Kate Johnson

October 01, 2010

September 30, 2010 (Toronto, Ontario) — Nicotine dependence is associated with the risk for attempted suicide, independent of comorbid psychiatric conditions, according to an analysis of a large cross-sectional survey presented at the Canadian Psychiatric Association 60th Annual Conference.

"To date this is the most comprehensive study of this connection, and it also confirms the fact that there seems to be something about smoking or the nicotine molecule that seems to have a suicidal effect by itself — it's not just factors related to the person," said James Bolton, MD, assistant professor of psychiatry and psychology at the University of Manitoba in Winnipeg, Canada, and lead investigator of the study.

The study used data from the 2004 to 2005 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), which included 34,653 community-dwelling American adults.

Using a cross-sectional analysis, the investigators evaluated the relationship of smoking status to documented suicide attempts, adjusting for psychiatric, physiologic, and sociodemographic variables.

"What's nice about the NESARC is that it assesses all 10 DSM-IV Axis II personality disorders as well as a comprehensive list of Axis I, which helped us tease out the role of comorbid psychiatric conditions," said Daniel Yaworski, MD, a psychiatrist at the University of Saskatchewan in Saskatoon, Canada, who presented the study.

Independent Association

After adjustment for variables, nicotine dependence was independently associated with an increased risk for attempted suicide (adjusted odds ratio [AOR], 1.78), "emphasizing a prosuicidal effect of nicotine," he reported.

"The data show that nicotine dependence or smoking is a possible risk factor for suicidal behavior," Dr. Bolton told Medscape Medical News. And even if down the road we find that it isn't nicotine per se, we're narrowing it down so that it's either nicotine or something very close to it that we're going to have to focus on for suicide prevention strategies.

Compared with not smoking, nicotine dependence within the past year was associated with a suicide attempt within the past year (AOR, 1.78), and smoking cessation was protective against suicide attempt (AOR, 0.15).

There was a trend toward an increased risk for suicide attempt with increased nicotine exposure (use before the age of 18 years, everyday use, and more than 20 cigarettes a day), but after adjustment for confounding factors this was not statistically significant.

Other psychiatrists who heard the presentation questioned the suggestion of causation.

"It's just an association," said Paul Kurdyak, MD, head of emergency crisis services and research at the Centre for Addiction and Mental Health in Toronto, Ontario, Canada.

"They are taking cross-sectional survey data and running a bunch of models and finding associations, but causation is extremely hard to demonstrate in these kinds of studies."

Nicotine Dependence Linked to Many Suicide Risk Factors

He said that nicotine dependence is strongly associated with many suicide risk factors, "so even though they ran a model to try and adjust for all that, the likelihood that traditional risk factors explain the suicide attempt finding rather than nicotine dependence alone is pretty high.

"If someone is smoking and has a severe and persistent mental illness I can't use it as a risk factor, but it's something I would take note of," commented Jennifer Brasch, MD, medical director of Psychiatric Emergency Services at St. Joseph's Healthcare and associate professor in the Department of Psychiatry and Behavioral Neurosciences at McMaster University in Hamilton, Ontario, Canada.

"Whether the smoking is a signal of a neurotransmitter deficit that people are trying to self-treat — we're not anywhere near knowing that."

Challenging the notion of a "prosuicidal" effect of nicotine, it has been hypothesized that nicotine may be used to self-medicate by individuals with depressive symptoms.

Several recent studies have suggested an antidepressant-like effect of nicotine on serotonin and dopamine neurotransmitters (Rev Neurol. 2009;49:661-667 and Behav Brain Res. 2009;197:150-156).

A recently published analysis of the same data by a separate group found a significant association (odds ratios, 1.60 – 1.87) of nicotine dependence with 4 personality disorders (PDs): schizotypal, borderline, narcissistic, and obsessive compulsive.

The associations were significant after controlling for covariates, including smoking exposure (Drug Alcohol Depend. 2010;108:141-145).

"Given that the adjustment for degree of smoking exposure did not change the significance or the magnitude of these associations, these disorder-specific mechanisms most likely include susceptibility to dependence conferred by maladaptive traits of these PDs or shared pathogenesis based on common neurobiological vulnerabilities," concluded the study authors.

For example, acetylcholinergic receptors are the most direct target of nicotine and play an important role in regulating cognitive, emotional, and physiologic processes.

"Altered function of this system may result in dysphoria, depression, anxiety, irritability, affect instability, aggression, and hostility," they write.

When reached for comment, the lead author of the study, Attila Pulay, MD, said the cross-sectional design of the nicotine/suicide study "would only yield an association."

"Even if the design was prospective, one should be extra cautious in inferring a causative relationship because factors not included in these models (for example, subthreshold or unmeasured psychiatric disorders or other conditions) might also confound this association.

"Nevertheless, I think these findings are valuable, as they help us better understand the psychopathology related to smoking and set up an important new direction for research,” said Dr. Pulay, who is visiting postdoctoral fellow in the Laboratory of Epidemiology and Biometry, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, in Bethesda, Maryland.

The investigators and commentators have disclosed no relevant financial relationships.

Canadian Psychiatric Association (CPA) 60th Annual Conference: Abstract PS5d. Presented September 24, 2010.


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