Specific gene linked to aggression.

• Position: Neuroscience

Researchers at Case Western Reserve University, Cleveland, Ohio, report finding a gene that is essential for normal levels of anxiety and aggression. Calling it the Pet-1 gene, scientists at the School of Medicine's Department of Neurosciences say that when this gene is removed or "knocked out" in a mouse, aggression and anxiety in adults are greatly elevated compared to a control (also called wild type) mouse. Other neurologic functions--such as motor coordination, feeding, and locomotor activity--do not appear altered in the knockout mouse.

Anxiety and aggression are normal and important behaviors that allow individuals to respond appropriately to threats or cope with a challenging environment. However, it is clear that uncontrollable or excessive anxiety and aggression can be counterproductive. "The behavior of Pet-1 knockout mice is strikingly reminiscent of some human psychiatric disorders that are characterized by heightened anxiety and violence," notes Evan Deneris, principal investigator of the study.

Previously, Deneris showed that, in the brain, Pet-1 is active solely in serotonin nerve cells or neurons, a relatively small number of cells that profoundly affect emotions. (Among the trillions of neurons in a human brain, only a few hundred thousand produce serotonin.) Serotonin is a chemical that acts as a messenger or neurotransmitter, allowing neurons to communicate with one another in the brain and spinal cord. It is important for ensuring an appropriate level of anxiety and aggression. Defective serotonin neurons have been linked to excessive anxiety, impulsive violence, and depression in humans. Antidepressant drugs such as Prozac and Zoloft work by increasing serotonin activity and are highly effective at treating many of these disorders. Yet, it is unknown why some people have dysfunctional serotonin neurons and whether this can be caused by defects in genes that are normally required for their early development.

"We have now shown that Pet-1 is required specifically for fetal development of serotonin neurons," indicates Deneris. In mice missing this gene, most serotonin neurons fail to be generated in...