Smoking and Schizophrenia

Thanks to research advances, scientists are learning how and why smoking and schizophrenia are so tightly linked. Nicotine — in cigarettes and other forms — appears to help normalize some of the cognitive and sensory deficits that people with this disorder experience. Scientists have looked inside the brain to uncover regions involved in deficits of schizophrenia and to learn how and where nicotine works to combat them. Now, enhanced knowledge is helping scientists develop drugs to treat this debilitating disorder.

The image above shows regions of the brain involved in learning and memory. People with schizophrenia have fewer and more poorly functioning nicotinic receptors in some of these regions, especially the hippocampus, cortex, and cells that wrap the thalamus. Research indicates that nicotine may improve cognitive and sensory deficits of schizophrenia by increasing deficient levels of the chemical dopamine in areas of the brain like the nucleus accumbens and prefrontal cortex.

Scientists have found that smoking and schizophrenia are tightly linked, but are not sure why. Could nicotine actually be helping the disorder? If so, then it is a double-edged sword, because smoking is a life-threatening behavior.

Now, new research on the effects of nicotine in people with schizophrenia is beginning to answer these questions and uncover clues that may help to treat this serious disorder. Schizophrenia is characterized by disordered thinking; hallucinations, such as hearing voices; and delusions, such as paranoid beliefs that people are conspiring against you.

Schizophrenia affects about 1 percent of the population and places a substantial burden on those afflicted, their families, and society.

Many people with schizophrenia smoke, and their unique smoking behaviors have led scientists to believe that nicotine, the addicting substance in tobacco, may represent a form of self-medication, normalizing some central nervous system deficits involved in the disorder.

People with schizophrenia smoke up to three times more than the general population and more than most psychiatric populations. Schizophrenia patients who smoke also have higher levels of nicotine in their bodies because they tend to extract more nicotine per cigarette than other smokers.

Nicotine and its brain receptors—proteins on the surface of cells that receive chemical messages—are keys to understanding the links between smoking and schizophrenia. Already, research has revealed that:

• Nicotine and its receptors are involved in functions such as cognition or thinking ability, reward, movement, and pain relief.
• Schizophrenia patients have fewer and more poorly functioning nicotinic receptors, especially in the hippocampus, cortex, and cells that wrap the thalamus—brain areas involved in several cognitive and sensory deficits of schizophrenia.
• Increased nicotine intake—from smoking cigarettes or sometimes from a skin patch, gum, or nasal spray—may temporarily normalize sensory disruptions of schizophrenia.

For example, nicotine may improve eye tracking abnormalities, mostly by altering activity in the hippocampus and brain areas involved in eye movement. Nicotine also has been reported to improve the brain’s ability to filter sounds and to respond and adapt to strong sensory inputs.

Cognitive ability in people with schizophrenia may get a boost from nicotine as well, including temporary enhancements in learning, memory, processing speed, and attention. Several studies have examined spatial working memory—the ability to hold information in the brain and recall it when prompted. Spatial working memory is involved in planning, judgment, and attention—tasks that people with schizophrenia find difficult. Schizophrenia patients who smoked or who received nasal spray nicotine temporarily enhanced their spatial working memory, and those who quit had further impairments.

Smoking also may help decrease medication side effects and other symptoms of schizophrenia. According to one study, receiving nicotine through a skin patch reversed the cognitive slowing associated with haloperidol, a common drug for schizophrenia. Nicotine may improve lack of motivation and indifference in this population, as well. However, it remains unclear if nicotine minimizes hallucinations and delusions, and some studies have reported that people with schizophrenia who quit smoking did not experience worsening of their symptoms.

Nicotine may help lessen some symptoms of schizophrenia by increasing deficient levels of the chemical dopamine—which is thought to regulate key emotional responses—in areas of the brain such as the nucleus accumbens and prefrontal cortex. The nucleus accumbens is involved in reward and pleasure, and the prefrontal cortex organizes complex cognitive and social behaviors.

Since evidence shows that nicotine positively affects schizophrenia, scientists are exploring drugs that act like nicotine in the brain but do not have adverse health consequences. Researchers now are working on safer and less toxic drugs that potentially could enhance cognition. These drugs may help treat schizophrenia.

One type of nicotinic receptor, known as the alpha-7 receptor, is proving to be a major target for schizophrenia drug development. These receptors are found in brain regions important for cognition, including the cortex and hippocampus. Already, scientists have completed preliminary tests of drugs for schizophrenic nonsmokers based on a toxin, called anabaseine, found in marine worms and ants. Subjects showed improved sensory processing and cognition, especially attention.

Scientists continue to research the biology and function of different nicotinic receptors. As knowledge advances, so will development of new and safer drugs to help treat schizophrenia. Hopefully, better symptom control also will lessen the desire for nicotine, and help people with schizophrenia snuff out smoking.