The human protocadherin (PCDH) gene clusters (PCDH-alpha, -beta and -gamma) encode a family of cell surface proteins that function in cell-to-cell interaction during the development of the brain. Distinct subsets of PCDH genes from all three clusters are randomly expressed in individual neurons, and this results in the generation of enormous single-cell PCDH diversity in neurons that are otherwise identical.

Autism spectrum disorders represent a major cause of disability both in the U.S. and worldwide, but medical treatments are nearly nonexistent. Many major pharmaceutical companies have closed down psychiatry-related drug development programs.

The goal of this project was to increase awareness of the need for brain tissue donation for autism research, and to thereby increase the number of people registered to donate and the number of actual donations. This project is the outreach program of Autism BrainNet.

Functional gastrointestinal (GI) symptoms have been frequently reported in children with autism spectrum disorders (ASD). The term ‘functional’ refers to the absence of structural abnormalities in the gut that can be identified by blood, radiographic or endoscopic tests. Functional GI symptoms are also common in the general population and account for a major portion of visits to gastroenterology and primary care practices. Abnormalities in the neural regulation of gut function and sensation have been implicated in the development of these complaints.

Autism is a heterogeneous brain disorder believed to have both genetic and environmental contributions. Epigenetic mechanisms, including modification of DNA and histones — proteins that store and organize DNA — allow an organism to respond to the environment through changes in gene expression. There is compelling evidence from human genetic association studies and animal models supporting a role for epigenetic dysregulation in autism. In particular, defects in MeCP2 protein function cause Rett syndrome. In this pilot study, Hongjun Song and his colleagues at Johns Hopkins University School of Medicine in Baltimore explored the role of DNA modifications in neuronal gene expression, plasticity, behavior and autism.

Mutation in many different genes has been found in individuals with autism, suggesting that there are many different ways to trigger the disorder. James Gusella and his colleagues previously found a number of autism genes whose normal function involves regulating the expression of other genes. This finding led them to consider that some effects of inactivating mutations in different autism genes might produce overlapping changes in overall gene expression. In this way, quite different genetic mutations might lead to autism by disrupting the same neurodevelopmental mechanisms.

Autism spectrum disorders represent a challenge for geneticists because of the heterogeneity of causes. Still, in a subset of people with autism, certain deleterious gene mutations have been identified, and most are involved in the formation of synapses — the points of contact between neurons. At first, these mutations alone were thought to be sufficient to cause autism, but studies suggest that the inheritance of ‘modifier genes,’ which alter the expression of other genes, might contribute to the wide behavioral variability observed in individuals with autism.

There are two emerging themes in research on genetic factors contributing to autism. First, autism is sometimes associated with small deletions within chromosomes, leaving the affected individual with only one copy of a group of neighboring genes. Second, mutations in proteins at synapses (sites of nerve cell communication) can contribute to autism. Mitchell Goldfarb and his colleagues aim to test whether these two themes can be integrated.

Cognitive and behavioral impairments in autism spectrum disorders are thought to result from changes in the structure and function of brain circuits. Disruption of the balance between excitation and inhibition in the neocortex has been proposed as a possible mechanism. This type of imbalance could lead to altered neuronal network connections that give rise to dramatic changes in the way the brain processes information and regulates behavior.