Nicotine May Treat Cognitive Impairments in Schizophrenia

Nicotine might act as a treatment for some symptoms of schizophrenia, according to two new studies.

Patients with schizophrenia have an increased tendency to smoke, and they to do so more heavily than the general public, researchers said in a statement released today (Jan. 11) by Elsevier, the company that publishes the journal Biological Psychiatry, in which the new studies appear.

Nicotine acts on two classes of brain cell receptors -- those with high and low affinity for nicotine. The low-affinity nicotine receptors include a molecule called the alpha-7 subunit, which is present in reduced numbers in people with schizophrenia, the researchers said.

The new studies suggest that drugs that stimulate these nicotine receptors might enhance function of the brain's cortex, and treat the cognitive impairments associated with schizophrenia, the researchers said.

In healthy monkeys, study researcher Graham Williams and colleagues at Yale University and pharmaceutical company AstraZeneca found that very low doses of AZD0328, a novel drug that acts on these receptors, produced improvements in their performance on a spatial working memory task.

"Our work demonstrates that that the neuronal nicotinic alpha-7 receptor plays a critical role in the core cognitive function of working memory, which is a key indicator of outcome in patients with schizophrenia," Williams said. "The function of the alpha-7 receptor may account for the ability of a partial agonist to induce long-term beneficial changes for high-order cognition at such low doses."

This influence on cortical function has also been shown by the work of Jason Tregellas, of the department of psychiatry at the Denver VA Medical Center, and colleagues. These researchers examined the effects of another compound that interacts with alpha-7 on the brain's 'default network' in people with schizophrenia.

The function of the default network, which is likely a major contributor to neuron activity that accounts for 60 to 80 percent of the brain's energy use, is different in people with schizophrenia.

Together, "these two studies provide additional support for a novel pharmacologic approach to treat cognitive impairments in schizophrenia", said Dr. John Krystal, the editor of Biological Psychiatry.

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