Difference between revisions of "Autism Spectrum Disorders"

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=='''Autism Spectrum Disorders'''<div style="float:right;padding:5px; background:green; border:2px solid black;">CNP LEVEL: Syndrome</div><br><br><br>==
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== '''Autism Spectrum Disorders''' ==
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<font color="purple" size="4">Click</font> on the Images below to learn about research findings in ASD<br><br><br>
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[[File:Brain_MRI_T1_movie.gif|100px|link=Neuroimaging|Neuroimaging]]  Neuroimaging
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[[Image:Anaphase_IF.gif|100px|link=Genetics|Genetics]]    Genetics
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[[Image:Human_genome.png|100px|link=Causes|Causes]]    Causes
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[[Image:Flores.gif|100px|link=Treatments|Treatments]]  Treatment
 
=== Basic Characteristics ===
 
=== Basic Characteristics ===
 
*'''Description'''
 
*'''Description'''
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Autism Spectrum Disorders is a clinical description of the developmental disorders which are characterized by impaired language development, social development, and learning.   
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Autism Spectrum Disorders is a clinical description of the developmental disorders which are characterized by impaired language development, social development, and learning.  According to NIMH estimates, 3.4 out of every 1000 children between 3-10 years of age have one of the disorders in the spectrum.   
  
 
They include:
 
They include:
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#[[Autism]]
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#[[PDD-NOS]]
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#'''[[Autism]]'''
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#[[Asperger's Syndrome]]
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#'''[[PDD-NOS]]'''
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#[[Rett Syndrome]]
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#'''[[Asperger's Syndrome]]'''
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#[[Childhood Disintegrative Disorder]]
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#'''[[Rett Syndrome]]'''
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#'''[[Childhood Disintegrative Disorder]]'''
  
 
Children with ASD have extremely delayed development.  Symptoms of this disorder usually start to appear between 12 to 36 months and consist of not reaching normal development benchmarks such as babbling by 12 months, speaking by 16 months, or a gradual loss of language or social skills. All children with ASD show deficits in social interactions, verbal and nonverbal communication.  They may also show repetitive behaviors and interests, or aggressive behavior.  
 
Children with ASD have extremely delayed development.  Symptoms of this disorder usually start to appear between 12 to 36 months and consist of not reaching normal development benchmarks such as babbling by 12 months, speaking by 16 months, or a gradual loss of language or social skills. All children with ASD show deficits in social interactions, verbal and nonverbal communication.  They may also show repetitive behaviors and interests, or aggressive behavior.  
  
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Although all children with ASD show similar deficits, the depth of these deficits can range drastically.  Some have very mild deficits like in [[Asperger's Syndrome]], where children have high levels of vocabulary and language skills. Others may have little to no spoken language functionality.  
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Three common patterns seen in the emergence of autistic symptoms are 1) early manifestation of symptoms, 2) almost normal development, then sudden loss of previously attained social, communicative, or motor skills, or 3) mild delays until approximately 2 years of age, followed by a developmental halt. Children with ASD who show early manifestation of symptoms do not necessarily have a worse outcome of the three subsets. Those who follow a pattern of regression appear to exhibit less autistic symptoms prior to onset of regression and worse outcomes afterward as compared to the children who follow the other two patterns of development. <sup>15</sup>
  
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*'''Causes'''
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See [[:Category:Core Deficits]]
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Scientists have not found the exact cause of ASD, although all would agree that there is a genetic basis.  Strong genetic factors have been found for some of these disorders such as in [[Rett Syndrome]], and there are simple tests for diagnostic purposes for these disorders.
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The difficulty in finding the cause of ASD partially lies in its definition, and partially on the complex interplay between genes that happens during development. ASD, like most other behavioral disorders, is diagnosed based off of observable characteristics of the child.  However, these diagnosis offer no direction as to which specific genes are defective.  Furthermore, two patients with ASD can present very similar symptoms and yet have different defective genes or causes.  For example, [[Rett Syndrome]] is caused by mutations in the gene MeCP2 while Tuberous Sclerosis is caused by mutations in TSC1 and TSC2.  It should be noted that both Rett Syndrome and Tuberous Sclerosis are very rare.
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*'''History'''
 
*'''History'''
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Prior to the 1970's, many people thought Autism Spectrum Disorders were a result of psychological causes, such as having an aloof mothering style. However, during the 1980's people began to note that chromosomal disorders and rare syndromes often co-occurred with ASD.  As a result, people began to suspect that ASD could have genetic underpinnings.  These suspicions were confirmed when, after the development of the [[ADI-R]] and [[ADOS]] as diagnostic tools and other technical advances, the first candidate gene association and resequencing studies, followed by whole-genome linking studies were done in the late 1990's.  These studies were used to identify loci of potential interest.
 
Prior to the 1970's, many people thought Autism Spectrum Disorders were a result of psychological causes, such as having an aloof mothering style. However, during the 1980's people began to note that chromosomal disorders and rare syndromes often co-occurred with ASD.  As a result, people began to suspect that ASD could have genetic underpinnings.  These suspicions were confirmed when, after the development of the [[ADI-R]] and [[ADOS]] as diagnostic tools and other technical advances, the first candidate gene association and resequencing studies, followed by whole-genome linking studies were done in the late 1990's.  These studies were used to identify loci of potential interest.
  
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===Core Deficits===
 
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Those who have ASD have identifiable core deficits recognized by scientists and clinicians.
 
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# Core Deficit of [[Joint Attention]]
 
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# Core Deficit of [[Social Communication]]
 
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# [[Repetitive behaviors or interests]]
 
  
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===Treatments===
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==== External Resources ====
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There are no drugs that can &ldquo;cure&rdquo; ASD.  There are a variety of treatments available which aim to improve social and communication skills. 
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Because of the complexity of ASD, there is no one treatment that works equally well for all people with ASD.  Some common treatments are:
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*[[Applied Behavior Analysis]] interventions
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* Links out:
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*[[Joint Attention]] interventions
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**[http://www.google.com/search?hl=en&q=autism+spectrum+disorder&btnG=Google+Search&aq=0&oq=autism+spectru Google: Autism Spectrum Disorder]
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**[http://en.wikipedia.org/wiki/Autism_spectrum Wikipedia: Autism Spectrum]
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**[http://www.ncbi.nlm.nih.gov/sites/entrez PubMed: Autism Spectrum Disorders]
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**-ucla cognitive atlas- (coming soon!)
  
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Some clinicians may [http://www.phenowiki.org/index.php5?title=Prescription_Medication&action prescribe medications] to target certain symptoms.
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* Database links
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====Citations====
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1. Keysers, Christian and Valeria Gazzola. Integrating simulation and theory of mind: from self to social cognition. ''Trends in Cognitive Sciences''. Vol 11:5 pg. 194-6; 2007 PMID 17344090
  
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=='''Neuroimaging'''==
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2. Bookheimer, S.Y. et. al. Frontal contributions to face processing differences in autism: Eviedence from fMRI of inverted face processing. "Journal of the International Neuropsychological Society". Cambridge University Press:14:922-32;2008 PMID 18954473
  
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There are have been many differences observed between typically developing children and those with ASD in neuroimaging studies using fMRI, EEG, transcranial magnetic stimulation, EMG, and structural MRI.
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3. Uddin et. al. Neural Basis of Self and Other Representation in Autism: An fMRI Study of Self-Face Recognition. ''PLoS ONE. 2008;3(10):e3526. Epub 2008 Oct 29'' PMID 18958161
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It has been hypothesized in the Mirror Neuron System Theory of Autism that the social/communication deficits in ASD arise because of differences in activation of the Mirror Neuron System (MNS), since the mirror neuron system plays an integral role in mediating understanding of emotional states of others. However, many different areas of the brain can participate in complex social/communicative tasks, making it difficult to single out just one neural area responsible for the widespread abnormalities in socialization and communication experienced by patients with ASD.  Much of current neuroimaging research in ASD operates under one of two different camps that attribute autism to different areas of less activation in the brain.  
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#'''Theory of Mind'''-Patients with ASD show lower or no activation in midline structures as compared to a control groups in many tasks, lending credence to the 'Theory Of Mind' explanation for social/communication deficits in patients with ASD. In this theory, patients with ASD have lower activation of mirror neurons in the midline structures which are responsible for "reflecting" about others' emotions or wants<sup>1,</sup>. Thus, patients have social/communication deficits because they have are unable to process the meaning of other peoples' emotions, which suggests a problem in executive processing.  
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4. Jones, J.R. et. al. Hypothesis: Dysregulation of Methylation of Brain-Expressed Genes on the X Chromosome and Autism Spectrum Disorders. ''American Journal of Medical Genetics Part A'' 146A:2213-2220 (2008). PMID 18698615
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#'''Simulation of System'''- Scientists who believe that the Simulation of System theory explains the social/communication deficits in ASD patients focus their research on shared circuits that are involved in both one's own emotions and other's emotions. Numerous studies have shown that when subjects witness a goal oriented task many different types of neurons are activated in addition to those in the midline structures. For example, when a person watches another person drink a glass of milk with an expression of disgust on his face, the premotor and parietal areas are activated for the action itself, the insula areas are activated in response to the emotion of disgust, and the secondary somatosensory area is activated for the sensations involved in the task. These are the same areas that would have been activated if we drank the milk and were ourselves disgusted. Thus, we are able to understand others' emotional states and intentions because contextual cues activate the same neural circuits that are activated when we perform the same task.  However, patients with ASD show diminished activation of these areas as compared to control groups.  So, in this theory, the social and communication difficulties arise in patients with ASD because these areas are less activated.  Consequently, they have difficulty "understanding" another's actions.<sup>1</sup>
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These two theories are not entirely incompatible and there have been some hypothesis on how the two theories could be integrated to provide a better explanation for the differences seen.
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5. Lush, Molly et. al. Current Developments in the Genetics of Autism: From Phenome to Genome. ''J Neuropathol Exp Neurol. 2008 September; 67(9):829-837. PMID 18716561
  
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'''Facial Processing''' Patients with ASD show less interest in human faces. Normal people perform much better at tasks where they have to identify or match faces that are upright versus inverted. ASD children on the other hand, show a noticeably less pronounced 'inversion effect' as compared to the normal population. Some scientists speculate that this may be because children with ASD process faces similarly to regular objects rather than assigning particular significance to faces, thereby reducing the inversion effect.  Another hypothesis is that ASD children may engage more in component processing rather than configural processing, thereby making the activation difference between processing upright faces versus inverted faces smaller. Differences in activation areas are in the frontal cortex and the amygdala, perhaps reflecting a difference in processing the meaning and significance of faces. <sup>2</sup>
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6. Arking DE et. al. A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism. Am J Hum Genet 2008;82:160-64. PMID 18179894
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Typically developing children also seem to activate the right prefrontal areas of the brain when doing self and other face processing while ASD children only activate this area when processing their own face.<sup>3</sup>
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===Analytical Techniques===
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7. Cook, E.H. and S. W. Scherer. Copy-number variations associated wtih neuropsychiatric conditions. Nature.2008 October;455(16) 919-23. PMID 18923514
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*[[Multi-Voxel Pattern Analysis]]
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=='''Genetics'''==
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8. Gilbert, S.J. et. al. Abnormal functional specialization within medial prefrontal cortex in high-functioning autism: a multi-voxel similarity analysis.  ''Brain: 2009(1). PMID 19174370
  
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A host of genes of interest have been identified through gene association studies, resequencing and, recently, the assessment of copy number variation (CNV).In particular, given the pathology of ASD, genes dealing with electrical conductance and neural transmission have been popular sites of study since synaptic dysfunction has been suggested as a unifying theme behind the various disorders in ASD.   
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9. Grandgeorge, Marine et. al. Environmental Factors Influence Language Development in Children with Autism Spectrum Disorders.  PLoS ONE. 2009;4(4):e4683. Epub 2009 Apr 9 PMID 19357766
  
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10. Happe, F. and Uta Frith.  The Weak coherence Account: Detail-focused Cognitive Style in Autism Spectrum Disorders.  ''J Autism Dev Disord. 2006 Jan;36(1):5-25.'' PMID 16450045
  
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Most approaches to finding loci of interest are under one of two assumptions:
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11. Schmitz C. Autism: neuropathology, alterations of the GABAergic system, and animal models.Int Rev Neurobiol. 2005;71:1-26. PMID 16512344
  
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#'''ASD is a result of interplay between many genes '''
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12. Emanuele E et. al. Low-grade endotoxemia in patients with severe autism. Neurosci Lett. 2010 Mar 8;471(3):162-5. PMID 20097267
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#'''There is one principle gene which contributes to many aspects of the disease.'''
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The idea that the symptoms of ASD is a result of the interaction of many different genes has been supported by linkage studies, and the fact that although many genes have been identified with causing ASD symptoms, each of these individual genes do not cause more than 1-2% of all ASD cases. However, data mining techniques such as hierarchical clustering and principle components analysis find that it is highly likely that there is 1 continuously distributed factor contributing to many aspects of ASD, thereby validating the existence of the second hypothesis. Additionally, statistical analysis of ASD family data suggest a large portion of ASDs may be the result of dominant de novo mutations that have reduced penetrance in families.
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13. Ashwood P et. al. Preliminary evidence of the in vitro effects of BDE-47 on innate immune responses in children with autism spectrum disorders.J Neuroimmunol. 2009 Mar 31;208(1-2):130-5. PMID 19211157
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'''Methylation'''-One other hypothesis that may account for the widespread genetic defects found in ASD patients is that there may be abnormal methylation of brain-expressed genes on the X chromosome which in turn causes abnormal expression levels of genes important during development. These alternations cause one or more genes on the single X chromosome in males to be either partially silenced or over-expressed. This similarly happens in females, but the random X-chromosome inactivation might lesson autism predisposition and prevalence in females. This proposal is consistent with the findings that males make up a significantly larger amounts of ASD cases than females.<sup>4</sup>
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'''Linkage and Association Studies'''
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Some likely candidate genes that have been explored include
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<table border = 1 cellpadding = 5>
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<tr><th>Gene</th><th>Function</th><th>Location</th></tr>
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<tr><td>UBE3A</td><td>transcribed protein is an enzyme that works in protein degradation</td><td>15q11-q13</td></tr>
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<tr><td>GABRB3</td><td>encodes a member of of a ligand gated ionic channels responsible for inhibition in nervous system</td><td>15q11-q12</td></tr>
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</table>
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Successful linkage studies in the past have been mostly based on affected sibling-pair designs in multiplex families.  However, there were no genome wide significant results probably because of small effect sizes that were a result of any single gene.  Even large scale studies showed only minor overlap, likely because of variety of phenotypes in ASD.  Recently though, use of endophenotypes and QTL mapping have increased the power of linkage and association studies. 
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==== Related Information ====
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* Task or test associated with this construct ''(vote for your favorite, or nominate a new one by editing this page)'':
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**[[ADOS]]
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**[[ADI-R]]
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* Indicators ''(dependent variables, conditions, or contrasts; measurement variables used for analysis)'' associated with this construct ''(vote or nominate by editing this page)'':
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* Closely related pages ''(vote or nominate related pages by editing this page)'':
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* CNP Level
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**Syndrome
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==== External Resources ====
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* Links out:
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**[http://www.google.com/search?hl=en&q=autism+spectrum+disorder&btnG=Google+Search&aq=0&oq=autism+spectru Google: Autism Spectrum Disorder]
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**[http://en.wikipedia.org/wiki/Autism_spectrum Wikipedia: Autism Spectrum]
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**[http://www.ncbi.nlm.nih.gov/sites/entrez PubMed: Autism Spectrum Disorders]
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**-ucla cognitive atlas- (coming soon!)
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* Database links
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====Citations====
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1. Keysers, Christian and Valeria Gazzola. Integrating simulation and theory of mind: from self to social cognition. ''Trends in Cognitive Sciences''. Vol 11:5 pg. 194-6; 2007
+
  
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2. Bookheimer, S.Y. et. al. Frontal contributions to face processing differences in autism: Eviedence from fMRI of inverted face processing. "Journal of the International Neuropsychological Society". Cambridge University Press:14:922-32;2008
+
14.Jyonouchi H et. al. Impact of innate immunity in a subset of children with autism spectrum disorders: a case control study.J Neuroinflammation. 2008 Nov 21;5:52. PMID 19025588
  
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3. Uddin et. al. Neural Basis of Self and Other Representation in Autism: An fMRI Study of Self-Face Recognition. ''PLoS ONE. 2008;3(10):e3526. Epub 2008 Oct 29''
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15. Kalb LG et. al. Onset Patterns Prior to 36 Months in Autism Spectrum Disorders.J Autism Dev Disord. 2010 Apr 2. PMID 20361243
  
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4. Jones, J.R. et. al. Hypothesis: Dysregulation of Methylation of Brain-Expressed Genes on the X Chromosome and Autism Spectrum Disorders. ''American Journal of Medical Genetics Part A'' 146A:2213-2220 (2008).
+
16. Keehn B et. al. Attentional networks in children and adolescents with autism spectrum disorder.J Child Psychol Psychiatry. 2010 Apr 26 PMID 20456535

Latest revision as of 15:46, 23 March 2016

Autism Spectrum Disorders
CNP LEVEL: Syndrome



Click on the Images below to learn about research findings in ASD


Neuroimaging Neuroimaging Genetics Genetics Causes Causes Treatments Treatment

Basic Characteristics

  • Description

Autism Spectrum Disorders is a clinical description of the developmental disorders which are characterized by impaired language development, social development, and learning. According to NIMH estimates, 3.4 out of every 1000 children between 3-10 years of age have one of the disorders in the spectrum.

They include:

  1. Autism
  2. PDD-NOS
  3. Asperger's Syndrome
  4. Rett Syndrome
  5. Childhood Disintegrative Disorder

Children with ASD have extremely delayed development. Symptoms of this disorder usually start to appear between 12 to 36 months and consist of not reaching normal development benchmarks such as babbling by 12 months, speaking by 16 months, or a gradual loss of language or social skills. All children with ASD show deficits in social interactions, verbal and nonverbal communication. They may also show repetitive behaviors and interests, or aggressive behavior.

Three common patterns seen in the emergence of autistic symptoms are 1) early manifestation of symptoms, 2) almost normal development, then sudden loss of previously attained social, communicative, or motor skills, or 3) mild delays until approximately 2 years of age, followed by a developmental halt. Children with ASD who show early manifestation of symptoms do not necessarily have a worse outcome of the three subsets. Those who follow a pattern of regression appear to exhibit less autistic symptoms prior to onset of regression and worse outcomes afterward as compared to the children who follow the other two patterns of development. 15

See Category:Core Deficits

  • History

Prior to the 1970's, many people thought Autism Spectrum Disorders were a result of psychological causes, such as having an aloof mothering style. However, during the 1980's people began to note that chromosomal disorders and rare syndromes often co-occurred with ASD. As a result, people began to suspect that ASD could have genetic underpinnings. These suspicions were confirmed when, after the development of the ADI-R and ADOS as diagnostic tools and other technical advances, the first candidate gene association and resequencing studies, followed by whole-genome linking studies were done in the late 1990's. These studies were used to identify loci of potential interest.


External Resources

  • Database links

Citations

1. Keysers, Christian and Valeria Gazzola. Integrating simulation and theory of mind: from self to social cognition. Trends in Cognitive Sciences. Vol 11:5 pg. 194-6; 2007 PMID 17344090

2. Bookheimer, S.Y. et. al. Frontal contributions to face processing differences in autism: Eviedence from fMRI of inverted face processing. "Journal of the International Neuropsychological Society". Cambridge University Press:14:922-32;2008 PMID 18954473

3. Uddin et. al. Neural Basis of Self and Other Representation in Autism: An fMRI Study of Self-Face Recognition. PLoS ONE. 2008;3(10):e3526. Epub 2008 Oct 29 PMID 18958161

4. Jones, J.R. et. al. Hypothesis: Dysregulation of Methylation of Brain-Expressed Genes on the X Chromosome and Autism Spectrum Disorders. American Journal of Medical Genetics Part A 146A:2213-2220 (2008). PMID 18698615

5. Lush, Molly et. al. Current Developments in the Genetics of Autism: From Phenome to Genome. J Neuropathol Exp Neurol. 2008 September; 67(9):829-837. PMID 18716561

6. Arking DE et. al. A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism. Am J Hum Genet 2008;82:160-64. PMID 18179894

7. Cook, E.H. and S. W. Scherer. Copy-number variations associated wtih neuropsychiatric conditions. Nature.2008 October;455(16) 919-23. PMID 18923514

8. Gilbert, S.J. et. al. Abnormal functional specialization within medial prefrontal cortex in high-functioning autism: a multi-voxel similarity analysis. Brain: 2009(1). PMID 19174370

9. Grandgeorge, Marine et. al. Environmental Factors Influence Language Development in Children with Autism Spectrum Disorders. PLoS ONE. 2009;4(4):e4683. Epub 2009 Apr 9 PMID 19357766

10. Happe, F. and Uta Frith. The Weak coherence Account: Detail-focused Cognitive Style in Autism Spectrum Disorders. J Autism Dev Disord. 2006 Jan;36(1):5-25. PMID 16450045

11. Schmitz C. Autism: neuropathology, alterations of the GABAergic system, and animal models.Int Rev Neurobiol. 2005;71:1-26. PMID 16512344

12. Emanuele E et. al. Low-grade endotoxemia in patients with severe autism. Neurosci Lett. 2010 Mar 8;471(3):162-5. PMID 20097267

13. Ashwood P et. al. Preliminary evidence of the in vitro effects of BDE-47 on innate immune responses in children with autism spectrum disorders.J Neuroimmunol. 2009 Mar 31;208(1-2):130-5. PMID 19211157

14.Jyonouchi H et. al. Impact of innate immunity in a subset of children with autism spectrum disorders: a case control study.J Neuroinflammation. 2008 Nov 21;5:52. PMID 19025588

15. Kalb LG et. al. Onset Patterns Prior to 36 Months in Autism Spectrum Disorders.J Autism Dev Disord. 2010 Apr 2. PMID 20361243

16. Keehn B et. al. Attentional networks in children and adolescents with autism spectrum disorder.J Child Psychol Psychiatry. 2010 Apr 26 PMID 20456535

Retrieved from "http://lcni-3.uoregon.edu/phenowiki/index.php?title=Autism_Spectrum_Disorders&oldid=8501"