Autism has been classically defined by its behavioral symptoms. Traditional medical research has focused on genetic or intrinsic brain-based causes of autism. While both of these are important, additional research has focused on the underlying disordered biochemistry seen in many individuals with autism. Many of these biomedical factors are amenable to treatment. This article will review the main pathophysiologic factors seen in individuals with autism spectrum disorders.
American Psychiatric Association.Diagnostic and statistical manual of mental disorders, 5th edition (DSM-V).Arlington, VA: American Psychiatric Publishing; 2013.
2.
Prevalence of autism spectrum disorders: autism and developmental disabilities monitoring network, 14 sites, United States, 2008.MMWR.http://www.cdc.gov/mmwr/pdf/ss/ss6103.pdf. Accessed October 10, 2013.
3.
SchaevitzLR, Berger-SweeneyJE. Gene-environment interactions and epigenetic pathways in autism: the importance of one-carbon metabolism.ILAR J.2012; 53(3-4): 322–40.
4.
PuD, ShenY, WuJ. Association between MTHFR gene polymorphisms and the risk of autism spectrum disorders: a meta-analysis.Autism Res.2013 May 7. doi: 10.1002/aur.1300. [Epub ahead of print]
5.
PascaSP, DroncaE, KaucsárTOne carbon metabolism disturbances and the C677T MTHFR gene polymorphism in children with autism spectrum disorders.J Cell Mol Med.2009; 13(10): 4229–38.
6.
AdamsJB, AudhyaT, McDonough-MeansSNutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity.Nutr Metab (Lond).2011; 8(1): 34.
7.
Kaluzna-CzaplinskaJ. Noninvasive urinary organic acids test to assess biochemical and nutritional individuality in autistic children.Clin Biochem.2011; 44(8-9): 686–91.
8.
Mousain-BoscM, RocheM, PolgeA, Pradal-PratD, RapinJ, BaliJP. Improvement in neurobehavioral disorders in children supplemented with magnesium-vitamin B6. II.Pervasive developmental disorder-autism. Magnes Res.2006; 19(1): 53–62.
9.
KocovskáE, FernellE, BillstedtE, MinnisH, GillbergC. Vitamin D and autism: clinical review.Res Dev Disabil.2012; 33(5): 1541–50.
10.
MostafaGA, Al-AyadhiLY. Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: relation to autoimmunity.J Neuroinflammation.2012Aug 17; 9: 201.
11.
BjorklundG. The role of zinc and copper in autism spectrum disorders.Acta Neurobiol Exp (Wars).2013; 73(2): 225–36.
12.
LauNM, GreenPH, TaylorAKMarkers of celiac disease and gluten sensitivity in children with autism.PLoS One.2013Jun 18; 8(6): e66155.
13.
D'EufemiaP, CelliM, FinocchiaroRAbnormal intestinal permeability in children with autism.Acta Paediatr.1996; 85(9): 1076–9.
14.
ReicheltKL, TveitenD, KnivsbergAM, Br⊘nstadG. Peptides’ role in autism with emphasis on exorphins.Microb Ecol Health Dis.2012; 23: 10.3402/mehd.v23i0.18958.
15.
ReicheltKL, KnivsbergAM. Can the pathophysiology of autism be explained by the nature of the discovered urine peptides?Nutr Neurosci.2003; 6(1): 19–28.
16.
ReicheltKL, KnivsbergAM. The possibility and probability of a gut-to-brain connection in autism.Ann Clin Psychiatry.2009; 21(4): 205–11.
17.
HerbertMR, BuckleyJA. Autism and dietary therapy: case report and review of the literature.J Child Neurol.2013; 28(8): 975–82.
18.
WhiteleyP, HaracoposD, KnivsbergAMThe ScanBrit randomised, controlled, single-blind study of a gluten-free and casein-free dietary intervention for children with autism spectrum disorders.Nutr Neurosci.2010; 13(2): 87–100.
19.
WhiteleyP, ShattockP, KnivsbergAMGluten- and casein-free dietary interventions for autism spectrum conditions.Front Hum Neurosci.2013Jan 4; 6: 344.
FinegoldSM, DowdSE, GontcharovaVPyrosequencing study of fecal microflora of autistic and control children.Anaerobe.2010; 16(4): 444–53.
26.
FinegoldSM. State of the art; microbiology in health and disease. Intestinal bacterial flora in autism.Anaerobe.2011; 17(6): 367–8.
27.
ShultzSR, MacFabeDF, OssenkoppKPIntracerebroventricular injection of propionic acid, an enteric bacterial metabolic end-product, impairs social behavior in the rat: implications for an animal model of autism.Neuropharmacology.2008; 54(6): 901–11.
28.
ShultzSR, MacfabeDF, MartinSIntracerebroventricular injections of the enteric bacterial metabolic product proprionic acid impair cognition and sensorimotor ability in the Long-Evans rat: further development of a rodent model of autism.Behav Brain Res.2009; 200(1): 33–41.
29.
SchwabMA, SauerSW, OkunJGSecondary mitochondrial dysfunction in propionic aciduria: a pathogenic role for endogenous mitochondrial toxins.Biochem J.2006; 398(1): 107–112.
30.
JamesSJ, CutlerP, MelnykSMetabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism.Am J Clin Nutr.2004; 80(6): 1611–17.
31.
MelnykS, FuchsGJ, SchulzEMetabolic imbalance associated with methylation dysregulation and oxidative damage in children with autism.J Autism Dev Disord.2012; 42(3): 367–77.
32.
JamesSJ, MelnykS, FuchsGEfficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism.Am J Clin Nutr.2009; 89(1): 425–30.
33.
JamesSJ, RoseS, MelnykSCellular and mitochondrial glutathione redox imbalance in lymphoblastoid cells derived from children with autism.FASEB J.2009; 23(8): 2374–83.
34.
AlbertiA, PirroneP, EliaM, WaringRH, RomanoC. Sulphation deficit in “low functioning” autistic children: a pilot study.Biol Psychiatry.1999; 46(3): 420–4.
35.
GiuliviC, ZhangYF, Omanska-KlusekAMitochondrial dysfunction in autism.JAMA.2010; 304(21): 2389–96.
36.
RossignolDA, BradstreetJJ. Evidence of mitochondrial dysfunction in autism and implications for treatment.Am J Biochem Biotechnology.2008; 4(2): 208–17.
37.
Celestino-SoperPB, ViolanteS, CrawfordELA common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism.Proc Natl Acad Sci U S A.2012: 109(21):7974–81.
38.
JamesSJ, MelnykS, JerniganSMetabolic endophenotype and related genotypes are associated with oxidative stress in children with autism.Am J Med Genet B Neuropsychiatr Genet.2006; 141B(8):947–56.
39.
WalkerSJ, FortunatoJ, GonzalezLG, KrigsmanA. Identification of a unique gene expression profile in children with regressive autism spectrum disorder (ASD) and ileocolitis.PLoS One.2013; 8(3): e58058.
40.
VargasDL, NascimbeneC, KrishnanC, ZimmermanAW, PardoCA. Neuroglial activation and neuroinflammation in the brain of patients with autism.Ann Neurol.2005; 57(1): 67–81.
41.
PardoCA, VargasDL, ZimmermanAW. Immunity, neuroglia and neuroinflammation in autism.Int Rev Psychiatry.2005; 17(6): 485–95.
42.
RodriguezJI, KernJK. Evidence of microglial activation in autism and its possible role in brain underconnectivity.Neuron Glia Biol.2011; 7(2-4): 205–213.
PessahIN, SeegalRF, LeinPJImmunologic and neurodevelopmental susceptibilities of autism.Neurotoxicology.2008; 29(3): 532–545.
45.
OnoreC, CareagaM, AshwoodP. The role of immune dysfunction in the pathophysiology of autism.Brain Behav Immun.2012; 26(3): 383–92.
46.
MolloyCA, MorrowAL, Meinzen-DerrJElevated cytokine levels in children with autism spectrum disorder.J Neuroimmunol.2006; 172(1-2): 198–205.
47.
LiX, ChauhanA, SheikhAMElevated immune response in the brain of autistic patients.J Neuroimmunol.2009; 207(1-2): 111–6.
48.
VojdaniA, MumperE, GranpeeshehDLow natural killer cell cytotoxic activity in autism: the role of glutathione, IL-2 and IL-15.J Neuroimmunol.2008; 205(1-2): 145–54.
49.
HeuerL, AshwoodP, SchauerJReduced levels of immunoglobulin in children with autism correlates with behavioral symptoms.Autism Res.2008; 1(5): 275–83.
50.
SinghVK. Phenotypic expression of autoimmune autistic disorder (AAD): a major subset of autism.Ann Clin Psychiatry.2009; 21(3): 148–61.
51.
SingerHS, MorrisCM, WilliamsPN, YoonDY, HongJJ, ZimmermanAW. Antibrain antibodies in children with autism and their unaffected siblings.J Neuroimmunol.2006; 178(1-2): 149–55.
52.
CabanlitM, WillsS, GoinesP, AshwoodP, Van de WaterJ. Brain-specific auto-antibodies in the plasma of subjects with autistic spectrum disorder.Ann N Y Acad Sci.2007; 1107: 92–103.
53.
DomesG, HeinrichsM, KumbierE, GrossmannA, HauensteinK, HerpertzSC. Effects of intranasal oxytocin on the neural basis of face processing in autism spectrum disorder.Biol Psychiatry.2013; 74(3): 164–71.