Autism: Causes

Pathogenesis (development of disease)

The cause of autism often remains unclear. Studies currently focus on the oxytocin receptor gene (OXTR) as a risk factor. One study discusses a dysbalance between amino acids (AS) overall and branched-chain amino acids (abbreviated BCAA for Branched-Chain Amino Acids) in particular: In patients with autism spectrum disorder (ASD), 31 amines were studied (including the 20 amino acids used for protein synthesis). Three constellations of amines, which (almost) only occurred in ASD patients, could be detected. The authors called these “ASD-associated amino acid dysregulation metabotypes” (AADM). This fits with the hypothesis that ASD is associated with dysfunction in the enzyme BCKDK (branched chain ketoacid dehydrogenase kinase). In addition, low BCAA levels have also been described as a cause of comorbid intellectual disability and autism. It is possible that high prenatal (“before birth”) estrogen is a trigger for autism: amniotic fluid samples from the Danish Biobank, from which the level of prenatal estrogen was determined, showed that estrogen levels were significantly higher on average in the 98 fetuses who later developed autism than in the 177 fetuses who did not.All that is known so far about the effect of prenatal estrogens is that they affect brain growth and “masculinize” the brain.

Etiology (Causes)

Biographical causes

  • Genetic burden from parents, grandparents (52.4%).
    • For parents who already have a child with an autism spectrum disorder (ASD), the risk for the offspring to also develop an ASD is
      • For female offspring at
        • 4.2% if it is an older brother with ASD.
        • 12.9% if it is an older sister with ASD.
      • For male offspring at
        • 12.9% if an older brother with ASD.
        • 16.7% if it is an older sister with ASD.
    • Cross-aggretation: younger siblings of ADHD children were also at increased risk of developing ASD (odds ratio 6.99; 3.42-14.27); younger siblings of ASD children were almost 4-fold more likely to develop ADHD (OR 3.70; 1.67-8.21)
    • Genetic risk dependent on gene polymorphisms:
      • Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
        • Genes: SLC25A12
        • SNP: rs4307059 in an intergenic region [autism spectrum disorders (ASD)].
          • Allele constellation: CT (1.19-fold).
          • Allele constellation: TT (1.42-fold)
        • SNP: rs2056202 in the gene SLC25A12 [autism spectrum disorders (ASD)].
          • Allele constellation: CT (0.8-fold).
          • Allele constellation: TT (0.64-fold)
        • SNP: rs2292813 in the gene SLC25A12 [autism spectrum disorders (ASD)].
          • Allele constellation: CT (0.75-fold).
          • Allele constellation: TT (0.56-fold)
        • SNP: rs10513025 in an intergenic region [autism spectrum disorders (ASD)].
          • Allele constellation: CT (0.55-fold).
          • Allele constellation: CC (> 0.55-fold)
    • Genetic diseases
      • Kanner syndrome – chromosome 7, 15 (unclear inheritance).
      • Asperger syndrome – chromosome 1, 3, 13 (unclear inheritance).
  • Maternal cannabis use (adjusted hazard ratio of 1.51, which has a 95% confidence interval of 1.17 to 1.96)
  • Smoking maternal grandmother – risk increase of.
  • Infections of the mother during pregnancy – pathogens of the TORCH complex (Toxoplasma, “Other”, rubella virus, cytomegalovirus and herpes simplex virus) (risk of the child to autism increased by 79%).
  • Age
    • Maternal age at conception – increasing maternal age from 30 to 34 years of age to highest risk in mothers over 40 years of age.
    • Age of father at conception > 40 years (5- to 6-fold higher risk for autistic traits than children born to fathers younger than 30 years of age
  • Migration status of parents (consensus-based statement).

Disease-related causes.

Endocrine, nutritional, and metabolic diseases (E00-E90).

Psyche – nervous system (F00-F99; G00-G99).

  • Maternal alcohol abuse during pregnancy (excluded risk factor: this is associated with significant cognitive impairment, numerous organic malformations, and other behavioral abnormalities in the child; but not autism spectrum disorders)
  • Early childhood brain damage
  • Cerebellar hypoplasia – underdevelopment of the cerebellum.

Pregnancy, childbirth and puerperium (O00-O99)

  • Infections of the mother during pregnancy – pathogens of the TORCH complex (Toxoplasma, “Other”, rubella virus, cytomegalovirus andHerpes simplex virus) (risk of the child to autism increased by 79%).

Laboratory diagnoses – laboratory parameters considered independent risk factors.

Medications taken by the mother during pregnancy:

  • Antidepressants?
    • Ingestion in second and/or third trimester (third trimester of pregnancy); 87% increase over children without exposure.
    • A meta-analysis and two registry studies find no differences for autism in exposed and unexposed siblings after SSRI ingestion by pregnant women.
  • Misoprostol – active ingredient used for gastric ulcers.
  • Thalidomide – sedative / sleeping pill, which became known through the so-called thalidomide scandal.
  • Valproic acid / valproate (active substance used in epilepsy).

Environmental pollution – intoxications (poisonings).

  • Dichlorodiphenyltrichloroethane (DDT) – pregnant women had significantly higher blood concentrations of DDT and its major metabolite dichlorodiphenyltrichloroethane p,p′-dichlorodiphenyl-dichloroethylene (p,p′-DDE).
  • Exposure to particulate matter and nitrogen dioxide during pregnancy and the first year of life.
  • Air pollution (diesel particulates, mercury, and lead, nickel, manganese and methylene chlorides).
  • Prenatal (pre-natal) exposure to pesticides.
    • Polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs)Note: Polychlorinated biphenyls are among the endocrine disruptors (synonym: xenohormones) that can harm health even in minute amounts by altering the endocrine system.
    • Glyphosate (odds ratio 1.16; 95% confidence interval 1.06 to 1.27), chlorpyrifos (odds ratio 1.13; 1.05-1.23), diazinon (odds ratio 1.11; 1.01-1.21), malathion (odds ratio 1.11; 1.01-1.22), avermectin (odds ratio 1.12; 1.04-1.22), and permethrin (odds ratio 1.10; 1.01-1.20).

Further