Copy number variation (CNV) of the 16p11.2 region is associated with numerous developmental problems, including an increased risk for autism. Little is known about how the function of the cortex differs between individuals with 16p11.2 deletions and duplications, and between those who have autism and those who do not. Charles Nelson and his colleagues set out to investigate these knowledge gaps in a sample of children with 16p11.2 CNVs using electrophysiological methods to assess cortical processing.

There is ample evidence of impaired sensory-motor acquisition in autism. Combined with anecdotal olfactory-behavioral reports, this suggests that individuals with autism may exhibit a specific olfactory profile. In the current study, Noam Sobel and his colleagues assessed olfactory performance in children undergoing diagnosis for autism. Their measure of performance was nasal airflow during sniffing of odorants. Given that sniffs are odorant-specific, such an assay provides a nonverbal measure of performance.

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.

Genetic factors have been known to play a role in the development of autism, but the contribution of common genetic variations — those that crop up in at least 1 percent of the general population — to the disorder is not known. Randy Buckner and his colleagues at Harvard University developed a new, highly efficient approach to explore the effects of these variations on brain functions associated with autism.

More than 100 genes have been associated with autism, but one challenge is to understand how gene mutations alter signaling between neurons to cause deficient social interaction, communication and repetitive behaviors. Partha Mitra, Josh Huang and their colleagues at Cold Spring Harbor Laboratory in New York propose to use systematic and large-scale techniques to develop a detailed neuroanatomical map in mouse models of autism.

The deletion of 27 genes in the 16p11.2 chromosomal region is associated with autism spectrum disorders, intellectual disability and obesity. To study the underlying cellular, molecular and anatomical basis of autism, Ricardo Dolmetsch and his colleagues at Stanford University in California have generated a mouse that lacks the same 27 genes on a corresponding chromosome in the mouse genome. Their goal, in collaboration with Jacqueline Crawley’s lab, is to characterize the neuroanatomical, neurophysiological and behavioral features of these mice.

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.

One of the core symptoms of autism spectrum disorders is impaired social interactions. One reason for this may be that individuals with autism do not experience the typical rewarding aspects of social interactions. There are specific brain areas that are critical for experiencing normal pleasures and specific chemicals in the brain that are thought to be important for promoting social interactions.

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.

Pavel Osten and his colleagues at Cold Spring Harbor Laboratory in New York study mouse brain circuits mediating social and other innate behaviors, such as aggression and sexual behaviors. The researchers use a novel automated whole-mount microscopy method called serial two-photon tomography and computational whole-brain analysis of the induction of the immediate early gene c‐FOS, a molecular marker of neuronal activation. This method allows them to map brain circuits mediating behaviors in control mice. It also enables them to identify brain circuit deficits that may underlie abnormal behaviors in genetic mouse models of autism.