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Protein & Cell Oct 2023The gut microbiota has been found to interact with the brain through the microbiota-gut-brain axis, regulating various physiological processes. In recent years, the... (Review)
Review
The gut microbiota has been found to interact with the brain through the microbiota-gut-brain axis, regulating various physiological processes. In recent years, the impacts of the gut microbiota on neurodevelopment through this axis have been increasingly appreciated. The gut microbiota is commonly considered to regulate neurodevelopment through three pathways, the immune pathway, the neuronal pathway, and the endocrine/systemic pathway, with overlaps and crosstalks in between. Accumulating studies have identified the role of the microbiota-gut-brain axis in neurodevelopmental disorders including autism spectrum disorder, attention deficit hyperactivity disorder, and Rett Syndrome. Numerous researchers have examined the physiological and pathophysiological mechanisms influenced by the gut microbiota in neurodevelopmental disorders (NDDs). This review aims to provide a comprehensive overview of advancements in research pertaining to the microbiota-gut-brain axis in NDDs. Furthermore, we analyzed both the current state of research progress and discuss future perspectives in this field.
Topics: Humans; Brain-Gut Axis; Autism Spectrum Disorder; Brain; Gastrointestinal Microbiome; Neurodevelopmental Disorders
PubMed: 37166201
DOI: 10.1093/procel/pwad026 -
Dialogues in Clinical Neuroscience Mar 2020This article describes the history of the diagnostic class of neurodevelopmental disorders (NDDs) up to DSM-5. We further analyze how the development of genetics will... (Review)
Review
This article describes the history of the diagnostic class of neurodevelopmental disorders (NDDs) up to DSM-5. We further analyze how the development of genetics will transform the classification and diagnosis of NDDs. In DSM-5, NDDs include intellectual disability (ID), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). Physicians in German-, French- and English-speaking countries (eg, Weikard, Georget, Esquirol, Down, Asperger, and Kanner) contributed to the phenomenological definitions of these disorders throughout the 18th and 20th centuries. These diagnostic categories show considerable comorbidity and phenotypic overlap. NDDs are one of the chapters of psychiatric nosology most likely to benefit from the approach advocated by the National Institute of Mental Health's Research Domain Criteria project. Genetic research supports the hypothesis that ID, ASD, ADHD, schizophrenia, and bipolar disorder lie on a neurodevelopmental continuum. The identification of recurrently observed copy number variants and disruptive gene variants in ASD (eg, CDH8, 16p11.2, SCN2A) led to the adoption of the genotype-first approach to characterize individuals at the etiological level. .
Topics: Diagnostic and Statistical Manual of Mental Disorders; Forecasting; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Neurodevelopmental Disorders
PubMed: 32699506
DOI: 10.31887/DCNS.2020.22.1/macrocq -
Annual Review of Neuroscience Jul 2022Mounting evidence indicates that microglia, which are the resident immune cells of the brain, play critical roles in a diverse array of neurodevelopmental processes... (Review)
Review
Mounting evidence indicates that microglia, which are the resident immune cells of the brain, play critical roles in a diverse array of neurodevelopmental processes required for proper brain maturation and function. This evidence has ultimately led to growing speculation that microglial dysfunction may play a role in neurodevelopmental disorder (NDD) pathoetiology. In this review, we first provide an overview of how microglia mechanistically contribute to the sculpting of the developing brain and neuronal circuits. To provide an example of how disruption of microglial biology impacts NDD development, we also highlight emerging evidence that has linked microglial dysregulation to autism spectrum disorder pathogenesis. In recent years, there has been increasing interest in how the gut microbiome shapes microglial biology. In the last section of this review, we put a spotlight on this burgeoning area of microglial research and discuss how microbiota-dependent modulation of microglial biology is currently thought to influence NDD progression.
Topics: Autism Spectrum Disorder; Brain; Gastrointestinal Microbiome; Humans; Microglia; Neurodevelopmental Disorders
PubMed: 35436413
DOI: 10.1146/annurev-neuro-110920-023056 -
Frontiers in Endocrinology 2022The internal and external environment of the mother during the developmental stages of the fetus affects the offspring's health. According to the developmental origins... (Review)
Review
The internal and external environment of the mother during the developmental stages of the fetus affects the offspring's health. According to the developmental origins of health and disease (DOHaD) theory, environmental factors influence the offspring and also affect health in adulthood. Recently, studies based on this theory have gained attracted attention because of their clinical utility in identifying the risk groups for various diseases. Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) can be caused by exposure to certain prenatal environments during pregnancy. This review describes the latest findings on the effect of prenatal environment on the onset mechanism of NDDs based on the DOHaD theory. Unravelling the molecular mechanisms underlying the pathogenesis of NDDs is important, because there are no therapeutic drugs for these disorders. Furthermore, elucidating the relationship between the DOHaD theory and NDDs will contribute to the popularization of preventive medicine.
Topics: Adult; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Female; Humans; Mothers; Neurodevelopmental Disorders; Pregnancy; Risk Factors
PubMed: 35370942
DOI: 10.3389/fendo.2022.860110 -
American Journal of Human Genetics Dec 2019While genes with an excess of de novo mutations (DNMs) have been identified in children with neurodevelopmental disorders (NDDs), few studies focus on DNM patterns where...
While genes with an excess of de novo mutations (DNMs) have been identified in children with neurodevelopmental disorders (NDDs), few studies focus on DNM patterns where the sex of affected children is examined separately. We considered ∼8,825 sequenced parent-child trios (n ∼26,475 individuals) and identify 54 genes with a DNM enrichment in males (n = 18), females (n = 17), or overlapping in both the male and female subsets (n = 19). A replication cohort of 18,778 sequenced parent-child trios (n = 56,334 individuals) confirms 25 genes (n = 3 in males, n = 7 in females, n = 15 in both male and female subsets). As expected, we observe significant enrichment on the X chromosome for females but also find autosomal genes with potential sex bias (females, CDK13, ITPR1; males, CHD8, MBD5, SYNGAP1); 6.5% of females harbor a DNM in a female-enriched gene, whereas 2.7% of males have a DNM in a male-enriched gene. Sex-biased genes are enriched in transcriptional processes and chromatin binding, primarily reside in the nucleus of cells, and have brain expression. By downsampling, we find that DNM gene discovery is greatest when studying affected females. Finally, directly comparing de novo allele counts in NDD-affected males and females identifies one replicated genome-wide significant gene (DDX3X) with locus-specific enrichment in females. Our sex-based DNM enrichment analysis identifies candidate NDD genes differentially affecting males and females and indicates that the study of females with NDDs leads to greater gene discovery consistent with the female-protective effect.
Topics: Child; Cohort Studies; Exome; Female; Gene Regulatory Networks; Genetic Markers; Genome-Wide Association Study; Humans; Male; Mutation; Neurodevelopmental Disorders; Phenotype; Sex Factors
PubMed: 31785789
DOI: 10.1016/j.ajhg.2019.11.003 -
Trends in Neurosciences Aug 2020Neurodevelopmental disorders (NDDs) are a class of disorders affecting brain development and function and are characterized by wide genetic and clinical variability. In... (Review)
Review
Neurodevelopmental disorders (NDDs) are a class of disorders affecting brain development and function and are characterized by wide genetic and clinical variability. In this review, we discuss the multiple factors that influence the clinical presentation of NDDs, with particular attention to gene vulnerability, mutational load, and the two-hit model. Despite the complex architecture of mutational events associated with NDDs, the various proteins involved appear to converge on common pathways, such as synaptic plasticity/function, chromatin remodelers and the mammalian target of rapamycin (mTOR) pathway. A thorough understanding of the mechanisms behind these pathways will hopefully lead to the identification of candidates that could be targeted for treatment approaches.
Topics: Humans; Mutation; Neurodevelopmental Disorders
PubMed: 32507511
DOI: 10.1016/j.tins.2020.05.004 -
Journal of Food and Drug Analysis Jul 2019Psychobiotics are a group of probiotics that affect the central nervous system (CNS) related functions and behaviors mediated by the gut-brain-axis (GBA) via immune,... (Review)
Review
Psychobiotics are a group of probiotics that affect the central nervous system (CNS) related functions and behaviors mediated by the gut-brain-axis (GBA) via immune, humoral, neural, and metabolic pathways to improve not only the gastrointestinal (GI) function but also the antidepressant and anxiolytic capacity. As a novel class of probiotics, the application of psychobiotics has led researchers to focus on a new area in neuroscience. In the past five years, some psychobiotics strains were reported to inhibit inflammation and decreased cortisol levels, resulting in an amelioration of the symptoms of anxiety and depression. Psychobiotics are efficacious in improving neurodegenerative and neurodevelopmental disorders, including autism spectrum disorder (ASD), Parkinson's disease (PD) and Alzheimer's disease (AD). Use of psychobiotics can improve GI function, ASD symptoms, motor functions of patients with PD and cognition in patients with AD. However, the evidence for the effects of psychobiotics on mental and neurological conditions/disorders remains limited. Further studies of psychobiotics are needed in order to determine into their effectiveness and mechanism as treatments for various psychiatric disorders in the future.
Topics: Humans; Mental Health; Neurodevelopmental Disorders; Probiotics
PubMed: 31324280
DOI: 10.1016/j.jfda.2019.01.002 -
Wiley Interdisciplinary Reviews.... Jan 2017Recent 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... (Review)
Review
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. WIREs Cogn Sci 2017, 8:e1398. doi: 10.1002/wcs.1398 For further resources related to this article, please visit the WIREs website.
Topics: Brain; Brain Mapping; Electroencephalography; Humans; Magnetic Resonance Imaging; Models, Neurological; Neurodevelopmental Disorders; Neuropsychological Tests; Research Design; Williams Syndrome
PubMed: 27906503
DOI: 10.1002/wcs.1398 -
Nature Reviews. Neurology Mar 2023Health-related conditions often differ qualitatively or quantitatively between individuals of different birth-assigned sexes and gender identities, and/or with different... (Review)
Review
Health-related conditions often differ qualitatively or quantitatively between individuals of different birth-assigned sexes and gender identities, and/or with different gendered experiences, requiring tailored care. Studying the moderating and mediating effects of sex-related and gender-related factors on impairment, disability, wellbeing and health is of paramount importance especially for neurodivergent individuals, who are diagnosed with neurodevelopmental conditions with uneven sex/gender distributions. Researchers have become aware of the myriad influences that sex-related and gender-related variables have on the manifestations of neurodevelopmental conditions, and contemporary work has begun to investigate the mechanisms through which these effects are mediated. Here we describe topical concepts of sex and gender science, summarize current knowledge, and discuss research and clinical challenges related to autism, attention-deficit/hyperactivity disorder and other neurodevelopmental conditions. We consider sex and gender in the context of epidemiology, behavioural phenotypes, neurobiology, genetics, endocrinology and neighbouring disciplines. The available evidence supports the view that sex and gender are important contributors to the biological and behavioural variability in neurodevelopmental conditions. Methodological caveats such as frequent conflation of sex and gender constructs, inappropriate measurement of these constructs and under-representation of specific demographic groups (for example, female and gender minority individuals and people with intellectual disabilities) limit the translational potential of research so far. Future research and clinical implementation should integrate sex and gender into next-generation diagnostics, mechanistic investigations and support practices.
Topics: Male; Female; Humans; Gender Identity; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Intellectual Disability
PubMed: 36747038
DOI: 10.1038/s41582-023-00774-6 -
Revista de Neurologia Oct 2022Neurodevelopmental disorders have a multifactorial etiology that results from the interaction between biological and environmental factors. The biological basis of many... (Review)
Review
INTRODUCTION
Neurodevelopmental disorders have a multifactorial etiology that results from the interaction between biological and environmental factors. The biological basis of many of these disorders is only partially understood, which makes therapeutic interventions, especially pharmacological ones, particularly difficult. The impact of medical cannabis on neurological and psychiatric disorders has been studied for a long time. This study aimed to review the currently available clinical and pre-clinical studies regarding the use of cannabinoids in pediatric neurodevelopmental disorders and to draw attention to the potential therapeutic role of cannabidiol in this field.
DEVELOPMENT
Cannabidiol is an endocannabinoid system modulator and exerts its effects on both developing and mature brains through numerous mechanisms. Cannabidiol holds a relatively high toxicity limit and current literature suggests that it may have anxiolytic, antipsychotic, and neuroprotective properties. Clinical evidence suggests that early treatment with cannabidiol might be a promising therapy for neurodevelopmental disorders, including intellectual disability, autism spectrum disorders, tics, and attention/deficit hyperactivity disorder.
CONCLUSIONS
This review hopefully draws attention to an emerging body of evidence concerning cannabidiol's significant potential to safely improve many of the common symptoms affecting children and adolescents with neurodevelopmental disorders, especially autism spectrum disorder.
Topics: Adolescent; Anti-Anxiety Agents; Antipsychotic Agents; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Cannabidiol; Cannabinoids; Child; Endocannabinoids; Humans; Medical Marijuana; Neurodevelopmental Disorders
PubMed: 36169325
DOI: 10.33588/rn.7507.2022123