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BACKGROUND: The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during the COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the internal validity of the co-primary outcome, a composite psychopathology "P-score". METHODS: The COH-FIT survey has been translated into 30 languages (two blind forward-translations, consensus, one independent English back-translation, final harmonization). To measure mental health, 1-4 items ("COH-FIT items") were extracted from validated questionnaires (e.g. Patient Health Questionnaire 9). COH-FIT items measured anxiety, depressive, post-traumatic, obsessive-compulsive, bipolar and psychotic symptoms, as well as stress, sleep and concentration. COH-FIT Items which correlated r ≥ 0.5 with validated companion questionnaires, were initially retained. A P-score factor structure was then identified from these items using exploratory factor analysis (EFA) and confirmatory factor analyses (CFA) on data split into training and validation sets. Consistency of results across languages, gender and age was assessed. RESULTS: From >150,000 adult responses by May 6th, 2022, a subset of 22,456 completed both COH-FIT items and validated questionnaires. Concurrent validity was consistently demonstrated across different languages for COH-FIT items. CFA confirmed EFA results of five first-order factors (anxiety, depression, post-traumatic, psychotic, psychophysiologic symptoms) and revealed a single second-order factor P-score, with high internal reliability (ω = 0.95). Factor structure was consistent across age and sex. CONCLUSIONS: COH-FIT is a valid instrument to globally measure mental health during infection times. The P-score is a valid measure of multidimensional mental health. ispartof: JOURNAL OF AFFECTIVE DISORDERS vol:326 pages:249-261 ispartof: location:Netherlands status: published

Background: Obstructive sleep apnea can have a negative impact on children’s and adolescents’ neurocognitive abilities and hinder their academic and adaptive progress in academic, social, and/or behavioral dimensions. In this retrospective cross-sectional study, we investigated the influence of body weight conditions and allergy status on long-term mental health, cognitive development, and quality of life in children and adolescents who snored. Methods: The study sample included 47 subjects (age range 4.1 to 15.3 years) who exhibited high levels of snoring and underwent home-based polysomnography between 2015 and 2019. Follow-up assessments (3 years on average between baseline and follow-up) entailed phone interviews with the subject’s parents/caregivers who completed three validated questionnaires investigating sleep, quality of life, and parental ratings. Results: We found a correlation between age at diagnosis and being retrospectively overweight and high levels of snoring. In addition to a higher risk of developing emotional symptoms (8.2% increase in retrospective overweight status for each unit increase in the emotional score at follow-up) and oppositional behavior (9% increase in retrospective overweight status for each unit of oppositional T points at follow-up), we also noted reduced long-term social symptoms (11% decrease in retrospective overweight status for each unit increase in the social score at follow-up) and cognitive symptoms (10.6% decrease in retrospective overweight status for each unit increase in the cognitive score at follow-up), as well as a 6.1% increase in retrospective allergy status for each unit increase in academic performance at follow-up. Conclusions: Snoring can have negative impacts on mental health and cognitive development in the long term. Early detection and intervention for neuropsychological disorders is important in children and adolescents who score high on snoring. In the long term, the effects of snoring on neuropsychological disorders may vary based on previous body weight and allergy status.

The COVID-19 pandemic has fast-tracked interest in telehealth methods to guarantee the continuity of care of children with Autism Spectrum Disorder (ASD). Store-and-forward telehealth approaches offer the opportunity to facilitate timely screening of ASD, allowing parents to record videos of their child’s behaviors, subsequently shared with clinicians that provide an assessment remotely. This study aimed to examine the psychometric properties of a new telehealth screening tool, the teleNIDA, administered in home settings for remote observation of early signs of ASD in toddlers aged 18–30 months. Results showed good psychometric properties of the teleNIDA, as compared to the gold standard in-person assessment, and the predictive validity on the diagnosis of ASD at 36 months was demonstrated. This study supports the teleNIDA as a promising level 2 screening tool for ASD able to speed up diagnostic and intervention processes.

Pediatric obstructive sleep apnea can negatively affect children’s neurocognitive function and development, hindering academic and adaptive goals. Questionnaires are suitable for assessing neuropsychological symptoms in children with sleep-disordered breathing. The study aimed to evaluate the effectiveness of using the Oxygen Desaturation Index compared to the Obstructive Apnea–Hypopnea Index in predicting long-term consequences of sleep-disordered breathing in children. We conducted a retrospective analysis of respiratory polysomnography recordings from preschool and school-age children (mean age: 5.8 ± 2.8 years) and followed them up after an average of 3.1 ± 0.8 years from the home-based polysomnography. We administered three validated questionnaires to the parents/caregivers of the children by phone. Our results showed that children with an Oxygen Desaturation Index (ODI) greater than one event per hour exhibited symptoms in four domains (physical, school-related, Quality of Life [QoL], and attention deficit hyperactivity disorder [ADHD]) at follow-up, compared to only two symptoms (physical and school-related) found in children with an Obstructive Apnea–Hypopnea Index greater than one event per hour at the time of diagnosis. Our study also found a significant correlation between the minimum SpO2 (%) recorded at diagnosis and several outcomes, including Pediatric Sleep Questionnaire (PSQ) scores, physical, social, and school-related outcomes, and ADHD index at follow-up. These results suggest that the Oxygen Desaturation Index could serve as a valuable predictor of long-term symptoms in children with sleep-disordered breathing, which could inform treatment decisions. Additionally, measuring minimum SpO2 levels may help assess the risk of developing long-term symptoms and monitor treatment outcomes.

The capacity of the Child Behavior Checklist 1½–5 (CBCL 1½–5) to identify children with autism spectrum disorder (ASD) at 18 months was tested on 37 children clinically referred for ASD and 46 children at elevated likelihood of developing ASD due to having an affected brother/sister. At 30 months the clinically referred children all received a confirmatory diagnosis, and 10 out of 46 siblings received a diagnosis of ASD. CBCL 1½-5 profiles were compared with a group of matched children with typical development (effect of cognitive level controlled for). The capacity of the CBCL 1½-5 DSM Oriented-Pervasive Developmental Problems scale to differentiate correctly between children diagnosed with ASD and children with typical development appeared dependent on group ascertainment methodology.

Youth with Attention-Deficit Hyperactivity Disorder (ADHD) may suffer from comorbid difficulties, such as anxiety–depressive symptoms, social withdrawal, and somatic complaints. Although stimulants remain the ADHD cornerstone treatment, mental fatigue, school problems and low self-esteem may persist, often being the most unacceptable symptoms for these patients. We present two cases of adolescents (14 and 15 years old) with methylphenidate-treated ADHD, where cognitive fatigability, depressive thoughts, anxiety, irritability, and poor social relationships remained. Based on clinical observation and the completion of parent and child rating scales, the aforementioned manifestations appeared to progressively reduce by the time of the subsequent control visits planned 1, 3, and 5 months after, following the use of vortioxetine (up to 10 mg/day) as add-on therapy to methylphenidate. No significant side effects were reported in both cases in a follow-up period of 3 months, also supporting the stability of the observed clinical improvement. Vortioxetine monotherapy has already been tested for the treatment of anxiety–depressive symptoms in youth, as well as ADHD in adulthood. The cases presented here suggest that vortioxetine could also be an effective option for ADHD treatment in childhood and adolescence, warranting further investigation of its potential benefits as both a monotherapy and adjunctive therapy to stimulants.

Equine-assisted activities and therapies (EAAT) have been suggested to improve adaptive behavior, and possibly motor function, in autism spectrum disorder (ASD). This study investigated the effects of EAAT on adaptive behavior and motor function in 15 children with ASD (13 males) aged 7–15 years as well as the impact of EAAT on the magnitude of stress in the parent–child system and the evolution in the child interaction with both the trained therapist and the therapeutic animal through the 20 weekly sessions of EAAT. EAAT were associated with greater adaptive behavior and coordination (all p ≤ 0.01) as well as a progressive improvement in the child’s abilities to respond to the increasing complexity of such form of positive behavioral support (all p < 0.001). However, EAAT did not prove to be effective in reducing parental distress. Collectively, preliminary evidence presented here may have important public health implications and gives reason to hope that EAAT could possibly be an effective option in ASD, warranting further investigation of its potential benefits in clinical trials among larger samples.

Neurodevelopmental disorders (NDDs) have been suggested to lie on a gradient continuum, all resulting from common brain disturbances, but with different degrees of impairment severity. This case-control study aimed to assess postural stability against such hypothesis in 104 children/adolescents aged 5–17, of whom 81 had NDDs and 23 were healthy controls. Compared to healthy controls, Autism Spectrum Disorder (ASD) resulted in the most severely impaired neurodevelopmental condition, followed by Attention Deficit Hyperactive Disorder (ADHD) and Tourette Syndrome (TS). In particular, while ASD children/adolescents performed worse than healthy controls in a number of sensory conditions across all parameters, ADHD children/adolescents performed worse than healthy controls only in the sway area for the most complex sensory conditions, when their vision and somatosensory functions were both compromised, and performance in Tourette Syndrome (TS) was roughly indistinguishable from that of healthy controls. Finally, differences were also observed between clinical groups, with ASD children/adolescents, and to a much lesser extent ADHD children/adolescents, performing worse than TS children/adolescents, especially when sensory systems were not operationally accurate. Evidence from this study indicates that poor postural control may be a useful biomarker for risk assessment during neurodevelopment, in line with predictions from the gradient hypothesis.

Background and objectives: Adolescence represents a critical period for rapid psychophysical and socio-cognitive changes, with implications for health and wellbeing in later life. From this perspective, the manifestation of unhealthy lifestyles and dysfunctional behaviors may reflect a change in wellbeing requiring alertness and prompt intervention. This study investigated lifestyle behaviors and coping strategies among Italian adolescents, also in relation to the ongoing COVID-19 pandemic, and whether they would predict a change in subjective wellbeing. Materials and Methods: In the period between 1 April and 10 April 2020, adolescents aged 15&ndash, 21 filled out an online survey consisting of 33 questions investigating socio-demographic characteristics, lifestyle behaviors, coping strategies, and subjective wellbeing. Results: Data was available on 306 participants. Most adolescents planned their daily routine (57.8%), engaging in structured activities (17.6&ndash, 67.3%) and developing new interests (54.6%), and gave a positive reading of the ongoing period (57.8%), thus revealing adaptive coping strategies. Family wise, even though it was hard to stay at home (66%) and difficulties emerged, including self-isolation (50.7%) and quarrels (31.7%), a relevant proportion of adolescents shared their feelings (40.5%) and revaluated their family relationships (29.4&ndash, 39.7%). In terms of social and school engagement, almost all adolescents kept contacts with their partner, friends, and teachers (90.2&ndash, 93.5%). School commitments at home were sufficiently preserved (63.1%), however adolescents expressed preoccupations about their educational path (56.2%). A change in subjective wellbeing (49.3%) and symptoms of anxiety (39.9%) were frequently reported. A number of factors predicted a change in subjective wellbeing, including adaptive coping strategies (physical activity, OR = 2.609, 95% confidence interval (CI) 1.297&ndash, 5.247, engaging in different activities than before, OR = 2.212, 95% CI 1.157&ndash, 4.230), family issues (finding hard to stay at home, OR = 3.852, 95% CI 1.953&ndash, 7.599, having quarrels, OR = 2.158, 95% CI 1.122&ndash, 4.150), school-related behaviors (fearing a negative educational outcome, OR = 1.971, 95% 1.063&ndash, 3.655), and female gender (OR = 3.647, 95% CI 1.694&ndash, 7.851). Conclusions: Both personal and environmental coping resources are relevant to subjective wellbeing in adolescence and should be taken into account for prevention and early intervention in youth mental health.

OBJECTIVE The pathophysiology of functional gastrointestinal disorders (FGIDs) is associated with dysfunction at various levels of the gut-brain axis. Hypervigilance can result in an increased tendency to report pain. In the present study, we aimed to explore whether hypervigilance can influence attentional processing in postural control in children with FGIDs. PATIENTS AND METHODS Fifty-nine participants classified into healthy subjects, those with FGIDs, and those with organic diseases (Org) based on Rome IV criteria were enrolled. Postural control under 6 sensory conditions was evaluated using a stabilometric platform. The mean velocity of the center of pressure (CoP) displacement in the anteroposterior direction and the mediolateral direction, the length of the CoP trajectory, and the sway area were also measured. RESULTS With visual and somatosensorial normal inputs, participants with FGIDs showed a higher number of anteroposterior (FGIDs: 4[interquartile range [IQR] 3-7], control [Cntl] 3 [IQR 3-4], P

The 2019 coronavirus disease (COVID-19) outbreak could result in higher levels of psychological distress, especially among people suffering from pre-existing mental health conditions. Young individuals with autism spectrum disorders (ASD) are particularly at risk due to their vulnerability to unpredictable and complex changes. This study aimed to investigate the impact of the COVID-19 pandemic on ASD individuals, whether any pre-pandemic sociodemographic or clinical characteristics would predict a negative outcome, and to narratively characterize their needs. Parents and guardians of ASD individuals filled out an online survey consisting of 40 questions investigating socio-demographic and clinical characteristics of their children, impact of the COVID-19 outbreak on their wellbeing and needs to deal with the emergency. Data were available on 527 survey participants. The COVID-19 emergency resulted in a challenging period for 93.9% of families, increased difficulties in managing daily activities, especially free time (78.1%) and structured activities (75.7%), and, respectively, 35.5% and 41.5% of children presenting with more intense and more frequent behavior problems. Behavior problems predating the COVID-19 outbreak predicted a higher risk of more intense (odds ratio (OR) = 2.16, 95% confidence interval (CI) 1.42&ndash, 3.29) and more frequent (OR = 1.67, 95% CI 1.13&ndash, 2.48) disruptive behavior. Even though ASD children were receiving different types of support, also requiring specialist (19.1%) or emergency (1.5%) interventions in a relatively low proportion of cases, a number of needs emerged, including receiving more healthcare support (47.4%), especially in-home support (29.9%), as well as interventions to tackle a potentially disruptive quarantine (16.8%). The COVID-19 outbreak has undoubtedly resulted in increased difficulties among ASD individuals.

In early 2020, a novel coronavirus (SARS-CoV-2) leading to a potentially fatal condition was discovered. Since then, the 2019 coronavirus disease (COVID-19) has spread worldwide becoming a pandemic. Beyond the risks strictly related to the infection, concerns have been expressed for the psychological impact that COVID-19 may have, especially on vulnerable individuals with pre-existing mental health conditions. Somatic symptom disorder (SSD) is characterized by a dysfunctional preoccupation with physical symptoms leading to excessive and unnecessary healthcare utilization. Despite being quite common, such condition remains underrecognized. We report a detailed clinical case of a 16 years old adolescent, who presented with a history suggestive of COVID-19 infection and associated psychological distress. Despite testing negative for the presence of SARS-CoV-2, his extreme and persisting health preoccupations required an inpatient admission to the Child and Adolescent Neuropsychiatric Unit. He responded rapidly to a low dose of antipsychotic and an antidepressant. Based on his medical history and current presentation, he received a diagnosis of SSD. When COVID-19-like symptoms occur, we highlight the importance of differentially diagnosing a possible exacerbation of a pre-existing SSD, triggered by fear of being infected. This may help preventing further burden to the healthcare system.

Motor abnormalities have been suggested to play a role in most neuropsychiatric disorders, as a potential generic neurodevelopmental vulnerability. However, they still represent a neglected area, with a paucity of empirical studies, especially in pediatric populations. This case-control study aimed to comprehensively assess motor functioning in children with atypical neurodevelopment and investigate whether any socio-demographic or clinical characteristics would concur with motor difficulties to distinguish children with neurodevelopmental disorders (NDD) from healthy controls. Socio-demographic (age and gender) and clinical (intelligence quotient, gait, movement, and coordination) data were collected on 114 children aged 5–15 (83 with NDD, 31 healthy controls). Male children were at significantly higher risk for NDD (OR: 13.023, p < 0.001). Furthermore, there was a statistically significant interaction between the total intelligence quotient and overall coordination such that increasing levels of total intelligence quotient appeared to protect against the likelihood of being diagnosed with an NDD, but only in the context of a preserved coordination (OR: 0.964, p = 0.038). Collectively, results may have important public health implications, as they point towards the development of new approaches to establish an early prognosis in neurodevelopment, including assessing motor difficulties and mitigating their impact on children’s quality of life.

Mosaic trisomy 20 is a genetic condition in which three chromosomes 20 are found in some cells. Its clinical phenotype seems to be highly variable, with most features not reported across all individuals and not considered pathognomonic of the condition. Limited and recent evidence indicates that neuropsychiatric manifestations may be more present in the context of trisomy 20 than was once thought. Here, we present a case of a 14-year-old female adolescent of White/Caucasian ethnicity with mosaic trisomy 20, who was admitted twice to an inpatient Child and Adolescent Neuropsychiatry Unit for persisting self-injury and suicidal ideation. A severe and complex neuropsychiatric presentation emerged at the cognitive, emotional, and behavioral levels, including mild neurodevelopmental issues, isolation, socio-relational difficulties, depressed mood, temper outbursts, irritability, low self-esteem, lack of interest, social anxiety, panic attacks, self-cutting, and low-average-range and heterogeneous intelligence quotient profile. Particularly, the patient was considered at high risk of causing harm, mainly to self, and appeared to be only partially responsive to medication, even when polypharmacy was attempted to improve clinical response. Except for school bullying, no other severe environmental risk factors were present in the patient’s history. The patient received a diagnosis of disruptive mood dysregulation disorder.

Anxiety is a manifestation of uncertain etiology, particularly in the pediatric population. It also has a high prevalence among individuals with neurodevelopmental disorders, especially those with Autism Spectrum Disorders (ASD). The Autism Spectrum includes numerous conditions characterized by heterogeneous expressions and many overlapping clinical areas. Anxiety disorder is combined with specific aspects linked to the diagnostic context in different manifestations of ASD. This chapter outlines the different profiles of anxiety disorder and analyzes clinical and prognostic indicators influencing the impact of anxiety symptoms on ASD. Results of a research project relevant to connectivity and anxiety topics are discussed, and along with therapeutic perspectives, our clinical experience has shown to be effective to restrict or treat anxiety disorders in the context of ASD.

Autism spectrum disorder (ASD) pathophysiology is not completely understood; however, altered inflammatory response and glutamate signaling have been reported, leading to the investigation of molecules targeting the immune-glutamatergic system in ASD treatment. Palmitoylethanolamide (PEA) is a naturally occurring saturated N-acylethanolamine that has proven to be effective in controlling inflammation, depression, epilepsy, and pain, possibly through a neuroprotective role against glutamate toxicity. Here, we systematically reviewed all human and animal studies examining PEA and its biobehavioral correlates in ASD. Studies indicate altered serum/brain levels of PEA and other endocannabinoids (ECBs)/acylethanolamines (AEs) in ASD. Altered PEA signaling response to social exposure and altered expression/activity of enzymes responsible for the synthesis and catalysis of ECBs/AEs, as well as downregulation of the peroxisome proliferator activated receptor-α (PPAR-α) and cannabinoid receptor target GPR55 mRNA brain expression, have been reported. Stress and exposure to exogenous cannabinoids may modulate ECBs/AEs levels and expression of candidate genes for neuropsychiatric disorders, with implications for ASD. Limited research suggests that PEA supplementation reduces overall autism severity by improving language and social and nonsocial behaviors. Potential neurobiological underpinnings include modulation of immune response, neuroinflammation, neurotrophy, apoptosis, neurogenesis, neuroplasticity, neurodegeneration, mitochondrial function, and microbiota activity, possibly through peroxisome proliferator-activated receptor-α (PPAR-α) activation.

Objective Although previous reports produced converging empirical evidence of a core deficit on visuospatial processing in children with a nonverbal learning disability (NLD), few studies compared the visuospatial profile of individuals with an autism spectrum disorder (ASD) or NLD in visuoconstructive and visuospatial working memory tasks. Nor did any of these studies investigate the role of the local bias, typically observed in ASD, when comparing these clinical groups. The present study aimed to analyze whether NLD and ASD share any characteristics. Method A group of participants with NLD (n = 17) was compared with another group who had ASD (n = 17) without intellectual disability (ID), and without a peak in visuospatial intelligence, and with a control group (n = 17). Participants aged from 8 to 18 years performed a visuoconstructive and a visuospatial working memory task in which global-local processing styles were manipulated. Results The analysis of their visuospatial processing clearly distinguished between the neuropsychological profiles of the group with ASD without ID and the group with NLD: the latter performed less well than the former in all domains. The participants with ASD without ID had a more heterogeneous visuospatial profile, showing a diminished sensitivity to perceptual cohesiveness only in the visuoconstructive task. Conclusions Examining different visuospatial domains and manipulating the cohesiveness of the stimuli might be useful for better discriminating between NLD and ASD without ID. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Contains fulltext : 168130.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To give a comprehensive overview of the phenotypic and genetic spectrum of STXBP1 encephalopathy (STXBP1-E) by systematically reviewing newly diagnosed and previously reported patients. METHODS: We recruited newly diagnosed patients with STXBP1 mutations through an international network of clinicians and geneticists. Furthermore, we performed a systematic literature search to review the phenotypes of all previously reported patients. RESULTS: We describe the phenotypic features of 147 patients with STXBP1-E including 45 previously unreported patients with 33 novel STXBP1 mutations. All patients have intellectual disability (ID), which is mostly severe to profound (88%). Ninety-five percent of patients have epilepsy. While one-third of patients presented with Ohtahara syndrome (21%) or West syndrome (9.5%), the majority has a nonsyndromic early-onset epilepsy and encephalopathy (53%) with epileptic spasms or tonic seizures as main seizure type. We found no correlation between severity of seizures and severity of ID or between mutation type and seizure characteristics or cognitive outcome. Neurologic comorbidities including autistic features and movement disorders are frequent. We also report 2 previously unreported adult patients with prominent extrapyramidal features. CONCLUSION: De novo STXBP1 mutations are among the most frequent causes of epilepsy and encephalopathy. Most patients have severe to profound ID with little correlation among seizure onset, seizure severity, and the degree of ID. Accordingly, we hypothesize that seizure severity and ID present 2 independent dimensions of the STXBP1-E phenotype. STXBP1-E may be conceptualized as a complex neurodevelopmental disorder rather than a primary epileptic encephalopathy.

We report the case of a child with partial biotinidase deficiency and autistic developmental disorder. We arrived at the diagnosis of biotinidase deficiency when the child was almost 4 years of age. Consequently, he began cofactor biotin treatment (10 mg daily) which did not resolve his autistic behavior. His younger brother was affected by partial biotinidase deficiency diagnosed at birth through our neonatal screening program. He was precociously treated with cofactor biotin therapy (10 mg daily) and did not show any behavioral abnormality or developmental delay. Since the brain is quite vulnerable to biotin deficiency, delayed biotin therapy could result in neurological damage. Our patient is the first case of partial biotinidase deficiency associated with autism. We hypothesize that the low biotinidase activity could have caused biotin deficiency in his brain and cerebrospinal fluids and consequently serious neurological problems, such as stereotyped and autistic behaviors, which were irreversible in spite of biotin supplementation.

Rare copy number variants (CNVs) disrupting ASTN2 or both ASTN2 and TRIM32 have been reported at 9q33.1 by genome-wide studies in a few individuals with neurodevelopmental disorders (NDDs). The vertebrate-specific astrotactins, ASTN2 and its paralog ASTN1, have key roles in glial-guided neuronal migration during brain development. To determine the prevalence of astrotactin mutations and delineate their associated phenotypic spectrum, we screened ASTN2/TRIM32 and ASTN1 (1q25.2) for exonic CNVs in clinical microarray data from 89 985 individuals across 10 sites, including 64 114 NDD subjects. In this clinical dataset, we identified 46 deletions and 12 duplications affecting ASTN2. Deletions of ASTN1 were much rarer. Deletions near the 3' terminus of ASTN2, which would disrupt all transcript isoforms (a subset of these deletions also included TRIM32), were significantly enriched in the NDD subjects (P = 0.002) compared with 44 085 population-based controls. Frequent phenotypes observed in individuals with such deletions include autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), speech delay, anxiety and obsessive compulsive disorder (OCD). The 3'-terminal ASTN2 deletions were significantly enriched compared with controls in males with NDDs, but not in females. Upon quantifying ASTN2 human brain RNA, we observed shorter isoforms expressed from an alternative transcription start site of recent evolutionary origin near the 3' end. Spatiotemporal expression profiling in the human brain revealed consistently high ASTN1 expression while ASTN2 expression peaked in the early embryonic neocortex and postnatal cerebellar cortex. Our findings shed new light on the role of the astrotactins in psychopathology and their interplay in human neurodevelopment.

Background The term "position effect" is used when the expression of a gene is deleteriously affected by an alteration in its chromosomal environment even though the integrity of the protein coding sequences is maintained. We describe a patient affected by epilepsy and severe neurodevelopment delay carrying a balanced translocation t(15;16)(p11.2;q12.1)dn that we assume caused a position effect as a result of the accidental juxtaposition of heterochromatin in the euchromatic region. Results FISH mapped the translocation breakpoints (bkps) to 15p11.2 within satellite III and the 16q12.1 euchromatic band within the ITFG1 gene. The expression of the genes located on both sides of the translocation were tested by means of real-time PCR and three, all located on der(16), were found to be variously perturbed: the euchromatic gene NETO2/BTCL2 was silenced, whereas VPS35 and SHCBP1, located within the major heterochromatic block of chromosome 16q11.2, were over-expressed. Pyrosequencing and chromatin immunoprecipitation of NETO2/BTCL2 and VPS35 confirmed the expression findings. Interphase FISH analysis showed that der(16) localised to regions occupied by the beta satellite heterochromatic blocks more frequently than der(15). Conclusions To the best of our knowledge, this is the first report of a heterochromatic position effect in humans caused by the juxtaposition of euchromatin/heterochromatin as a result of chromosomal rearrangement. The overall results are fully in keeping with the observations in Drosophila and suggest the occurrence of a human heterochromatin position effect associated with the nuclear repositioning of the der(16) and its causative role in the patient's syndromic phenotype.

OBJECTIVE: The objective of this study was to replicate an association study on a newly collected Italian autism spectrum disorder (ASD) cohort by studying the genetic markers associated with ASDs from recent genome-wide and candidate gene association studies. METHODS: We have genotyped 746 individuals from 227 families of the Italian Autism Network using allelic discrimination TaqMan assays for seven common single-nucleotide polymorphisms: rs2292813 (SLC25A12 gene), rs35678 (ATP2B2 gene), rs4307059 (between CDH9 and CDH10 genes), rs10513025 (between SEMA5A and TAS2R1 genes), rs6872664 (PITX1 gene), rs1861972 (EN2 gene), and rs4141463 (MACROD2 gene). A family-based association study was conducted. RESULTS: A significant association was found for two of seven markers: rs4307059 T allele (odds ratio: 1.758, SE=0.236; P-value=0.017) and rs35678 TC genotype (odds ratio: 0.528, SE=0.199; P-value=0.0013). CONCLUSION: A preferential allele transmission of two markers located at loci previously associated with social and verbal communication skill has been confirmed in patients of a new ASD family sample.

Background The safety and effectiveness of psychotropic drug use in the paediatric population is widely debated, in particular because of the lack of data concerning long term effects. In Italy the prevalence of psychotropic drug prescriptions increased in the early 2000s and decreased afterwards. In such a context, a study with the aim to estimate the incidence and prevalence of psychotropic drug prescription in the paediatric population and to describe diagnostic and therapeutic approaches was performed. Methods The study population was composed of 76,000 youths less than 18 years and living in the area covered by the local health unit of Verona, Italy. The data source was the Verona local health unit's administrative prescription database. Prevalence and incidence of antidepressant and/or antipsychotic drug prescriptions in the 2004-2008 period were estimated. Children and adolescents receiving antidepressant and/or antipsychotic drug prescriptions between 1 January 2005 and 31 December 2006 were identified and questionnaires were sent to the prescribers with the aim to collect data concerning diagnostic and therapeutic approaches, and care strategies. Results The prevalence of psychotropic drug prescriptions did not change in the 2004-2008 period, while incidence slightly increased (from 7.0 in 2005 to 8.3 per 10,000 in 2008). Between 1 January 2005 and 31 December 2006, 111 youths received at least one psychotropic drug prescription, 91 of whom received antidepressants. Only 28 patients attended child and adolescent psychiatry services. Information concerning diagnostic and therapeutic approaches, and care strategies was collected for 52 patients (47%). Anxiety-depressive syndrome and attention disorders were the diseases for which psychotropic drugs were most commonly prescribed. In all, 75% youths also received psychological support and 20% were prescribed drugs for 2 or more years. Conclusions Despite the low drug prescription prevalence, the finding that most children were not cared for by child and adolescent psychiatric services is of concern and calls for a systematic, continuous monitoring of psychopharmacological treatments.