Neurodevelopmental disorders

Recent technological advances allow us to measure how the infant brain functions in ways that were not possible just a decade ago. Although methodological advances are exciting, we must also consider how theories guide research: what we look for and how we explain what we find. Indeed, the ways in which research findings are interpreted affects the design of policies, educational practices, and interventions. Thus, the theoretical approaches adopted by scientists have a real impact on the lives of children with neurodevelopmental disorders (NDDs) and their families, as well as on the wider community. Here, we introduce and compare two theoretical approaches that are used to understand NDDs: the neuropsychological account and neuroconstructivism. We show how the former, adult account, is inadequate for explaining NDDs and illustrate this using the examples of Williams syndrome and specific language impairment. Neuroconstructivism, by contrast, focuses on the developing organism and is helping to change the way in which NDDs are investigated. Whereas neuropsychological static approaches assume that one or more ‘modules’ (e.g., visuospatial ability in Williams syndrome) are impaired while the rest of the system is spared (e.g., language in Williams syndrome), neuroconstructivism proposes that basic‐level deficits have subtle cascading effects on numerous domains over development. Neuroconstructivism leads researchers to embrace complexity by establishing large research consortia to integrate findings at multiple levels (e.g., genetic, neural, cognitive, environmental) across developmental time

Allergic fetal priming leads to developmental, behavioral and neurobiological changes in mice.

The state of the mother's immune system during pregnancy has an important role in fetal development and disruptions in the balance of this system are associated with a range of neurologic, neuropsychiatric and neurodevelopmental disorders. Epidemiological and clinical reports reveal various clues that suggest a possible association between developmental neuropsychiatric disorders and family history of immune system dysfunction. Over the past three decades, analogous increases have been reported in both the incidence of neurodevelopmental disorders and immune-related disorders, particularly allergy and asthma, raising the question of whether allergic asthma and characteristics of various neurodevelopmental disorders share common causal links. We used a mouse model of maternal allergic asthma to test this novel hypothesis that early fetal priming with an allergenic exposure during gestation produces behavioral deficits in offspring. Mothers were primed with an exposure to ovalbumin (OVA) before pregnancy, then exposed to either aerosolized OVA or vehicle during gestation. Both male and female mice born to mothers exposed to aerosolized OVA during gestation exhibited altered developmental trajectories in weight and length, decreased sociability and increased marble-burying behavior. Moreover, offspring of OVA-exposed mothers were observed to have increased serotonin transporter protein levels in the cortex. These data demonstrate that behavioral and neurobiological effects can be elicited following early fetal priming with maternal allergic asthma and provide support that maternal allergic asthma may, in some cases, be a contributing factor to neurodevelopmental disorders

Visual illusions: An interesting tool to investigate developmental dyslexia and autism spectrum disorder

A visual illusion refers to a percept that is different in some aspect from the physical stimulus. Illusions are a powerful non-invasive tool for understanding the neurobiology of vision, telling us, indirectly, how the brain processes visual stimuli. There are some neurodevelopmental disorders characterized by visual deficits. Surprisingly, just a few studies investigated illusory perception in clinical populations. Our aim is to review the literature supporting a possible role for visual illusions in helping us understand the visual deficits in developmental dyslexia and autism spectrum disorder. Future studies could develop new tools – based on visual illusions – to identify an early risk for neurodevelopmental disorders

Clinical impact of splicing in neurodevelopmental disorders.

Clinical exome sequencing is frequently used to identify gene-disrupting variants in individuals with neurodevelopmental disorders. While splice-disrupting variants are known to contribute to these disorders, clinical interpretation of cryptic splice variants outside of the canonical splice site has been challenging. Here, we discuss papers that improve such detection

Overview of the Role of Environmental Factors in Neurodevelopmental Disorders

Evidence implicates environmental factors in the pathogenesis of diverse complex neurodevelopmental disorders. However, the identity of specific environmental chemicals that confer risk for these disorders, and the mechanisms by which environmental chemicals interact with genetic susceptibilities to influence adverse neurodevelopmental outcomes remain significant gaps in our understanding of the etiology of most neurodevelopmental disorders. It is likely that many environmental chemicals contribute to the etiology of neurodevelopmental disorders but their influence depends on the genetic substrate of the individual. Research into the pathophysiology and genetics of neurodevelopmental disorders may inform the identification of environmental susceptibility factors that promote adverse outcomes in brain development. Conversely, understanding how low-level chemical exposures influence molecular, cellular, and behavioral outcomes relevant to neurodevelopmental disorders will provide insight regarding gene-environment interactions and possibly yield novel intervention strategies

The relationship between psychopathy traits and neurodevelopmental disorders in forensic populations : a systematic PRISMA review

Background: Numerous studies investigate the rate of neurodevelopmental disorders in forensic populations. Studies have also investigated the rate of psychopathy in such settings. However, there appears to be a paucity of studies looking at both of these (co-morbidity between these disorders) and the possible relationships between the two in forensic populations. Method: Presented here are the findings from a systematic review conducted, following PRISMA guidelines, of the peer-reviewed literature. The review identified studies that investigated the rate and/or relationship of neurodevelopmental disorders (Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorders) and psychopathy in a forensic sample population without relying on previous childhood diagnosis of neurodevelopmental disorders. Results: Twenty-two studies were identified which investigated the rate and/or relationship of neurodevelopmental disorders and psychopathy in a forensic sample population without relying on previous childhood diagnosis of neurodevelopmental disorders such as attention-deficit/hyperactivity disorder and autism spectrum disorders. Conclusion: The findings highlight the need for the development of screening and diagnostic tools especially targeted at offenders and validated for this purpose

Maltreatment-associated neurodevelopmental disorders: a co-twin control analysis

Background: Childhood maltreatment (CM) is strongly associated with psychiatric disorders in childhood and adulthood. Previous findings suggest that the association between CM and psychiatric disorders is partly causal and partly due to familial confounding, but few studies have investigated the mechanisms behind the association between CM and neurodevelopmental disorders (NDDs). Our objective was to determine whether maltreated children have an elevated number of NDDs and whether CM is a risk factor for an increased NDD ‘load’ and increased NDD symptoms when controlling for familial effects. Methods: We used a cross-sectional sample from a population-representative Swedish twin study, comprising 8,192 nine-year-old twins born in Sweden between 1997 and 2005. CM was defined as parent-reported exposure to emotional abuse/neglect, physical neglect, physical abuse, and/or sexual abuse. Four NDDs were measured with the Autism–Tics, AD/HD, and other comorbidities inventory. Results: Maltreated children had a greater mean number of NDDs than nonmaltreated children. In a co-twin control design, CM-discordant monozygotic twins did not differ significantly for their number of NDDs, suggesting that CM is not associated with an increased load of NDDs when genetic and shared environmental factors are taken into account. However, CM was associated with a small increase in symptoms of attention-deficit/hyperactivity disorder and autism spectrum disorder in CM-discordant MZ twins, although most of the covariance of CM with NDD symptoms was explained by common genetic effects. Conclusions: Maltreated children are at higher risk of having multiple NDDs. Our findings are, however, not consistent with the notion that CM causes the increased NDD load in maltreated children. Maltreated children should receive a full neurodevelopmental assessment, and clinicians should be aware that children with multiple NDDs are at higher risk of maltreatment

Perinatal insults and neurodevelopmental disorders may impact Huntington's disease age of diagnosis

Introduction: The age of diagnosis of Huntington's disease (HD) varies among individuals with the same HTT CAG-repeat expansion size. We investigated whether early-life events, like perinatal insults or neurodevelopmental disorders, influence the diagnosis age. Methods: We used data from 13,856 participants from REGISTRY and Enroll-HD, two large international multicenter observational studies. Disease-free survival analyses of mutation carriers with an HTT CAG repeat expansion size above and including 36 were computed through Kaplan-Meier estimates of median time until an HD diagnosis. Comparisons between groups were computed using a Cox proportional hazard survival model adjusted for CAG-repeat expansion length. We also assessed whether the group effect depended on gender and the affected parent. Results: Insults in the perinatal period were associated with an earlier median age of diagnosis of 45.00 years (95%CI: 42.07–47.92) compared to 51.00 years (95%CI: 50.68–51.31) in the reference group, with a CAG-adjusted hazard ratio of 1.61 (95%CI: 1.26–2.06). Neurodevelopmental disorders were also associated with an earlier median age of diagnosis than the reference group of 47.00 years (95% CI: 43.38–50.62) with a CAG-adjusted hazard ratio of 1.42 (95%CI: 1.16–1.75). These associations did not change significantly with gender or affected parent. Conclusions: These results, derived from large observational datasets, show that perinatal insults and neurodevelopmental disorders are associated with earlier ages of diagnosis of magnitudes similar to the effects of known genetic modifiers of HD. Given their clear temporal separation, these early events may be causative of earlier HD onset, but further research is needed to prove causation

Developmental Functioning of Infants and Toddlers with Neurodevelopmental Disorders

Autism spectrum disorder (ASD), epilepsy, and cerebral palsy (CP) are some of the most common neurodevelopmental disorders among children with prevalence rates of 1.85% (Maenner et al., 2020), 1.2% (Zack & Kobau, 2017), and between 0.21 and 0.31% (Christensen et al., 2013), respectively. These neurodevelopmental disorders are highly comorbid with each other and with other disorders, such as intellectual disability (ID). While previous research has investigated developmental functioning in these neurodevelopmental disorders, it has primarily focused on only two at a time and in older children or adults. The current study aimed to investigate developmental functioning in these neurodevelopmental disorders and an atypical control group using the Battelle Developmental Inventory, Second Edition (BDI-2). The current sample included four groups (i.e., ASD, seizures, CP, atypical control), with 253 infants and toddlers in each. The results indicated significant differences in overall developmental functioning, in addition to individual subdomains of the BDI-2. These findings provide the basis for further research to investigate comorbidities of the three neurodevelopmental disorders and parse out the impact of ID

Translational animal models of autism and neurodevelopmental disorders.

Autism is a neurodevelopmental disorder whose diagnosis is based on three behavioral criteria: unusual reciprocal social interactions, deficits in communication, and stereotyped repetitive behaviors with restricted interests. A large number of de novo single gene mutations and chromosomal deletions are associated with autism spectrum disorders. Based on the strong genetic evidence, mice with targeted mutations in homologous genes have been generated as translational research tools. Mouse models of autism have revealed behavioral and biological outcomes of mutations in risk genes. The field is now poised to employ the most robust phenotypes in the most replicable mouse models for preclinical screening of novel therapeutics