Smoking and Schizophrenia Linked by Alterations in Brain Nicotine Signals
Schizophrenia is associated with increased rates and intensity of tobacco smoking. A growing body of research suggests that the relationship between schizophrenia and smoking stems, in part, from an effort by patients to use nicotine to self-medicate symptoms and cognitive impairment associated with the disease.
A new study, published in the current issue of Biological Psychiatry, sheds light on this hypothesis. The authors found that the level of nicotine receptors in the brain was lower in schizophrenia patients than in a matched healthy group. Further, smoking, which is known to increase the levels of receptors for nicotine in the brain, had this effect in both groups, although was blunted in schizophrenia.
However, in the schizophrenia group, the smoking-related increase in the level of nicotine receptors was associated with lower levels of social withdrawal, blunted emotional and motivational responses, as well as better cognitive function.
Nicotine mimics the actions of a natural chemical messenger, acetylcholine, which stimulates the receptors for nicotine in the brain. So, to conduct this work, Yale University School of Medicine researchers used single photon emission computed tomography to quantify the availability of nicotinic acetylcholine receptors (β2*-nAChRs) in smoking and nonsmoking individuals with schizophrenia and healthy subjects.
First author and Assistant Professor Dr. Irina Esterlis details their findings, “We found a blunted effect of tobacco smoking on the β2*-nAChR system in individuals with schizophrenia. Furthermore, we found that lower receptor availability of β2*-nAChRs in smokers with schizophrenia is associated with worse negative symptoms and worse performance on tests of executive function.”
These findings may be relevant to the high rates of smoking in schizophrenia.
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.
“The data seem to suggest that smoking might produce some clinical benefits for some patients by increasing the availability of receptor targets for nicotine in the brain,” commented Dr. John Krystal, Editor ofBiological Psychiatry. “This finding adds to evidence that brain nicotine-related signaling might play a role for new medications developed to treat schizophrenia.”
Esterlis agreed and added, “These findings suggest that β2*-nAChRs may be a target for developing treatments for negative symptoms and cognitive deficits associated with schizophrenia, for which no effective treatments exist.”
The article is “In Vivo Evidence for β2 Nicotinic Acetylcholine Receptor Subunit Upregulation in Smokers as Compared With Nonsmokers With Schizophrenia” by Irina Esterlis, Mohini Ranganathan, Frederic Bois, Brian Pittman, Marina R. Picciotto, Lara Shearer, Alan Anticevic, Jon Carlson, Mark J. Niciu, Kelly P. Cosgrove, and D. Cyril D’Souza (doi: 10.1016/j.biopsych.2013.11.001). The article appears in Biological Psychiatry, Volume 76, Issue 6 (September 15, 2014), published by Elsevier.
Nicotine Therapy for Schizophrenia?
Nicotine Therapy for Schizophrenia?
Individuals who suffer from schizophrenia may be more inclined to smoke cigarettes because the nicotine reduces negative symptom severity, researchers report.
Negative symptoms are defined as a decline or absence in the traits needed for normal functioning. These include loss of interest in everyday activities, lack of emotion, social withdrawal, reduced ability to plan or carry out activities, neglect of personal hygiene, and loss of motivation.
“Although smoking has a wide range of well-established ill effects on human health, these findings do raise the possibility of exploring nicotinic pathways for novel treatments of schizophrenia,” said the researchers.
In two large independent samples, researchers found that Chinese men with schizophrenia were more than twice as likely to smoke cigarettes compared to those without schizophrenia, and half as likely to quit smoking.
Among the combined 1,139 male patients with schizophrenia, smoking was found to be consistently and significantly associated with reduced negative symptoms on the Positive and Negative Syndrome Scale, and it remained consistent even after researchers took into account antipsychotic use.
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Notes for editors
Full text of the article is available to credentialed journalists upon request; contact Rhiannon Bugno at +1 214 648 0880 or .(JavaScript must be enabled to view this email address). Journalists wishing to interview the authors may contact Dr. Irina Esterlis at .(JavaScript must be enabled to view this email address).
The authors’ affiliations, and disclosures of financial and conflicts of interests are available in the article.
John H. Krystal, M.D., is Chairman of the Department of Psychiatry at the Yale University School of Medicine, Chief of Psychiatry at Yale-New Haven Hospital, and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here.
About Biological Psychiatry
Biological Psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.
The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.
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