The first studies of epidemiology reported a prevalence rate of 4.5 per 10,000. Subsequent studies have tended to report higher rates, on balance around 9 children per 10,000. Although there has been much interest in higher rates in recent years, that is, whether the frequency of autism is increasing, several factors make it difficult to interpret the nature of the apparent increase. For example, diagnostic criteria have changed and current approaches were designed to work well in children over the range of cognitive ability levels. Secondly, rates reported vary depending on other factors, (e.g., sample size, with highest rates in reported in the smallest samples). There is also more general awareness of the condition. Given the importance of labels for service delivery (particularly in the United States), diagnostic substitution (e.g., assignment to PDD rather than mental retardation) can be problematic particularly for studies based on reports from schools and service providers.
Demographic, Gender, Cultural, and Ethnic Issues
In Kanner's first paper, many parents of autistic children were remarkably successful, leading to the impression of an association between social class and autism. However, subsequent studies have failed to reveal such an association. It appears that Kanner's initial sample reflected referral bias. Ethnic and cultural issues have been little studied in autism. While current diagnostic criteria appear to work well, there may be major differences in treatment. Gender differences have been consistently reported in autism, boys being 3–4 more times more likely than girls to have autism. However, this disparity is more marked at the upper end of the IQ distribution and, conversely, the ratio is less among children with more severe cognitive disability. This might either reflect a lower threshold for brain dysfunction in males or the fact that factor(s) causing autism in females must be more severe (Fombonne, 2005).
In the first decades after autism was identified, there was much speculation that experiential factors might be involved in autism. However, as time went on, evidence (e.g., high rates of seizure disorder, persistence of primitive reflexes, “soft” neurological signs) suggested brain involvement. When the confusion between autism and schizophrenia was clarified, the focus began to shift toward brain and genetic mechanisms.
The initial impression that there was no role for genetic factors in autism was discarded when the first twin samples were collected. Twin studies have revealed high levels of concordance for monozygotic twins compared to same-sex fraternal twins (although even in the latter the rate of autism was significantly increased over the population rate). Family studies reveal prevalence rates of between 2% and 10% in siblings. Even when siblings do not have autism, they have an increased risk for language, learning, and social development problems. There are higher rates of mood and anxiety problems in family members. Although specific modes of inheritance are not yet well established, it is clear that autism is a strongly genetic disorder. Efforts are now underway to identify potential genetic mechanisms. Of the multiple genes involved, at least some of these are likely to be identified in the next few years (Rutter, 2005).
As noted, high rates of seizure disorder in autism suggest brain involvement. Although autism has been reported in association with many other conditions, these reports are based on case association rather than controlled studies with careful methodology. So, for example, what appeared to be a strong association of autism with congenital rubella became much less clear as, over time, the “autistic features” of such children markedly diminish. The strongest associations of autism with medical conditions are with two strongly genetic disorders: Fragile X syndrome and tuberous sclerosis (Minshew et al., 2005).
As the importance of genetic factors became apparent there has been less attention to studies of obstetrical risk, but some recent work has appeared. It is possible that a predisposition to autism interacts with perinatal factors in the pathogenesis of the condition. Although there has been much interest in the role of environmental factors in autism, supporting data are limited at present.
Different brain systems have been studied. Given the diversity of symptoms and clinical features it seems likely that multiple neural systems are involved. On the other hand it is clear that not all systems are involved, and sometimes autism is seen in children with good cognitive ability. Abnormalities in the limbic system, temporal and frontal lobes have been suggested. Postmortem studies have revealed abnormalities in the cortex (e.g., in the microarchitecture and cortical “minicolumns,” and in neuronal packing and size). A recent finding has been the report of overall brain size increase in children with autism. It remains unclear whether the increase is generalized or local. There is much speculation that brain connectivity is adversely affected.
The possible role of immunological factors in autism has been hypothesized, for example, that maternal antibodies are directed against the fetus during the pregnancy. A recent paper reports abnormalities in the placentas of children with autism.
There has been much controversy about the role of environmental factors in autism, particularly the MMR vaccine. Persistent measles infection in combination with gastrointestinal vulnerability or the effect of thimerasol (a mercury containing compound) have been hypothesized, but larger, controlled studies have not provided consistent support. A small set of children with autism clearly do have significant developmental regression, but this may be both coincident with and unrelated to immunization. The study of “regressive” autism remains an important topic.