Missing brain protein may explain cases of severe over-worry

U.S. molecular biologists say a missing brain protein may be the culprit in cases of severe over-worry, or when people are fearful without reason. Senior author Jean Shih of the University of Southern California's School of Pharmacy and Keck School of Medicine, and colleagues examined mice without the enzymes monoamine oxidase A and B -- MAO A/B -- which sit next to each other in a human's genetic code as well as on that of mice. Prior research found an association between deficiencies of these enzymes in humans and developmental disabilities along the autism spectrum, such as clinical perseverance, which is the inability to change or modulate actions within social context. "These mice may serve as an interesting model to develop interventions to these neuropsychiatric disorders," Shih said in a statement. "The severity of the changes in the MAO A/B knockout mice compared to MAO A knockout mice supports the idea that the severity of autistic-like features may be correlated to the amounts of monoamine levels, particularly at early developmental stages." Comparing mice without MAO A/B with their wild-type litter mates, the study, published in the Proceedings of the National Academy of Sciences, found significant differences in how the mice without MAO A/B processed fear and other types of learning. Mice without MAO A/B and wild mice were put in a new, neutral environment and given a mild electric shock. All mice showed learned fear the next time they were tested in the same environment, but the MAO A/B knockout mice displaying a greater degree of fear. "When both enzymes are missing, it significantly increases the levels of neurotransmitters, which causes developmental changes, which leads to differential expression of receptors that are very important for synaptic plasticity -- a measure of learning -- and to behavior that is quite similar to what we see along the autism spectrum," Shih said.