Theories regarding the etiology of autism
(2-19-15)Genetic models
concordance rates in identical twins high (36% to 91% across several studies; 75% most commonly cited figure); concordance rates in fraternal twins low ("zero"; "less than 20%") in these same studies.
the "zero" reports seem unusual given that fraternal twins share (on average) 25% of their genes; possibly reflects the effect of low sample sizes in many studies
the evidence seems strong that autistic disorder has a genetic etiology; the specific genotype, however, is unclear there may be both more than one genetic form, with variable expressions of the genetic forms
likely polygenetic inheritance (see Brock, Jimerson, & Hansen, 2006)
HOXA1 has been reported to be a gene associate with risk for autism
other genes suspected of involvement in autism
Chromosome 17
HOX (Homeobox) genes
5HTT (serotonin--5-hydroxytryptamine) transporter gene
Chromosome 15
GABRB3 (gamma-aminobutyric A receptor b3) gene
Chromosome 7
HOX (Homeobox) genes
Chromosome 2
HOX (Homeobox) genes
Glutamate transporter gene (SLC25A12)
X chromosome
Fragile X genes
Chromosome 11
HRAS (C-Harvey-ras) gene
Environmental factors
"Obstetric suboptimality": while a number of studies have suggested prenatal factors are associated with autism, no specific factor has clear emerged as the "cause" of autism. Composite measures of the pregnancy and delivery ("optimality") such as maternal age, prenatal disease exposure, and neonatal respiratory distress has been found to be associated with risk of autism. Whether this is a cause or an effect remains debated.
prenatal Rubella exposure increases risk of autism
thalidomide exposure during the 20th to 24th weeks of pregnancy increases risk of autism
possibly premature exposure to valproic acid (Depakene, Depakote) increases risk of autism
rare cases of lead encephalopathy (lead poisoning leading to brain damage) resulting in an "autistic like" syndrome in children (most common sequela of brain injury is mental retardation (severe exposure) and/or learning disorder and behavior disorders (milder exposure)
Developmental neurobiology
the brain grows more rapidly during the first year of postnatal life in children who will be diagnosed with autism, and the greatest growth occurs in those children who show the most severe symptoms of autism (see Brock, Jimerson, & Hansen, 2006)
studies have found evidence of neuroanatomical abnormalities in children diagnosed as autistic: minicolumns in the frontal and temporal lobes tend to be more numerous, smaller, and less compact in their arrangement (see Brock, Jimerson, & Hansen, 2006)
up to 30 % of children diagnosed with autism have elevated blood levels of serotonin, a finding described as "hyperserotonemia"; this my reflect decreased availability of the neurotransmitter in the brain
Diathesis-stress models
early Rutter: inherited tendency toward language disorder + early brain injury affecting arousal regulation
a nice model that appears not to have been supported by available data
but multifactorial models may well have some role in explaining autism
Final common pathway models
"different diseases producing different types of CNS pathology can play an etiologic role in autism" (Ritvo et al., 1990, p. 1614)
Theory of Mind
"the ability to attribute independent mental states to self and others in order to predict and explain actions" (Happe, 1994, p. 215)
"While it is tempting to argue that theory-of-mind deficits may underlie poor pretend or symbolic play, joint visual attention, and other social deficits in autism, this may not be true if affected children show symptoms before the normal emergence of theory of mind in normal children . . . . Instead, perhaps, a lack of theory of mind in autism could stem from an earlier failure to attend to social cues, a reliance on superficial features or aspects, or a failure to attend to socially relevant or affective cues, emotions, expressions, gestures, or vocalizations in others" (Bradshaw, 2001, p. 180)
Similarities with autoimmune disorders
familial predisposition
associated immunological abnormalities
a relationship with season of birth (viruses)
male:female ration of 4 or 5 to 1
Comi et al. (1999) report an increased incidence of autoimmune diseases (especially rheumatoid arthritis) and a decreased incidence of allergies in mothers of children with autism; they further reported a dose-effect relationship between family members with autoimmune disorders and risk of autism
Extreme male brain theory
E-S Theory of psychological sex differences (Simon Baron-Cohen)
empathizing
systemizing
Dr. Baron-Cohen believes that individuals with autism have limited to zero activity in the "empathizing circuits" of their brains; but high activity in the "systemizing circuits"
while reading stories to make judgments about a character's intentions, motives, or states of mind--they show reduced activity in dorsomedial prefrontal cortex (Baron-Cohen, 2011, pp. 100-101)
while looking at photos of a person's eyes and asked to infer what the person might be thinking about or feeling--they show show underactivity in the frontal operculum, amygdala, and anterior insula (Baron-Cohen, 2011, p. 101)