Addicted to Nicotine
A National Research Forum

Section V: Psychobiology of Nicotine Addiction
Neil E. Grunberg, Ph.D., Chair

COMORBIDITY AND SMOKING

John R. Hughes, M.D.
Department of Psychiatry, Psychology, and Family Practice
University of Vermont

Introduction

Increased initiation, decreased cessation, and increased nicotine dependence have been associated with several behavioral traits and disorders. These associations are often strong. Although the rates of current psychiatric disorders among smokers are small, more prevalent occurrence of simple psychological distress appears to undermine cessation.

There are three possibilities for explaining this association: (1) Behavioral variables could be causing smoking changes, (2) smoking changes could be causing behavioral changes, or (3) some third variable could be associated with both the behavior and the smoking pattern.

What We Know

Causality can be estimated from epidemiological data by examining the consistency, strength, temporal precedence, dose-responsivity, and biological plausibility of any association. Using these criteria, major findings thus far are as follows:

• Psychological distress (e.g., dysphoria in teenagers), psychiatric disorders (e.g., attention deficit disorder), and substance use and dependence have prospectively predicted the onset of smoking and the inability to stop smoking in at least a couple of studies. Personality effects are weak. Interestingly, whether a past history of psychiatric disorders and drug dependence predict inability to stop is unclear.

• Smoking onset prospectively predicts drug use and dependence and, although not well studied given the normal ages of onset, probably prospectively predicts psychiatric disorders.

• Smoking cessation prospectively predicts psychological distress and in a few cases, probably predicts relapse of psychiatric disorders. Whether it predicts relapse to drug dependence is unclear.

• In terms of third variable explanations, genetic makeup has very consistently predicted both behavioral variables and smoking. Whether behavior patterns, such as poor self-esteem and subassertiveness, cause both smoking and psychiatric disorders has not been studied.

• Plausible biological and behavioral mechanisms are important in assessing causality, and several have been hypothesized to account for these associations. For example, smokers have less MAO A and MAO B, which should predispose them to depression. Also, patients with schizophrenia have an inability to habituate to repeated stimuli, which appears to occur because of differences in nicotine receptors in the brain. In animals and in humans, nicotine induces cross-tolerance to alcohol, perhaps increasing alcohol intake and thus dependence among smokers.

In summary:

• Smoking onset, nicotine dependence, and cessation are associated with several psychiatric and alcohol and other drug abuse diagnoses. However, its association with the more common, less severe forms of psychological distress may be more important.

• There are several plausible biological and behavioral hypotheses to explain whether smoking causes psychological problems, psychological problems cause smoking, or some third variable causes both.

What We Need To Know More About

First, several associations are debatable. Since the evidence is contradictory, large, generalizable studies are needed to determine whether smokers with a past history of alcoholism and depression have a more difficult time stopping smoking and whether smoking cessation can induce relapse to alcohol or other drug abuse or psychiatric disorders.

Second, the probability that those smokers who find it easier to stop, eventually do, suggests that comorbidity may be even more prevalent among the remaining future smokers. We need survey data to determine whether comorbidity is increasing or decreasing over time.

Third, we need to test existing hypotheses to account for comorbidity via experimental designs, including testing third variables that might account for associations. Replication will be important, as many hypotheses have one or two studies to support them, but no more. Until biological and behavioral mechanisms are elucidated, designing prevention treatment interventions for comorbid smokers will be difficult. The hypotheses that have the most evidence thus far, or are the more plausible, include the following:

• Some genotype predisposes to both smoking and psychiatric/drug abuse problems.

• Nicotine is a potent reinforcer in children with certain behavioral deficits (e.g., difficulty concentrating), because nicotine improves this deficit.

• Smoking-induced changes in MAO predispose to depression.

• Smoking induces tolerance to alcohol, which decreases the aversive effects of alcohol.

Fourth, we need to know whether treatments for psychiatric comorbidity influence smoking. For example, generalizable experimental trials could replicate whether methadone increases smoking, clozapine decreases smoking, and haloperidol increases smoking.

Fifth, we need to know whether treatments for smoking influence comorbidity. For example, generalizable experimental trials may show whether cessation increases or decreases drug use or sobriety in abusers of alcohol and other drugs, whether cessation precipitates relapse to depression, and so forth.

The following questions should be answered:

• Do smokers with a past history of depression and alcohol or other drug abuse have a more difficult time stopping, and can cessation of smoking cause a relapse in these disorders?

• Does comorbidity increase over time?

• Which of the many mechanisms hypothesized to explain comorbidity are valid; that is, can these be shown in several experiments?

• Does treatment of alcohol or other drug abuse or psychiatric disorders influence smoking, and does treatment of smoking influence the outcome of alcohol or other drug abuse or psychiatric disorders?

Recommended Reading

Fertig, J.B., and Allen, J.P. Anonymous Alcohol and Tobacco: From Basic Science to Clinical Practice. Washington, DC: Supt. of Docs., U.S. Govt. Print. Off., 1995.

Glassman, A.H. Cigarette smoking: Implications for psychiatric illness. Am J Psychiatry 150:546-553, 1993.

Lavin, M.R.; Siris, S.G.; and Mason, S.E. What is the clinical importance of cigarette smoking in schizophrenia? Am J Addict 5(3):189-208, 1996.