Autism pathophysiology

Jump to: navigation, search

Autism Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Autism from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Criteria

History and Symptoms

Physical Examination

Laboratory Findings

CT

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Behavioral Therapy

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Autism pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Autism pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Autism pathophysiology

CDC on Autism pathophysiology

Autism pathophysiology in the news

Blogs on Autism pathophysiology

Directions to Hospitals Treating Type page name here

Risk calculators and risk factors for Autism pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]

Overview

Despite extensive investigation, 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.

Pathophysiology

  • Autism appears to result from developmental factors that affect many or all functional brain systems,[2] and leads to disruption in the development of the brain.[3]
  • Neuroanatomical studies and study in the area on genetic inheritance have suggested that autism occurs after conception.
  • Enviromental factors play an important role in the development of autism after an anomaly in the brain leads to activation of pathological pathways.[4]

Structural changes in the brain

  • Although many major structures of the human brain have been implicated, almost all postmortem studies have been of individuals who also had mental retardation, making it difficult to draw conclusions.[3]
  • Brain weight and volume and head circumference tend to be greater in autistic children.[5]
  • The cellular and molecular bases f pathological early overgrowth are not known, nor is it known whether the overgrown neural systems cause autism's characteristic signs.

Major mechanisms

Heterochrony (disturbed neural migration)

  • The sensory and motor deficits associated with autism seem to be secondary to developmental change in the rate of events during division of germinal cells leading to abnormal migration of daughter cells to their target regions

Immune system disruption

  • GI abnormalities and immune imbalance have been known to be involved in the parthenogenesis of autism. Repeated GI infections may also lead to an immune imbalance.
  • Neuroinflammation consist of activation of microglial cells and innate neuroimmune system. The effectors of neuroimmune system have been found in the brain and cerebrospinal fluid (CSF) of ASD patient[9]
  • Interactions between the immune system and the nervous system begin early during embryogenesis, and successful neurodevelopment depends on a balanced immune response.
  • Several symptoms consistent with a poorly regulated immune response have been reported in autistic children.
  • It is possible that aberrant immune activity during critical periods of neurodevelopment is part of the mechanism of some forms of ASD.[10]
  • As autoantibodies have not been associated with pathology, are found in diseases other than ASD, and are not always present in ASD,[11] the relationship between immune disturbances and autism remains unclear and controversial.[7]
  • Several neurotransmitter abnormalities have been detected in autism, notably increased blood levels of serotonin. Whether these lead to structural or behavioral abnormalities is unclear.[1]
  • Also, some inborn errors of metabolism are associated with autism but probably account for less than 5% of cases.

Mirror neuron system theory

  • The mirror neuron system (MNS) theory of autism hypothesizes that distortion in the development of the MNS plays a major role in the development of impairment in social and communication skills.
  • The MNS operates when an animal performs an action or observes another animal of the same species perform the same action.
  • The MNS may contribute to an individual's understanding of other people by mimicing their behavior via embodied simulation of their actions, intentions, and emotions.[12]
  • 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's. The level of reduced functionality of the mirror neuron system directly correlates with the severity of autism.[13]
  • However, individuals with autism also have abnormal brain activation in many circuits outside the MNS[14] Despite the mirror neuron theory, children suffering from autism are able to imitate goal-directed behaviors.[15]

Task negative network

  • A 2008 study of autistic adults found evidence for altered functional organization of the task-negative network, a large-scale brain network involved in social and emotional processing, with intact organization of the task-positive network, used in sustained attention and goal-directed thinking.[16]
  • A 2008 brain-imaging study found a specific pattern of signals in the cingulate cortex which differs in individuals with ASD.[17]

Disruptions in high level neural connections and synchronization

  • 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.[18]
  • Evidence for this theory has been found in functional neuroimaging studies on autistic individuals[19] and by a brain wave 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.[20]
  • Other evidence suggests the underconnectivity is mainly within each hemisphere of the cortex and that autism is a disorder of the association cortex.[21]

Neuropsychology

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.
  • Hyper-systemizing hypothesizes that autistic individuals can systematize—that is, they can develop internal rules of operation to handle internal events—but are less effective at empathizing by handling events generated by other agents.[22]
  • It extends the extreme male brain theory, which hypothesizes that autism is an extreme case of the male brain, defined psychometrically as individuals in whom systemizing is better than empathizing.[23]
  • This in turn is related to the earlier theory of mind, which hypothesizes that autistic behavior arises from an inability to ascribe mental states to oneself and others.
  • The theory of mind is supported by autistic children's atypical responses to the Sally-Anne test for reasoning about others' motivations,[24] and is mapped well from the mirror neuron system theory of autism.[13]
  • The second category focuses on nonsocial or general processing. Executive dysfunction hypothesizes that autistic behavior results in part from deficits in flexibility, planning, and other forms of executive function.
  • A strength of the theory is predicting stereotyped behavior and narrow interests;[25] a weakness is that executive function deficits are not found in young autistic children.
  • 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.[26]
  • A related theory—enhanced perceptual functioning—focuses more on the superiority of locally oriented and perceptual operations in autistic individuals.[27]
  • 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.[28]
  • A combined theory based on multiple deficits may prove to be more useful.[29]

Associated Conditions

Bipolar Disorder

Bipolar disorder, or manic-depression, is itself comorbid with a number of conditions, including autism.[32] Autism includes some symptoms commonly found in mood and anxiety disorders.[33]

Bowel Disease

Some children with autism also have gastrointestinal (GI) symptoms, but there is a lack of published rigorous data to support the theory that autistic children have more or different GI symptoms than usual.[34] It has been claimed that up to fifty percent of children with autism experience persistent gastrointestinal tract problems, ranging from mild to moderate degrees of inflammation in both the upper and lower intestinal tract. This has been described as a syndrome, autistic enterocolitis, by Dr. Andrew Wakefield; this diagnostic terminology, however, has been questioned by medical experts. Constipation, often with overflow, or encopresis, is often associated with developmental disorders in children, and is often difficult to resolve, especially among those with behavioral and communication problems.[35]

Depression and Anxiety Disorders

Phobias, depression and other psychopathological disorders have often been described along with ASD but this has not been assessed systematically.[36]

Fragile X Syndrome

Fragile X syndrome is the most common inherited form of mental retardation. It was so named because one part of the X chromosome has a defective piece that appears pinched and fragile when under a microscope. Fragile X syndrome affects about two to five percent of people with ASD.[citation needed] It is important to have an autistic checked for Fragile X, especially if the parents are considering having another child. If one child has Fragile X, there is a one-in-two chance that boys born to the same parents will have Fragile X (see Mendelian genetics).[citation needed] Other members of the family who may be contemplating having a child may also wish to be checked for the syndrome.

Hyperactivity and Attention Abnormalities

Attention-deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed and controversial neuropsychiatric disorders among children, and is increasingly recognized as afflicting adults as well. Its symptoms include inattention, hyperactivity, and impulsivity. According to sources such as the CDC, the causes are currently unknown, and it is thought that the term covers a variety of related disorders. There is no single medical test that can accurately diagnose ADHD, though there are assessment tools.

Mental Retardation

Autism is associated with mental retardation: a 2001 British study of 26 autistic children found about 30% with intelligence in the normal range (IQ above 70), 50% with mild to moderate retardation, and about 20% with severe to profound retardation (IQ below 35). For ASD other than autism the association is much weaker: the same study reported about 94% of 65 children with PDD-NOS or Asperger's had normal intelligence.[37] When tested, some areas of ability may be normal or superior, while others may be especially weak. For example, an autistic individual may do well on the parts of the test that measure visual skills but earn low scores on the language subtests.[38]

A 2006 review questioned the common assumption that most children with autism are mentally retarded.[39] It is possible that the association between mental retardation and autism is not because they usually have common causes, but because the presence of both makes it more likely that both will be diagnosed.[40]

Neuroinflammation and Immune Disorders

The role of the immune system and neuroinflammation in the development of autism is controversial. Until recently, there was scant evidence supporting immune hypotheses, but research into the role of immune response and neuroinflammation may have important clinical and therapeutic implications. The exact role of heightened immune response in the central nervous system (CNS) of patients with autism is uncertain, but may be a primary factor in triggering and sustaining many of the comorbid conditions associated with autism. Recent studies indicate the presence of heightened neuroimmune activity in both the brain tissue and the cerebrospinal fluid of patients with autism, supporting the view that heightened immune response may be an essential factor in the onset of autistic symptoms.[41]

Nonverbal Learning Disorder

In Nonverbal learning disorder (NLD) there are a number of over-lapping signs and symptoms of Savant Syndrome traits and behaviors in some youngsters. Of special interest, however, is the observation and debate about the overlap particularly between NLD and the clinical characteristics of Asperger's Disorder, such as high verbal abilities, compromised motor and coordination abilities, and unique social and relationship difficulties. Clinically, Asperger's is part of the autistic spectrum. It has also been postulated that Asperger's is in fact a part of the far end spectrum of Nonverbal Learning Disorders. Proponents of this analysis point out that as high as 80% of Asperger's Disorder persons have neuro-psychological profiles consistent with NLD. Fitzgerald and Corvin have argued that the diagnosis of Asperger's is more useful clinically, and that NLD is "an example of excessive diagnostic splitting.

Motor Clumsiness

The initial accounts of Asperger syndrome[42] and other diagnostic schemes[43] include descriptions of motor clumsiness. Children with ASD may be delayed in acquiring motor skills that require motor dexterity, such as bicycle riding or opening a jar, and may appear awkward or "uncomfortable in their own skin". They may be poorly coordinated, or have an odd or bouncy gait or posture, poor handwriting, or problems with visual-motor integration, visual-perceptual skills, and conceptual learning.[42][44] They may show problems with proprioception (sensation of body position) on measures of apraxia (motor planning disorder), balance, tandem gait, and finger-thumb apposition.[42]

Obsessive-compulsive Disorder

Obsessive-compulsive disorder is characterized by recurrent obsessional thoughts or compulsive acts. Obsessional thoughts are ideas, images or impulses that enter the individual's mind again and again in a stereotyped form. They are almost invariably distressing (because they are violent or obscene, or simply because they are perceived as senseless) and the sufferer often tries, unsuccessfully, to resist them. They are, however, recognized as the individual's own thoughts, even though they are involuntary and often repugnant.

Compulsive acts or rituals are stereotyped behaviours that are repeated again and again. They are not inherently enjoyable, nor do they result in the completion of inherently useful tasks. It must be recognized that this is different from the obsessions that are a feature of autism spectrum disorders in that the obsessions are not enjoyable or in any way beneficial, which can sometimes be the case with autism, for instance an obsession to study an interest.

Tourette Syndrome

The prevalence of Tourette syndrome among individuals with autism is estimated to be 6.5%, higher than the 2% to 3% prevalence for the general population. Several hypotheses for this association have been advanced, including common genetic factors and dopamine or serotonin abnormalities.[31]

Seizures

ASD is also associated with epilepsy, with variations in risk of epilepsy due to age, cognitive level, and type of language disorder.[45][46] One in four autistic children develops seizures, often starting either in early childhood or adolescence.[citation needed] Seizures, caused by abnormal electrical activity in the brain, can produce a temporary loss of consciousness (a "blackout"), a body convulsion, unusual movements, or staring spells. Sometimes a contributing factor is a lack of sleep or a high fever. An EEG can help confirm the seizure's presence.

Sensory Problems

  1. REDIRECT Template:Further
  • From a page move: This is a redirect from a page that has been moved (renamed). This page was kept as a redirect to avoid breaking links, both internal and external, that may have been made to the old page name.

Unusual responses to sensory stimuli are more common and prominent in autistic children, although there is no good evidence that sensory symptoms differentiate autism from other developmental disorders.[47] The responses may be more common in children: a pair of studies found that autistic children had impaired tactile perception while autistic adults did not. The same two studies also found that autistic individuals had more problems with complex memory and reasoning tasks such as Twenty Questions; these problems were somewhat more marked among adults.[48] Several studies have reported associated motor problems that include poor muscle tone, poor motor planning, and toe walking; ASD is not associated with severe motor disturbances.[49]

Tuberous Sclerosis

Tuberous sclerosis is a rare genetic disorder that causes benign tumors to grow in the brain as well as in other vital organs. It has a consistently strong association with the autism spectrum. One to four percent of autistic people also have tuberous sclerosis.[citation needed] Studies have reported that between 25% and 61% of individuals with tuberous sclerosis meet the diagnostic criteria for autism with an even higher proportion showing features of a broader pervasive developmental disorder.[50]

Metabolic Conditions

Several metabolic defects, such as phenylketonuria, are associated with autistic symptoms.[51]

Genetics

Syndromic autism

The following genes have been implicated in the development of autism phenotype in the presence of intellectual and other abnormalities of the syndrome producing the autistic phenotype:

Syndrome Gene involved Major abnormalities
Fragile X syndrome FMR1
  • Large protruding ears
  • Long face
  • Macro-orchidism
  • Developmental delay
  • Attention problem
  • ASD
Rett's syndrome MECP2
Tuberous sclerosis TSC1, TSC2
Neurofibromatosis 1 NF1
Cohen syndrome COH1
Timothy syndrome CACNA1C
Smith--Lemli-Opitz syndrome DHCR7
  • Bitemporal narrowing
  • Upturned nose
  • Micrognathia
  • Finger and feet abnormalities
  • Developmental delay
  • Learning disability
  • Hand mannerisms
Williams Beuren syndrome 7q11.23 deletion
Prader-Willi syndrome 15q11-q13 deletion (paternal)
Angelman syndrome 15q11-q13 deletion (maternal)

Gross pathology

On gross pathology, brains of patients suffering from autism exhibit the following findings:

Microscopic pathology

On microscopy, autism and autism spectrum disorders show abnormalities of the following regions of the brain:[52]

References

  1. 1.0 1.1 Penn HE (2006). "Neurobiological correlates of autism: a review of recent research". Child Neuropsychol. 12 (1): 57–79. doi:10.1080/09297040500253546. PMID 16484102.
  2. 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.
  3. 3.0 3.1 Amaral DG, Schumann CM, Nordahl CW (2008). "Neuroanatomy of autism". Trends Neurosci. 31 (3): 137–45. doi:10.1016/j.tins.2007.12.005. PMID 18258309.
  4. Casanova MF (2007). "The neuropathology of autism". Brain Pathol. 17 (4): 422–33. doi:10.1111/j.1750-3639.2007.00100.x. PMID 17919128.
  5. DiCicco-Bloom E, Lord C, Zwaigenbaum L; et al. (2006). "The developmental neurobiology of autism spectrum disorder". J Neurosci. 26 (26): 6897–906. doi:10.1523/JNEUROSCI.1712-06.2006. PMID 16807320.
  6. Courchesne E, Pierce K, Schumann CM; et al. (2007). "Mapping early brain development in autism". Neuron. 56 (2): 399–413. doi:10.1016/j.neuron.2007.10.016. PMID 17964254.
  7. 7.0 7.1 Schmitz C, Rezaie P (2008). "The neuropathology of autism: where do we stand?". Neuropathol Appl Neurobiol. 34 (1): 4–11. doi:10.1111/j.1365-2990.2007.00872.x. PMID 17971078.
  8. 8.0 8.1 8.2 Persico AM, Bourgeron T (2006). "Searching for ways out of the autism maze: genetic, epigenetic and environmental clues". Trends Neurosci. 29 (7): 349–58. doi:10.1016/j.tins.2006.05.010. PMID 16808981.
  9. Pardo CA, Vargas DL, Zimmerman AW (December 2005). "Immunity, neuroglia and neuroinflammation in autism". Int Rev Psychiatry. 17 (6): 485–95. doi:10.1080/02646830500381930. PMID 16401547.
  10. Ashwood P, Wills S, Van de Water J (2006). "The immune response in autism: a new frontier for autism research". J Leukoc Biol. 80 (1): 1–15. doi:10.1189/jlb.1205707. PMID 16698940.
  11. Wills S, Cabanlit M, Bennett J, Ashwood P, Amaral D, Van de Water J (2007). "Autoantibodies in autism spectrum disorders (ASD)". Ann N Y Acad Sci. 1107: 79–91. doi:10.1196/annals.1381.009. PMID 17804535.
  12. MNS and autism:
  13. 13.0 13.1 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.
  14. Frith U, Frith CD (2003). "Development and neurophysiology of mentalizing" (PDF). Philos Trans R Soc Lond B Biol Sci. 358 (1431): 459–73. doi:10.1098/rstb.2002.1218. PMID 12689373.
  15. Hamilton AFdC (2008). "Emulation and mimicry for social interaction: a theoretical approach to imitation in autism". Q J Exp Psychol. 61 (1): 101–15. doi:10.1080/17470210701508798. PMID 18038342.
  16. Kennedy DP, Courchesne E (2008). "The intrinsic functional organization of the brain is altered in autism". Neuroimage. 38 (4): 1877–85. doi:10.1016/j.neuroimage.2007.10.052. PMID 18083565.
  17. Chiu PH, Kayali MA, Kishida KT; et al. (2008). "Self responses along cingulate cortex reveal quantitative neural phenotype for high-functioning autism". Neuron. 57 (3): 463–73. doi:10.1016/j.neuron.2007.12.020. PMID 18255038. Lay summaryTechnol Rev (2007-02-07).
  18. 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.
  19. Williams DL, Goldstein G, Minshew NJ (2006). "Neuropsychologic functioning in children with autism: further evidence for disordered complex information-processing". Child Neuropsychol. 12 (4–5): 279–98. doi:10.1080/09297040600681190. PMC 1803025. PMID 16911973.
  20. Murias M, Webb SJ, Greenson J, Dawson G (2007). "Resting state cortical connectivity reflected in EEG coherence in individuals with autism". Biol Psychiatry. 62 (3): 270–3. doi:10.1016/j.biopsych.2006.11.012. PMID 17336944.
  21. Minshew NJ, Williams DL (2007). "The new neurobiology of autism: cortex, connectivity, and neuronal organization". Arch Neurol. 64 (7): 945–50. PMID 17620483.
  22. 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.
  23. Baron-Cohen S (2002). "The extreme male brain theory of autism". Trends Cogn Sci. 6 (6): 248–54. doi:10.1016/S1364-6613(02)01904-6. PMID 12039606.
  24. 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.
  25. Hill EL (2004). "Executive dysfunction in autism". Trends Cogn Sci. 8 (1): 26–32. doi:10.1016/j.dr.2004.01.001. PMID 14697400.
  26. 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.
  27. 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.
  28. 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.
  29. Rajendran G, Mitchell P (2007). "Cognitive theories of autism". Dev Rev. 27 (2): 224–60. doi:10.1016/j.dr.2007.02.001.
  30. Folstein SE, Rosen-Sheidley B (2001). "Genetics of autism: complex aetiology for a heterogeneous disorder". Nat Rev Genet. 2 (12): 943–55. doi:10.1038/35103559. PMID 11733747.
  31. 31.0 31.1 Zafeiriou DI, Ververi A, Vargiami E (2007). "Childhood autism and associated comorbidities". Brain Dev. 29 (5): 257–72. doi:10.1016/j.braindev.2006.09.003. PMID 17084999.
  32. McElroy SL (2004). "Diagnosing and treating comorbid (complicated) bipolar disorder". The Journal of clinical psychiatry. 65 Suppl 15: 35–44. PMID 15554795.
  33. Towbin KE, Pradella A, Gorrindo T, Pine DS, Leibenluft E (2005). "Autism spectrum traits in children with mood and anxiety disorders". Journal of child and adolescent psychopharmacology. 15 (3): 452–64. doi:10.1089/cap.2005.15.452. PMID 16092910.
  34. Erickson CA, Stigler KA, Corkins MR, Posey DJ, Fitzgerald JF, McDougle CJ (2005). "Gastrointestinal factors in autistic disorder: a critical review". J Autism Dev Disord. 35 (6): 713–27. doi:10.1007/s10803-005-0019-4. PMID 16267642.
  35. Encopresis, University of Iowa Health Care, Center for Disabilities and Development, accessed August 17, 2006
  36. Matson JL, Nebel-Schwalm MS (2007). "Comorbid psychopathology with autism spectrum disorder in children: an overview". Res Dev Disabil. 28 (4): 341–52. doi:10.1016/j.ridd.2005.12.004. PMID 16765022.
  37. Chakrabarti S, Fombonne E (2001). "Pervasive developmental disorders in preschool children". JAMA. 285 (24): 3093–9. PMID 11427137.
  38. Dawson M, Soulières I, Gernsbacher MA, Mottron L (2007). "The level and nature of autistic intelligence". Psychological science : a journal of the American Psychological Society / APS. 18 (8): 657–62. doi:10.1111/j.1467-9280.2007.01954.x. PMID 17680932.
  39. Edelson, MG (2006). "Are the majority of children with autism mentally retarded? a systematic evaluation of the data". Focus Autism Other Dev Disabl. 21 (2): 66–83. Retrieved 2007-04-15.
  40. Skuse DH (2007). "Rethinking the nature of genetic vulnerability to autistic spectrum disorders". Trends Genet. 23 (8): 387–95. doi:10.1016/j.tig.2007.06.003. PMID 17630015.
  41. Pardo CA, Vargas DL, Zimmerman AW (2005). "Immunity, neuroglia and neuroinflammation in autism". International review of psychiatry (Abingdon, England). 17 (6): 485–95. doi:10.1080/02646830500381930. PMID 16401547.
  42. 42.0 42.1 42.2 McPartland J, Klin A (2006). "Asperger's syndrome". Adolesc Med Clin. 17 (3): 771–88. doi:10.1016/j.admecli.2006.06.010. PMID 17030291.
  43. Ehlers S, Gillberg C (1993). "The epidemiology of Asperger's syndrome. A total population study". J Child Psychol Psychiat. 34 (8): 1327–50. doi:10.1111/j.1469-7610.1993.tb02094.x. PMID 8294522. Retrieved 2007-09-18.
  44. Klin A (2006). "Autism and Asperger syndrome: an overview". Rev Bras Psiquiatr. 28 (suppl 1): S3–S11. PMID 16791390.
  45. Tuchman R, Rapin I (2002). "Epilepsy in autism". Lancet Neurol. 1 (6): 352–8. doi:10.1016/S1474-4422(02)00160-6. PMID 12849396.
  46. Levisohn PM (2007). "The autism-epilepsy connection". Epilepsia. 48 (Suppl 9): 33–5. PMID 18047599.
  47. Rogers SJ, Ozonoff S (2005). "Annotation: what do we know about sensory dysfunction in autism? A critical review of the empirical evidence". J Child Psychol Psychiatry. 46 (12): 1255–68. doi:10.1111/j.1469-7610.2005.01431.x. PMID 16313426.
  48. Williams DL, Goldstein G, Minshew NJ (2006). "Neuropsychologic functioning in children with autism: further evidence for disordered complex information-processing". Child Neuropsychol. 12 (4–5): 279–98. doi:10.1080/09297040600681190. PMID 16911973.
  49. Ming X, Brimacombe M, Wagner GC (2007). "Prevalence of motor impairment in autism spectrum disorders". Brain Dev. doi:10.1016/j.braindev.2007.03.002. PMID 17467940.
  50. Harrison JE, Bolton, PF (1997). "Annotation: Tuberous sclerosis". Journal of Child Psychology and Psychiatry. 38: 603–614. PMID 9315970.
  51. Manzi B, Loizzo AL, Giana G, Curatolo P (2008). "Autism and metabolic diseases". J Child Neurol. 23 (3): 307–14. doi:10.1177/0883073807308698. PMID 18079313.
  52. Santangelo SL, Tsatsanis K (2005). "What is known about autism: genes, brain, and behavior". Am J Pharmacogenomics. 5 (2): 71–92. PMID 15813671.
  53. Casanova MF, El-Baz AS, Kamat SS, Dombroski BA, Khalifa F, Elnakib A, Soliman A, Allison-McNutt A, Switala AE (October 2013). "Focal cortical dysplasias in autism spectrum disorders". Acta Neuropathol Commun. 1: 67. doi:10.1186/2051-5960-1-67. PMC 3893372. PMID 24252498.



Linked-in.jpg