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In this pre-registered study, we ask how people's emotional responses under threat may be causally affected by what is available to them in the environment, i.e. environmental affordances. For this purpose, we introduce a novel behavioral paradigm using horror movie stimuli to simulate threats. The study illustrates that affordances, specifically items present in the environment, are instrumental in modulating both behavioral choices (approach or avoidance) and emotional expressions of anger and fear. We found that, approach-related resources, such as possession of a weapon, heightened anger and the propensity to confront the threat. This underscores the influence of environmental affordances on emotional regulation and supports a theoretical framework that connects instrumental motives with the variability of emotional and behavioral responses based on affordances. The research, while innovative, recognizes the constraints of simulated threats and controlled settings, suggesting avenues for future exploration in more naturalistic environments., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Improving teachers' knowledge and skills in dealing with adolescent suicidality may be important for prevention. We evaluated the feasibility and acceptability of a theatre-based gatekeeper teacher training for adolescent suicide prevention (SPES project). Self-reported changes in knowledge and self-efficacy were also investigated. Based on a quasi-experimental repeated measures design, secondary schools were invited to participate in one of two intervention groups (theatre workshop or attending a theatre performance) or a control group (no intervention). Assessments were conducted prior to the intervention, shortly following it and 3 months later. Attendance and retention were indicators of feasibility. Knowledge and self-efficacy were assessed longitudinally using anonymous questionnaires. Data were analyzed using linear mixed models. 191 teachers (84.3% women; Mage = 46.8, SD = 9.8) participated in the study (63 workshop, 66 performance and 62 control group). Attendance was 92% in the workshop group and 94% in the performance group. The retention rate after three months was 51% in the workshop group and 53% in the performance group. Teachers in both groups reported greater knowledge of adolescent suicide ( p < 0.001) and higher gatekeeper self-efficacy ( p < 0.05) than the control group. The SPES project was found to be feasible and acceptable. Both the workshop and the performance viewing may improve teachers' knowledge and self-efficacy in recognizing signs of suicide risk in adolescents.

Background: Anorexia nervosa (AN) and obesity (OB) are relevant concerns in adolescence. Despite their contrasting phenotypes, they share common pathogenic origins and may be present in the same individual at different times. We explored the psychopathology and attachment features of adolescents with AN who did (AN-ow) or did not (AN-nw) have previous overweight, compared with OB adolescents and healthy control (HC) adolescents., Method: In total, 148 female adolescents referred to an outpatient clinic for an eating disorder (66 for AN and 42 for OB) and 40 HCs were assessed using self-administered instruments that measured parenting, attachment, eating, and general psychopathology. Group differences were tested by analysis of covariance, and correlations between variables were examined., Results: AN-ow, AN-nw, and OB adolescents had greater interpersonal distrust and avoidance of relationships, compared with HC adolescents. AN-nw and AN-ow adolescents displayed a higher need for approval and a drive to thinness and interpersonal distrust, compared with HC adolescents. AN-ow adolescents displayed lower paternal care and higher ineffectiveness, asceticism, social insecurity, and depression, compared with HC adolescents. Compared with AN-nw adolescents, AN-ow adolescents felt more ineffective and more ascetic. The dynamics linking the psychopathological features clearly distinguished the four groups., Conclusions: AN-ow is a well-identified subtype of AN, with specific features that differ from AN-nw; some of these features are shared with OB. A therapeutic approach tailored to AN-ow adolescents should consider these features., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Amianto, Sertori, Davico, Marcotulli and Vitiello.)

Importance: There are suggestions that school pressure may be stressful and a factor in child and adolescent mental health disturbances, but data about this association are scarce and inconclusive., Objective: To assess whether varying degrees of school interruption were associated with changes in emergency department (ED) psychiatric visits of children and adolescents before and after the COVID-19 outbreak., Design, Setting, and Participants: A cross-sectional observational study was conducted at 9 urban university hospitals in Italy. All ED visits from January 1, 2018, to December 31, 2021, for psychiatric reasons of patients younger than 18 years were examined for demographic characteristics and type of psychopathologic factors. Data analysis was conducted from July 1 to August 31, 2023., Exposure: The disruption in the usual succession of school and holiday periods brought on by the COVID-19 pandemic at different times and with various degrees of intensity., Main Outcomes and Measures: Total number of pediatric ED visits, psychiatric ED visits, and psychiatric ED visits categorized by specific reasons (eg, psychomotor agitation, suicide ideation [SI] or suicide attempt [SA], and eating disorders) on a weekly basis., Results: A total of 13 014 psychiatric ED visits (1.3% of all pediatric ED visits) were recorded (63.2% females; mean [SD] age, 13.8 [3.8] years). The number of ED psychiatric visits increased over time (incidence rate ratio [IRR], 1.19; 95% CI, 1.16-1.22 for each year). Significant increases in ED visits were observed for eating disorders (294.8%), SI (297.8%), and SA (249.1%). School opening, but not social lockdown restriction, was associated with an increase in the number of ED psychiatric visits (IRR, 1.29; 95% CI, 1.23-1.34), which was evident for females and for SI with SA. Socioeconomic status was associated with an increase in psychiatric visits for males (IRR, 1.12; 95% CI, 1.04-1.20) but not females (IRR, 1.04; 95% CI, 0.98-1.10)., Conclusions and Relevance: In this study, school opening was associated with an increased incidence of acute psychiatric emergencies among children and adolescents, suggesting that school can be a substantial source of stress with acute mental health implications.

Aim: After the COVID-19 pandemic, the need for intensive nutritional care in patients affected with anorexia nervosa (AN) increased. The use of NGT was often used to overcome renutrition difficulties. This systematic review explores the evidence concerning the psychological effects of an enteral nasogastric tube (NGT) feeding on patients with AN., Methods: A systematic review following PRISMA guidelines was conducted on electronic databases, including papers from January 2010 to December 2023. The keywords used combined anorexia nervosa, NGT, nasogastric tube, and tube feeding, with MeSH terms. No language limit was imposed. Reviews were excluded from the search., Results: A total of 241 studies matched the keywords. Nevertheless, 236 studies were excluded from the review because they did not match the inclusion criteria. A total of six studies met the inclusion criteria. Of these, three studies were case series, one was a quantitative study of follow up and one was a qualitative exploratory study. The included studies described the hospitalization of patients with AN treated with a nasogastric tube; among these, only one study focused directly on the psychological correlates of nasogastric tube treatment using interviews with patients and medical staff. Included studies suggest that NGT feeding, even if faced in the first instance with prejudices and fears by patients, parents, and staff, is useful not only for weight increase in treatment-resistant patients with AN, but also alleviates their stress from feeding and, in general, it is psychologically well tolerated. Nevertheless, recent in-depth research on the issue is lacking and the existing has a low methodological quality; thus, many psychological effects of NGT application remain underexplored., Conclusions: Although the results suggest good psychological tolerance of the device, the limited data available recommend that more attention should be addressed by the researchers to the psychological consequences of the use of NGT in the treatment of AN since it is a nutrition disorder with prominent psychological roots. Further studies are needed.

Aims: Diabetic neuropathy (DN) is one of the most insidious microvascular complications in patients with type 1 diabetes (T1DM) and initial signs may appear during childhood. The aim of this study is to evaluate associations between the Nerve Conduction Studies (NCS) outcomes at enrollment with neuropathy screening questionnaires performed six years later in a cohort of asymptomatic adolescents followed up until early adulthood, affected by T1DM., Methods: We performed NCS in a cohort of seventy-two adolescents with T1DM and eighteen healthy controls. Six years later, screening questionnaires for DN were proposed: Michigan Neuropathy Screening Instrument (MNSI, specific for symptoms of somatic dysfunction), Composite Autonomic Symptom Score 31 (COMPASS 31, specific for abnormalities of the autonomic component) and Clarke questionnaire (perception of hypoglycemia). Thirty-two TD1M subjects agreed to participate in the follow-up; main clinical-metabolic parameters, including the number of episodes of hypoglycemia in the past twelve months, were collected., Results: 11.8% of subjects showed changes compatible with DN through the MNSI questionnaire, while 41% declared a reduced perception of hypoglycemia on the Clarke questionnaire. No significant correlation was observed between the clinical-metabolic parameters or altered response to NCS and scores of MNSI and COMPASS 31 questionnaires. On the other hand, an association was observed between NCS abnormalities and a high number of hypoglycemic events after six years (97-fold increased risk, p  = 0.009)., Conclusion: The frequency of somatic alterations in the study population is 11.8%, whereas the frequency of symptoms correlated with autonomic damage is about 41%. An autonomic impairment recorded at NCS may represent a six-year risk factor for increased hypoglycemic episodes, even if more extensive studies are needed to investigate this possible relationship further., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tinti, Canavese, Nobili, Marcotulli, Daniele, Rabbone and de Sanctis.)

Epidemiological investigations have indicated that insufficient sleep is prevalent among adolescents, posing a globally underestimated health risk. Sleep fragmentation and sleep loss during adolescence have been linked to concurrent emotional dysregulation and an increase in impulsive, risk-taking behaviors, including a higher likelihood of substance abuse. Among the most widely used substances, alcohol stands as the primary risk factor for deaths and disability among individuals aged 15-49 worldwide. While the association between sleep loss and alcohol consumption during adolescence is well documented, the extent to which prior exposure to sleep loss in adolescence contributes to heightened alcohol use later in adulthood remains less clearly delineated. Here, we analyzed longitudinal epidemiological data spanning 9 years, from adolescence to adulthood, including 5497 participants of the Avon Longitudinal Study of Parents And Children cohort. Sleep and alcohol measures collected from interviews and questionnaires at 15 and 24 years of age were analyzed with multivariable linear regression and a cross-lagged autoregressive path model. Additionally, we employed a controlled preclinical experimental setting to investigate the causal relationship underlying the associations found in the human study and to assess comorbid behavioral alterations. Preclinical data were collected by sleep restricting Marchigian Sardinian alcohol preferring rats (msP, n=40) during adolescence and measuring voluntary alcohol drinking concurrently and in adulthood. Polysomnography was used to validate the efficacy of the sleep restriction procedure. Behavioral tests were used to assess anxiety, risky behavior, and despair. In humans, after adjusting for covariates, we found a cross-sectional association between all sleep parameters and alcohol consumption at 15 years of age but not at 24 years. Notably, alcohol consumption (Alcohol Use Disorder Identification Test for Consumption) at 24 years was predicted by insufficient sleep at 15 years whilst alcohol drinking at 15 years could not predict sleep problems at 24. In msP rats, adolescent chronic sleep restriction escalated alcohol consumption and led to increased propensity for risk-taking behavior in adolescence and adulthood. Our findings demonstrate that adolescent insufficient sleep causally contributes to higher adult alcohol consumption, potentially by promoting risky behavior.

Background: An association between sensationalized media reporting and subsequent increase in suicidal behavior has been documented, and adolescents are especially vulnerable to imitative influences. The aims of this study were to examine the characteristics of the articles reporting adult and adolescent (under age 18) suicides in the Italian press and to assess adherence to the World Health Organization (WHO) guidelines for responsible reporting. Methods : The print versions of the three newspapers with the widest national distribution in Italy were searched for all the articles on incident suicides printed over a 7-month period (July 2022 to February 2023). Articles were examined for adherence to the WHO guidelines. Results: Overall, 213 articles were identified, reporting on 122 individual suicide cases (88.5% adults and 11.5% adolescents). Of the articles, 78.9% were on adults and 21.1% on adolescents, with a ratio articles/suicide cases of 1.6 for adults and 3.2 for adolescents ( p  < 0.0001). Adolescent suicide articles had more words (mean 612.5 ± SD 275.6) than adult ones (462.1 ± 267.7, p  = 0.001). Potentially harmful reporting features were present in both the adult and adolescent articles (12-82%). Few articles (0-15%) included protective features. Articles on adolescents were more adherent to the WHO guidelines for omitting specific information of suicide method and location. Conclusions : Significant differences were found in the press reporting of adolescent versus adult suicides, with adolescent suicides receiving more attention in terms of the number of articles and article length. Suicide press reporting can be improved. A close collaboration between journalists and suicide prevention experts may be beneficial.

Aim: Concerns have been raised about possible neuropsychiatric sequelae of COVID-19. The objective of this study was to examine the plausibility of long-term mental health consequences of COVID-19 by assessing a sample of children after the resolution of the acute SARS-CoV-2 infection., Method: As part of a systematic follow-up assessment of pediatric patients with COVID-19 conducted at two university children's hospitals, 50 children (56% males) aged 8 to 17 years (median 11.5), 26% with previous multisystem inflammatory syndrome in children (MIS-C), without a prior history of neuropsychiatric disorders, received a battery of clinical neuropsychiatric and neuropsychological rating scales that included the Pediatric Migraine Disability Assessment (PedMIDAS), Sleep Disturbance Scale for Children (SDSC), Multidimensional Anxiety Scale for Children (MASC-2), Child Depression Inventory (CDI-2), Child Behavior Checklist (CBCL), and the NEPSY II (Neuropsychological Assessment, Second Edition). The assessments were conducted between 1 and 18 months (median 8 months) after the acute infection., Results: The CBCL internalizing symptoms score was in the clinical range for 40% of the participants (vs. a population expected rate of about 10%, p < 0.001). A sleep disturbance was detected in 28%, clinically significant anxiety in 48%, and depressive symptoms in 16%. The NEPSY II scores showed impairment in attention and other executive functions in 52%, and memory deficits in 40% of the children., Conclusions: These data from direct assessment of a sample of children who had SARS-CoV-2 infection show higher than expected rates of neuropsychiatric symptoms, thus supporting the possibility that COVID-19 may have mental health sequelae long after the resolution of the acute infection.

Objective: Sleep disturbance and emotional dysregulation (ED) are common and often functionally impairing in young children with neurodevelopmental disorders (NDD). This study investigated the relationship between sleep disturbance and ED in a sample of preschoolers with ASD, intellectual disability, or global developmental delay, and examined possible predictors of their persistence over time., Methods: All children under 6 years of age clinically referred between July 2018 and May 2022 to two neuropsychiatric specialized centers for NDD received a comprehensive diagnostic evaluation, including the Child Behavior Checklist 1.5-5 (CBCL), the Autism Diagnostic Observation Schedule-2 (ADOS-2), and standardized tests of cognitive and global development. Sleep disturbances were assessed with the CBCL-sleep score, and ED with the CBCL Attention, Aggression, and Anxious/Depressed scales (CBCL-AAA). A reassessment of sleep and ED was conducted after 6 months or longer, including the Child Sleep Habits Questionnaire (CSHQ). Multivariate analyses and mixed linear regression models were conducted., Results: A total of 136 children, 75.7% male, median age 38.27 months, IQR 15.39, 41.2% with global developmental disorder (GDD) or intellectual disability (ID) participated in the study. Of them, 64.7% were diagnosed with autism spectrum disorder (ASD) and 35.3% with other NDD (w/o ASD). Sleep disturbances (CBCL-Sleep) and ED (CBCL-AAA) were positively correlated (p < 0.001), after accounting for age, ID/GDD and autism symptom severity, in both the entire sample and separately in each diagnostic group (ASD and NDD w/o ASD). Seventy-five children (55%) were reassessed a mean 17.2 months afterwards. There was persistence of the positive correlation between sleep problems and ED (p < 0.001) in both the entire sample and each diagnostic group. The longitudinal mixed linear model showed that ED at follow-up was predicted by baseline sleep problems (p = 0.008), ED (p < 0.001), and ASD severity (p = 0.015)., Conclusions: Sleep disturbances are significantly associated with ED in young children with NDD, either with or without ASD, both cross-sectionally and prospectively over time. Sleep problems represent an important comorbidity and a potential treatment target for improving emotional stability in NDD., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Hospitals can be especially stressful for children with autism spectrum disorder (ASD) due to the communication and social skills deficits, lower capacity to adapt to disruption, and sensory hypersensitivity that are typical of these patients., Purpose: This study investigated how health-care professionals (HPs) experienced the clinical care and management of children with ASD undergoing medical testing in a day hospital setting, and assessed the rate of successful completion of laboratory tests and instrumental examinations., Methods: A cross-sectional questionnaire was administered to 45 HPs, inquiring about their experience in obtaining blood and urine tests, ECG, audiometry, and EEG from children with ASD. The clinical sample included 153 consecutively referred children with ASD (74.5% males, mean age 5.6 years) undergoing a medical diagnostic work-up as part of their diagnostic evaluation. The success rate of completing the various assessments was examined., Results: HPs identified aggressive behavior and communication deficits as the major challenges when providing care to children with ASD. The parents were seen as an important resource for managing the children. The completion rate of the laboratory tests and instrumental examinations was high (between 88.5% and 98.4% according to the specific type of examination). The lowest non-completion rate was found for the EEG (12.5%)., Conclusions: Despite considerable challenges being reported by HPs in managing children with ASD, the scheduled assessments could be completed in the large majority of cases. Targeted approaches to preventing aggressive behaviors and obviating the communication barriers in children with ASD undergoing hospital exams are warranted.

Background: This study longitudinally investigated mental health indicators, body mass index (BMI), and access to school and health-care services in children with Prader-Willi syndrome (PWS) and community controls (CC) during the first wave of the COVID-19 pandemic., Methods: The parents of 71 children (34 PWS and 37 CC) aged 6-17 years completed an online questionnaire during the initial COVID-19 lockdown (T0) and the subsequent partial (T1) and full re-opening (T2). We examined access to school and health-care services, BMI, and mental health (DSM-5 Parent/Guardian Rated Cross-Cutting Syndrome Measure) across the three time-points. For BMI and DSM-5 measure, we tested within- (Friedman's ANOVA repeated measures) and between- (robustified linear mixed-models, rLMM) group differences over time., Results: Around 30% of PWS children maintained contact with medical personnel through telemedicine. PWS children kept contact with both teachers and classmates at a lower rate than CC. At all time-points, BMI was higher in PWS than CC. During partial reopening, while children with PWS had a decrease in BMI, CC showed an increase, with a significant interaction time*group interaction. Mental symptoms significantly declined in both groups, although in CC the decrease was greater than in PWS., Conclusions: PWS children were at a disadvantage during the COVID-19 outbreak for lower access to school than CC. The improvement of mental health in both groups with the reopening confirms the importance of social activities outside the family. The decrease in BMI in the PWS group indicates the positive role of caregivers' monitoring on eating habits of children.

Suicide is a leading cause of death all over the world. Suicide prevention is possible and should be pursued through a variety of strategies. The importance of the arts for positive health outcomes has been increasingly evidenced. This scoping review aimed to identify the possible role of the performing arts-defined as a type of art performed through actions such as music, dance, or drama executed alive by an artist or other participant in the presence of an audience,-in suicide prevention programs. PubMed, Embase, PsycINFO, CINAHL, ProQuest Psychology Database, Scopus, and Web of Science were searched using terms in English for publications of original studies that included performing arts in suicide prevention programs. Thirty-five studies conducted between 1981 and 2021 were identified, of which only five were randomized clinical trials and four quasi-randomized studies. Interventions used different performing arts to improve awareness, self-efficacy, and soft skills relevant to suicide prevention. Studies were addressed mainly to gatekeepers but also directly to at-risk populations. While the study designs do not allow inferences to be drawn about the effectiveness of performing arts in preventing suicide, the review found that performing arts have been successfully implemented in suicide prevention programs. Research to evaluate the possible therapeutic benefit is warranted.

Schizophrenia is a severely debilitating neurodevelopmental disorder that requires continuous multidisciplinary treatment. Early onset schizophrenia (EOS, onset before 18) is associated with poorer outcomes than the adult-onset type. The transition from adolescent to adult mental healthcare services (AMHS) poses various challenges for maintaining continuity of care. The heterogeneous availability of specialized mental health services and resources for people with schizophrenia across Europe and the inadequacy of training programs in creating a shared culture and knowledge base between child and adult mental health professionals are major challenges at the policy level. More flexible and individualized transition timing is also needed. While changes in the relationship between patients, caregivers and mental health professionals at a time when young people should acquire full responsibility for their own care are challenges common to all mental health disorders, these are particularly relevant to the care of schizophrenia because of the severe associated disability. This Expert Opinion Paper examines the main aspects of transitioning of care in schizophrenia with the aim of identifying the challenges and the potential approaches that could enhance continuity of care., Competing Interests: Declaration of Competing Interest CA has been a consultant to or has received honoraria or grants from Acadia, Angelini, Biogen, Boehringer, Gedeon Richter, Janssen Cilag, Lundbeck, Medscape, Minerva, Otsuka, Pfizer, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda., (Copyright © 2022. Published by Elsevier B.V.)

Human endogenous retroviruses (HERVs) are relics of ancestral infections and represent 8% of the human genome. They are no longer infectious, but their activation has been associated with several disorders, including neuropsychiatric conditions. Enhanced expression of HERV-K and HERV-H envelope genes has been found in the blood of autism spectrum disorder (ASD) patients, but no information is available on syncytin 1 (SYN1), SYN2, and multiple sclerosis-associated retrovirus (MSRV), which are thought to be implicated in brain development and immune responses. HERV activation is regulated by TRIM28 and SETDB1, which are part of the epigenetic mechanisms that organize the chromatin architecture in response to external stimuli and are involved in neural cell differentiation and brain inflammation. We assessed, through a PCR realtime Taqman amplification assay, the transcription levels of pol genes of HERV-H, -K, and -W families, of env genes of SYN1, SYN2, and MSRV, as well as of TRIM28 and SETDB1 in the blood of 33 ASD children (28 males, median 3.8 years, 25-75% interquartile range 3.0-6.0 y) and healthy controls (HC). Significantly higher expressions of TRIM28 and SETDB1, as well as of all the HERV genes tested, except for HERV-W- pol , were found in ASD, as compared with HC. Positive correlations were observed between the mRNA levels of TRIM28 or SETDB1 and every HERV gene in ASD patients, but not in HC. Overexpression of TRIM28/SETDB1 and several HERVs in children with ASD and the positive correlations between their transcriptional levels suggest that these may be main players in pathogenetic mechanisms leading to ASD.

Abnormalities in the plasma amino acid and/or urinary organic acid profile have been reported in autism spectrum disorder (ASD). An imbalance between excitatory and inhibitory neuronal activity has been proposed as a mechanism to explain dysfunctional brain networks in ASD, as also suggested by the increased risk of epilepsy in this disorder. This study explored the possible association between presence of EEG paroxysmal abnormalities and the metabolic profile of plasma amino acids and urinary organic acids in children with ASD. In a sample of 55 children with ASD (81.8% male, mean age 53.67 months), EEGs were recorded, and 24 plasma amino acids and 56 urinary organic acids analyzed. EEG epileptiform discharges were found in 36 (65%) children. A LASSO regression, adjusted by age and sex, was applied to evaluate the association of plasma amino acids and urinary organic acids profiles with the presence of EEG epileptiform discharges. Plasma levels of threonine (THR) (coefficient = -0.02, p = 0.04) and urinary concentration of 3-Hydroxy-3-Methylglutaric acid (HMGA) (coefficient = 0.04, p = 0.02) were found to be associated with the presence of epileptiform discharges. These results suggest that altered redox mechanisms might be linked to epileptiform brain activity in ASD.

Aim: Emotional dysregulation (ED), defined by deficits in the ability to monitor and modulate the valence, intensity, and expression of emotions, is typically expressed with irritability, tantrums, mood fluctuations, and self-harm in young children with autism spectrum disorder (ASD). Although ED does not represent a diagnostic feature of ASD, its manifestations are an important contributor to functional impairment and clinical referral. This study aims to examine the relationship between ED and adaptive functioning in preschoolers clinically referred for ASD or other neurodevelopmental disorders., Methods: A sample of 100 children (74% males, mean age 39.4 ± 12.3 months), consecutively referred to a university clinic for neurodevelopmental disorders, received clinical assessments of psychopathology with the CBCL and the Autism Diagnostic Interview-Revised, of ED- with the CBCL-Attention, Anxious/Depressed, and Aggression index (CBCL-AAA), of autism symptom severity with the ADOS-2 Calibrated Severity Score (ADOS-CSS), and of global developmental/cognitive delay (GDD) with the WPPSI-IV or other age-appropriate standardized scales. Adaptive functioning was measured with the ABAS-II. Sixty-five children met DSM-5 criteria for ASD. Multivariate regression models were applied to evaluate the relative contribution of ED, ASD severity and GDD to the ABAS-II general (GAC), conceptual (CAD), social (SAD), and practical (PAD) adaptive functioning domains., Results: Overall ( n = 100), lower adaptive functioning was associated with higher CBCL-AAA ( p = 0.003), higher ADOS-CSS (p < 0.001), and presence of GDD ( p = 0.023). In the ASD group ( n = 65), worse CAD was predicted by GDD ( p = 0.016), and worse SAD and PAD by higher ADOS-CSS ( p = 0.032) and ED ( p = 0.002). No sex differences were detected in the study variables., Conclusion: Together with the severity of global developmental delay and of autism symptoms, ED is a significant contributor to impairment in adaptive functioning among young children with a neurodevelopmental disorder and, in particular, with ASD. ED could represent a specific target for early interventions aimed at enhancing adaptive functioning in early childhood., Competing Interests: In the last 2 years, BV has received consultant fees or honoraria from Medice, Menarini, and Angelini Pharmaceuticals. FR has received sponsorship or fee for advisory board from Roche, Novartis, Biogen, PTC Therapeutics, Sanofi Genzyme, Sarepta/biogen and CD has received consultant fee from Roche and Lundbeck, and DM has received consultant fee from Ethos Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Davico, Marcotulli, Cudia, Arletti, Ghiggia, Svevi, Faraoni, Amianto, Ricci and Vitiello.)

Objectives: Sydenham's Chorea (SC) is a neuropsychiatric disorder and a major manifestation of acute rheumatic fever. The erroneous assumption that SC is a benign and self-limiting disease, has led to a lack of high-quality scientific evidence of the therapeutical and prognostic features of SC., Study Design: We retrospectively analyzed the medical records of patients <18-years old with SC in 17 Italian pediatric centers. Recorded data included clinical, instrumental and laboratory parameters. Prognostic risk factors including treatment regimens were assessed with univariate and multivariate sub-analysis., Results: We included 171 patients with SC. 66% had generalized chorea, and 34% hemichorea. 81% had carditis (subclinical in 65%). Additional neurological symptoms were reported in 60% of the patients, mainly dysarthria and dysgraphia. 51% had neuropsychiatric symptoms at onset, which persisted after 12 months in 10%. Among psychiatric manifestations, the most common was anxiety disorder/depression (77%). Neurological remission was reached by 93% of the patients at 6 months; 9% relapsed. Patients were treated as follows: 11% penicillin alone, 37% immunomodulatory therapy, 16% symptomatic drugs (i.e. anti-seizure medication, dopamine antagonists) and 37% both symptomatic and immunomodulatory treatment. Neurological outcome did not differ between groups. Patients receiving symptomatic drugs had a higher risk of relapse on multivariate analysis (p = 0.045)., Conclusions: Treatment of SC was largely heterogeneous. Based on our results, immunomodulatory therapy did not show higher efficacy at medium term, although it was associated to a slightly lower risk of relapse compared to symptomatic therapy. Longitudinal studies are needed to assess specific risk factors and best treatment options., Competing Interests: Declaration of competing interest All Authors declare that they have no conflict of interest to disclose., (Copyright © 2021 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Objective: By forcing closure of schools, curtailing outpatient services, and imposing strict social distancing, the COVID-19 pandemic has abruptly affected the daily life of millions worldwide, with still unclear consequences for mental health. This study aimed to evaluate if and how child and adolescent psychiatric visits to hospital emergency departments (EDs) changed during the pandemic lockdown, which started in Italy on February 24, 2020., Methods: We examined all ED visits by patients under 18 years of age in the 7 weeks prior to February 24, 2020, and in the subsequent 8 weeks of COVID-19 lockdown at two urban university hospitals, in Turin and Rome, Italy. ED visits during the corresponding periods of 2019 served as a comparison using Poisson regression modeling. The clinician's decision to hospitalize or discharge home the patient after the ED visit was examined as an index of clinical severity., Results: During the COVID-19 lockdown, there was a 72.0% decrease in the number of all pediatric ED visits (3,395) compared with the corresponding period in 2019 (12,128), with a 46.2% decrease in psychiatric visits (50 vs 93). The mean age of psychiatric patients was higher in the COVID-19 period (15.7 vs 14.1 years). No significant changes were found in hospitalization rate or in the prevalence distribution of the primary reason for the psychiatric ED visit (suicidality, anxiety/mood disorders, agitation)., Conclusions: In the first 8 weeks of the COVID-19-induced social lockdown, the number of child and adolescent psychiatric ED visits significantly decreased, with an increase in patient age. This decrease does not appear to be explained by severity-driven self-selection and might be due to a reduction in psychiatric emergencies or to the implementation of alternative ways of managing acute psychopathology., (© Copyright 2021 Physicians Postgraduate Press, Inc.)

Aim: The coronavirus disease 2019 (COVID-19) pandemic has abruptly changed the life of millions as travel and social contacts have been severely restricted. We assessed the psychological impact of COVID-19 on adults and children, with special attention to health care workers (HCWs). Methods: A self-rated online survey, including the Impact of Event Scale-Revised (IES-R) for adults and the Children Revised Impact of Event Scale-Revised-13 items (CRIES-13) for their 8-18-year-old offspring, was conducted in Italy on March 20-26, 2020. Linear mixed-effects models were applied to the data, accounting for age, sex, education, and other demographic characteristics. Results: Data were available from 2,419 adults (78.4% females, mean age 38.1 ± SD 13.1 years; 15.7% HCW) and 786 children (50.1% male, mean age 12.3 ± 3.2 years). Median (IQR) IES-R score was 30.0 (21.0-40.0), corresponding to mild psychological impact, with 33.2% reporting severe psychological impact. IES-R was lower in HCWs (29.0) than non-HCWs (31.0), but HCWs directly involved in COVID-19 care had higher scores [33.0 (26.0-43.2)] than uninvolved HCWs [28.0 (19.0-36.0)]. Median CRIES-13 score was [21.0 (11.0-32.0)], with 30.9% of the children at high risk for post-traumatic stress disorder. Parent and child scores were correlated. Conclusions: Up to 30% of adult and children in the pandemic area are at high risk for post-traumatic stress disturbances. The risk is greater for HCWs directly involved in COVID-19 care and for their children., Competing Interests: In last 2 years, BV has received consultant fees or honoraria from Medice, Lundbeck, and Angelini Pharmaceuticals, and from law firms Goodwin & Procter and Haynes & Boone. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Davico, Ghiggia, Marcotulli, Ricci, Amianto and Vitiello.)

Purpose: The COVID-19 pandemic and related lockdown measures drastically changed health care and emergency services utilization. This study evaluated trends in emergency department (ED) access for seizure-related reasons in the first 8 weeks of lockdown in Italy., Methods: All ED accesses of children (<14 years of age) at two university hospitals, in Turin and Rome, Italy, between January 6, 2020 and April 21, 2020, were examined and compared with the corresponding periods of 2019., Results: During the COVID-19 lockdown period (February 23-April 21, 2020), there was a 72 % decrease in all pediatric ED accesses over the corresponding 2019 period (n = 3,395 vs n = 12,128), with a 38 % decrease in seizure-related accesses (n = 41 vs n = 66). The observed decrease of seizure-related ED accesses was not accompanied by significant changes in age, sex, type of seizure, or hospitalization rate after the ED visit., Conclusion: The COVID-19 lockdown was accompanied by a sudden decrease in seizure-related hospital emergency visits. School closure, social distancing, reduced risk of infection, and increased parental supervision are some of the factors that might have contributed to the finding., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Synaptic Vesicle Protein 2 (SV2) comprises a recently evolved family of proteins unique to secretory vesicles that undergo calcium-regulated exocytosis. In this review we consider SV2s' structural features, evolution, and function and discuss its therapeutic potential as the receptors for an expanding class of drugs used to treat epilepsy and cognitive decline., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Failure of anti-amyloid-β peptide (Aβ) therapies against Alzheimer's disease (AD), a neurodegenerative disorder characterized by high amounts of the peptide in the brain, raised the question of the physiological role of Aβ released at low concentrations in the healthy brain. To address this question, we studied the presynaptic and postsynaptic mechanisms underlying the neuromodulatory action of picomolar amounts of oligomeric Aβ 42 (oAβ 42 ) on synaptic glutamatergic function in male and female mice. We found that 200 pm oAβ 42 induces an increase of frequency of miniature EPSCs and a decrease of paired pulse facilitation, associated with an increase in docked vesicle number, indicating that it augments neurotransmitter release at presynaptic level. oAβ 42 also produced postsynaptic changes as shown by an increased length of postsynaptic density, accompanied by an increased expression of plasticity-related proteins such as cAMP-responsive element binding protein phosphorylated at Ser133, calcium-calmodulin-dependent kinase II phosphorylated at Thr286, and brain-derived neurotrophic factor, suggesting a role for Aβ in synaptic tagging. These changes resulted in the conversion of early into late long-term potentiation through the nitric oxide/cGMP/protein kinase G intracellular cascade consistent with a cGMP-dependent switch from short- to long-term memory observed in vivo after intrahippocampal administration of picomolar amounts of oAβ 42 These effects were present upon extracellular but not intracellular application of the peptide and involved α7 nicotinic acetylcholine receptors. These observations clarified the physiological role of oAβ 42 in synaptic function and memory formation providing solid fundamentals for investigating the pathological effects of high Aβ levels in the AD brains. SIGNIFICANCE STATEMENT High levels of oligomeric amyloid-β 42 (oAβ 42 ) induce synaptic dysfunction leading to memory impairment in Alzheimer's disease (AD). However, at picomolar concentrations, the peptide is needed to ensure long-term potentiation (LTP) and memory. Here, we show that extracellular 200 pm oAβ 42 concentrations increase neurotransmitter release, number of docked vesicles, postsynaptic density length, and expression of plasticity-related proteins leading to the conversion of early LTP into late LTP and of short-term memory into long-term memory. These effects require α7 nicotinic acetylcholine receptors and are mediated through the nitric oxide/cGMP/protein kinase G pathway. The knowledge of Aβ function in the healthy brain might be useful to understand the causes leading to its increase and detrimental effect in AD., (Copyright © 2019 the authors.)

Avoidance of innate threats is often in conflict with motivations to engage in exploratory approach behavior. The neural pathways that mediate this approach-avoidance conflict are not well resolved. Here we isolated a population of dopamine D1 receptor (D1R)-expressing neurons within the posteroventral region of the medial amygdala (MeApv) in mice that are activated either during approach or during avoidance of an innate threat stimulus. Distinct subpopulations of MeApv-D1R neurons differentially innervate the ventromedial hypothalamus and bed nucleus of the stria terminalis, and these projections have opposing effects on investigation or avoidance of threatening stimuli. These projections are potently modulated through opposite actions of D1R signaling that bias approach behavior. These data demonstrate divergent pathways in the MeApv that can be differentially weighted toward exploration or evasion of threats.

The molecular substrate of age-associated cognitive decline (AACD) is still elusive. Evidence indicates that AACD is related to synaptic impairment in hippocampus, but different hippocampal regions play different roles, with the dorsal hippocampus (DH) associated to spatial learning, and the ventral hippocampus (VH) crucial for emotionality. If changes in hippocampal function contributes to AACD, this contribution may be reflected in alterations of synaptic protein levels. A commonly used approach to investigate this issue is western blotting. When this technique is applied to the entire hippocampus and the cognitive impairment is evaluated by a single task, changes in expression of a protein might undergo a "dilution effect", as they may occur only in a given hippocampal region. We show that two behavioral tests yield more accurate results than one test in evaluating the function of the whole rat hippocampus by studying the expression of synaptotagmin 1 (SYT1), a vesicular protein whose expression in aged hippocampus is reportedly inconsistent. Analysis of SYT1 levels in the whole hippocampus of rats selected by the Morris water maze (MWM) test only failed to highlight a difference, whereas analysis of SYT1 levels in the whole hippocampus of rats categorized by both the MWM and the step-through passive avoidance (STPA) tests demonstrated a significant increase of SYT1 level in impaired rats. These findings, besides showing that SYT1 increases in impaired aged rats, suggest that using the whole hippocampus in blotting studies may prevent false negative results only if animals are categorized with tests exploring both DH and VH.

Presynaptic proteins are potential therapeutic targets for epilepsy and other neurological diseases. We tested the hypothesis that chronic treatment with the SV2A ligand levetiracetam affects the expression of other presynaptic proteins. Results showed that in rat neocortex no significant difference was detected in SV2A protein levels in levetiracetam treated animals compared to controls, whereas levetiracetam post-transcriptionally decreased several vesicular proteins and increased LRRK2, without any change in mRNA levels. Analysis of SV2A interactome indicates that the presynaptic proteins regulation induced by levetiracetam reported here is mediated by this interactome, and suggests that LRRK2 plays a role in forging the pattern of effects.