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Autism may reflect excitation-inhibition imbalance in brain, study finds

A study by Stanford University investigators suggests that key features of autism reflect an imbalance in signaling from excitatory and inhibitory neurons in a portion of the forebrain, and that reversing the imbalance could alleviate some of its hallmark symptoms.

In a series of experiments conducted on a mouse model of the disorder, the scientists showed that reducing the ratio of excitatory to inhibitory signaling countered hyperactivity and deficits in social ability, two classic symptoms of autism in humans.

The study is published in Science Translational Medicine. Karl Deisseroth, professor of bioengineering and of psychiatry and behavioral sciences, is the study’s senior author. The lead author is former graduate student Aslihan Selimbeyoglu, PhD.

In 2011, Deisseroth’s group published a study in Nature showing that autismlike behavioral deficits could be induced in ordinary mice by elevating the ratio of excitatory to inhibitory neuronal firing patterns in the mice’s medial prefrontal cortex. The new study shows that decreasing that ratio restores normal behavior patterns in a strain of lab mice bioengineered to mimic human autism. These mice carry a mutation equivalent to a corresponding mutation in humans that is associated with autism spectrum disorder.

Autism incidence increasing

For reasons that are not understood, the incidence of autism spectrum disorder has increased steadily in recent years, said Deisseroth, a practicing psychiatrist. Around 1 in 80 American children may be diagnosed with the disorder, which is characterized by repetitive behaviors and difficulty with social interaction. To date, there are no medications that treat the fundamental underpinnings of the disorder.

“In all of psychiatry, there’s no lab test that can diagnose this condition,” said Deisseroth. “It’s been associated with numerous genetic variants, many of which appear to exert only small individual influences.”

Deisseroth, who holds the D.H. Chen Professorship, notes that UCSF psychiatrist John Rubenstein and his colleagues, among others, have theorized that an excitation-inhibition imbalance might account for these phenomena. While myriad genetic variations contribute to autism, many of them may do so by impairing, in diverse ways, a single process or a small number of processes necessary for overall healthy brain function, such as a balance between excitatory and inhibitory signaling in key brain regions. One of those regions is the medial prefrontal cortex, which plays a major role in executive functions, such as planning, prediction, attention and integrating information from other individuals’ behaviors and speech for clues as to what they might be thinking.