People with schizophrenia not only smoke, they smoke more heavily than the general public, leading some researchers to believe that nicotine may be acting as a treatment for some symptoms of schizophrenia.
Two papers published in the January issue of Biological Psychiatry suggest that drugs that stimulate nicotinic receptors in the brain might enhance cortical function and treat cognitive impairments associated with schizophrenia.
Nicotine acts through two general classes of brain receptors, those with high and low affinity for nicotine. The low affinity class of nicotinic receptors contains what is called the alpha-7 subunit, and people with schizophrenia have fewer of these than the general population.
In their study of healthy monkeys, Graham Williams, M.D., and colleagues at Yale University and AstraZeneca found that very low doses of AZD0328, a novel drug that acts as an alpha-7 agonist, produced both acute and persistent 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,” explained Dr. Williams.
“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 been exemplified by the work of a research team lead by Jason Tregellas, Ph.D. These researchers examined the effects of DMXB-A, a novel alpha-7 partial agonist, on the brain’s”‘default network” in people with schizophrenia.
The default network is active when the brain is at rest and not focused on external tasks; it allows the mind to “wander” easily from one thought to the next. This network is likely a major contributor to the intrinsic neuronal activity that accounts for 60-80 percent of the brain’s energy use, works differently in people with schizophrenia.
Dr. Tregellas summarized their findings: “We found that DMXB-A altered default network activity in people with schizophrenia in a pattern consistent with improved function of the network. We also found that these neuronal differences were related to the genotype of the alpha-7 nicotinic receptor and to drug-related improvements in symptoms.”
Together, “these two studies provide additional support for a novel pharmacologic approach to treat cognitive impairments in schizophrenia,” observed Dr. John Krystal, Editor of Biological Psychiatry.