Social Anxiety in Neurodevelopmental Disorders: The Case of Fragile X Syndrome.

Despite significant advances in understanding and treating social anxiety in the general population, progress in this area lags behind for individuals with intellectual disability. Fragile X syndrome is the most common cause of inherited intellectual disability and is associated with an elevated prevalence rate of social anxiety. The phenotype of fragile X syndrome encompasses multiple clinically significant characteristics that are posed as risk markers for social anxiety in other populations. Here, evidence is reviewed that points to physiological hyperarousal, sensory sensitivity, emotion dysregulation, cognitive inflexibility, and intolerance of uncertainty as primary candidates for underlying mechanisms of heightened social anxiety in fragile X syndrome. A multilevel model is presented that provides a framework for future research to test associations.

An integrated perspective for the diagnosis and therapy of neurodevelopmental disorders - From an engineering point of view.

Neurodevelopmental disorders (NDDs) are complex conditions with largely unknown pathophysiology. While many NDD symptoms are familiar, the cause of these disorders remains unclear and may involve a combination of genetic, biological, psychosocial, and environmental risk factors. Current diagnosis relies heavily on behaviorally defined criteria, which may be biased by the clinical team's professional and cultural expectations, thus a push for new biological-based biomarkers for NDDs diagnosis is underway. Emerging new research technologies offer an unprecedented view into the electrical, chemical, and physiological activity in the brain and with further development in humans may provide clinically relevant diagnoses. These could also be extended to new treatment options, which can start to address the underlying physiological issues. When combined with current speech, language, occupational therapy, and pharmacological treatment these could greatly improve patient outcomes. The current review will discuss the latest technologies that are being used or may be used for NDDs diagnosis and treatment. The aim is to provide an inspiring and forward-looking view for future research in the field.

Prevalence of autistic traits in functional neurological disorder and relationship to alexithymia and psychiatric comorbidity.

INTRODUCTION: In a cohort of adults with Functional Neurological Disorder (FND), we aim to: METHODS: 91 patients participating in a FND 5-week outpatient program completed baseline self-report questionnaires for total phobia, somatic symptom severity, attention deficit hyperactivity disorder (ADHD) and dyslexia. Patients were grouped by Autism Spectrum Quotient (AQ-10) score of <6 or ≥ 6 and compared for significant differences in tested variables. This analysis was repeated with patients grouped by alexithymia status. Simple effects were tested using pairwise comparisons. Multistep regression models tested direct relationships between autistic traits and psychiatric comorbidity scores, and mediation by alexithymia. RESULTS: 36 patients (40%) were AQ-10 positive (scoring ≥6 on AQ-10). A further 36 patients (across AQ-10 positive and AQ-10 negative groups) (40%) screened positive for alexithymia. AQ-10 positive patients scored significantly higher for alexithymia, depression, generalised anxiety, social phobia, ADHD, and dyslexia. Alexithymia positive patients scored significantly higher for generalised anxiety, depression, somatic symptoms severity, social phobia, and dyslexia. Alexithymia score was found to mediate the relationship between autistic trait and depression scores. CONCLUSION: We demonstrate a high proportion of autistic and alexithymic traits, in adults with FND. A higher prevalence of autistic traits may highlight a need for specialised communication approaches in FND management. Mechanistic conclusions are limited. Future research could explore links with interoceptive data.

Sobrecarga de madres de niños y adolescentes con trastornos del neurodesarrollo / Burden of mothers of children and adolescents with neurodevelopmental disorders

El cuidado de niños y adolescentes con trastornos del neurodesarrollo implica altas demandas físicas, financieras y emocionales y puede asociarse con el surgimiento de sobrecarga parental. Como consecuencia, aumenta la frecuencia de empeoramiento conductual del menor y de trastornos depresivos y de ansiedad en el adulto responsable. Se describen los casos de tres madres de pacientes con trastornos del desarrollo que presentaron sobrecarga parental para aumentar la visibilización de esta problemática en ámbitos pediátricos. Todos los hijos estaban recibiendo plan psicofarmacológico por la presencia de alteraciones conductuales y solo uno tenía acompañante terapéutico. La detección temprana y derivación de los padres con sobrecarga es imprescindible para mejorar la calidad de vida de los niños y los adolescentes con trastornos del neurodesarrollo y sus familias

Introduction: The care of children and adolescents with neurodevelopmental disorders involves high physical, financial and emotional demands, and it may be associated with the emergence of parenting stress. As a result, there is an increase in the frequency of minor behavioral worsening and depressive and anxiety disorders in the responsible adult. The cases of three mothers of patients with developmental disorders are described in order the visibility of this problem in pediatric settings. All the children were receiving psychotropics for the presence of behavioral alterations and only one had a therapeutic companion. Conclusion: Early detection and referral of parenting stress is essential to improve the quality of life of children and adolescents with neurodevelopmental disorders and their families. Objectives: to describe the initial clinical findings of patients with CVID diagnosed at Hospital de Niños Sor Maria Ludovica, between 1981 and 2019. 19 patients were included, 14 were male (74%). All Patients Had a history of recurrent infections, most frequently pneumonia (74%) and acute otitis media (42%). 9 patients suffered from chronic diarrhea (47%), with associated malabsorption in 6 of them. Thirty-two presented with severe malnutrition and 1 patient with gastric metaplasia. One Patient Had Splenomegaly and 1 had Evans´ syndrome. Bronchiectasis were found in 42% of patients at the time of diagnosis. Early suspicion of CVID from pediatricians is essential in order to arrive at a proper diagnosis

Quality of life of children with neurodevelopmental disorders and their parents during the COVID-19 pandemic: a 1-year follow-up study.

This study aimed to reveal changes in the quality of life (QOL) of children with neurodevelopmental disorders and their parents, and the interaction between their QOL and parental mental state during the coronavirus 2019 (COVID-19) pandemic. Eighty-nine school-aged children and parents participated in surveys in May 2020 (T1) and May 2021 (T2). The parents completed questionnaires that assessed their QOL, depression, parenting stress, and living conditions. Children's temporary mood status was evaluated using the self-reported visual analog scale (VAS). Children's QOL and VAS at T2 were higher than their QOL at T1. Parents' QOL at T2 was lower than their QOL at T1. Severe parental depression at T1 had a synergistic effect on severe parenting stress and severe depressive state at T2. Additionally, children's high QOL at T1 had a synergistic effect on low parenting stress and children's high QOL at T2. Furthermore, children's low VAS scores and parents' low QOL at T2 were associated with deterioration of family economic status. Children and parents' QOL changed during the prolonged COVID-19 pandemic. Improvement in children's QOL was influenced by reduced maternal depressive symptoms. Public support for parental mental health is important to avoid decreasing QOL.

Analysis of Neurodevelopmental Disorders in Offspring of Mothers With Eating Disorders in Sweden.

Importance: Despite indices of impaired neurodevelopment in children of mothers with eating disorders, it remains unclear whether these children are at increased risk of developing neuropsychiatric diseases. Objective: To evaluate the association between maternal eating disorders, whether preexisting or ongoing during pregnancy, and offspring neuropsychiatric disease risk. Design, Setting and Participants: This population-based prospective cohort study used the Swedish Medical Birth Registry and identified singleton births registered between from January 1, 1990, and December 31, 2012. Children of exposed mothers with eating disorders were matched with comparator children of mothers without diagnoses of eating disorders. To adjust for unmeasured shared familial factors, a cluster of exposed children with full maternal cousin comparators was identified. Follow-up was completed on December 31, 2017. Data were analyzed from August 31, 2020, to April 30, 2021. Exposures: Maternal eating disorder diagnosis. Main Outcomes and Measures: All children were followed up from 1 year of age for autism spectrum disorder (ASD) and from 3 years of age for attention-deficit/hyperactivity disorder (ADHD). The relative risk of ASD and ADHD was assessed among exposed children, stratified by eating disorder subtype and ongoing vs previous disease, adjusted for potential confounders, including parental socioeconomic status and comorbidities. Results: Among the 52 878 children included in the analysis, maternal eating disorder exposure (n = 8813) was associated with an increased risk of ADHD (hazard ratio [HR] for anorexia nervosa, 1.42 [95% CI, 1.23-1.63]; HR for bulimia nervosa, 1.91 [95% CI, 1.43-2.54]; and HR for unspecified eating disorder, 2.00 [95% CI, 1.72-2.32]) and ASD (HR for anorexia nervosa, 2.04 [95% CI, 1.58-2.63]; HR for bulimia nervosa, 2.70 [95% CI, 1.68-4.32]; and HR for unspecified eating disorder, 1.95 [95% CI, 1.49-2.54]). After adjustment for parental confounders, the risk of ADHD remained significantly increased, whereas the risk of ASD in children to mothers with bulimia nervosa was no longer significant. Ongoing anorexia nervosa was associated with a significantly higher risk of ADHD (HR, 2.52 [95% CI, 1.86-3.42]) and ASD (HR, 3.98 [95% CI, 2.49-6.27]) compared with previous disease (HRs, 1.26 [95% CI, 1.06-1.48] and 1.81 [95% CI, 1.38-2.38], respectively). Results based on the family cluster were similar to those of the main analysis for maternal exposure to anorexia nervosa and bulimia nervosa. Conclusions and Relevance: These findings suggest that children born to mothers with eating disorders, in particular disorders that were active during pregnancy, were at increased risk of developing ADHD and ASD. The association could not be fully explained by parental psychiatric comorbidities, and among children of mothers with anorexia nervosa and bulimia nervosa, it could not be explained by unmeasured familial confounding.

Impaired social cognition caused by perinatal protein malnutrition evokes neurodevelopmental disorder symptoms and is intergenerationally transmitted.

Nutritional inadequacy before birth and during postnatal life can seriously interfere with brain development and lead to persistent deficits in learning and behavior. In this work, we asked if protein malnutrition affects domains of social cognition and if these phenotypes can be transmitted to the next generation. Female mice were fed with a normal or hypoproteic diet during pregnancy and lactation. After weaning, offspring were fed with a standard chow. Social interaction, social recognition memory, and dominance were evaluated in both sexes of F1 offspring and in the subsequent F2 generation. Glucose metabolism in the whole brain was analyzed through preclinical positron emission tomography. Genome-wide transcriptional analysis was performed in the medial prefrontal cortex followed by gene-ontology enrichment analysis. Compared with control animals, malnourished mice exhibited a deficit in social motivation and recognition memory and displayed a dominant phenotype. These altered behaviors, except for dominance, were transmitted to the next generation. Positron emission tomography analysis revealed lower glucose metabolism in the medial prefrontal cortex of F1 malnourished offspring. This brain region showed genome-wide transcriptional dysregulation, including 21 transcripts that overlapped with autism-associated genes. Our study cannot exclude that the lower maternal care provided by mothers exposed to a low-protein diet caused an additional impact on social cognition. Our results showed that maternal protein malnutrition dysregulates gene expression in the medial prefrontal cortex, promoting altered offspring behavior that was intergenerationally transmitted. These results support the hypothesis that early nutritional deficiency represents a risk factor for the emergence of symptoms associated with neurodevelopmental disorders.

The impact of the environment on neurodevelopmental disorders in early childhood.

OBJECTIVES: To review the literature about the environmental impact on children's mental, behavior, and neurodevelopmental disorders. SOURCES OF DATA: A nonsystematic review of papers published on MEDLINE-PubMed was carried out using the terms environment and mental health or psychiatric disorders or neurodevelopmental disorders. SUMMARY OF FINDINGS: Psychopathology emerges at different developmental times as the outcome of complex interactions between nature and nurture and may impact each person in different ways throughout childhood and determine adult outcomes. Mental health is intertwined with physical health and is strongly influenced by cultural, social and economic factors. The worldwide prevalence of psychiatric disorders in children and adolescents is 13.4%, and the most frequent are anxiety, disruptive behavior disorders, attention deficit hyperactivity disorder and depression. Neurodevelopment begins at the embryonic stage and continues through adulthood with genetic differences, environmental exposure, and developmental timing acting synergistically and contingently. Early life experiences have been linked to a dysregulation of the neuroendocrine-immune circuitry which results in alterations of the brain during sensitive periods. Also, the environment may trigger modifications on the epigenome of the differentiating cell, leading to changes in the structure and function of the organs. Over 200 million children under 5 years are not fulfilling their developmental potential due to the exposure to multiple risk factors, including poverty, malnutrition and unsafe home environments. CONCLUSIONS: Continued support for the promotion of a protective environment that comprises effective parent-child interactions is key in minimizing the effects of neurodevelopmental disorders throughout the lifetime.

Mobile media exposure and use in children aged zero to five years with diagnosed neurodevelopmental disability.

OBJECTIVE: The present study was conducted to determine the extent of exposure to and use of mobile devices by children (aged 0-60 months) with a diagnosed neurodevelopmental disability. DESIGN: A self-report survey-based design was employed. SETTING: Questionnaires were administered at a tertiary care hospital in Mumbai, India. PARTICIPANTS: The study included a convenience sample of 423 children with a neurodevelopmental disability (aged 0-60 months). The self-report survey was administered to the parents of the children. RESULTS: Analyses showed that 92.7% (n = 392) of all respondents have smartphones. 61% (n = 258) of the respondents stated that their children used mobile devices before 2 years of age. 58% (n = 246) of the parents gave children devices while feeding. A statistically significant difference was found in the mobile media usage between groups of children with different diagnoses (p < 0.001). Children diagnosed with ASD appeared to spend the largest amount of time on mobile media (m = 180.44 mins), as compared to children included with other diagnoses. Of the diagnosed children, only 13.4% (n = 57) of parents were informed about the possible negative effects of media use by their paediatricians. CONCLUSION: The results suggest premature mobile media habits, frequent use and lack of awareness about the effects of mobile media usage among children diagnosed with a neurodevelopmental disability. We suggest there is a need to update recommendations for caregivers on the use of mobile media by young children with disability.Implications for rehabilitationThe usage and consequences of mobile media use differ based on the type of neurodevelopmental disorder diagnosis. Parents of children with neurodevelopmental disorders often use mobile media as a distraction while engaging in various activities themselves, this information helps identify times at which mobile media might be purposefully used by parents as distractorsThere is an urgent need for clinical guidelines regarding mobile media usage among young children with neurodevelopmental disorders.

Impact of School Closures due to COVID-19 on Children with Neurodevelopmental Disorders in Japan.

In March 2020, many schools were closed to prevent the spread of COVID-19 in Japan, and it is predicted that many children, especially those with neurodevelopmental disorders (NDDs), will be affected emotionally and behaviorally. Here, we examined the impact of school closures due to COVID-19 on school-aged children with NDDs using the Child Behavior Checklist. Totally, data on 121 children diagnosed with autism spectrum disorder, attention-deficit hyperactivity disorder, and/or intellectual disorder were analyzed and it was found that externalizing and aggressive behavior increased in all NDDs, regardless of the type of diagnosis. A clear prospect is important for children with NDDs children to lead a stable life, and more generous supports for children with NDDs and their families are needed.

Along the fringes of Agency: neurodevelopmental account of the obsessive mind.

The experiential core of the obsessive mind rests on subtle, primary mental phenomena (such as obsessions and so called "sensory phenomena") which precede and trigger behavioral compulsions. Converging evidence supports a possible pathophysiological role for altered corollary discharge (phenotypically expressed in sensorimotor symptoms and contributing to a reduced Sense of Agency [SoA]), in the neurodevelopment of obsessions and "sensory phenomena." In phenomenological terms, "sensory phenomena" may represent the subjective experiential resonance of an individual history of persistent inaccurate sensory predictions, whereas accompanying manifestations, such as the obsessive need for order and symmetry, may represent a compensatory attempt to mitigate "sensory phenomena" (eg, by increasing the sensory predictability of the surrounding world). Since disturbances of both SoA and Sense of Ownership have been thematized as potential pathogenetic factors in the neurodevelopment of the psychotic mind, a dimensional account of altered sensorimotor prediction may partly explain the affinities (and high comorbidity) between obsessive-compulsive disorder and schizophrenia spectrum disorders.

COVID-19 and UK family carers: policy implications.

Informal (unpaid) carers are an integral part of all societies and the health and social care systems in the UK depend on them. Despite the valuable contributions and key worker status of informal carers, their lived experiences, wellbeing, and needs have been neglected during the COVID-19 pandemic. In this Health Policy, we bring together a broad range of clinicians, researchers, and people with lived experience as informal carers to share their thoughts on the impact of the COVID-19 pandemic on UK carers, many of whom have felt abandoned as services closed. We focus on the carers of children and young people and adults and older adults with mental health diagnoses, and carers of people with intellectual disability or neurodevelopmental conditions across different care settings over the lifespan. We provide policy recommendations with the aim of improving outcomes for all carers.

Stress symptoms and resilience factors in children with neurodevelopmental disabilities and their parents during the COVID-19 pandemic.

OBJECTIVE: This study examined the impact of the coronavirus disease 2019 (COVID-19) pandemic in Italy by specifically looking at the psychosocial response of children/adolescents with neurodevelopmental disabilities (NDD) and their parents, and explored which factors could potentially contribute to increasing or mitigating stress-related behaviors in children/adolescents as well as their parents' stress. METHOD: An online anonymous survey was designed to investigate family demographic characteristics, COVID-19 outbreak and restriction-related variables, children/adolescents' behavioral regulation problems, parental stress, and resilience. Data were collected from 1,472 parents (83.1% mothers) of 1632 NDD children/adolescents (33.7% females). RESULTS: Compared to pre-emergency, parents reported a significant increase in their children's behavioral regulation problems: Anxious/depressed behavior, Attention problems, and Aggressive behavior (p < .001), and they reported feeling more Overwhelmed and Burdened (p < .001) as parents but less Unfulfilled, Numbness, Devastated, and Angry (p < .001). A hierarchical stepwise regression analysis revealed that both behavioral regulation problems in NDD children/adolescents and parental stress are-at least partially-buffered by resilience factors in parents (Perception of self, Planned future, Family cohesion). CONCLUSIONS: Results showed that behavioral regulation problems in children/adolescents with NDD and parental stress increased. However, parental resilience can act as a protective factor, counterbalancing parental difficulties in the care of their NDD children during the emergency. Identifying risk and protective factors impacting the psychosocial response ofchildren/adolescents with NDD and their parents is essential to implement appropriate support interventions both for parents and children/adolescents with NDD during the COVID-19 pandemic. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Rhythm and timing as vulnerabilities in neurodevelopmental disorders.

Millions of children are impacted by neurodevelopmental disorders (NDDs), which unfold early in life, have varying genetic etiologies and can involve a variety of specific or generalized impairments in social, cognitive and motor functioning requiring potentially lifelong specialized supports. While specific disorders vary in their domain of primary deficit (e.g. autism spectrum disorder (social), attention-deficit/hyperactivity disorder (attention), developmental coordination disorder (motor) and developmental language disorder (language)), comorbidities between NDDs are common. Intriguingly, many NDDs are associated with difficulties in skills related to rhythm, timing and synchrony though specific profiles of rhythm/timing impairments vary across disorders. Impairments in rhythm/timing may instantiate vulnerabilities for a variety of NDDs and may contribute to both the primary symptoms of each disorder as well as the high levels of comorbidities across disorders. Drawing upon genetic, neural, behavioural and interpersonal constructs across disorders, we consider how disrupted rhythm and timing skills early in life may contribute to atypical developmental cascades that involve overlapping symptoms within the context of a disorder's primary deficits. Consideration of the developmental context, as well as common and unique aspects of the phenotypes of different NDDs, will inform experimental designs to test this hypothesis including via potential mechanistic intervention approaches. This article is part of the theme issue 'Synchrony and rhythm interaction: from the brain to behavioural ecology'.

Congenital Zika Infection and the Risk of Neurodevelopmental, Neurological, and Urinary Track Disorders in Early Childhood. A Systematic Review.

It was late 2015 when Northeast Brazil noticed a worrying increase in neonates born with microcephaly and other congenital malformations. These abnormalities, characterized by an abnormally small head and often neurological impairment and later termed Congenital Zika Syndrome, describe the severity of neurodevelopmental and nephrological outcomes in early childhood, and the implication of microcephaly at birth. The purpose of the study was to describe the neurodevelopmental outcomes in children exposed to Zika virus during fetal life, with and without microcephaly at birth. The systematic review included research studies about the neurodevelopmental outcomes with and without microcephaly, as well as nephrological outcomes in early childhood. We searched PubMed, Crossref, PsycINFO, Scopus, and Google Scholar publications and selected 19 research articles published from 2018 to 2021. Most studies have linked the severity of microcephaly in childbirth to the neurodevelopmental and urinary outcomes in early childhood. However, most children without microcephaly at birth develop typically, while others may be at risk for language impairment.

Harnessing rare variants in neuropsychiatric and neurodevelopment disorders-a Keystone Symposia report.

Neurodevelopmental neuropsychiatric disorders, such as autism spectrum disorder and schizophrenia, have strong genetic risk components, but the underlying mechanisms have proven difficult to decipher. Rare, high-risk variants may offer an opportunity to delineate the biological mechanisms responsible more clearly for more common idiopathic diseases. Indeed, different rare variants can cause the same behavioral phenotype, demonstrating genetic heterogeneity, while the same rare variant can cause different behavioral phenotypes, demonstrating variable expressivity. These observations suggest convergent underlying biological and neurological mechanisms; identification of these mechanisms may ultimately reveal new therapeutic targets. At the 2021 Keystone eSymposium "Neuropsychiatric and Neurodevelopmental Disorders: Harnessing Rare Variants" a panel of experts in the field described significant progress in genomic discovery and human phenotyping and raised several consistent issues, including the need for detailed natural history studies of rare disorders, the challenges in cohort recruitment, and the importance of viewing phenotypes as quantitative traits that are impacted by rare variants.

Disruptions in global network segregation and integration in adolescents and young adults with fetal alcohol spectrum disorder.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is a significant public health problem that is associated with a broad range of physical, neurocognitive, and behavioral effects resulting from prenatal alcohol exposure (PAE). Magnetic resonance imaging (MRI) has been an important tool for advancing our knowledge of abnormal brain structure and function in individuals with FASD. However, whereas only a small number of studies have applied graph theory-based network analysis to resting-state functional MRI (fMRI) data in individuals with FASD additional research in this area is needed. METHODS: Resting-state fMRI data were collected from adolescent and young adult participants (ages 12-22) with fetal alcohol syndrome (FAS) or alcohol-related neurodevelopmental disorder (ARND) and neurotypically developing controls (CNTRL) from previous studies. Group independent components analysis (gICA) was applied to fMRI data to extract components representing functional brain networks. Functional network connectivity (FNC), measured by Pearson correlation of the average independent component (IC) time series, was analyzed under a graph theory framework to compare network modularity, the average clustering coefficient, characteristic path length, and global efficiency between groups. Cognitive intelligence, measured by the Wechsler Abbreviated Scale of Intelligence (WASI), was compared and correlated to global network measures. RESULTS: Group comparisons revealed significant differences in the average clustering coefficient, characteristic path length, and global efficiency. Modularity was not significantly different between groups. The FAS and ARND groups scored significantly lower than the CNTRL group on Full Scale IQ (FS-IQ) and the Vocabulary subtest, but not the Matrix Reasoning subtest. No significant associations between intelligence and graph theory measures were detected. CONCLUSION: Our results partially agree with previous studies examining global graph theory metrics in children and adolescents with FASD and suggest that the exposure to alcohol during prenatal development leads to disruptions in aspects of functional network segregation and integration.

Fussy Eating among Children and Their Parents: Associations in Parent-Child Dyads, in a Sample of Children with and without Neurodevelopmental Disorders.

Parents are important agents in shaping children's eating habits. However, the associations between children's and parents' eating behaviors are complex and may be convoluted for various reasons, such as parenting feeding styles, stressful mealtimes, and children's neurodevelopmental disorders (ND), such as Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD). The purpose of this study was to analyze associations between parents and their children's fussy eating, in a cross-sectional sample of children, with and without ND. Ninety-seven parents answered screening questionnaires prior to an intervention study. Associations were investigated using two-way ANOVAs and chi-square analyses. Overall, children with ND accepted fewer food items and consumed unhealthier foods more frequently than children without ND. Fussy eating parents had children who accepted fewer food items and consumed unhealthier foods more frequently than children whose parents were not fussy eaters. Interaction effects were not significant. A higher proportion of fussy eating parents, than non-fussy eating parents, had children who had difficulties with combined foods and hidden ingredients. The findings highlight the need for further investigation into the relationships between parents' influence on their children's eating behavior and food consumption, as well as possible reciprocal impacts.