59The last prevalence estimates

in the United States, released by the Centers for Disease Control recently,60 reached 1 in 88 child in 2008, while their previous estimate was one in 110 in 2006. However, most of the studies are not comparable in method or in the populations studied. One hypothesis is that this increase is the result of enlargement of diagnostic criteria, and the growing importance of screening for ASDs. The results of an epidemiological study from England, based on a national sample from 2007, support this hypothesis. Inhibitors,research,lifescience,medical Indeed the authors found a rate of about 1% in adults across the entire age range, without a significant reduction in the older part of the sample, as one would expect if the prevalence had increased in recent years.61 However, another

study suggested that diagnostic substitution, especially for the most severe cases, and Inhibitors,research,lifescience,medical better ascertainment, especially for children at the less severe end of the spectrum, explain only a part of the linear increase observed in the California Inhibitors,research,lifescience,medical registry.62 While the hypothesis of an increased incidence in relation to environmental factors could not be confirmed nor excluded definitely, studies using the same protocol several years apart are required.63 Nevertheless, it seems reasonable to think that there may be both a real increase in the number of cases and an increase in the detection of affected children, and one should not wait for the results Inhibitors,research,lifescience,medical of these studies to search for environmental factors increasing risk for autism. Immune dysfunction Several lines of evidence support the hypothesis of immune changes in autism. First, Inhibitors,research,lifescience,medical several

studies have shown abnormalities in the peripheral immune system such as T-cell dysfunction, autoantibody production, increase in the number of activated B cells and NK cells, and increase in proinflammatory cytokines.64-66 Moreover, a landmark study provided evidence for microglial and astroglial activation in brain of patients with ASD.67 The most prominent microglial reaction was heptaminol observed in the cerebellum and cerebral white matter. The authors also found, in the cerebrospinal fluid of other patients, an increase of proinflammatory and modulatory cytokines. Another study consistently reported microglial activation in the dorsolateral prefrontal cortex in brains of patients with ASD.68 This neuroglial response may result from either a primary disturbance of neuroglial function or unknown factors that disturb prenatal or postnatal CNS development. Transcriptome The first comprehensive gene-expression analysis of brains of patients with ASD Cyclopamine recently reported differences in transcriptome organization between autistic and normal brain.