Social deficits associated with autism, schizophrenia induced in mice

Researchers at Stanford University School of Medicine have been able to switch on, and then switch off, social-behavior deficits in mice that resemble those seen in people with autism and schizophrenia, thanks to a technology that allows scientists to precisely manipulate nerve activity in the brain.

In synchrony with this experimentally induced socially aberrant behavior, the mice exhibited a brain-wave pattern called gamma oscillation that has been associated with autism and schizophrenia in humans, the researchers say.

The findings, to be published online in Nature on July 27, lend credence to a hypothesis that has been long floated but hard to test, until now.

They mark the first demonstration, the researchers said, that elevating the brain's susceptibility to stimulation can produce social deficits resembling those of autism and schizophrenia, and that then restoring the balance eases those symptoms.

Autism spectrum disorder and schizophrenia each affect nearly 1 percent of all people. At present, there are no good drugs for mitigating the social-behavioral deficits of either disorder.

While they differ in many ways, each syndrome is extremely complex, involving diverse deficits including social dysfunction. Mice are social animals, and there are many well-established tests of sociability in these animals.

Social behavior can't be ascribed to a single brain region, said Karl Deisseroth, MD, PhD, associate professor of psychiatry and behavioral sciences and of bioengineering and the study's senior author.

"To form a coherent pattern of another individual, you need to quickly integrate all kinds of sensations. And that's just the tip of the iceberg," said Deisseroth, a practicing psychiatrist who routinely sees autistic-spectrum patients.

"It's all changing, millisecond by millisecond, as both you and the other individual act and react. You have to constantly alter your own predictions about what's coming next. This kind of interaction is immensely more uncertain than, for example, predator/prey activity. It seems that it has to involve the whole brain, not just one or another part of it."

One intriguing hypothesis holds that social dysfunctions characteristic of autism and schizophrenia may stem from an altered balance in the propensity of excitatory versus inhibitory nerve cells in the brain to fire, resulting in an overall hyper-responsiveness to stimulation.

Evidence for this hypothesis includes the higher seizure rate among patients with autism, and the fact that many autistic children's brains exhibit elevated levels of a high-frequency brain-wave pattern -- known as "gamma oscillation" -- that can be picked up by an electroencephalogram.

Many schizophrenics also exhibit social deficits as well as higher levels of this anomalous brain-wave pattern, even at rest.

In addition, said Deisseroth, "autistic kids seem to be over-responding to environmental stimuli." For instance, they find eye contact overwhelming, or may cover their ears if there are too many people talking at once.