A newly discovered genetic condition called TMLHE deficiency results in the loss of the ability to make carnitine in the body. Arthur Beaudet and his colleagues at Baylor College of Medicine in Houston, Texas, hypothesize that carnitine deficiency in the brain can cause autism, and that dietary supplementation with carnitine may prevent or reverse autism symptoms associated with TMLHE deficiency.

A hallmark of autism is impairment in reciprocal social interaction, including inadequate eye contact and failure to recognize emotions. Research shows that the neuropeptide oxytocin modulates social behavior. In mice, rats, monkeys and sheep, for instance, administration of oxytocin enhances social recognition, memory of peers, and development of partner preference and bonding. In people, including those with autism, oxytocin nasal spray can significantly enhance social cognition.

Several genes have been identified that contribute to the risk of developing autism spectrum disorders. Studies of infants at high risk (‘baby siblings’ of children with autism) have yielded exciting new findings about the earliest signs of the disorder, raising the hope that children could be diagnosed and therefore treated at an earlier age.

There is an immense need to find new treatments for children with autism. While some current therapies are effective, there is a lack of treatments that have a clear scientific basis. There is significant evidence to show that children with autism have decreased antioxidant defenses. This may lead to changes in the way cells function and contribute to the symptoms that children experience.

Inflammatory mechanisms have been implicated in autism. Treatments that modulate the immune system and inflammatory response, such as Trichuris suis ova (TSO), a parasitic worm called whipworm helminth, may be an experimental therapeutic option. Individuals with autism may have an increased immune response due to excess type 1 T-helper cells, which increases chronic inflammation. Individuals with autism may also have less of anti-inflammatory cytokines released by type 2 T-helper cells, which decreases chronic inflammation. It has been noted that some individuals with autism have improvements in behavioral symptoms when they have a fever, which further suggests that factors that influence the immune system and inflammation may have a role in autism etiology and potential treatments.

The observation that some individuals with autism show clinical improvement in response to fever suggests that symptoms may be modulated by brain systems or enzymes that become altered at high temperatures or by immune-inflammatory factors. The febrile hypothesis of autism stems from this observation. The effect could be due to the direct effect of temperature on enzymes that are heat-labile (can be changed or activated at high temperatures) or on gene expression in the brain. It could also be due to a resulting change in the immune inflammatory system or an increase in the functionality of a previously dysfunctional system in the locus coeruleus, a brain region that modulates physiological responses.

Stephen Bent’s primary goal in this project was to determine whether a randomized, controlled trial of a treatment for children with autism could be conducted entirely over the phone and Internet. He and his team designed an Internet-based clinical trial platform within the Interactive Autism Network (IAN), an online community and longitudinal study of more than 13,000 families that include a child with autism.

The Simons Foundation has funded five university-based medical centers to identify and study a large number of individuals (~200 families within two years) with a recurrent genetic variation (deletion or duplication of segment 16p11.2) that increases their risk of developing autism spectrum and other neuro­developmental disorders. The immediate goal is to identify medical, cognitive, neural and behavioral profiles shared by this genetically identified group. Families are recruited through web-based networks or referral by clinical genetic centers or testing laboratories. Extensive psychological and neurological testing and neuroimaging with a uniform protocol will take place at the collaborating medical centers.

For individuals with autism, the process of socialization is derailed at a very early age. Typically developing babies are drawn more toward socially relevant aspects of their environment (e.g. people, particularly their eyes) than toward inanimate objects. Ami Klin and Warren Jones at Yale University have found that this is not the case for children with autism, who often possess a great deal of knowledge about their world, but are profoundly lacking in socialization.

Large-scale population studies are valuable for elucidating gene-environment interactions that contribute to the risk of autism. Young Shin Kim and her colleagues at Yale University are assembling a large-scale collection of autism-related data from a group of children in South Korea who show a variety of symptoms across the autism spectrum.