Targeting nicotine receptors to treat cognitive impairments in schizophrenia

Jan 11, 2011

Smoking is a common problem for patients with schizophrenia. The increased tendency of patients diagnosed with this disorder is to not only smoke, but to do so more heavily than the general public. This raises the possibility that nicotine may be acting as a treatment for some symptoms of schizophrenia.

Nicotine acts through two general classes of , those with high and low affinity for nicotine. The low affinity class of nicotinic receptors contains the alpha-7 subunit, which is present in reduced numbers in people with schizophrenia.

Two papers published in the January 1st issue of suggest that drugs that stimulate these alpha-7 subunit-containing nicotinic receptors might enhance cortical function and treat cognitive impairments associated with schizophrenia.

In their study of healthy monkeys, Graham Williams 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 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 Jason Tregellas and colleagues. These researchers examined the effects of DMXB-A, a novel alpha-7 partial agonist, on the brain's 'default network' in people with schizophrenia. Function of the default network, which is likely a major contributor to the intrinsic that accounts for 60-80% of the brain's energy use, is different 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 ", observed Dr. John Krystal, Editor of Biological Psychiatry.

Explore further: Discovery hints at why stress is more devastating for some

More information: The first article mentioned is "Immediate and Sustained Improvements in Working Memory After Selective Stimulation of α7 Nicotinic Acetylcholine Receptors" by Stacy A. Castner, Gennady N. Smagin, Timothy M. Piser, Yi Wang, Jeffrey S. Smith, Edward P. Christian, Ladislav Mrzljak, and Graham V. Williams. Castner and Williams are affiliated with the Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, and VA Connecticut Healthcare System, West Haven, Connecticut. Smagin, Piser, Wang, Smith, Christian, and Mrzljak are from AstraZeneca Pharmaceuticals, Wilmington, Delaware.

The second mentioned article is "Effects of an Alpha 7-Nicotinic Agonist on Default Network Activity in Schizophrenia" by Jason R. Tregellas, Jody Tanabe, Donald C. Rojas, Shireen Shatti, Ann Olincy, Lynn Johnson, Laura F. Martin, Ferenc Soti, William R. Kem, Sherry Leonard, and Robert Freedman. Tregellas, Tanabe, Rojas, Shatti, Olincy, Johnson, Martin, Leonard, and Freedman are affiliated with the Department of Psychiatry, Denver VA Medical Center, VISN19 MIRECC and University of Colorado—Denver, Aurora, Colorado. Tanabe is also from the Department of Radiology, University of Colorado—Denver, Aurora, Colorado. Soti and Kem are with the Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida.

The articles appear in Biological Psychiatry, Volume 69, Number 1 (January 1, 2011)

add to favorites email to friend print save as pdf

Related Stories

Glutamate: Too much of a good thing in schizophrenia?

Oct 27, 2008

Is schizophrenia a disorder of glutamate hyperactivity or hypoactivity? While the predominant hypothesis for many years was that schizophrenia was a glutamate deficit disorder, there is growing evidence of glutamate hyperactivity ...

Protein marker for schizophrenia risk

Jul 08, 2008

A protein found in immune cells may be a reliable marker for schizophrenia risk, report researchers in a new proteomics study appearing in the July issue of Molecular and Cellular proteomics.

Recommended for you

Discovery hints at why stress is more devastating for some

4 hours ago

Some people take stress in stride; others are done in by it. New research at Rockefeller University has identified the molecular mechanisms of this so-called stress gap in mice with very similar genetic backgrounds—a ...

Family dinners reduce effects of cyberbullying in adolescents

16 hours ago

Sharing regular family meals with children may help protect them from the effects of cyberbullying, according to a study by McGill professor Frank Elgar, Institute for Health and Social Policy. Because family meal times represent ...

The Edwardians were also fans of brain training

22 hours ago

Brain-training programmes are all the rage. They are part of a growing digital brain-health industry that earned more than US$1 billion in revenue in 2012 and is estimated to reach US$6 billion by 2020. The extent to which they actually improve brain function re ...

Report advocates improved police training

Aug 29, 2014

A new report released yesterday by the Mental Health Commission of Canada identifies ways to improve the mental health training and education that police personnel receive.

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

NonRational
not rated yet Jan 11, 2011
Having been around many schizophrenics, this trait of smoking is something that is hard to miss. Across the board, I heard the response from these sufferers that smoking worked wonders for them. I hope some kind of treatment results from this work