correlates of pharmacological-therapy outcomes in children and adolescents with ADHD. Methods We reviewed a short series of articles that investigated the results of functional NIRS (fNIRS) on developmental-age ADHD. The review was limited to fNIRS studies that investigated the cortical responses that occurred during neuropsychological tasks in ADHD patients who received methylphenidate or atomoxetine. Results The majority of the reviewed studies revealed the presence of increased oxygenated hemoglobin concentrations in the prefrontal cortex following pharmacotherapy in ADHD samples. A higher frequency of right-lateralized results was found. Limitations The considered studies are characterized by substantial methodological heterogeneity in terms of the patients’ medication status and washout period, explored cerebral regions, and neuropsychological tasks. Conclusions fNIRS seems to be a promising tool for the detection of pharmacological-treatment biomarkers in samples of children and adolescents with ADHD.

Milk and its derivatives are the basis of human nutrition since childhood. Given their importance within a balanced diet, the determination of carbohydrates in milk and its derivatives is fundamental for two reasons: one of alimentary origin related to intolerances and the other one of technological origin, especially for PDO (Protected Designation of Origin) products. The dietetic approach, including lactose-free products, has a crucial role in the management of lactose intolerance, but labelling and compositional rules indicating the absence or reduced presence of lactose in food are currently not harmonised at Union level. Considering the above-mentioned issues and the absence of official methods for the determination of low sugar concentrations, we propose a new and simple IC-HRMS method to detect carbohydrates in milk and different lactose-free derivatives, which can allow the definition of concentration limits useful to characterise products suitable for specific dietary regimes.

Organophosphate compounds (OPs) interfere with neurodevelopment and are neurotoxic for humans and animals. They are first biotransformed to the more toxic oxon form, and then hydrolyzed to specific metabolites by the enzyme paraoxonase/arylesterase, encoded by the gene PON1 located on human chr. 7q21.3. In autism spectrum disorder (ASD) and in attention-deficit/hyperactivity disorder (ADHD), a correlation between OP exposure and disease onset has been reported. In this case-control study, we aimed to replicate our previous work showing reduced levels of serum PON1 arylesterase activity in Italian and Caucasian-American ASD samples, and to extend our analysis to other neurodevelopmental disorders, namely ADHD and developmental language disorder (DLD), also known as specific language impairment (SLI). The arylesterase activity, measured using standard spectrophotometric methods, is significantly reduced in the ADHD, and not in the ASD sample compared with the controls. Our previous results seemingly stem from spuriously high arylesterase levels in the former control sample. Finally, genotyping SNPs rs705379 and rs662 using TDI-FP, a significant effect of rs705379 alleles on the serum arylesterase activity is observed in all of the subgroups tested, regardless of diagnosis, as well as a lack of association between PON1 gene polymorphisms and ASD/ADHD susceptibility in the Italian population. In summary, the serum arylesterase activity is reduced in children and adolescents with ADHD, and this reduction is not due to the functional PON1 gene variants assessed in this study. Based on previous literature, it may more likely reflect enhanced oxidative stress than specific genetic underpinnings.

BackgroundGlyco-metabolic deteriorations are the most limiting adverse reactions to antipsychotics in the long term. They have been incompletely investigated and the properties of antipsychotics that determine their magnitude are not clarified.To rank antipsychotics by the magnitude of glyco-metabolic alterations and to associate it to their pharmacological and chemical properties, we conducted a network meta-analysis.MethodsWe searched PubMed, Embase, and Psycinfo on 10 September 2020. We selected studies containing the endpoint-baseline difference or the distinct values of at least one outcome among glucose, HbA1c, insulin, HOMA-IR, triglycerides, total/HDL/LDL cholesterols. Of 2094 articles, 46 were included in network meta-analysis. Study quality was assessed by the RoB 2 and ROBINS-I tools. Mean differences (MD) were obtained by random-effects network meta-analysis; relations between MD and antipsychotic properties were analyzed by linear regressions. Antipsychotic properties investigated were acidic and basic pKa, polar surface area, polarizability, and occupancies of D2, H1, M1, M3, α1A, α2A, 5-HT1A, 5-HT2A, 5-HT2C receptors.ResultsWe meta-analyzed 46 studies (11 464 patients); on average, studies lasted 15.47 weeks, patients had between 17.68 and 61.06 years of mean age and 61.64% were males. Olanzapine and clozapine associated with greater deteriorations, aripiprazole and ziprasidone with smaller deteriorations. Higher polarizability and 5-HT1A receptor occupancy were associated with smaller deteriorations, H1, M1, and M3 receptor occupancies with larger deteriorations.ConclusionsDrug rankings may guide antipsychotic switching toward metabolically safer drugs. Mechanistic insights may suggest improvements for combination therapies and drug development. More data are required regarding newer antipsychotics.

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting up to 5.3% of children and 2.5% of adults depending on the country considered. Current pharmacological treatments for ADHD are based on stimulant or non-stimulant medications, targeting dopaminergic and noradrenergic systems in the frontal cortex and dopaminergic system in the basal ganglia. These drugs are effective and safe for the majority of patients, whereas about 20% of treated patients do not tolerate current therapies or experience insufficient efficacy. The adequate treatment of ADHD is necessary to allow a proper social placement and prevent the acquisition of additional, more severe, comorbidities.We conducted a review of the scientific literature and of unpublished/ongoing clinical trials to summarize the advances made in the last 10 years (2010-2020) for the pharmacological treatment of ADHD. We found many pharmacological mechanisms beyond dopaminergic and noradrenergic ones have been investigated in patients.Some emerging drugs for ADHD may be promising as add-on treatment especially in children, amantadine to enhance cognitive functions and tipepidine for hyperactivity/impulsivity. Stand-alone emerging treatments for ADHD include viloxazine and dasotraline, which will soon have more clinical data available to support market access requests.

Honey contaminations could derive from intensive agriculture and industrial activities, but also from beekeeper treatments. In EU no MRLs for antibiotics in honey are set, only a minimum required performance limit for chloramphenicol of 0.3 μg kg−1 is recommended. Screening tests are available, characterised by their rapidity and simple use. Due to their high rate of false positives and the need to meet zero tolerance levels for antibiotics, their presence in samples was investigated using a liquid chromatography High Resolution Mass Spectrometry (LC-HRMS) multiclass antibiotic residue method, comparing the results with those of previous screening tests. The confirmatory method showed good sensitivity: CCα and CCβ ranging from 0.03 to 4.80 ng g−1 and from 0.12 to 5.56 ng g−1, respectively. Ninety-eight honey samples from different geographical areas, analysed by two screening tests, showed a high percentage of false positives. This is fundamental to guarantee honey safety, especially, for organic production.

Large population studies estimated that the frequency of food allergies is increasing worldwide. In the last two decades, a 'second wave' of the allergy epidemic has emerged as a growing public health problem. EU regulation strengthened information to consumers about allergens in pre-packed food, since December 2014 it has been extended to non-prepacked foods by the Regulation (EU) No 1169/2011 of the European Commission. The present work aims to present a five-year survey on the presence of nine types of allergen in several foods, including food of animal origin and baby food. The concentration found for each irregular allergen is generally low, but some samples with no gluten indication contained a concentration above 10 mg kg

Despite various advances in the study of the neurobiological underpinnings of personality traits, the specific neural correlates associated with character and temperament traits are not yet fully understood. Therefore, this study aims to fill this gap by exploring the biochemical basis of personality, which is explored with the temperament and character inventory (TCI), during brain development in a sample of adolescents. Twenty-six healthy adolescents (aged between 13 and 21 years; 17 males and 9 females) with behavioral and emotional problems underwent a TCI evaluation and a 3T single-voxel proton magnetic resonance spectroscopy (1H MRS) acquisition of the anterior cingulate cortex (ACC). Absolute metabolite levels were estimated using LCModel: significant correlations between metabolite levels and selective TCI scales were identified. Specifically, phosphocreatine plus creatine (PCr+Cre) significantly correlated with self-directedness, positively, and with a self-transcendence (ST), negatively, while glycerophosphocholine plus phosphocholine (GPC+PC) and myo-inositol negatively correlated with ST. To the best of our knowledge, this is the first study reporting associations of brain metabolites with personality traits in adolescents. Therefore, our results represent a step forward for personality neuroscience within the study of biochemical systems and brain structures.

Background Bullying as a specific subtype of adverse life events is a major risk factor for poor mental health. Although many questionnaires on bullying are available, so far none covers bullying retrospectively throughout school and working life. To close this gap, the Bullying Scale for Adults (BSA) was designed. Methods Based on data of 622 participants from five European countries collected in the prospective multicenter Personalized Prognostic Tools for Early Psychosis Management (PRONIA) study, we investigated whether the BSA is a reliable and valid measurement for bullying and whether there is a difference across different diagnostic groups of early mental disorders (recent onset depressive/ psychotic patients, patients at clinical high-risk of psychosis) and healthy controls. Results Bullying experiences were significantly less frequent in healthy controls than in patient groups, with no significant differences between the three clinical groups. The BSA exhibited a high item scale discrimination (r > .3) and very good internal consistency (Cronbach's α = .93). Four factors were identified: 1. Sexual harassment, 2. Emotional Abuse, 3. Physical Abuse, 4. Problems at school. The highly significant correlation between bullying, and childhood adversities and trauma (r = .645, p Discussion The BSA is the first validated questionnaire that, in retrospective, reliably records various aspects of bullying (incl. its consequences) not only throughout childhood but also working life. It can be used to assess bullying as a transdiagnostic risk factor of mental disorders in different mental disorders, esp. psychosis and depression.

In the past decade, converging evidence has suggested that motor impairment is one of the most consistent markers, alongside sociocommunicative difficulties, for autism spectrum disorder (ASD). Indeed, widespread anomalies of movement have been described in the ASD context. These motor abnormalities could have critical implications for subsequent cognitive and social development. Nevertheless, this area of development is particularly underexamined in the autism-related context, and early intervention programs commonly focus on the core symptoms of the condition. In the present work, we review and discuss the findings from recent studies that investigated the effect of interventions regarding fundamental motor skills in autistic children. Although the limited nature of the literature prevents researchers from drawing definitive conclusions, the results from the studies discussed here demonstrated potentially significant improvements in the motor abilities of autistic children after the interventions. Only a subset of the reviewed studies explored possible changes in the sociocommunicative domain after the motor skills improvements, and they had not concordant, although promising, conclusions. Overall, in consideration of the well-documented motor impairment people with the condition, the present findings highlight the importance of including motor skills training within the rehabilitation programs designed for autistic children. Furthermore, this narrative review encourages future interventional trials to consider motor skills as a possible target for reducing activity limitations and participation restrictions of autistic children.

Background ADHD is frequently comorbid with anxiety and mood disorders, which may increase the severity of inattention and hyperactivity symptoms. Emotional symptoms (anxiety, irritability, mood lability) also affect patients without comorbidity or emerge as adverse drug events. The influence of ADHD drugs on emotional symptoms demands investigation to improve therapies. Methods Systematic review of trials reporting adverse events in patients pharmacologically treated for ADHD. Meta-analysis of the occurrence of irritability, anxiety, apathy, reduced talk, sadness, crying, emotional lability, biting nails, staring, perseveration, euphoria. Meta-regression analysis. Results Forty-five trials were meta-analysed. The most frequently reported outcomes were irritability, anxiety, sadness, and apathy. Methylphenidates, especially immediate-release formulations, were most studied; amphetamines were half as studied and were predominantly mixed amphetamine salts. Reports on atomoxetine were scant. Meta-analysis showed that methylphenidates reduced the risk of irritability, anxiety, euphoria, whereas they worsened the risk of apathy and reduced talk; amphetamines worsened the risk of emotional lability. Factors influencing risks were study year and design, patients’ sex and age, drug dose and release formulation. Limitations Possible discrepancy between adverse events as indicated in clinical trials and as summarised herein. Confounding due to the aggregation of drugs into groups; uninvestigated sources of bias; incomplete lists of adverse events; lack of observations on self-injury. Conclusions Methylphenidates appeared safer than amphetamines, although younger patients and females may incur higher risks, especially with high-dose, immediate-release methylphenidates. Only atomoxetine holds a black-box warning, but amphetamines and methylphenidates also did not show a safe profile regarding mood and emotional symptoms.

Widespread antibiotic use and the antimicrobial resistance phenomenon demand new analytical methods and the use of non-conventional matrices increasingly necessary for safe food control. We present a method developed to detect six common antibiotics used in poultry breeding, in the unconventional matrix, feathers, compared to muscle and liver. The analysis for the presence of two β-lactams (penicillin V, amoxicillin), two fluoroquinolones (enrofloxacin, ciprofloxacin), one phenicol (thiamphenicol) and one macrolide (tylosin) was validated and achieved by HPLC–HRMS, with the ultimate aim to identify untargeted metabolites in broilers subjected to different therapeutic protocols. All the validated method parameters met the regulatory requirements. Muscle and liver were not effective matrices when the withdrawal periods were largely respected. Conversely, feathers proved a promising matrix for the detection of all the studied antibiotics, in the range of 8.72–1885.32 ng g−1, except penicillin V. Like other nonconventional matrices, such as teeth, the antibiotics detected in feathers existed in their unmetabolised form.

The present study evaluates the implementation of the Coping Power Program (CPP)-Child Component in a group of patients with attention deficit/hyperactivity disorder (ADHD), and explores the effects of this treatment on changes in the primary and associated symptoms of ADHD. A clinical sample of 50 children and preadolescents (8–13 years) with ADHD was involved. The clinical sample was split into a treatment group (TG; N = 26), which was included in the child training program (CPP), and a control group (CG; N = 24), which was placed on a waiting list. The Clinical Global Impression-Severity (CGI-S) and the Child Behavior Checklist 6–18 (CBCL 6–18) were assessed at baseline and at the end of treatment. The outcomes were assessed as a CBCL-subscale response rate and a CGI-S shift. Our results showed a significant improvement in children’s global functioning and in emotional and behavioral symptoms. The children in the TG were more likely to shift from a more severe functional impairment class to a less severe one (69.2% of TG vs. 20.8% of CG). Further, the CGI-S scores diminished significantly in the TG (p

Background Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by deficits in cognitive and emotional self-control. Optical technique acquisitions, such as near infrared spectroscopy (NIRS), seem to be very promising during developmental ages, as they are non- invasive techniques and less influenced by body movements than other neuroimaging methods. Recently, these new techniques are being widely used to measure neural correlates underlying neuropsychological deficits in children with ADHD. Methods In a short series of articles, we will review the results of functional NIRS (fNIRS) studies in children with ADHD. The present brief review will focus on the results of the fNIRS studies that investigate cortical activity during neuropsychological and/or emotional tasks. Results According to the reviewed studies, children and adolescents with ADHD show peculiar cortical activation both during neurological and emotional tasks, and the majority of the reviewed studies revealed lower prefrontal cortex activation in patients compared to typically developmental controls. Limitations a consistent interpretation of these results is limited by the substantial methodological heterogeneity including patients’ medication status and washout period, explored cerebral regions, neuropsychological tasks, number of channels and sampling temporal resolutions. Conclusions fNIRS seems to be a promising tool for investigating neural substrates of emotional dysregulation and executive function deficits in individuals with ADHD during developmental ages.

This fMRI study investigated mental simulation of state/psychological and action verbs during adolescence. Sixteen healthy subjects silently read verbs describing a motor scene or not (STIMULUS: motor, state/psychological verbs) and they were explicitly asked to imagine the situation or they performed letter detection preventing them from using simulation (TASK: imagery vs. letter detection). A significant task by stimuli interaction showed that imagery of state/psychological verbs, as compared to action stimuli (controlled by the letter detection) selectively increased activation in the right supramarginal gyrus/rolandic operculum and in the right insula, and decreased activation in the right intraparietal sulcus. We compared these data to those from a group of older participants (Tomasino et al. 2014a). Activation in the left supramarginal gyrus decreased for the latter group (as compared to the present group) for imagery of state/psychological verbs. By contrast, activation in the right superior frontal gyrus decreased for the former group (as compared to the older group) for imagery of state/psychological verbs.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder mainly characterised by deficits in social communication as well as by narrow patterns of behaviour and interests (American Psychiatric Association, 2013), often accompanied by language, intellectual and sensory impairments. The severity of these impairments may lead to deficits in the development of daily living activities such as simple meal preparation and feeding, community skills (e.g. buying groceries), personal care (e.g. dressing) and personal hygiene skills (bathing, toileting, hand washing, teeth brushing) needed for independence. Among others, the lack of independence in personal hygiene skills increases the burden of the caregiver and makes children with ASD more dependent (Flynn & Healy, 2012). Therefore, it is important to develop tools for helping individuals with ASD in increasing their ability to perform these basic life activities which will lead to savings that can be invested in other critical areas of needs.

The antibiotic overuse in zoothechnics, due to prophylactic and therapeutic treatments, or to their growth-promoting activity, is a major cause for the onset of widespread antibiotic resistance. Of particular relevance to this study, is the antibiotic abuse in pig breeding. Despite the comprehensive literature on residue controls in pig muscle, data on pig urine, a non-invasive, on-farm collectable matrix, are lacking. Therefore, we validated an HPLC-MS/MS method to detect 29 antimicrobials from eight classes and applied it to 43 anonymous pig urine and muscle paired samples and fulfilled the parameters in agreement with the Commission Decision 2002/657/UE. The analytical limits were moreover much lower than the maximum residue limits (MRLs) required by the Commission Regulation 37/2010/UE. In the samples, antibiotics were usually detected at higher frequencies and concentrations in urine than muscle. Urine proved a useful tool to detect antibiotic administration and their excessive use in pig farming is depicted.

Natural corticosteroids include two families of substances: mineralocorticoids and glucocorticoids. Several drugs of similar structure and biological activity have been synthesized and are currently used in the clinical practice. Beside legal pharmacological treatments, these drugs have been consistently misused in animal breeding. One of the most abused corticosteroids is prednisolone. For many years, prednisolone has been considered of exclusive synthetic origin, but nowadays a debate about its possible endogenous production is under way. Several studies have been addressed to ascertain the potential relationship between stressful conditions, such as transportation and slaughtering, and endogenous production of prednisolone. In order to verify further the effect of stressful conditions, our laboratory analysed urine samples collected from the cows participating to the “Batailles des Reines” (a traditional contest based on ritual and spontaneous fights of pregnant cows), to verify if an endogenous prednisolone production may occur in these animals. We developed and validated a LC-MS/MS method for the simultaneous determination of cortisol, cortisone, prednisolone and five of its metabolites. The method was applied to the analysis of urine samples collected from “Batailles des Reines” competitions in 2012 and 2013. All these samples had been previously analysed within an anti-doping control program and tested compliant to all screenings.

Veterinary drugs usually have rapid clearance rates in the liver and kidney, hampering their detection in conventional matrices such as the liver or urine. Pharmacological principles such as esterification may be applied to facilitate the administration of veterinary drugs and increase drug half-life. Prednisolone, whose therapeutic administration is regulated for food producing animals in the EU, is available in its acetate form as well as nandrolone, a banned anabolic steroid, which may be obtained as nandrolone phenylpropionate and estradiol as a benzoyl ester. While the distribution and accumulation of lipophilic and hydrophilic substances in human teeth have been well documented, studies on residues in bovine teeth are lacking. We hypothesised that analysis of bovine teeth could be used to detect both regulated and banned veterinary drugs. Steroids may be illegally used as growth promoters in food producing animals, alone or combined with β2-agonists; therefore, we developed, and validated, in accordance with the Commission Decision 2002/657/EC, two analytical confirmatory LC-MS/MS methods to detect these classes of compounds following a unique liquid extraction procedure. Finally, we analysed teeth from three male Friesian veal calves treated with intramuscular estradiol benzoate, oral prednisolone acetate or intramuscular nandrolone phenylpropionate in combination with oral ractopamine, respectively, and from seven bovines from the food chain. Teeth from treated animals were positive for their respective drugs, with the exception of nandrolone phenylpropionate. One sample from a food chain bovine was positive for isoxsuprine, one of the seven β2-agonists studied. Non-esterified forms of the steroids were not found. These results demonstrate that bovine teeth are a suitable matrix for the determination of pseudoendogenous substances or illicit administration of veterinary drugs.

Polyunsaturated fatty acids (PUFAs) biostatus has been proposed as possible attention deficit hyperactivity disorder (ADHD) diagnosis biomarker. The present exploratory study aimed to investigate the association between PUFAs biostatus and cerebral cortex metabolism measured by functional Near Infrared Spectroscopy (fNIRS) in a sample of children with and without ADHD. 24 children with ADHD and 22 typically developing (TD) peers, aged 8&ndash, 14, were recruited. Linoleic, arachidonic, docosahexaenoic and eicosapentaenoic acids levels were evaluated in whole blood. All children underwent fNIRS while performing an n-back working memory task. Between groups comparisons revealed lower levels of arachidonic acid in children with ADHD and stronger NIRS signal in TD participants, especially when completing more difficult tasks. Correlations conducted between fNIRS activation and PUFA biostatus revealed several associations between hemodynamic changes in the frontoparietal regions and fatty acids profile across participants. This result was also confirmed by the multiple hierarchical regression analyses that remarked an inverse effect of eicosapentaenoic acid levels on oxyhemoglobin values in right frontoparietal region. Such preliminary findings, if confirmed, would suggest that PUFAs could play a role in atypical neurodevelopment.

Quantitative evaluation of gait has been considered a useful tool with which to identify subtle signs of motor system peculiarities in autism spectrum disorder (ASD). However, there is a paucity of studies reporting gait data in ASD as well as investigating learning processes of locomotor activity. Novel advanced technologies that couple treadmills with virtual reality environments and motion capture systems allows the evaluation of gait patterns on multiple steps and the effects of induced gait perturbations, as well as the ability to manipulate visual and proprioceptive feedbacks. This study aims at describing the gait pattern and motor performance during discrete gait perturbation of drug-naive, school-aged children with ASD compared to typically developing (TD) peers matched by gender and age. Gait analysis was carried out in an immersive virtual environment using a 3-D motion analysis system with a dual-belt, instrumented treadmill. After 6 min of walking, 20 steps were recorded as baseline. Then, each participant was exposed to 20 trials with a discrete gait perturbation applying a split-belt acceleration to the dominant side at toe-off. Single steps around perturbations were inspected. Finally, 20 steps were recorded during a post-perturbation session. At baseline, children with ASD had reduced ankle flexion moment, greater hip flexion at the initial contact, and greater pelvic anteversion. After the discrete gait perturbation, variations of peak of knee extension significantly differed between groups and correlated with the severity of autistic core symptoms. Throughout perturbation trials, more than 60% of parameters showed reliable adaptation with a decay rate comparable between groups. Overall, these findings depicted gait peculiarities in children with ASD, including both kinetic and kinematic features; a motor adaptation comparable to their TD peers, even though with an atypical pattern; and a motor adaptation rate comparable to TD children but involving different aspects of locomotion. The platform showed its usability with children with ASD and its reliability in the definition of paradigms for the study of motor learning while doing complex tasks, such as gait. The additional possibility to accurately manipulate visual and proprioceptive feedback will allow researchers to systematically investigate motor system features in people with ASD.

Motor abnormalities are highly prevalent in children with autism spectrum disorder and are strongly predictive of adaptive functioning. Despite the documented sex bias in the prevalence of the disorder, the impact of sex differences on motor abnormalities has been overlooked. The goal of this study was to investigate differences in the motor profile of boys and girls with autism spectrum disorder aged 3–11 years using a multimethod approach. Ninety-eight children with autism spectrum disorder and 98 typically developing children were assessed using the Movement Assessment Battery for Children 2, the Developmental Coordination Disorder Questionnaire, and the kinematic analysis of a reach-to-drop task. Results from principal components analysis on reach-to-drop-dependent measures indicated four components, accounting for kinematic parameters of the motor task. Irrespective of sex, children with autism spectrum disorder showed worse scores on Movement Assessment Battery for Children 2 and Developmental Coordination Disorder Questionnaire subscales than typically developing children. Interestingly, a diagnosis-by-sex interaction was found on a kinematic feature measured in the last part of the movement, with girls with autism spectrum disorder presenting altered motor anticipation. Although preliminary, these findings suggested that sex-related nuances in motor functioning of children with autism spectrum disorder could be insufficiently captured by existing motor measures. Lay abstract Motor peculiarities are often reported in children with autism spectrum disorder and may predict subsequent adaptive functioning and quality of life. Although the sex bias in the prevalence of the disorder is well documented, little is known about differences in motor profile in males and females with autism spectrum disorder. Our goal was to study differences in motor functioning of boys and girls with autism spectrum disorder aged 3–11 years compared with typically developing children. Their motor performances were evaluated using a multimethod approach, including standardized motor tests, caregiver reports, and a detailed motion capture analysis of a simple reach-to-drop movement. We found that, irrespective of sex, children with autism spectrum disorder had worse scores than typically developing children on standardized tests and on caregiver reports. Interestingly, girls with autism spectrum disorder, but not boys, presented altered motor anticipation in reach-to-drop. Our findings emphasize the need for more sex-specific assessment of motor function in autism spectrum disorder.

The use of corticosteroids and anabolic steroids in food producing animals is regulated or banned in the European Union (EU). However, their use as growth promoters cannot be excluded. Milk replacers, considered by EU legislation as feeds, may be a good way of administration of these compounds. In order to improve the control of growth promoter utilization in animal husbandry and preventing possible consequences to animal welfare, we developed a method for multiresidue analysis of prednisolone, prednisone, dexamethasone, cortisone, cortisol, 17α- and 17β-boldenone and their precursor androstadienedione (ADD), testosterone, epitestosterone, 17α- and 17β-nandrolone, and trenbolone in powdered milk for calves. All analytes were extracted, after a common deproteinization and defatting sample pre-treatment, by a unique immunoaffinity column and analysed by liquid chromatography tandem mass spectrometry (LC–MS/MS) in both positive and negative electrospray ionization (ESI) modes. The method was validated according to the criteria of the Commission Decision 2002/657/CE. The analytical limits were from 0.39 to 0.73 ng mL−1 for the decision limit (CCα) and 0.46–0.99 ng mL−1 for detection capability (CCβ). The analysis of 50 samples of milk replacers for calves, always revealed the presence of cortisol and cortisone (average concentrations 2.56 and 1.06 ng mL−1, respectively), frequently testosterone and epitestosterone (1.24 and 0.63 ng mL−1, respectively), occasionally β-nandrolone (0.82 ng mL−1) and prednisolone (0.41 ng mL−1). The other anabolic steroids were never found.

Antibiotics are widely used in livestock production as disease treatment, prevention and improve feeding efficiency. In this study three screenings and a multiclass method by Liquid Chromatography tandem Mass High Resolution Spectrometry (LC-HRMS) were developed and used to evaluate the antimicrobial substance incidence in 254 raw bovine milks involved in PDO cheese production in Northern Italy. The LC-HRMS results were compared to assess the frequency of false and negative results in term of reliability of screening methods. An investigation in relation to the quantified residues evaluating their possible negative impact on milk starter cultures in a simulated cheese-making process was presented. Lincomycin residues were observed in 30 samples, with 11.8% frequency and 17.29 ppb as mean value below its MRL. Three samples showed oxytetracycline respectively at 15.05, 0.82 and 1.59 ppb and two cefapirin and spyramycin at trace level. False positives with an acceptable frequency were observed by using the 3 kits confirming this approach useful for monitoring plans. Considering lincomycin, negative effect was demonstrated toward lactic acid bacteria activity in term of bacteria counts, pH and acidity during cheese making simulation. This represents a critical aspect considering both the economic value of PDO cheeses and the antibiotic resistance diffusion.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children and adolescents, with environmental and biological causal influences. Pharmacological medication is the first choice in ADHD treatment; recently, many studies have concentrated on dietary supplementation approaches to address nutritional deficiencies, to which part of non-responses to medications have been imputed. This review aims to evaluate the efficacy of non-pharmacological supplementations in children or adolescents with ADHD. We reviewed 42 randomized controlled trials comprised of the following supplementation categories: polyunsaturated fatty acids (PUFAs), peptides and amino acids derivatives, single micronutrients, micronutrients mix, plant extracts and herbal supplementations, and probiotics. The reviewed studies applied heterogeneous methodologies, thus making it arduous to depict a systematic overview. No clear effect on single cognitive, affective, or behavioral domain was found for any supplementation category. Studies on PUFAs and micronutrients found symptomatology improvements. Peptides and amino acids derivatives, plant extracts, herbal supplementation, and probiotics represent innovative research fields and preliminary results may be promising. In conclusion, such findings, if confirmed through future research, should represent evidence for the efficacy of dietary supplementation as a support to standard pharmacological and psychological therapies in children and adolescents with ADHD.

This study aimed to investigate the efficacy of docosahexaenoic acid (DHA) dietary supplementation on behavior and cognition in school-aged, drug-naive children with attention-deficit/hyperactivity disorder (ADHD). A total of 50 participants with ADHD aged 7 to 14 were enrolled in a 6-month randomized, placebo-controlled clinical trial and received either DHA or placebo. The primary outcome measure was the change in the ADHD rating scale IV Parent Version–Investigator (ADHD-RS-IV) after 4 and 6 months. Secondary outcome measures included Conners Parent Rating Scale-revised, other behavioral rating scales including quality of life and global functioning, and computerized cognitive tasks. Baseline assessment also addressed the blood fatty acids profile. No superiority of DHA supplement to placebo was observed on ADHD-RS-IV, the a priori primary outcome. DHA supplementation showed a significant, nonetheless quite small, effect on children’s psychosocial functioning, emotional problems, and focused attention. Neither major nor minor adverse events were reported throughout the trial. This study shows that 6-month DHA supplementation has no beneficial effect on the symptoms of ADHD in school-aged, drug-naive children with an established diagnosis of ADHD. Nevertheless, the 6 months treatment with supplemental DHA appears to have small positive effects on other behavioral and cognitive difficulties, which, in light of the absence of side-effects, could be reasonably followed up in future intervention studies. ( https://clinicaltrials.gov/ct2/show/NCT01796262 : The Effects of DHA on Attention Deficit and Hyperactivity Disorder (DADA)).

Aims.Many studies of various stress reactive phenotypes suggest that 5-HTTLPR short allele carriers (S-carriers) are characterised by the stable trait of negative affectivity that is converted to psychopathology only under conditions of stress. In this study, we examined the moderating role of the 5-HTTLPR on the relationship between two objective chronic risk factors, i.e. socioeconomic status (SES) and family structure, and internalising symptoms across adolescence.Methods.A multigroup path analysis was employed in a general adolescent population sample of a 5-year follow-up study.Results.Internalising problems were significantly more stable in theS-carriers. The focus on the main dimensions of internalising problems, i.e. anxiety and depression, revealed two different developmental patterns. In theS-carriers Anxiety problems seemed to be more stable and to predict a possible evolution towards the development of Depressive problems. In the long allele homozygotes (LL-subjects) the anxiety trait was significantly less stable, and, in late-adolescence, seemed to be significantly predicted by SES, suggesting a possible gene–environment interaction (G × E). Family structure seemed to play a role in a G × E perspective only until early-adolescence, while during late-adolescence SES seemed to play a pivotal role in interaction with 5-HTTLPR, with the S-allele playing a protective role.Conclusions.Future models of the developmental link between environmental adversities and internalising behaviour therefore need to consider that the effect of G × E interaction, may be associated with internalising behaviour via different mechanisms during different time frames and that shifts in the strength of this effect should be expected across development.

Over the last 15 years, considerable interest has been given to the potential role of omega-3 polyunsaturated fatty acids (PUFAs) for understanding pathogenesis and treatment of neurodevelopmental and psychiatric disorders. This review aims to systematically investigate the scientific evidence supporting the hypothesis on the omega-3 PUFAs deficit as a risk factor shared by different pediatric neuropsychiatric disorders. Medline PubMed database was searched for studies examining blood docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) status in children with neuropsychiatric disorders. Forty-one published manuscripts were compatible with the search criteria. The majority of studies on attention-deficit/hyperactivity disorder (ADHD) and autism found a significant decrease in DHA levels in patients versus healthy controls. For the other conditions examined—depression, juvenile bipolar disorder, intellectual disabilities, learning difficulties, and eating disorders (EDs)—the literature was too limited to draw any stable conclusions. However, except EDs, findings in these conditions were in line with results from ADHD and autism studies. Results about EPA levels were too inconsistent to conclude that EPA could be associated with any of the conditions examined. Finally, correlational data provided, on one hand, evidence for a negative association between DHA and symptomatology, whereas on the other hand, evidence for a positive association between EPA and emotional well-being. Although the present review underlines the potential involvement of omega-3 PUFAs in the predisposition to childhood neuropsychiatric disorders, more observational and intervention studies across different diagnoses are needed, which should integrate the collection of baseline PUFA levels with their potential genetic and environmental influencing factors.

The present study examined the extent to which individual differences in personality that have been previously associated with aggression in non-clinical subjects (Caprara et al., European Journal of Personality, 27(3), 290–303, 2013, Caprara et al., Developmental Psychology, 50(1), 71–85, 2014) account for aggression among adolescents referred to psychiatric services with diagnosis within the externalizing spectrum (i.e., conduct disorder, oppositional defiant disorder, and attention deficit hyperactivity disorder). In particular a conceptual model was examined in which individual differences in basic traits (i.e., emotional instability and agreeableness), lower order traits (i.e., irritability and hostile rumination), and social cognitive mechanisms (i.e., moral disengagement) account for aggressive behavior. One hundred and nine adolescents (81 males, 74.3%), ranging in age from 11 to 18 (M = 13.83, SD = 1.70) and referred to psychiatric services for the above diagnoses, participated at the study. Adolescents filled in questionnaires measuring the Big Five traits, as well as irritability, hostile rumination, and moral disengagement; their parents filled in the Child Behavior Checklist to assess children’s aggressive behavior. Findings corroborated the posited pattern of relations previously found in non-clinical samples. In accordance with those findings, moral disengagement largely mediated the association between traits and aggressive behavior. The model explained a significant portion of variance in aggressive behavior. As a novelty, findings showed a direct association between emotional instability and aggressive behavior, pointing to the major relevance of emotional disregulation in adolescents referred for externalizing problem behaviors in comparison to non-clinical adolescents.

Researchers’ interest have recently moved toward the identification of recurrent psychopathological profiles characterized by concurrent elevations on different behavioural and emotional traits. This new strategy turned to be useful in terms of diagnosis and outcome prediction. We used a person-centred statistical approach to examine whether different groups could be identified in a referred sample and in a general-population sample of children and adolescents, and we investigated their relation to DSM-IV diagnoses. A latent class analysis (LCA) was performed on the Child Behaviour Checklist (CBCL) syndrome scales of the referred sample (N=1225), of the general-population sample (N=3418), and of the total sample. Models estimating 1-class through 5-class solutions were compared and agreement in the classification of subjects was evaluated. Chi square analyses, a logistic regression, and a multinomial logistic regression analysis were used to investigate the relations between classes and diagnoses. In the two samples and in the total sample, the best-fitting models were 4-class solutions. The identified classes were Internalizing Problems (15.68%), Severe Dysregulated (7.82%), Attention/Hyperactivity (10.19%), and Low Problems (66.32%). Subsequent analyses indicated a significant relationship between diagnoses and classes as well as a main association between the severe dysregulated class and comorbidity. Our data suggested the presence of four different psychopathological profiles related to different outcomes in terms of psychopathological diagnoses. In particular, our results underline the presence of a profile characterized by severe emotional and behavioural dysregulation that is mostly associated with the presence of multiple diagnosis.

In this systematic review, we will consider and debate studies that have explored the effects of ω-3 polyunsaturated fatty acids (PUFAs) in three major, and somehow related, developmental psychiatric disorders: Autism, Attention Deficit and Hyperactivity disorder and Psychosis. The impact of ω-3 PUFAs on clinical symptoms and, if possible, brain trajectory in children and adolescents suffering from these illnesses will be reviewed and discussed, considering the biological plausibility of the effects of omega-3 fatty acids, together with their potential perspectives in the field. Heterogeneity in study designs will be discussed in the light of differences in results and interpretation of studies carried out so far

It is well established that adversities and GRIN2B (coding an N-methyl-D-aspartate receptor subunit) are independently associated with behavioral and cognitive impairments in childhood. However, a high proportion of children exposed to adversities have good, long-term outcomes. We hypothesized that among children exposed to adversities, GRIN2B variants would predict the worst cognitive and behavioral outcomes. 6 single nucleotide polymorphisms of GRIN2B were genotyped in 625 children aged 6-11 years from an Italian community-based sample. The interacting effect of GRIN2B variants with 4 measures of adversities [low socioeconomic status (SES), preterm delivery, maternal smoking during pregnancy, and absence of breastfeeding] was investigated upon blindly assessed cognitive abilities (vocabulary, block design, digit spans of Wechsler's Intelligence Scale, and Rey complex figure) and parents-rated behavioral problems (Child Behavior Checklist/6-18). Rs2268119 × SES interaction (Hotelling's Trace = 0.07; F(12,1154) = 3.53; p = 0.00004) influenced behavior, with more attention problems among children in the 'either A/T or T/T genotype and low SES' group, compared to all other groups. This interaction effect was not significant in an independent, replication sample of 475 subjects from an Italian community-based sample. GRIN2B variants predict children with the worst outcome in attention functioning among children exposed to low SES. Our findings, if replicated, could help in the identification of children with the highest risk and may prompt cost-effective preventive/treatment strategies.

In a short series of articles, we will review the evidence for genotype by environment interaction (G × E) in developmental psychopathology. We will focus specifically on the characteristics of types of exposure assessed with respect to both their methods and findings. This article aims to review the studies exploring the moderating role of serotonin transporter on the effect of environmental adversities over time, particularly during childhood and adolescence, which is when level of internalizing symptoms and prevalence of mood disorders change substantially. Environmental adversities will not include abuse and maltreatment that have been reviewed before (see Bellani et al. 2012) and child's broader social ecology that will be reviewed in the next section.

Objective To evaluate through a comprehensive protocol, the psychopathological profile of DMD boys. The primary aim of this observational study was to describe the emotional and behavioural profile and the neurodevelopmental problems of Italian boys with Duchenne Muscular Dystrophy (DMD); the secondary aim was to explore the relation between psychopathological profile and DMD genotype. Method 47 DMD boys, aged 2–18, were included in the study and assessed through structured and validated tools including Wechsler scales or Griffiths for cognitive ability, Child Behavior Check List (CBCL), Youth Self Report (YSR) and Strengths and Difficulties Questionnaire (SDQ) for emotional and behavioural features. Patients “at risk” based on questionnaires scores were evaluated by a clinical structured interview using Development and Well Being Assessment (DAWBA) or Autism Diagnostic Observation Schedule (ADOS), as required. Results The 47 enrolled patients, defined with a Full Scale Intelligence Quotient (FSIQ) of 80.38 (one SD below average), and presenting a large and significant difference in FSIQ in relation to the site of mutation along the dystrophin gene (distal mutations associated with a more severe cognitive deficit), were showing Internalizing Problems (23.4%) and Autism Spectrum Disorders (14.8%). Interestingly, an association of internalizing problems with distal deletion of the DMD gene is documented. Conclusion Even though preliminary, these data show that the use of validated clinical instruments, that focus on the impact of emotional/behaviour problems on everyday life, allows to carefully identify clinically significant psychopathology.

Calf milk replacers are low-cost feeds that contain available, digestible protein. During their reconstitution, however, the addition of drugs, such as antibiotics, could make them a very simple route for illicit treatment for therapeutic, preventive, or growth-promoting purposes. We developed an HPLC-MS/MS method, preceded by a unique extraction step, able to identify 17 antibiotics from seven classes (penicillins, tetracyclines, fluoroquinolones, sulfonamides, cephalosporins, amphenicols, and lincosamides) in this matrix. Prior to solid phase extraction (SPE), the sample underwent deproteinization and defatting. The method was fully validated according to Commission Decision 2002/657/EC. Decision limits (CCα) and detection capability (CCβ) were in the ranges of 0.13–1.26 and 0.15–1.47 ng/mL, respectively. Thirty-eight samples were finally analyzed, showing the occasional presence of marbofloxacin (six samples) and amoxicillin (one sample).

The causal relationship between antidepressants and the increase of self-injury and suicide in the paediatric age is highly debated. The black-box warnings about increased risks of suicidal thinking and behaviour in children and young adults, led to a reduction in both treatment and diagnosis of depression also in adults, in the face of an increasing need for therapies. The debate originates also from contrasting reports in the literature.We carried out an interpretative review of the most recent reports (2012-2014), from which three topics emerged.First, the presence of populations with different baseline risks of self-injury among published works introduced bias in the results. Second, the application of inappropriate or excessively variegated outcome measures for self-injury introduced confounding factors that prevent the successful conduction of meta-analyses. This hinders constructive debate involving different groups, as shown in the correspondence by senior authors in the field. Third, the regulatory actions that limited the prescription of antidepressants were taken in perspective of scientific advances, not yet due. This turned temporary cautions into long-lasting limitations.While some clinical improvements can already be suggested, only the fulfilment of this debate will allow to revise the black-box warnings and to improve the antidepressant therapies.

Aims.Adolescence is a critical transition phase between childhood and adulthood, when the burden of mental disorder may still be prevented. The aim of this study was to evaluate the continuity and discontinuity of behavioural problems in adolescence while taking into account the multiple co-variation of psychopathological traits and the complex role of recent stressful life events (SLEs).Methods.This is a 5-year follow-up investigation of emotional and behavioural problems assessed by the newly developed Child Behavior Checklist (CBCL) DSM-Oriented Scales (DOSs) in 420 general population subjects aged 15–19 years.Results.The DOSs showed good stability, even when multiple co-variation was taken into account. Longitudinal data showed that homotypic evolution of psychopathology was to be expected in the first place. Equifinality and multifinality were also found. Oppositional Defiant Problems emerged to be polyvalent predictors of both internalizing and externalizing problems. Furthermore, Oppositional Defiant Problems predicted more SLEs, which in turn predicted more Depression, Anxiety and Oppositional Defiant Problems. Mediational analyses confirmed the role of SLEs in partially accounting for the continuity of Oppositional Defiant Problems and for the heterotypic progression towards Affective Problems.Conclusions.These data underscore early adolescence behavioural problems as an important focus for primary and secondary intervention.

Ethical, legal, and social issues related to the collection, storage, and use of biospecimens and data derived from children raise critical concerns in the international debate. So far, a number of studies have considered a variety of the individual issues crucial to pediatric biobanking such as decision making, privacy protection, minor recontact, and research withdrawal by focusing on theoretical or empirical perspectives. Our research attempted to analyze such issues in a comprehensive manner by exploring practices, rules, and researcher opinions regarding proxy consent, minor assent, specimens and data handling, and return of results as faced in 10 European countries. Because of the lack of comparative analyses of these topics, a pilot study was designed. Following a qualitative methodology, a questionnaire draft mostly including open-ended queries was developed, tested, and sent by e-mail to a selected group of researchers dealing with pediatric biobanking (n=57). Returned questionnaires (n=31) highlighted that the collection, storage, distribution, and use of biospecimens and data from children were widely practiced in the contacted laboratories. In most cases, pediatric biobanking was subjected to national or local regulations covering adult biobanks (n=26). Informed consent was generally given by parents or legal representatives (n=17). Children's opinions were frequently sought and taken into account (n=16). However, minors were usually not recontacted at the age of maturity to express their own choices (n=26). Based on the collected data, dedicated recommendations are needed to govern unique ethical and regulatory issues surrounding pediatric biobanking.