Schizophrenics are three times more likely to smoke than people in the general population. They also are heavy smokers. While the number of schizophrenics, who smoke, is almost 90%, about 60 to 70 % of individuals with bipolar disorder smoke. These are high numbers compared to the 20-30 % of smokers in the general population (Schizophrenia and Cigarette Smoking, www.schizophrenia.com)). Schizophrenics may use cigarettes to self-medicate, because smoking gives symptom relief. Nicotine patches and nasal sprays also appear to lessen symptoms (Smoking and Schizophrenia, www.sfn.org). Nicotine is the major component of tobacco smoke that acts on brain cells or neurons. A new study in mice in the Proceedings of the National Academy of Science (2008) showed that nicotine upregulates the neurotransmitter gamma-aminobutyric acid (GABA) in response to nicotine. The elevation of GABA is probably unrelated to nicotine’s addictive effect.
GABA decreases the ability of other neurotransmitters to work. GABA prevents us from becoming overly emotional or anxious. “GABA is the communications speed controller, making sure all brain communications are operating at the right speed and with the correct intensity”, writes Joseph M. Carver, Clinical Psychologist. When there is too little GABA, we become overstimulated and engage in excessive and impulsive behavior. When there is too much GABA, we become overly relaxed and sedated. The levels of GABA are low in schizophrenia and bipolar disorder as well as in epilepsy and other seizure disorders. Previous studies showed that GABA-producing cells have nicotine receptors to which nicotine can bind.
In the study in mice, researchers injected the mice with amounts of nicotine equivalent to what heavy smokers would consume. The experiments uncovered a specific pathway by which nicotine increases GABA synthesis. Nicotine bound to nicotine receptors on neurons in the frontal cortex and hippocampus of the brain. After binding to these receptors, nicotine dramatically down-regulated the production of an enzyme called DNA methyltransferase 1 (DNMT1). The loss or reduction of DNMT1 allowed brain cells to make more GABA. When nicotine was prevented from binding to the nicotinic receptor, DNMT1 could not be decreased and GABA levels could not be raised.
Understanding the mechanism of how nicotine affects GABA synthesis, may lead to new drugs and treatments for schizophrenia and bipolar disorder. New treatments with nicotine or drugs that mimic nicotine may help individuals to stop smoking and prevent the deleterious health effects of tobacco smoke.
Proceedings of the National Academy of Sciences (2008) 105: 16356-16361