Asperger syndrome pathophysiology: Difference between revisions

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{{Asperger syndrome}}
{{Asperger syndrome}}


{{CMG}}
{{CMG}} {{AE}} {{SHA}}


==Pathophysiology==
== Overview ==
{{further|[[Autism#Mechanism|Mechanism of autism]]}}
The exact pathophysiology of Asperger Syndrome is unknown, however some [[neuroimaging]] and neuropsychological studies have reported some findings.<ref name="pmid29167722">{{cite journal| author=Faridi F, Khosrowabadi R| title=Behavioral, Cognitive and Neural Markers of Asperger Syndrome. | journal=Basic Clin Neurosci | year= 2017 | volume= 8 | issue= 5 | pages= 349-359 | pmid=29167722 | doi=10.18869/nirp.bcn.8.5.349 | pmc=5691167 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29167722  }} </ref><ref name="pmid18563474">{{cite journal| author=Woodbury-Smith MR, Volkmar FR| title=Asperger syndrome. | journal=Eur Child Adolesc Psychiatry | year= 2009 | volume= 18 | issue= 1 | pages= 2-11 | pmid=18563474 | doi=10.1007/s00787-008-0701-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18563474  }} </ref>
[[Image:FMRI.jpg|thumb|left|[[Functional magnetic resonance imaging]] provides some evidence for both underconnectivity and mirror neuron theories.<ref name="Just" /><ref name="Iacoboni" />]]


* Asperger syndrome appears to result from developmental factors that affect many or all functional brain systems, as opposed to localized effects.<ref name="Mueller">{{cite journal |journal= Ment Retard Dev Disabil Res Rev |date=2007 |volume=13 |issue=1 |pages=85–95 |title= The study of autism as a distributed disorder |author= Müller RA |doi=10.1002/mrdd.20141 |pmid=17326118}}</ref> Although the specific underpinnings of AS or factors that distinguish it from other ASDs are unknown, and no clear pathology common to individuals with AS has emerged, it is still possible that AS's mechanism is separate from other ASD.<ref>{{cite journal |journal= Aust N Z J Psychiatry |year=2002 |volume=36 |issue=6 |pages=762–70 |title= A clinical and neurobehavioural review of high-functioning autism and Asperger's disorder |author= Rinehart NJ, Bradshaw JL, Brereton AV, Tonge BJ |pmid=12406118 |doi=10.1046/j.1440-1614.2002.01097.x}}</ref> [[Neuroanatomy|Neuroanatomical]] studies and the associations with [[Teratology|teratogens]] strongly suggest that the mechanism includes alteration of brain development soon after conception. Abnormal migration of embryonic cells during fetal development may affect the final structure and connectivity of the brain, resulting in alterations in the neural circuits that control thought and behavior.<ref>{{cite journal |author= Berthier ML, Starkstein SE, Leiguarda R |title= Developmental cortical anomalies in Asperger's syndrome: neuroradiological findings in two patients |journal= J Neuropsychiatry Clin Neurosci |volume=2 |issue=2 |pages=197–201 |year=1990 |pmid=2136076}}</ref> Several theories of mechanism are available; none are likely to be complete explanations.<ref>{{cite journal |author= Happé F, Ronald A, Plomin R |title= Time to give up on a single explanation for autism |journal= Nat Neurosci |date=2006 |volume=9 |issue=10 |pages=1218–20 |pmid=17001340 |doi=10.1038/nn1770}}</ref>
== Pathophysiology ==
* The underconnectivity theory hypothesizes underfunctioning high-level neural connections and synchronization, along with an excess of low-level processes.<ref name="Just">{{cite journal |journal= Cereb Cortex |year=2007 |volume=17 |issue=4 |pages=951–61 |title= Functional and anatomical cortical underconnectivity in autism: evidence from an FMRI study of an executive function task and corpus callosum morphometry |author= Just MA, Cherkassky VL, Keller TA, Kana RK, Minshew NJ |doi=10.1093/cercor/bhl006 |pmid=16772313 |url=http://cercor.oxfordjournals.org/cgi/content/full/17/4/951}}</ref> It maps well to general-processing theories such as [[weak central coherence theory]], which hypothesizes that a limited ability to see the big picture underlies the central disturbance in ASD.<ref>{{cite journal |author= Happé F, [[Uta Frith|Frith U]] |title= The weak coherence account: detail-focused cognitive style in autism spectrum disorders |journal= J Autism Dev Disord |date=2006 |volume=36 |issue=1 |pages=5–25 |doi=10.1007/s10803-005-0039-0 |pmid=16450045}}</ref> A related theory—enhanced perceptual functioning—focuses more on the superiority of locally oriented and [[perceptual]] operations in autistic individuals.<ref>{{cite journal |journal= J Autism Dev Disord |date=2006 |volume=36 |issue=1 |pages=27–43 |title= Enhanced perceptual functioning in autism: an update, and eight principles of autistic perception |author= Mottron L, [[Michelle Dawson|Dawson M]], Soulières I, Hubert B, Burack J |doi=10.1007/s10803-005-0040-7 |pmid=16453071}}</ref>


* The [[Mirror neuron|mirror neuron system]] (MNS) theory hypothesizes that alterations to the development of the MNS interfere with imitation and lead to Asperger's core feature of social impairment.<ref name="Iacoboni">{{cite journal |journal= Nat Rev Neurosci |date=2006 |volume=7 |issue=12 |pages=942–51 |title= The mirror neuron system and the consequences of its dysfunction |author= Iacoboni M, Dapretto M |doi=10.1038/nrn2024 |pmid=17115076}}</ref><ref>{{cite journal |journal= Sci Am |year=2006 |volume=295 |issue=5 |pages=62–9 |title= Broken mirrors: a theory of autism |author= [[Vilayanur S. Ramachandran|Ramachandran VS]], Oberman LM |pmid=17076085 |url=http://psy.ucsd.edu/chip/pdf/brokenmirrors_asd.pdf |format=PDF |accessdate=2008-04-17}}</ref> For example, one study found that activation is delayed in the core circuit for imitation in individuals with AS.<ref>{{cite journal |journal= Ann Neurol |year=2004 |volume=55 |issue=4 |pages=558–62 |title= Abnormal imitation-related cortical activation sequences in Asperger's syndrome |author= Nishitani N, Avikainen S, Hari R |doi=10.1002/ana.20031 |pmid=15048895}}</ref> This theory maps well to social cognition theories like the [[theory of mind]], which hypothesizes that autistic behavior arises from impairments in ascribing mental states to oneself and others,<ref>{{cite journal |author= Baron-Cohen S, Leslie AM, Frith U |title= Does the autistic child have a 'theory of mind'? |journal=Cognition |volume=21 |issue=1 |pages=37–46 |year=1985 |doi=10.1016/0010-0277(85)90022-8 |pmid=2934210 |url=http://ruccs.rutgers.edu/~aleslie/Baron-Cohen%20Leslie%20&%20Frith%201985.pdf |format=PDF |accessdate=2007-06-28}}</ref> or [[EQ SQ theory|hyper-systemizing]], which hypothesizes that autistic individuals can systematize internal operation to handle internal events but are less effective at [[Empathy|empathizing]] by handling events generated by other agents.<ref>{{cite journal |author= [[Simon Baron-Cohen|Baron-Cohen S]] |title= The hyper-systemizing, assortative mating theory of autism |journal= Prog Neuropsychopharmacol Biol Psychiatry |date=2006 |volume=30 |issue=5 |pages=865–72 |doi=10.1016/j.pnpbp.2006.01.010 |pmid=16519981}}</ref>
Neuroimaging studies have shown structural and functional brain abnormalities in patients with Asperger (AS) such as:<ref name="pmid29167722">{{cite journal| author=Faridi F, Khosrowabadi R| title=Behavioral, Cognitive and Neural Markers of Asperger Syndrome. | journal=Basic Clin Neurosci | year= 2017 | volume= 8 | issue= 5 | pages= 349-359 | pmid=29167722 | doi=10.18869/nirp.bcn.8.5.349 | pmc=5691167 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29167722  }} </ref><ref name="pmid18563474">{{cite journal| author=Woodbury-Smith MR, Volkmar FR| title=Asperger syndrome. | journal=Eur Child Adolesc Psychiatry | year= 2009 | volume= 18 | issue= 1 | pages= 2-11 | pmid=18563474 | doi=10.1007/s00787-008-0701-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18563474  }} </ref>


* Other possible mechanisms include [[serotonin]] dysfunction<ref>{{cite journal |journal= Am J Psychiatry |year=2006 |volume=163 |issue=5 |pages=934–6 |title= Cortical serotonin 5-HT<sub>2A</sub> receptor binding and social communication in adults with Asperger's syndrome: an in vivo SPECT study |author= Murphy DG, Daly E, Schmitz N ''et al.'' |doi=10.1176/appi.ajp.163.5.934 |pmid=16648340}}</ref> and [[cerebellar]] dysfunction.<ref>{{cite journal |journal=Cerebellum |year=2005 |volume=4 |issue=4 |pages=279–89 |title= Behavioural aspects of cerebellar function in adults with Asperger syndrome |author= Gowen E, Miall RC |doi=10.1080/14734220500355332 |pmid=16321884}}</ref>
*There has been a report on developmental problems of [[neuronal migration]] in the [[cerebral cortex]] during pregnancy and fetal development in patients with AS which may result in problems in the connectivity of the brain cortex.<ref name="pmid2136076">{{cite journal| author=Berthier ML, Starkstein SE, Leiguarda R| title=Developmental cortical anomalies in Asperger's syndrome: neuroradiological findings in two patients. | journal=J Neuropsychiatry Clin Neurosci | year= 1990 | volume= 2 | issue= 2 | pages= 197-201 | pmid=2136076 | doi=10.1176/jnp.2.2.197 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2136076  }} </ref>
*Smaller gray matter in the ventromedial aspect of the [[temporal lobe]]<ref name="pmid15540637">{{cite journal| author=Kwon H, Ow AW, Pedatella KE, Lotspeich LJ, Reiss AL| title=Voxel-based morphometry elucidates structural neuroanatomy of high-functioning autism and Asperger syndrome. | journal=Dev Med Child Neurol | year= 2004 | volume= 46 | issue= 11 | pages= 760-4 | pmid=15540637 | doi=10.1017/s0012162204001306 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15540637  }} </ref> and bilateral caudate and left [[thalamus]] <ref name="pmid18673405">{{cite journal| author=McAlonan GM, Suckling J, Wong N, Cheung V, Lienenkaemper N, Cheung C | display-authors=etal| title=Distinct patterns of grey matter abnormality in high-functioning autism and Asperger's syndrome. | journal=J Child Psychol Psychiatry | year= 2008 | volume= 49 | issue= 12 | pages= 1287-95 | pmid=18673405 | doi=10.1111/j.1469-7610.2008.01933.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18673405  }} </ref>.
*Greater [[white matter]] around the [[basal ganglia]] and left inferior parietal lobe, but lower white matter volume in the right [[corpus callosum]].<ref name="pmid19356262">{{cite journal| author=McAlonan GM, Cheung C, Cheung V, Wong N, Suckling J, Chua SE| title=Differential effects on white-matter systems in high-functioning autism and Asperger's syndrome. | journal=Psychol Med | year= 2009 | volume= 39 | issue= 11 | pages= 1885-93 | pmid=19356262 | doi=10.1017/S0033291709005728 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19356262  }} </ref>
*Larger amygdala and hippocampal in patients with AS is associated to their difficulty with emotional reactivity<ref name="pmid23672532">{{cite journal| author=Semrud-Clikeman M, Fine JG, Bledsoe J, Zhu DC| title=Magnetic resonance imaging volumetric findings in children with Asperger syndrome, nonverbal learning disability, or healthy controls. | journal=J Clin Exp Neuropsychol | year= 2013 | volume= 35 | issue= 5 | pages= 540-50 | pmid=23672532 | doi=10.1080/13803395.2013.795528 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23672532  }} </ref>
*Smaller anterior cingulate cortex (ACC) in AS patients is associated with  their difficulty with self monitoring of behavior.<ref name="pmid23672532" />
*Lesion in the white matter of the right [[middle temporal gyrus]].<ref name="pmid10671397">{{cite journal| author=Volkmar FR, Klin A, Schultz RT, Rubin E, Bronen R| title=Asperger's disorder. | journal=Am J Psychiatry | year= 2000 | volume= 157 | issue= 2 | pages= 262-7 | pmid=10671397 | doi=10.1176/appi.ajp.157.2.262 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10671397  }} </ref>
*Lower fractional [[anisotropy]] (FA) is seen mostly bilaterally and in the white matter ([[internal capsule]], frontal, temporal, parietal and occipital lobe, [[Cingulum (anatomy)|cingulum]] and corpus callosum).<ref name="pmid20625995">{{cite journal| author=Bloemen OJ, Deeley Q, Sundram F, Daly EM, Barker GJ, Jones DK | display-authors=etal| title=White matter integrity in Asperger syndrome: a preliminary diffusion tensor magnetic resonance imaging study in adults. | journal=Autism Res | year= 2010 | volume= 3 | issue= 5 | pages= 203-13 | pmid=20625995 | doi=10.1002/aur.146 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20625995  }} </ref>
*Localized disconnection in cerebellar neural pathways may lead to abnormalities in adaptive social behavior.<ref name="pmid18495494">{{cite journal| author=Catani M, Jones DK, Daly E, Embiricos N, Deeley Q, Pugliese L | display-authors=etal| title=Altered cerebellar feedback projections in Asperger syndrome. | journal=Neuroimage | year= 2008 | volume= 41 | issue= 4 | pages= 1184-91 | pmid=18495494 | doi=10.1016/j.neuroimage.2008.03.041 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18495494  }} </ref>
*Abnormal functional connectivity of medial [[temporal lobe]] structures (amygdala and parahippocampus gyrus) is associated with difficulty in social cognition in AS patients.<ref name="pmid15860339">{{cite journal| author=Welchew DE, Ashwin C, Berkouk K, Salvador R, Suckling J, Baron-Cohen S | display-authors=etal| title=Functional disconnectivity of the medial temporal lobe in Asperger's syndrome. | journal=Biol Psychiatry | year= 2005 | volume= 57 | issue= 9 | pages= 991-8 | pmid=15860339 | doi=10.1016/j.biopsych.2005.01.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15860339  }} </ref>
*Abnormal dysactivation of the [[frontal lobe]] (during neuropsychological tests).<ref name="pmid8556839">{{cite journal| author=Fletcher PC, Happé F, Frith U, Baker SC, Dolan RJ, Frackowiak RS | display-authors=etal| title=Other minds in the brain: a functional imaging study of "theory of mind" in story comprehension. | journal=Cognition | year= 1995 | volume= 57 | issue= 2 | pages= 109-28 | pmid=8556839 | doi=10.1016/0010-0277(95)00692-r | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8556839  }} </ref><ref name="pmid9051780">{{cite journal| author=Happé F, Ehlers S, Fletcher P, Frith U, Johansson M, Gillberg C | display-authors=etal| title='Theory of mind' in the brain. Evidence from a PET scan study of Asperger syndrome. | journal=Neuroreport | year= 1996 | volume= 8 | issue= 1 | pages= 197-201 | pmid=9051780 | doi=10.1097/00001756-199612200-00040 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9051780  }} </ref><ref name="pmid12959489">{{cite journal| author=Mundy P| title=Annotation: the neural basis of social impairments in autism: the role of the dorsal medial-frontal cortex and anterior cingulate system. | journal=J Child Psychol Psychiatry | year= 2003 | volume= 44 | issue= 6 | pages= 793-809 | pmid=12959489 | doi=10.1111/1469-7610.00165 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12959489  }} </ref><ref name="pmid10388796">{{cite journal| author=Ring HA, Baron-Cohen S, Wheelwright S, Williams SC, Brammer M, Andrew C | display-authors=etal| title=Cerebral correlates of preserved cognitive skills in autism: a functional MRI study of embedded figures task performance. | journal=Brain | year= 1999 | volume= 122 ( Pt 7) | issue=  | pages= 1305-15 | pmid=10388796 | doi=10.1093/brain/122.7.1305 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10388796  }} </ref>
*Abnormal activation in the temporal cortex during face discrimination.<ref name="pmid10768694">{{cite journal| author=Schultz RT, Gauthier I, Klin A, Fulbright RK, Anderson AW, Volkmar F | display-authors=etal| title=Abnormal ventral temporal cortical activity during face discrimination among individuals with autism and Asperger syndrome. | journal=Arch Gen Psychiatry | year= 2000 | volume= 57 | issue= 4 | pages= 331-40 | pmid=10768694 | doi=10.1001/archpsyc.57.4.331 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10768694  }} </ref>
*Decreased activation of fusiform and extrastriate cortices during facial emotion processing.<ref name="pmid17400195">{{cite journal| author=Deeley Q, Daly EM, Surguladze S, Page L, Toal F, Robertson D | display-authors=etal| title=An event related functional magnetic resonance imaging study of facial emotion processing in Asperger syndrome. | journal=Biol Psychiatry | year= 2007 | volume= 62 | issue= 3 | pages= 207-17 | pmid=17400195 | doi=10.1016/j.biopsych.2006.09.037 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17400195  }} </ref>
*Executive dysfunctions are associated with abnormality in neural connectivity of the brain cortex.<ref name="pmid28042973">{{cite journal| author=Han YM, Chan AS| title=Disordered cortical connectivity underlies the executive function deficits in children with autism spectrum disorders. | journal=Res Dev Disabil | year= 2017 | volume= 61 | issue=  | pages= 19-31 | pmid=28042973 | doi=10.1016/j.ridd.2016.12.010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28042973  }} </ref>
*Neuroimaging patterns of AS patients were the same in static stimuli (photo of a face) and dynamic stimuli (real face).<ref name="urlThe influence of static versus naturalistic stimuli on face processing in children with and without Asperger syndrome or high-functioning autism">{{cite web |url=http://hdl.handle.net/20.500.11937/22503 |title=The influence of static versus naturalistic stimuli on face processing in children with and without Asperger syndrome or high-functioning autism |format= |work= |accessdate=}}</ref>


===Associated Conditions===
Some chemical markers associated with AS include:<ref name="pmid29167722" />
*AS is associated with [[tic]]s, [[Tourette syndrome]], and [[bipolar disorder]], and the repetitive behaviors of AS have many similarities with the symptoms of [[obsessive-compulsive disorder]] and [[obsessive-compulsive personality disorder]].<ref>{{cite journal |author= Gillberg C, Billstedt E |title= Autism and Asperger syndrome: coexistence with other clinical disorders |journal= Acta Psychiatr Scand |volume=102 |issue=5 |pages=321–30 |year=2000 |doi=10.1034/j.1600-0447.2000.102005321.x |pmid=11098802}}</ref> Although many of these studies are based on psychiatric clinic samples without using standardized measures, it seems reasonable to conclude that comorbid conditions are relatively common.


<br />
* Increase in [[N-Acetylaspartic acid|N-acetyl aspartate]]/[[choline]] (NAA/Cho) level in the right anterior cingulate is associated with higher scores in obsessive compulsive scale in patients with AS.<ref name="pmid17846198">{{cite journal| author=Oner O, Devrimci-Ozguven H, Oktem F, Yagmurlu B, Baskak B, Munir KM| title=Proton MR spectroscopy: higher right anterior cingulate N-acetylaspartate/choline ratio in Asperger syndrome compared with healthy controls. | journal=AJNR Am J Neuroradiol | year= 2007 | volume= 28 | issue= 8 | pages= 1494-8 | pmid=17846198 | doi=10.3174/ajnr.A0625 | pmc=3166641 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17846198  }} </ref>
* Increased in the activity of the presynaptic dopamine system  in the [[striatum]] and frontal [[cortex]] in patients with AS.<ref name="pmid15073509">{{cite journal| author=Nieminen-von Wendt TS, Metsähonkala L, Kulomäki TA, Aalto S, Autti TH, Vanhala R | display-authors=etal| title=Increased presynaptic dopamine function in Asperger syndrome. | journal=Neuroreport | year= 2004 | volume= 15 | issue= 5 | pages= 757-60 | pmid=15073509 | doi=10.1097/00001756-200404090-00003 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15073509  }} </ref>
* There is an association in cortical [[serotonin]] 5-HT2A receptor binding and social communication in patients with AS.<ref name="pmid16648340">{{cite journal| author=Murphy DG, Daly E, Schmitz N, Toal F, Murphy K, Curran S | display-authors=etal| title=Cortical serotonin 5-HT2A receptor binding and social communication in adults with Asperger's syndrome: an in vivo SPECT study. | journal=Am J Psychiatry | year= 2006 | volume= 163 | issue= 5 | pages= 934-6 | pmid=16648340 | doi=10.1176/ajp.2006.163.5.934 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16648340  }} </ref>
* Administration of [[oxytocin]] may improve emotion recognition, affective speech comprehension, increase eye gaze, and social interaction in patients with AS.<ref name="pmid24067301">{{cite journal| author=Domes G, Kumbier E, Heinrichs M, Herpertz SC| title=Oxytocin promotes facial emotion recognition and amygdala reactivity in adults with asperger syndrome. | journal=Neuropsychopharmacology | year= 2014 | volume= 39 | issue= 3 | pages= 698-706 | pmid=24067301 | doi=10.1038/npp.2013.254 | pmc=3895247 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24067301  }} </ref>
 
Neuropsychological abnormalities in AS are:<ref name="pmid18563474">{{cite journal| author=Woodbury-Smith MR, Volkmar FR| title=Asperger syndrome. | journal=Eur Child Adolesc Psychiatry | year= 2009 | volume= 18 | issue= 1 | pages= 2-11 | pmid=18563474 | doi=10.1007/s00787-008-0701-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18563474  }} </ref>
 
* Difficulty in passing [[theory of mind]] tasks
* Executive dysfunction
* Tendency to interpret visual stimuli in parts rather than wholes (poor central coherence)
* There are studies that suggest in patients with AS there is a Verbal IQ (VIQ) > Poor Performance IQ (PIQ) profile which shows strength on verbal skills relative to visuospatial skills and non-verbal problem solving ([[Nonverbal learning disorder|nonverbal learning disability]])<ref name="LincolnCourchesne1998">{{cite journal|last1=Lincoln|first1=Alan|last2=Courchesne|first2=Eric|last3=Allen|first3=Mark|last4=Hanson|first4=Ellen|last5=Ene|first5=Michaela|title=Neurobiology of Asperger Syndrome|year=1998|pages=145–163|doi=10.1007/978-1-4615-5369-4_8}}</ref>


== Associated Conditions ==
== Associated Conditions ==
Asperger Syndrome (AS) is associated with several conditions which include:
Asperger Syndrome (AS) is associated with several conditions which include:


* Attention deficit hyperactivity disorder (most common in pediatric patients) (ADHD)<ref name="pmid9786442">{{cite journal| author=Ghaziuddin M, Weidmer-Mikhail E, Ghaziuddin N| title=Comorbidity of Asperger syndrome: a preliminary report. | journal=J Intellect Disabil Res | year= 1998 | volume= 42 ( Pt 4) | issue=  | pages= 279-83 | pmid=9786442 | doi=10.1111/j.1365-2788.1998.tb01647.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9786442  }} </ref>
*[[Attention-deficit hyperactivity disorder|Attention deficit hyperactivity disorder]] (ADHD) (most common in pediatric patients)<ref name="pmid9786442">{{cite journal| author=Ghaziuddin M, Weidmer-Mikhail E, Ghaziuddin N| title=Comorbidity of Asperger syndrome: a preliminary report. | journal=J Intellect Disabil Res | year= 1998 | volume= 42 ( Pt 4) | issue=  | pages= 279-83 | pmid=9786442 | doi=10.1111/j.1365-2788.1998.tb01647.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9786442  }} </ref>
 
*[[Depression]] (most common in adolescent and adult patients)<ref name="pmid9786442" /><ref name="pmid21515028">{{cite journal| author=Lugnegård T, Hallerbäck MU, Gillberg C| title=Psychiatric comorbidity in young adults with a clinical diagnosis of Asperger syndrome. | journal=Res Dev Disabil | year= 2011 | volume= 32 | issue= 5 | pages= 1910-7 | pmid=21515028 | doi=10.1016/j.ridd.2011.03.025 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21515028  }} </ref>
* Depression (most common in adolescent and adult patients)<ref name="pmid9786442" />
*[[Bipolar disorder]]<ref name="pmid9786442" /><ref name="pmid21515028" />
 
*[[Tourette syndrome]]<ref name="pmid9786442" />
** Major depression<ref name="pmid9786442" />
*[[Obsessive compulsive disorder|Obsessive compulsive disorder (OCD)]]<ref name="pmid9786442" /><ref name="pmid21515028" />
** Dysthymia<ref name="pmid9786442" />
*[[Tic disorder]]<ref name="pmid9786442" />
 
*[[Anxiety]] disorders<ref name="pmid21515028" />
* Bipolar disorder<ref name="pmid9786442" />
*[[Schizophrenia]]<ref name="pmid26936160">{{cite journal| author=Marinopoulou M, Lugnegård T, Hallerbäck MU, Gillberg C, Billstedt E| title=Asperger Syndrome and Schizophrenia: A Comparative Neuropsychological Study. | journal=J Autism Dev Disord | year= 2016 | volume= 46 | issue= 7 | pages= 2292-304 | pmid=26936160 | doi=10.1007/s10803-016-2758-9 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26936160  }} </ref> 
 
*[[Nonverbal learning disorder|Non-verbal learning disability]]<ref name="pmid15473168">{{cite journal| author=Cederlund M, Gillberg C| title=One hundred males with Asperger syndrome: a clinical study of background and associated factors. | journal=Dev Med Child Neurol | year= 2004 | volume= 46 | issue= 10 | pages= 652-60 | pmid=15473168 | doi=10.1017/s0012162204001100 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15473168  }} </ref>
* Tourette’s syndrom<ref name="pmid9786442" />
*Difficulty in falling asleep, sleepiness after awakening and during daytime and poor sleep quality<ref name="pmid14981336">{{cite journal| author=Tani P, Lindberg N, Joukamaa M, Nieminen-von Wendt T, von Wendt L, Appelberg B | display-authors=etal| title=Asperger syndrome, alexithymia and perception of sleep. | journal=Neuropsychobiology | year= 2004 | volume= 49 | issue= 2 | pages= 64-70 | pmid=14981336 | doi=10.1159/000076412 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14981336  }} </ref>
* Obsessive compulsive disorder<ref name="pmid9786442" />
* There have been case-reports of Asperger Syndrome (AS) associated with [[Aminoaciduria|aminoaciduria,]]<ref name="pmid3664113">{{cite journal| author=Miles SW, Capelle P| title=Asperger's syndrome and aminoaciduria: a case example. | journal=Br J Psychiatry | year= 1987 | volume= 150 | issue=  | pages= 397-400 | pmid=3664113 | doi=10.1192/bjp.150.3.397 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3664113  }} </ref> [[ligamentous laxity]]<ref name="pmid2273016">{{cite journal| author=Tantam D, Evered C, Hersov L| title=Asperger's syndrome and ligamentous laxity. | journal=J Am Acad Child Adolesc Psychiatry | year= 1990 | volume= 29 | issue= 6 | pages= 892-6 | pmid=2273016 | doi=10.1097/00004583-199011000-00008 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2273016  }} </ref> and recurrent [[hypersomnia]]<ref name="pmid1644738">{{cite journal| author=Berthier ML, Santamaria J, Encabo H, Tolosa ES| title=Recurrent hypersomnia in two adolescent males with Asperger's syndrome. | journal=J Am Acad Child Adolesc Psychiatry | year= 1992 | volume= 31 | issue= 4 | pages= 735-8 | pmid=1644738 | doi=10.1097/00004583-199207000-00023 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1644738  }} </ref>.
* Tic disorder<ref name="pmid9786442" />
* Anxiety  
* Schizophrenia  


==References==
==References==

Latest revision as of 16:57, 22 June 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shakiba Hassanzadeh, MD[2]

Overview

The exact pathophysiology of Asperger Syndrome is unknown, however some neuroimaging and neuropsychological studies have reported some findings.[1][2]

Pathophysiology

Neuroimaging studies have shown structural and functional brain abnormalities in patients with Asperger (AS) such as:[1][2]

  • There has been a report on developmental problems of neuronal migration in the cerebral cortex during pregnancy and fetal development in patients with AS which may result in problems in the connectivity of the brain cortex.[3]
  • Smaller gray matter in the ventromedial aspect of the temporal lobe[4] and bilateral caudate and left thalamus [5].
  • Greater white matter around the basal ganglia and left inferior parietal lobe, but lower white matter volume in the right corpus callosum.[6]
  • Larger amygdala and hippocampal in patients with AS is associated to their difficulty with emotional reactivity[7]
  • Smaller anterior cingulate cortex (ACC) in AS patients is associated with their difficulty with self monitoring of behavior.[7]
  • Lesion in the white matter of the right middle temporal gyrus.[8]
  • Lower fractional anisotropy (FA) is seen mostly bilaterally and in the white matter (internal capsule, frontal, temporal, parietal and occipital lobe, cingulum and corpus callosum).[9]
  • Localized disconnection in cerebellar neural pathways may lead to abnormalities in adaptive social behavior.[10]
  • Abnormal functional connectivity of medial temporal lobe structures (amygdala and parahippocampus gyrus) is associated with difficulty in social cognition in AS patients.[11]
  • Abnormal dysactivation of the frontal lobe (during neuropsychological tests).[12][13][14][15]
  • Abnormal activation in the temporal cortex during face discrimination.[16]
  • Decreased activation of fusiform and extrastriate cortices during facial emotion processing.[17]
  • Executive dysfunctions are associated with abnormality in neural connectivity of the brain cortex.[18]
  • Neuroimaging patterns of AS patients were the same in static stimuli (photo of a face) and dynamic stimuli (real face).[19]

Some chemical markers associated with AS include:[1]

  • Increase in N-acetyl aspartate/choline (NAA/Cho) level in the right anterior cingulate is associated with higher scores in obsessive compulsive scale in patients with AS.[20]
  • Increased in the activity of the presynaptic dopamine system in the striatum and frontal cortex in patients with AS.[21]
  • There is an association in cortical serotonin 5-HT2A receptor binding and social communication in patients with AS.[22]
  • Administration of oxytocin may improve emotion recognition, affective speech comprehension, increase eye gaze, and social interaction in patients with AS.[23]

Neuropsychological abnormalities in AS are:[2]

  • Difficulty in passing theory of mind tasks
  • Executive dysfunction
  • Tendency to interpret visual stimuli in parts rather than wholes (poor central coherence)
  • There are studies that suggest in patients with AS there is a Verbal IQ (VIQ) > Poor Performance IQ (PIQ) profile which shows strength on verbal skills relative to visuospatial skills and non-verbal problem solving (nonverbal learning disability)[24]

Associated Conditions

Asperger Syndrome (AS) is associated with several conditions which include:

References

  1. ↑ 1.0 1.1 1.2 Faridi F, Khosrowabadi R (2017). "Behavioral, Cognitive and Neural Markers of Asperger Syndrome". Basic Clin Neurosci. 8 (5): 349–359. doi:10.18869/nirp.bcn.8.5.349. PMC 5691167. PMID 29167722.
  2. ↑ 2.0 2.1 2.2 Woodbury-Smith MR, Volkmar FR (2009). "Asperger syndrome". Eur Child Adolesc Psychiatry. 18 (1): 2–11. doi:10.1007/s00787-008-0701-0. PMID 18563474.
  3. ↑ Berthier ML, Starkstein SE, Leiguarda R (1990). "Developmental cortical anomalies in Asperger's syndrome: neuroradiological findings in two patients". J Neuropsychiatry Clin Neurosci. 2 (2): 197–201. doi:10.1176/jnp.2.2.197. PMID 2136076.
  4. ↑ Kwon H, Ow AW, Pedatella KE, Lotspeich LJ, Reiss AL (2004). "Voxel-based morphometry elucidates structural neuroanatomy of high-functioning autism and Asperger syndrome". Dev Med Child Neurol. 46 (11): 760–4. doi:10.1017/s0012162204001306. PMID 15540637.
  5. ↑ McAlonan GM, Suckling J, Wong N, Cheung V, Lienenkaemper N, Cheung C; et al. (2008). "Distinct patterns of grey matter abnormality in high-functioning autism and Asperger's syndrome". J Child Psychol Psychiatry. 49 (12): 1287–95. doi:10.1111/j.1469-7610.2008.01933.x. PMID 18673405.
  6. ↑ McAlonan GM, Cheung C, Cheung V, Wong N, Suckling J, Chua SE (2009). "Differential effects on white-matter systems in high-functioning autism and Asperger's syndrome". Psychol Med. 39 (11): 1885–93. doi:10.1017/S0033291709005728. PMID 19356262.
  7. ↑ 7.0 7.1 Semrud-Clikeman M, Fine JG, Bledsoe J, Zhu DC (2013). "Magnetic resonance imaging volumetric findings in children with Asperger syndrome, nonverbal learning disability, or healthy controls". J Clin Exp Neuropsychol. 35 (5): 540–50. doi:10.1080/13803395.2013.795528. PMID 23672532.
  8. ↑ Volkmar FR, Klin A, Schultz RT, Rubin E, Bronen R (2000). "Asperger's disorder". Am J Psychiatry. 157 (2): 262–7. doi:10.1176/appi.ajp.157.2.262. PMID 10671397.
  9. ↑ Bloemen OJ, Deeley Q, Sundram F, Daly EM, Barker GJ, Jones DK; et al. (2010). "White matter integrity in Asperger syndrome: a preliminary diffusion tensor magnetic resonance imaging study in adults". Autism Res. 3 (5): 203–13. doi:10.1002/aur.146. PMID 20625995.
  10. ↑ Catani M, Jones DK, Daly E, Embiricos N, Deeley Q, Pugliese L; et al. (2008). "Altered cerebellar feedback projections in Asperger syndrome". Neuroimage. 41 (4): 1184–91. doi:10.1016/j.neuroimage.2008.03.041. PMID 18495494.
  11. ↑ Welchew DE, Ashwin C, Berkouk K, Salvador R, Suckling J, Baron-Cohen S; et al. (2005). "Functional disconnectivity of the medial temporal lobe in Asperger's syndrome". Biol Psychiatry. 57 (9): 991–8. doi:10.1016/j.biopsych.2005.01.028. PMID 15860339.
  12. ↑ Fletcher PC, Happé F, Frith U, Baker SC, Dolan RJ, Frackowiak RS; et al. (1995). "Other minds in the brain: a functional imaging study of "theory of mind" in story comprehension". Cognition. 57 (2): 109–28. doi:10.1016/0010-0277(95)00692-r. PMID 8556839.
  13. ↑ Happé F, Ehlers S, Fletcher P, Frith U, Johansson M, Gillberg C; et al. (1996). "'Theory of mind' in the brain. Evidence from a PET scan study of Asperger syndrome". Neuroreport. 8 (1): 197–201. doi:10.1097/00001756-199612200-00040. PMID 9051780.
  14. ↑ Mundy P (2003). "Annotation: the neural basis of social impairments in autism: the role of the dorsal medial-frontal cortex and anterior cingulate system". J Child Psychol Psychiatry. 44 (6): 793–809. doi:10.1111/1469-7610.00165. PMID 12959489.
  15. ↑ Ring HA, Baron-Cohen S, Wheelwright S, Williams SC, Brammer M, Andrew C; et al. (1999). "Cerebral correlates of preserved cognitive skills in autism: a functional MRI study of embedded figures task performance". Brain. 122 ( Pt 7): 1305–15. doi:10.1093/brain/122.7.1305. PMID 10388796.
  16. ↑ Schultz RT, Gauthier I, Klin A, Fulbright RK, Anderson AW, Volkmar F; et al. (2000). "Abnormal ventral temporal cortical activity during face discrimination among individuals with autism and Asperger syndrome". Arch Gen Psychiatry. 57 (4): 331–40. doi:10.1001/archpsyc.57.4.331. PMID 10768694.
  17. ↑ Deeley Q, Daly EM, Surguladze S, Page L, Toal F, Robertson D; et al. (2007). "An event related functional magnetic resonance imaging study of facial emotion processing in Asperger syndrome". Biol Psychiatry. 62 (3): 207–17. doi:10.1016/j.biopsych.2006.09.037. PMID 17400195.
  18. ↑ Han YM, Chan AS (2017). "Disordered cortical connectivity underlies the executive function deficits in children with autism spectrum disorders". Res Dev Disabil. 61: 19–31. doi:10.1016/j.ridd.2016.12.010. PMID 28042973.
  19. ↑ "The influence of static versus naturalistic stimuli on face processing in children with and without Asperger syndrome or high-functioning autism".
  20. ↑ Oner O, Devrimci-Ozguven H, Oktem F, Yagmurlu B, Baskak B, Munir KM (2007). "Proton MR spectroscopy: higher right anterior cingulate N-acetylaspartate/choline ratio in Asperger syndrome compared with healthy controls". AJNR Am J Neuroradiol. 28 (8): 1494–8. doi:10.3174/ajnr.A0625. PMC 3166641. PMID 17846198.
  21. ↑ Nieminen-von Wendt TS, Metsähonkala L, Kulomäki TA, Aalto S, Autti TH, Vanhala R; et al. (2004). "Increased presynaptic dopamine function in Asperger syndrome". Neuroreport. 15 (5): 757–60. doi:10.1097/00001756-200404090-00003. PMID 15073509.
  22. ↑ Murphy DG, Daly E, Schmitz N, Toal F, Murphy K, Curran S; et al. (2006). "Cortical serotonin 5-HT2A receptor binding and social communication in adults with Asperger's syndrome: an in vivo SPECT study". Am J Psychiatry. 163 (5): 934–6. doi:10.1176/ajp.2006.163.5.934. PMID 16648340.
  23. ↑ Domes G, Kumbier E, Heinrichs M, Herpertz SC (2014). "Oxytocin promotes facial emotion recognition and amygdala reactivity in adults with asperger syndrome". Neuropsychopharmacology. 39 (3): 698–706. doi:10.1038/npp.2013.254. PMC 3895247. PMID 24067301.
  24. ↑ Lincoln, Alan; Courchesne, Eric; Allen, Mark; Hanson, Ellen; Ene, Michaela (1998). "Neurobiology of Asperger Syndrome": 145–163. doi:10.1007/978-1-4615-5369-4_8.
  25. ↑ 25.0 25.1 25.2 25.3 25.4 25.5 Ghaziuddin M, Weidmer-Mikhail E, Ghaziuddin N (1998). "Comorbidity of Asperger syndrome: a preliminary report". J Intellect Disabil Res. 42 ( Pt 4): 279–83. doi:10.1111/j.1365-2788.1998.tb01647.x. PMID 9786442.
  26. ↑ 26.0 26.1 26.2 26.3 Lugnegård T, Hallerbäck MU, Gillberg C (2011). "Psychiatric comorbidity in young adults with a clinical diagnosis of Asperger syndrome". Res Dev Disabil. 32 (5): 1910–7. doi:10.1016/j.ridd.2011.03.025. PMID 21515028.
  27. ↑ Marinopoulou M, Lugnegård T, Hallerbäck MU, Gillberg C, Billstedt E (2016). "Asperger Syndrome and Schizophrenia: A Comparative Neuropsychological Study". J Autism Dev Disord. 46 (7): 2292–304. doi:10.1007/s10803-016-2758-9. PMID 26936160.
  28. ↑ Cederlund M, Gillberg C (2004). "One hundred males with Asperger syndrome: a clinical study of background and associated factors". Dev Med Child Neurol. 46 (10): 652–60. doi:10.1017/s0012162204001100. PMID 15473168.
  29. ↑ Tani P, Lindberg N, Joukamaa M, Nieminen-von Wendt T, von Wendt L, Appelberg B; et al. (2004). "Asperger syndrome, alexithymia and perception of sleep". Neuropsychobiology. 49 (2): 64–70. doi:10.1159/000076412. PMID 14981336.
  30. ↑ Miles SW, Capelle P (1987). "Asperger's syndrome and aminoaciduria: a case example". Br J Psychiatry. 150: 397–400. doi:10.1192/bjp.150.3.397. PMID 3664113.
  31. ↑ Tantam D, Evered C, Hersov L (1990). "Asperger's syndrome and ligamentous laxity". J Am Acad Child Adolesc Psychiatry. 29 (6): 892–6. doi:10.1097/00004583-199011000-00008. PMID 2273016.
  32. ↑ Berthier ML, Santamaria J, Encabo H, Tolosa ES (1992). "Recurrent hypersomnia in two adolescent males with Asperger's syndrome". J Am Acad Child Adolesc Psychiatry. 31 (4): 735–8. doi:10.1097/00004583-199207000-00023. PMID 1644738.


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