In good news for a change, the U. S. House of Representatives approved a bill allocating $1 billion for research and treatment for Autism Spectrum Disorders. This week, I saw two reports about the role of the amygdala in autism and Rett syndrome, which has aspects of autism. Because the amygdala is involved in emotions and social behaviors, I got to thinking about whether treating the symptom (abnormal social behavior) cures the disease.

In news@nature.com, Narelle Towie reports on a study of amygdala size in people with autism in Archives of General Psychiatry. According to the article, children with autism tend to have enlarged amygdalas. The authors found that adults with autism who most avoided eye contact (a common symptom in autism) had smaller amygdalas than other adults and children with autism. Therefore, the authors concluded that the amygdala may be hyperexcitable in children with autism, which may lead to amygdalar cell death and symptom progression in adults.

Rett syndrome is a neurodevelopmental disorder marked by mental retardation, seizures and ataxia that is associated with mutations in the methyl-CpG-binding protein MeCP2. People with Rett syndrome commonly show dysfunctional social behavior and aspects of autism as well as increased anxiety. In PNAS, McGill et al. report increased anxiety-like behavior and enhanced physiological response to stress in mice hypomorphic for Mecp2, which is a mouse model of Rett syndrome. Relative to wild-type mice, the ‘Rett’ mice had increased expression of corticotropin-releasing hormone (CRH) in the paraventricular nucleus of the hypothalamus, the central nucleus of the amygdala and the bed nucleus of the stria terminalis, where it is thought to regulate stress, fear and anxiety, respectively. Bound MeCP2 recruits histone acetylases and histone and DNA methyltransferases, which inhibit gene expression. So, does MeCP2 normally bind to the CRH gene and restrict its expression? Yes indeed! The authors found MeCP2 bound to CRH promoters in wild-type, but not MeCP2 hypomorph mice. So, the increased anxiety in people with Rett syndrome may be mediated by excess CRH.

Treatment with CRH inhibitors might help people with Rett syndrome feel less anxious. Is it possible that restraining fear and anxiety would alleviate some of the abnormal social behavior in these patients? For that matter, would treatments to restrain amygdalar activity treat the social symptoms of Autism Spectrum Disorders, or would it help block disease progression altogether?