Neurological dysfunction screening in a cohort of adolescents with type 1 diabetes: a six-year follow-up.

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.

Adolescent chronic sleep restriction promotes alcohol drinking in adulthood: evidence from epidemiological and preclinical data.

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.

Suicide in the press: an analysis of newspaper coverage of adolescent versus adult suicides in Italy.

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.

A Neuropsychiatric Assessment of Children with Previous SARS-CoV-2 Infection.

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.

Working with Children with Autism Undergoing Health-Care Assessments in a Day Hospital Setting: A Perspective from the Health-Care Professionals.

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.

Sleep disturbances and emotional dysregulation in young children with autism spectrum, intellectual disability, or global developmental delay.

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.

Children with Prader-Willi Syndrome and COVID-19: a longitudinal study of the effect of social re-opening after the lockdown.

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.

Performing Arts in Suicide Prevention Strategies: A Scoping Review.

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.

Enhanced Expression of Human Endogenous Retroviruses, TRIM28 and SETDB1 in Autism Spectrum Disorder.

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.

The transition from adolescence to adulthood in patients with schizophrenia: Challenges, opportunities and recommendations.

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.

Association between EEG Paroxysmal Abnormalities and Levels of Plasma Amino Acids and Urinary Organic Acids in Children with Autism Spectrum Disorder.

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.

Emotional Dysregulation and Adaptive Functioning in Preschoolers With Autism Spectrum Disorder or Other Neurodevelopmental Disorders.

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.

A nationwide study on Sydenham's chorea: Clinical features, treatment and prognostic factors.

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.

Impact of the COVID-19 Pandemic on Child and Adolescent Psychiatric Emergencies.

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.

Psychological Impact of the COVID-19 Pandemic on Adults and Their Children in Italy.

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.

Where have the children with epilepsy gone? An observational study of seizure-related accesses to emergency department at the time of COVID-19.

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.

Neuromodulatory Action of Picomolar Extracellular Aß42 Oligomers on Presynaptic and Postsynaptic Mechanisms Underlying Synaptic Function and Memory.

Failure of anti-amyloid-ß peptide (Aß) 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 Aß 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 Aß42 (oAß42) on synaptic glutamatergic function in male and female mice. We found that 200 pm oAß42 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. oAß42 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 Aß 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 oAß42 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 oAß42 in synaptic function and memory formation providing solid fundamentals for investigating the pathological effects of high Aß levels in the AD brains.SIGNIFICANCE STATEMENT High levels of oligomeric amyloid-ß42 (oAß42) 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 oAß42 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 Aß function in the healthy brain might be useful to understand the causes leading to its increase and detrimental effect in AD.

Synaptic vesicle protein 2: A multi-faceted regulator of secretion.

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.

Divergent medial amygdala projections regulate approach-avoidance conflict behavior.

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.

Two Behavioral Tests Allow a Better Correlation Between Cognitive Function and Expression of Synaptic Proteins.

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.