The findings of cytogenetic abnormalities and single gene disorders associated with AD indicate genetic heterogeneity and different modes of inheritance in individual families.
The three disorders autism, Asperger syndrome (AS) and pervasive developmental disorder-not otherwise specified (PDD-NOS) are currently conceptualised by most researchers as a continuum of the same disorder with varying degrees of severity, associated intellectual functioning and medical conditions, possibly also including the broader autism phenotype (BAP) [].
Non-genetic medical conditions (phenocopies) are rare, however, they are especially relevant with regard to the prevention of AD.
Autistic disorders (AD) are a group of disorders characterised by the three core problem areas: qualitative impairment in social interaction and communication, and restricted repetitive and stereotyped patterns of behaviour, interests, and activities [].
There is no credible evidence that vaccines cause autism.
But the most powerful proof-of-concept evidence derives from studies specifically linking autism to exposures in early pregnancy - thalidomide, misoprostol, and valproic acid; maternal rubella infection; and the organophosphate insecticide, chlorpyrifos.
Expanded research is needed into environmental causation of autism.
Autism, schizophrenia and bipolar disorder have traditionally been considered as separate disease entities, although they do share some common behavioral characteristics and cognitive deficits.
Autism, schizophrenia and bipolar disorder are effectively syndromic constellations of symptoms that define groups of patients with broadly similar outcomes and responses to treatment.
These findings suggest that schizophrenia, autism and other neurodevelopmental disorders may share underlying pathogenic mechanisms and challenges the view that these are completely unrelated diagnostic entities.
The involvement of α-neurexins in pre-synaptic neurotransmission suggests a functional link with voltage-gated calcium channels [,], which are integral to pre-synaptic function and plasticity and have been implicated to be involved in autism, schizophrenia and bipolar disorder [,-,].
However, recent data point to the need to consider a broader clinical spectrum that includes also autism and mental retardation/cognitive impairment [].
Data from single-gene studies are inconsistent with a hypothesis based on independence, in that autism and schizophrenia share associated genes more often than expected by chance.
Data from CNVs provides statistical support for the hypothesis that autism and schizophrenia are associated with reciprocal variants, such that at four loci, deletions predispose to one disorder, whereas duplications predispose to the other.
Finally, data from studies of head and brain size phenotypes indicate that autism is commonly associated with developmentally-enhanced brain growth, whereas schizophrenia is characterized, on average, by reduced brain growth.
These convergent lines of evidence appear most compatible with the hypothesis that autism and schizophrenia represent diametric conditions with regard to their genomic underpinnings, neurodevelopmental bases, and phenotypic manifestations as reflecting under-development versus dysregulated over-development of the human social brain.
However, differentiation between the partial overlap and diametric hypotheses using these data is precluded by limited overlap in the specific genetic markers analyzed in both autism and schizophrenia.
Furthermore, both neurexins and neuroligins have been strongly implicated in autistic disorder, a neurodevelopmental condition that shows strong overlap with SLI [-].
The CNTNAP2 gene has recently been implicated in multiple neurodevelopmental disorders, including Gilles de la Tourette syndrome [], schizophrenia [], epilepsy [,], autism [,-], ADHD [] and mental retardation [] (Table ).
The disorder shows significant overlap with associated developmental conditions, such as attention deficit hyperactivity disorder (ADHD), speech sound disorder (SSD), dyslexia and autism [].
This same region has also been implicated in a quantitative language-related trait (age at first word) in autism [].
To illustrate this, we describe several candidate neural systems for the social communication impairment seen in autism, and the characteristic behavioral and physiological manifestations associated with these that could be incorporated into phenotypic assessments.
At the same time, in the neuroimaging literature, the body of research identifying candidate neural systems underlying aspects of autistic impairment has grown considerably, fueled by the advent of technologies such as functional magnetic resonance imaging (fMRI).
This article presents a review of the genetics of autism and describes the genetic approaches that have been applied, including the phenotypic strategies that have been used to address heterogeneity and optimize the power of these genetic studies.
Yet the findings from these neuroimaging studies have not been incorporated to inform the collection of samples for genetic studies of autism, which are predominantly based on a diagnosis of the disorder.
Recent evidence has emerged that children with autism may have altered folate or methionine metabolism, which suggests the folate-methionine cycle may play a key role in the etiology of autism.
The variance in results can be attributed to heterogeneity between subjects with autism, sampling issues, and the wide range of analytic techniques used.
A systematic literature review was conducted of studies reporting data for metabolites, interventions, or genes of the folate-methionine pathway in autism.
The review concluded that further research is required with appropriately standardized and adequately powered study designs before any definitive conclusions can be made about the role for a dysfunctional folate-methionine pathway in the etiology of autism.
The following is a review of the most recent research concerning the potential role of immune system dysfunction in autism.
This body of literature has expanded dramatically over the past few years as researchers continue to identify immune anomalies in individuals with autism.
Additionally, data concerning the cellular immune system in children with autism suggest there may be a defect in signaling pathways that are shared by the immune and central nervous systems.
The most exciting of these recent findings is the discovery of autoantibodies targeting brain proteins in both children with autism and their mothers.
Furthermore, while autism and PD differ in other associated symptom domains that shape the course of each disorder, both disorders share some phenomenology in the core domain of repetitive behaviors and involve basal ganglia and frontal lobe dysfunction, similar to OC disorder (OCD).
Accordingly, examination of the similarities and differences between autism and PD may provide insight into the pathophysiology and treatment of OC spectrum disorders.
Therefore, exploring the dynamic relationship between circadian rhythms and sleep throughout development provides valuable insight into those sleep problems associated with autism.
A growing body of research has identified significant sleep problems in children with autism.
Reviewing normal and dysfunctional relationships between sleep and circadian rhythms will enable comparisons to sleep problems in children with autism, prompt a reexamination of existing literature and offer suggestions for future inquiry.
Disturbed sleep-wake patterns and abnormal hormone profiles in children with autism suggest an underlying impairment of the circadian timing system.
Ultimately, a better understanding of sleep and circadian rhythms in children with autism may help guide appropriate treatment strategies and minimize the negative impact of these disturbances on both the children and their families.
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