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Mechanism

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Autism's symptoms result from maturation-related changes in various systems of the brain. How autism occurs is not well understood. Its mechanism can be divided into two areas: the pathophysiology of brain structures and processes associated with autism, and the neuropsychological linkages between brain structures and behaviors.[1] The behaviors appear to have multiple pathophysiologies.[2]

Pathophysiology

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Two diagrams of major brain structures implicated in autism. The upper diagram shows the cerebral cortex near the top and the basal ganglia in the center, just above the amygdala and hippocampus. The lower diagram shows the corpus callosum near the center, the cerebellum in the lower rear, and the brain stem in the lower center.
Autism affects the amygdala, cerebellum, and many other parts of the brain.[3]

Unlike many other brain disorders, such as Parkinson's, autism does not have a clear unifying mechanism at either the molecular, cellular, or systems level; it is not known whether autism is a few disorders caused by mutations converging on a few common molecular pathways, or is (like intellectual disability) a large set of disorders with diverse mechanisms.[4] Autism appears to result from developmental factors that affect many or all functional brain systems,[5] and to disturb the timing of brain development more than the final product.[3] Neuroanatomical studies and the associations with teratogens strongly suggest that autism's mechanism includes alteration of brain development soon after conception.[6] This anomaly appears to start a cascade of pathological events in the brain that are significantly influenced by environmental factors.[7] Just after birth, the brains of autistic children tend to grow faster than usual, followed by normal or relatively slower growth in childhood. It is not known whether early overgrowth occurs in all autistic children. It seems to be most prominent in brain areas underlying the development of higher cognitive specialization.[8] Hypotheses for the cellular and molecular bases of pathological early overgrowth include the following:

Interactions between the immune system and the nervous system begin early during the embryonic stage of life, and successful neurodevelopment depends on a balanced immune response. Aberrant immune activity during critical periods of neurodevelopment is possibly part of the mechanism of some forms of ASD.[16] Although some abnormalities in the immune system have been found in specific subgroups of autistic individuals, it is not known whether these abnormalities are relevant to or secondary to autism's disease processes.[17] As autoantibodies are found in conditions other than ASD, and are not always present in ASD,[18] the relationship between immune disturbances and autism remains unclear and controversial.[10]

Neurochemical systems

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The relationship of neurochemicals to autism is not well understood; several have been investigated, with the most evidence for the role of serotonin and of genetic differences in its transport.[19] The role of group I metabotropic glutamate receptors (mGluR) in the pathogenesis of fragile X syndrome, the most common identified genetic cause of autism, has led to interest in the possible implications for future autism research into this pathway.[20] Some data suggest an increase in several growth hormones; other data argue for diminished growth factors.[21] Also, some inborn errors of metabolism are associated with autism, but probably account for less than 5% of cases.[22]

Brain systems

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Mirror neuron system
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The mirror neuron system (MNS) theory of autism hypothesizes that distortion in the development of the MNS interferes with imitation and leads to autism's core features of social impairment and communication difficulties. The MNS operates when an animal performs an action or observes another animal perform the same action. The MNS may contribute to an individual's understanding of other people by enabling the modeling of their behavior via embodied simulation of their actions, intentions, and emotions.[23] Several studies have tested this hypothesis by demonstrating structural abnormalities in MNS regions of individuals with ASD, delay in the activation in the core circuit for imitation in individuals with Asperger syndrome, and a correlation between reduced MNS activity and severity of the syndrome in children with ASD.[24] However, individuals with autism also have abnormal brain activation in many circuits outside the MNS[25] and the MNS theory does not explain the normal performance of autistic children on imitation tasks that involve a goal or object.[26]

A human brain viewed from above. About 10% is highlighted in yellow and 10% in blue. There is only a tiny (perhaps 0.5%) green region where they overlap.
Autistic individuals tend to use different areas of the brain (yellow) for a movement task compared to a control group (blue).[27]

ASD-related patterns of low function and aberrant activation in the brain differ depending on whether the brain is doing social or nonsocial tasks.[28]

Default Network vs. “Task-positive” Central Executive Network
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ASD-related patterns of low function and aberrant activation in the brain differ depending on whether the brain is doing social or nonsocial tasks. [29] A 2008 brain-imaging study found a specific pattern of signals in the cingulate cortex which differs in individuals with ASD.[30]Even more recently, evidence suggests that an entire network of brain regions involved in social and emotional processing, the default network or "Default mode" Network (DMN), shows reduced functional connectivity. In other words, the brain regions do not communicate in the same way that they would in a typical brain. [31] Two main hubs of the DMN, the posterior cingulate cortex and medial prefrontal cortex, appear to be hypoactive relative to neurotypical adults, which may disrupt the functioning of the entire network. [31] Dysfunction in DMN connectivity is prominent in adolescents and young adults with autism, suggesting that manifestation of DMN dysfunction may occur early in development.[31] In contrast to the dysfunction in the DMN network, intact connectivity has been observed in a “central executive” network that is involved in sustained attention, cognitive control, and goal-directed thinking. In people with autism, this network (often called the task-positive network) and the DMN are not negatively correlated in time (as has been found in typical adults), suggesting a possible imbalance in switching between the two networks, and possibly reflecting a disturbance of self-referential thought.[32]

Salience Network
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The Salience Network (SN) is a network that is anchored in the anterior cingulate and the anterior insula. This network is thought to be involved in detecting, integrating, and filtering relevant interoceptive, autonomic, and emotional information to guide attention and action.[33] The SN also includes two important subcortical structures: the amygdala and the substantia nigra/ventral tegmental area. These structures are thought to play a major role in detecting emotional and reward salience. Both functional MRI studies of social processing [29] and MRI studies that measure the size of brain regions[31] have shown dysfunction of the SN in individuals with autism. One of the regions consistently showing significant hypoactivity in autism is the right anterior insula[31]. Dysfunction in this network may result in problems using internal body sensations to guide attention to salient social and other events, with significant consequences for both cognition and self-monitoring [34],.

Recent studies demonstrate that in the typical brain the anterior insula provides an altering signal to initiate appropriate responses to salient stimuli. [31] Because the anterior insula is underactive during social processing in individuals with autism,[35] ineffective salience mapping of socially relevant cues may result in atypical social interactions.[29] In contrast, hyperactivity of the anterior insula has been consistently implicated in anxiety disorders.[36] [37] The anterior insula is proposed to play a key role in experiencing negative and worrisome thoughts, as well as coordinating avoidance behaviors in individuals prone to anxiety.[36] These are noteworthy findings because anxiety disorders are a common comorbid feature of many disorders, including autism.[31] Therefore, hyperactivity of the anterior insula or other nodes of the SN may lead to pathologically enhanced salience detection in some situations[31] (but not others). These findings may give explanation to many of the phenotypic or behavioral presentations of the disorder. For instance, symptoms like stimulatory behavior, increased anxiety, or neuroticism may be consequence of the anterior insula misattributing emotional salience to mundane events.[31]

Triple Network Model
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Because the default mode network, the salience network, and the central executive networks discussed above appear to underlie prominent features of many major psychiatric and neurological disorders (including autism, schizophrenia, ADHD, AD, FTD, depression and epilepsy),[38] a common framework was recently proposed for understanding dysfunction across disorders: the Triple Network Model.[31] This model proposes that deficits in engaging and disengaging these networks play a significant role in many disorders, including autism. By studying networks instead of specific brain regions, it may be possible to gain new insights into understanding dysfunction across a number of disorders.[31]

A significant number of disorders have symptoms that overlap with autism spectrum disorders, and autism spectrum diagnoses tend to be comorbid with other disorders. For instance, many individuals with autism may also be diagnosed with or show symptoms of depression, anxiety, obsessive-compulsive tendencies, and more.[38] The Triple Network Model framework may help us understand why these comorbidities occur, and allow us to tailor interventions. Designing individualized interventions is important because autism manifests differently across individuals, often varying from individual to individual. Researchers focusing on the etiology of autism are beginning to recognize that symptoms cannot be ascribed to the isolated operations of single brain areas.[31] The Triple Network Model reflects a shift from studying specific brain region to studying coordinated brain networks. While it may remain unclear what initially causes the disturbances in brain function that characterize autism, understanding how they manifest in large-scale network function may provide insights into predicting dysfunctional behavior patterns and designing appropriate interventions, for autism as well as for a wide range of other psychopathologies.[31]

Additional theories
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Underconnectivity theory
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The underconnectivity theory of autism hypothesizes that autism is marked by underfunctioning high-level neural connections and synchronization, along with an excess of low-level processes.[39] Evidence for this theory has been found in functional neuroimaging studies on autistic individuals[40] and by a brainwave study that suggested that adults with ASD have local overconnectivity in the cortex and weak functional connections between the frontal lobe and the rest of the cortex.[41] Other evidence suggests the underconnectivity is mainly within each hemisphere of the cortex and that autism is a disorder of the association cortex.[42]

Stimuli processing in Autism
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From studies based on event-related potentials, transient changes to the brain's electrical activity in response to stimuli, there is considerable evidence for differences in autistic individuals with respect to attention, orientation to auditory and visual stimuli, novelty detection, language and face processing, and information storage; several studies have found a preference for nonsocial stimuli.[43] For example, magnetoencephalography studies have found evidence in autistic children of delayed responses in the brain's processing of auditory signals.[44]

Autism and schizophrenia
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In the genetic area, relations have been found between autism and schizophrenia based on duplications and deletions of chromosomes; research showed that schizophrenia and autism are significantly more common in combination with 1q21.1 deletion syndrome. Research on autism/schizophrenia relations for chromosome 15 (15q13.3), chromosome 16 (16p13.1) and chromosome 17 (17p12) are inconclusive.[45]

Neuropsychology

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Two major categories of cognitive theories have been proposed about the links between autistic brains and behavior.

The first category focuses on deficits in social cognition. The empathizing–systemizing theory postulates that autistic individuals can systemize—that is, they can develop internal rules of operation to handle events inside the brain—but are less effective at empathizing by handling events generated by other agents. An extension, the extreme male brain theory, hypothesizes that autism is an extreme case of the male brain, defined psychometrically as individuals in whom systemizing is better than empathizing;[46] this extension is controversial, as many studies contradict the idea that baby boys and girls respond differently to people and objects.[47]

These theories are somewhat related to the earlier theory of mind approach, which hypothesizes that autistic behavior arises from an inability to ascribe mental states to oneself and others. The theory of mind hypothesis is supported by autistic children's atypical responses to the Sally–Anne test for reasoning about others' motivations,[46] and the mirror neuron system theory of autism described in Pathophysiology maps well to the hypothesis.[24] However, most studies have found no evidence of impairment in autistic individuals' ability to understand other people's basic intentions or goals; instead, data suggests that impairments are found in understanding more complex social emotions or in considering others' viewpoints.[48]

The second category focuses on nonsocial or general processing: the executive functions such as working memory, planning, inhibition. In his review, Kenworthy states that "the claim of executive dysfunction as a causal factor in autism is controversial", however, "it is clear that executive dysfunction plays a role in the social and cognitive deficits observed in individuals with autism".[49] Tests of core executive processes such as eye movement tasks indicate improvement from late childhood to adolescence, but performance never reaches typical adult levels.[50] A strength of the theory is predicting stereotyped behavior and narrow interests;[51] two weaknesses are that executive function is hard to measure[49] and that executive function deficits have not been found in young autistic children.[52]

Weak central coherence theory hypothesizes that a limited ability to see the big picture underlies the central disturbance in autism. One strength of this theory is predicting special talents and peaks in performance in autistic people.[53] A related theory—enhanced perceptual functioning—focuses more on the superiority of locally oriented and perceptual operations in autistic individuals.[54] These theories map well from the underconnectivity theory of autism.

Neither category is satisfactory on its own; social cognition theories poorly address autism's rigid and repetitive behaviors, while the nonsocial theories have difficulty explaining social impairment and communication difficulties.[55] A combined theory based on multiple deficits may prove to be more useful.[56]


  1. ^ Penn HE. Neurobiological correlates of autism: a review of recent research. Child Neuropsychol. 2006;12(1):57–79. doi:10.1080/09297040500253546. PMID 16484102.
  2. ^ Cite error: The named reference London was invoked but never defined (see the help page).
  3. ^ a b Amaral DG, Schumann CM, Nordahl CW. Neuroanatomy of autism. Trends Neurosci. 2008;31(3):137–45. doi:10.1016/j.tins.2007.12.005. PMID 18258309.
  4. ^ Geschwind DH. Autism: many genes, common pathways? Cell. 2008;135(3):391–5. doi:10.1016/j.cell.2008.10.016. PMID 18984147.
  5. ^ Müller RA. The study of autism as a distributed disorder. Ment Retard Dev Disabil Res Rev. 2007;13(1):85–95. doi:10.1002/mrdd.20141. PMID 17326118.
  6. ^ Cite error: The named reference Arndt was invoked but never defined (see the help page).
  7. ^ Casanova MF. The neuropathology of autism. Brain Pathol. 2007;17(4):422–33. doi:10.1111/j.1750-3639.2007.00100.x. PMID 17919128.
  8. ^ Cite error: The named reference Geschwind-2009 was invoked but never defined (see the help page).
  9. ^ Courchesne E, Pierce K, Schumann CM et al. Mapping early brain development in autism. Neuron. 2007;56(2):399–413. doi:10.1016/j.neuron.2007.10.016. PMID 17964254.
  10. ^ a b Schmitz C, Rezaie P. The neuropathology of autism: where do we stand? Neuropathol Appl Neurobiol. 2008;34(1):4–11. doi:10.1111/j.1365-2990.2007.00872.x. PMID 17971078.
  11. ^ a b c Persico AM, Bourgeron T. Searching for ways out of the autism maze: genetic, epigenetic and environmental clues. Trends Neurosci. 2006;29(7):349–58. doi:10.1016/j.tins.2006.05.010. PMID 16808981.
  12. ^ Südhof TC. Neuroligins and neurexins link synaptic function to cognitive disease. Nature. 2008;455(7215):903–11. doi:10.1038/nature07456. PMID 18923512.
  13. ^ Kelleher RJ 3rd, Bear MF. The autistic neuron: troubled translation? Cell. 2008;135(3):401–6. doi:10.1016/j.cell.2008.10.017. PMID 18984149.
  14. ^ Bear MF, Dölen G, Osterweil E, Nagarajan N. Fragile X: translation in action. Neuropsychopharmacology. 2008;33(1):84–7. doi:10.1038/sj.npp.1301610. PMID 17940551.
  15. ^ Tuchman R, Moshé SL, Rapin I. Convulsing toward the pathophysiology of autism. Brain Dev. 2009;31(2):95–103. doi:10.1016/j.braindev.2008.09.009. PMID 19006654.
  16. ^ Ashwood P, Wills S, Van de Water J. The immune response in autism: a new frontier for autism research. J Leukoc Biol. 2006;80(1):1–15. doi:10.1189/jlb.1205707. PMID 16698940.
  17. ^ Stigler KA, Sweeten TL, Posey DJ, McDougle CJ. Autism and immune factors: a comprehensive review. Res Autism Spectr Disord. 2009;3(4):840–60. doi:10.1016/j.rasd.2009.01.007.
  18. ^ Wills S, Cabanlit M, Bennett J, Ashwood P, Amaral D, Van de Water J. Autoantibodies in autism spectrum disorders (ASD). Ann N Y Acad Sci. 2007;1107:79–91. doi:10.1196/annals.1381.009. PMID 17804535.
  19. ^ Levy SE, Mandell DS, Schultz RT. Autism. Lancet. 2009;374(9701):1627–38. doi:10.1016/S0140-6736(09)61376-3. PMID 19819542.
  20. ^ Dölen G, Osterweil E, Rao BS, Smith GB, Auerbach BD, Chattarji S, Bear MF. Correction of fragile X syndrome in mice. Neuron. 2007;56(6):955–62. doi:10.1016/j.neuron.2007.12.001. PMID 18093519.
  21. ^ Hughes JR. A review of recent reports on autism: 1000 studies published in 2007. Epilepsy Behav. 2008;13(3):425–37. doi:10.1016/j.yebeh.2008.06.015. PMID 18627794.
  22. ^ Cite error: The named reference Manzi was invoked but never defined (see the help page).
  23. ^ MNS and autism:
  24. ^ a b Iacoboni M, Dapretto M. The mirror neuron system and the consequences of its dysfunction. Nat Rev Neurosci. 2006;7(12):942–51. doi:10.1038/nrn2024. PMID 17115076.
  25. ^ Frith U, Frith CD. Development and neurophysiology of mentalizing [PDF]. Philos Trans R Soc Lond B Biol Sci. 2003;358(1431):459–73. doi:10.1098/rstb.2002.1218. PMID 12689373. PMC 1693139.
  26. ^ Hamilton AFdC. Emulation and mimicry for social interaction: a theoretical approach to imitation in autism. Q J Exp Psychol. 2008;61(1):101–15. doi:10.1080/17470210701508798. PMID 18038342.
  27. ^ Powell K. Opening a window to the autistic brain. PLoS Biol. 2004;2(8):E267. doi:10.1371/journal.pbio.0020267. PMID 15314667. PMC 509312.
  28. ^ Di Martino A, Ross K, Uddin LQ, Sklar AB, Castellanos FX, Milham MP. Functional brain correlates of social and nonsocial processes in autism spectrum disorders: an activation likelihood estimation meta-analysis. Biol Psychiatry. 2009;65(1):63–74. doi:10.1016/j.biopsych.2008.09.022. PMID 18996505.
  29. ^ a b c Di Martino A, Ross K, Uddin LQ, Sklar AB, Castellanos FX, Milham MP. Functional brain correlates of social and nonsocial processes in autism spectrum disorders: an activation likelihood estimation meta-analysis. Biol Psychiatry. 2009;65(1):63–74. doi:10.1016/j.biopsych.2008.09.022. PMID 18996505.
  30. ^ Chiu PH, Kayali MA, Kishida KT et al. Self responses along cingulate cortex reveal quantitative neural phenotype for high-functioning autism. Neuron. 2008;57(3):463–73. doi:10.1016/j.neuron.2007.12.020. PMID 18255038. Lay summary: Technol Rev, 2007-02-07.
  31. ^ a b c d e f g h i j k l m Menon, V. (2011). Large-scale brain networks and psychopathology: a unifying triple network model. Trends In Cognitive Sciences, 15(10), 483-506. doi:10.1016/j.tics.2011.08.003
  32. ^ Broyd SJ, Demanuele C, Debener S, Helps SK, James CJ, Sonuga-Barke EJS. Default-mode brain dysfunction in mental disorders: a systematic review. Neurosci Biobehav Rev. 2009;33(3):279–96. doi:10.1016/j.neubiorev.2008.09.002. PMID 18824195.
  33. ^ Seeley, W.W. et al. (2007) Dissociable intrinsic connectivity networks for salience processing and executive control. J. Neurosci. 27, 2349–2356
  34. ^ Menon, V. and Uddin, L.Q. (2010) Saliency, switching, attention and control: a network model of insula function. Brain Struct. Funct. 214, 655–667
  35. ^ Uddin, L.Q. and Menon, V. (2009) The anterior insula in autism: under-connected and under-examined. Neurosci. Biobehav. Rev. 33, 1198–1203
  36. ^ a b Paulus, M.P. and Stein, M.B. (2006) An insular view of anxiety. Biol. Psychiatry 60, 383–387
  37. ^ Stein, M.B. et al. (2007) Increased amygdala and insula activation during emotion processing in anxiety-prone subjects. Am. J. Psychiatry 164, 318–327
  38. ^ a b Kring, A. M., Davison, G. C., Neale, J. M., & Johnson, S. (2007). Abnormal psychology. Wiley.
  39. ^ Just MA, Cherkassky VL, Keller TA, Kana RK, Minshew NJ. Functional and anatomical cortical underconnectivity in autism: evidence from an FMRI study of an executive function task and corpus callosum morphometry. Cereb Cortex. 2007;17(4):951–61. doi:10.1093/cercor/bhl006. PMID 16772313.
  40. ^ Williams DL, Goldstein G, Minshew NJ. Neuropsychologic functioning in children with autism: further evidence for disordered complex information-processing. Child Neuropsychol. 2006;12(4–5):279–98. doi:10.1080/09297040600681190. PMID 16911973.
  41. ^ Murias M, Webb SJ, Greenson J, Dawson G. Resting state cortical connectivity reflected in EEG coherence in individuals with autism. Biol Psychiatry. 2007;62(3):270–3. doi:10.1016/j.biopsych.2006.11.012. PMID 17336944.
  42. ^ Minshew NJ, Williams DL. The new neurobiology of autism: cortex, connectivity, and neuronal organization. Arch Neurol. 2007;64(7):945–50. doi:10.1001/archneur.64.7.945. PMID 17620483.
  43. ^ Jeste SS, Nelson CA 3rd. Event related potentials in the understanding of autism spectrum disorders: an analytical review. J Autism Dev Disord. 2009;39(3):495–510. doi:10.1007/s10803-008-0652-9. PMID 18850262.
  44. ^ Roberts TP, Schmidt GL, Egeth M et al. Electrophysiological signatures: magnetoencephalographic studies of the neural correlates of language impairment in autism spectrum disorders. Int J Psychophysiol. 2008;68(2):149–60. doi:10.1016/j.ijpsycho.2008.01.012. PMID 18336941.
  45. ^ Crespi B, Stead P, Elliot M. Evolution in health and medicine Sackler colloquium: Comparative genomics of autism and schizophrenia. Proc. Natl. Acad. Sci. U.S.A.. 2010;107(Suppl 1):1736–41. doi:10.1073/pnas.0906080106. PMID 19955444.
  46. ^ a b Baron-Cohen S. Autism: the empathizing–systemizing (E-S) theory [PDF]. Ann N Y Acad Sci. 2009 [archived May 13, 2012];1156:68–80. doi:10.1111/j.1749-6632.2009.04467.x. PMID 19338503.
  47. ^ Spelke ES. Sex differences in intrinsic aptitude for mathematics and science?: a critical review [PDF]. Am Psychol. 2005;60(9):950–8. doi:10.1037/0003-066X.60.9.950. PMID 16366817.
  48. ^ Hamilton AFdC. Goals, intentions and mental states: challenges for theories of autism. J Child Psychol Psychiatry. 2009;50(8):881–92. doi:10.1111/j.1469-7610.2009.02098.x. PMID 19508497.
  49. ^ a b Kenworthy L, Yerys BE, Anthony LG, Wallace GL. Understanding executive control in autism spectrum disorders in the lab and in the real world. Neuropsychol Rev. 2008;18(4):320–38. doi:10.1007/s11065-008-9077-7. PMID 18956239.
  50. ^ O'Hearn K, Asato M, Ordaz S, Luna B. Neurodevelopment and executive function in autism. Dev Psychopathol. 2008;20(4):1103–32. doi:10.1017/S0954579408000527. PMID 18838033.
  51. ^ Hill EL. Executive dysfunction in autism. Trends Cogn Sci. 2004;8(1):26–32. doi:10.1016/j.dr.2004.01.001. PMID 14697400.
  52. ^ Cite error: The named reference Sigman was invoked but never defined (see the help page).
  53. ^ Happé F, Frith U. The weak coherence account: detail-focused cognitive style in autism spectrum disorders. J Autism Dev Disord. 2006;36(1):5–25. doi:10.1007/s10803-005-0039-0. PMID 16450045.
  54. ^ Mottron L, Dawson M, Soulières I, Hubert B, Burack J. Enhanced perceptual functioning in autism: an update, and eight principles of autistic perception. J Autism Dev Disord. 2006;36(1):27–43. doi:10.1007/s10803-005-0040-7. PMID 16453071.
  55. ^ Happé F, Ronald A, Plomin R. Time to give up on a single explanation for autism. Nat Neurosci. 2006;9(10):1218–20. doi:10.1038/nn1770. PMID 17001340.
  56. ^ Rajendran G, Mitchell P. Cognitive theories of autism. Dev Rev. 2007;27(2):224–60. doi:10.1016/j.dr.2007.02.001.
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