Tue, 14 Oct 2008 10:38 CDT
When it comes to cigarettes, schizophrenics just can't seem to get enough. They're two to three times more likely to smoke than the general population, and patients have been known to puff through up to four packs a day. New research on mice may explain this behavior: Nicotine spurs the production of a key neural protein that's scarce in schizophrenics--and that may help relieve their symptoms.
The 100 billion neurons in our brains are continually signaling one another. These impulses are like cars zooming through a city without traffic lights to deliver a message--they would pile up and the messages would get garbled. To keep neural signal traffic flowing, the brain uses certain neurotransmitters as stoplights to prevent neurons from firing out of turn. Reduced levels of one such neurotransmitter, called gamma-aminobutyric acid (GABA), characterizes the brains of schizophrenia patients. Researchers think that without the stoplight effect of GABA, signals in the schizophrenic brain overlap and get jumbled in a sort of neural traffic jam, resulting in hallucinations, disorganized thinking, and anxiety.
Previous studies have pinpointed nicotine receptors on the surface of GABA-making cells. That observation, plus the knowledge that schizophrenics often abuse cigarettes and report relief from their symptoms afterward led Alessandro Guidotti, a neuroscientist at the University of Illinois in Chicago, and colleagues, to explore the connection between nicotine and GABA production. They wanted to determine whether smoking represented an unconscious attempt at self-medication in schizophrenics.
The team injected groups of six normal mice with the equivalent amount of nicotine as someone would receive from smoking 20 to 30 cigarettes at a time (about one pack). Some groups received the treatment once every 3 hours for 4 days--simulating constant, heavy smoking--and the second group received the treatment only once. Mice that received the largest amount of nicotine produced up to 38% less of a protein called DNA methyltransferase 1 (DNMT1), which led to a surge in the protein that produces GABA
, the researchers report online this week in the Proceedings of the National Academy of Sciences
. The researchers speculate that high levels of nicotine switch off DNMT1, which is present in large amounts in the schizophrenic brain. Patients with the disorder may crave cigarettes because they are trying to tamp these DNAMT1 levels and get their GABA flowing, the team concludes. "The goal now is to study what else besides GABA is affected by the increase in DNMT1," says Guidotti.
Francine Benes, a psychiatrist at Harvard University's McLean Hospital in Belmont, Massachusetts, says these initial findings represent an important step forward in schizophrenia research. Understanding the molecular mechanisms involved in GABA synthesis can lead to more specific, possibly nicotine-derived schizophrenia treatments, she explains. "And the more specific treatments get, the more likely they are to be effective," Benes says.