Asperger syndrome pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Pathophysiology
Asperger syndrome appears to result from developmental factors that affect many or all functional brain systems, as opposed to localized effects.[3] 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.[4] Neuroanatomical studies and the associations with 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.[5] Several theories of mechanism are available; none are likely to be complete explanations.[6]- The underconnectivity theory hypothesizes underfunctioning high-level neural connections and synchronization, along with an excess of low-level processes.[1] 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.[7] A related theory—enhanced perceptual functioning—focuses more on the superiority of locally oriented and perceptual operations in autistic individuals.[8]
- The 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.[2][9] For example, one study found that activation is delayed in the core circuit for imitation in individuals with AS.[10] 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,[11] or hyper-systemizing, which hypothesizes that autistic individuals can systematize internal operation to handle internal events but are less effective at empathizing by handling events generated by other agents.[12]
- Other possible mechanisms include serotonin dysfunction[13] and cerebellar dysfunction.[14]
Associated Conditions
AS is associated with tics, 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.[15] 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.
Pathophysiology
Asperger Syndrome (AS) causes some chemical, structural and functional abnormalities which include: Faridi
- Chemical markers:
- Higher level of N-acetyl aspartate/choline (NAA/Cho) level at the right anterior cingulate (oner 2007)
- [18F] F-Dopa influx(k) increase in the striatum, putamen ,caudate nucleus and frontal cortex (affected dopaminergic system) (neieminen von 2004)
- Changes in NAA/Cho are positively correlated with the obsessive compulsive scale that is affected in AS. (faridi
- Changes in serotonin in the brain affect the processing of emotional faces (Daly et al., 2008)
- Administration of oxytocin could improve performance facial emotion recognition task (Domes, Kumbier, Heinrichs, & Herpertz 2013) and may improve affective speech comprehension and increase eye gaze, emotion recognition as well as social interaction (Domes et al., 2013)
- Brain structural changes
- Lower grey matter volumes in the bilateral amygdala, hippocampus gyrus, prefrontal lobe, medial frontal gyrus, left occipital gyrus, right cerebellum, limbic striatal, bilateral caudate, left thalamus, putamen and precuneus (McAlonan et al., 2008; Ameis et al., 2011, Semrud-Clikeman & Fine, 2011)
- Greater grey matter volumes at the bilateral inferior parietal lobule and the left fusiform gyrus (farid)
- Higher volume of white matter around the basal ganglia, left parietal lobe, but lower white matter volume at the right frontal region and corpus callosum (McAlonan et al., 2009)
- Lower fractional anisotropy in the short intracerebellar fibers and right superior cerebellar peduncle (bilateral and in the white matter in the internal capsule, frontal, temporal, parietal and occipital lobe, cingulum and corpus callosum) (Bloemen et al., 2010)
- Abnormal volumes of hippocampus, amygdala and anterior cingulate cortex (ACC) (faridi)
- Abnormality in the anatomy and structure of the brain cause the cognitive.
- Abnormality in the ACC, amygdala and hippocampal areas in patients with AS contirbute to their difficulty with modulating of emotional reactivity (Semrud-Clikeman, Fine, Bledsoe, & Zhu, 2013).
- Localized cerebral abnormalities discharge adaptive social behavior (Catani et al., 2008)
- Volumetric exes at the inferior parietal lobule is linked to synesthesia (Welchew et al., 2005)
- Dysfunction of motor circuits in the frontostriatal and cerebellar reflect chaotic movement (Nayate, Bradshaw, Rinehart, 2005)
association between abnormalities and size of some particles in the brain has been observed. For instance measures of entropy and uniformity have been reported to be related to the volume of the caudate nuclei. In terms of global features, average of the grey matter volume is related to the size of the cerebellar vermis (Radulescu et al., 2012) and there is no positive relationship between the total brain volume and size of thalamus in AS group (Hardan et al., 2007).- There are lesions in the occipital lobe in areas responsible for visual/spatial reasoning (Semrud-Clikeman & Fine, 2011).
- Brain functional changes
- There is a hypothesis that AS is associated with atypical decreased functional connectivity between nodes in the default mode network (Funai,Bharadwaj, Grissom, 2007) and executive control network (Han & Chan, 2017).
- Abnormal functions in cerebella, frontal and temporal lobes, and the limbic system (Sugihara, Ouchi. Nakamura, Sekine, & Mori 2007)
- Abnormality in the functional integration of amygdala and parahippocampal gyrus (Welchew et al., 2005)
- Neuroimaging patterns of AS patients are not affected by stimuli type (static and dynamic faces) (Horlin et al., 2013). For example, story task and cartoon task activate the same region of the brain (medial prefrontal region) (Castelli, 2002)
- Main emotions, manifested by face, can activate fusiform and extra striates (Deeley et al., 2007)
Associated Conditions
Asperger Syndrome (AS) is associated with several conditions which include:
- Attention deficit hyperactivity disorder (most common in pediatric patients) (ADHD)[16]
- Depression (most common in adolescent and adult patients)[16][17]
- Bipolar disorder[16][17]
- Tourette’s syndrom[16]
- Obsessive compulsive disorder[16][17]
- Tic disorder[16]
- Anxiety disorders[17]
- Schizophrenia[18]
- Non-verbal learning disability[19]
- Difficulty in falling asleep, sleepiness after awakening and during daytime and poor sleep quality[20]
- There have been case-reports of Asperger Syndrome (AS) associated with aminoaciduria,[21] ligamentous laxity[22] and recurrent hypersomnia[23].
References
- ↑ 1.0 1.1 Just MA, Cherkassky VL, Keller TA, Kana RK, Minshew NJ (2007). "Functional and anatomical cortical underconnectivity in autism: evidence from an FMRI study of an executive function task and corpus callosum morphometry". Cereb Cortex. 17 (4): 951–61. doi:10.1093/cercor/bhl006. PMID 16772313.
- ↑ 2.0 2.1 Iacoboni M, Dapretto M (2006). "The mirror neuron system and the consequences of its dysfunction". Nat Rev Neurosci. 7 (12): 942–51. doi:10.1038/nrn2024. PMID 17115076.
- ↑ Müller RA (2007). "The study of autism as a distributed disorder". Ment Retard Dev Disabil Res Rev. 13 (1): 85–95. doi:10.1002/mrdd.20141. PMID 17326118.
- ↑ Rinehart NJ, Bradshaw JL, Brereton AV, Tonge BJ (2002). "A clinical and neurobehavioural review of high-functioning autism and Asperger's disorder". Aust N Z J Psychiatry. 36 (6): 762–70. doi:10.1046/j.1440-1614.2002.01097.x. PMID 12406118.
- ↑ 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. PMID 2136076.
- ↑ Happé F, Ronald A, Plomin R (2006). "Time to give up on a single explanation for autism". Nat Neurosci. 9 (10): 1218–20. doi:10.1038/nn1770. PMID 17001340.
- ↑ Happé F, Frith U (2006). "The weak coherence account: detail-focused cognitive style in autism spectrum disorders". J Autism Dev Disord. 36 (1): 5–25. doi:10.1007/s10803-005-0039-0. PMID 16450045.
- ↑ Mottron L, Dawson M, Soulières I, Hubert B, Burack J (2006). "Enhanced perceptual functioning in autism: an update, and eight principles of autistic perception". J Autism Dev Disord. 36 (1): 27–43. doi:10.1007/s10803-005-0040-7. PMID 16453071.
- ↑ Ramachandran VS, Oberman LM (2006). "Broken mirrors: a theory of autism" (PDF). Sci Am. 295 (5): 62–9. PMID 17076085. Retrieved 2008-04-17.
- ↑ Nishitani N, Avikainen S, Hari R (2004). "Abnormal imitation-related cortical activation sequences in Asperger's syndrome". Ann Neurol. 55 (4): 558–62. doi:10.1002/ana.20031. PMID 15048895.
- ↑ Baron-Cohen S, Leslie AM, Frith U (1985). "Does the autistic child have a 'theory of mind'?" (PDF). Cognition. 21 (1): 37–46. doi:10.1016/0010-0277(85)90022-8. PMID 2934210. Retrieved 2007-06-28.
- ↑ Baron-Cohen S (2006). "The hyper-systemizing, assortative mating theory of autism". Prog Neuropsychopharmacol Biol Psychiatry. 30 (5): 865–72. doi:10.1016/j.pnpbp.2006.01.010. PMID 16519981.
- ↑ Murphy DG, Daly E, Schmitz N; 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/appi.ajp.163.5.934. PMID 16648340.
- ↑ Gowen E, Miall RC (2005). "Behavioural aspects of cerebellar function in adults with Asperger syndrome". Cerebellum. 4 (4): 279–89. doi:10.1080/14734220500355332. PMID 16321884.
- ↑ Gillberg C, Billstedt E (2000). "Autism and Asperger syndrome: coexistence with other clinical disorders". Acta Psychiatr Scand. 102 (5): 321–30. doi:10.1034/j.1600-0447.2000.102005321.x. PMID 11098802.
- ↑ 16.0 16.1 16.2 16.3 16.4 16.5 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.
- ↑ 17.0 17.1 17.2 17.3 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.