1. Psychiatric Comorbidity of Smoking and Nicotine Dependence: An Epidemiologic Perspective Naomi Breslau, Ph.D. Department of Epidemiology Michigan State University College of Human Medicine email: breslau@epi.msu.edu

2. A recent report in the JAMA called attention to the observation that smokers are disproportionately persons with mental illness.

3. The connection between smoking and substance abuse has a long history. However, the association between smoking and mental disorders has been recognized since approximately 1990.

4. “Persons with a current mental disorder consumed approximately 44.3% of cigarettes smoked by the U.S. population.” ( Lasser et al., 2000, JAMA)

5. National Comorbidity Survey (NCS) A representative sample of 8,098 persons 15-54 years of age in the U.S. surveyed in 1990 - 1992. Information on smoking was gathered in a representative subset of 4,414.

6. Lifetime History of Daily Smoking “Did you ever smoke daily for one month or more?”

7. Lifetime Comorbidity of Smoking and Disorders The odds ratio estimates smokers’ risk for a specific DSM-IIIR disorder relative to persons who never smoked daily.

8. Lifetime Comorbidity of Daily Smoking Anxiety disordersOR (95% CI) GAD2.4 (1.5, 3.7) Panic disorder1.7 (1.1, 2.5) Agoraphobia1.6 (1.1, 2.4) Social phobia1.4 (1.1, 1.7) Simple phobia1.6 (1.2, 2.0) All significant at p<0.05 (NCS; n=4414)

9. Lifetime Comorbidity of Daily Smoking Affective disordersOR (95% CI) Depression1.7 (1.3, 2.2) Dysthymia1.7 (1.2, 2.4) All significant at p<0.05 (NCS; n=4414)

10. Lifetime Comorbidity of Daily Smoking All significant at p<0.05 (NCS; n=4414) Substance disordersOR (95% CI) Alcohol abuse3.3 (2.6, 4.1) Alcohol dependence4.0 (3.0, 5.4) Drug abuse2.6 (1.5, 4.3) Drug dependence3.4 (2.4, 4.9)

11. Lifetime Comorbidity of Daily Smoking Other disordersOR (95% CI) Conduct disorder2.2 (1.7, 3.0) ASPD*4.3 (2.2, 8.4) All significant at p<0.05 (NCS; n=4414) *ASPD, antisocial personality disorder

12. Lifetime Comorbidity of Daily Smoking Psychiatric disordersOR (95% CI) Any anxiety dx1.5 (1.3, 1.8) Any affective dx1.8 (1.4, 2.2) Any substance dx3.2 (2.6, 4.0) All significant at p<0.05 (NCS; n=4414)

13. Although depression and anxiety predominate in females, the strength of the associations with smoking is similar in both sexes.

14. Conversely, although substance use disorders are more prevalent in males than females, the strength of the associations with smoking varies little between the sexes.

15. The associations of psychiatric disorders with tobacco dependence are stronger than with non-dependent smoking.

16. Dependent smokers OR (95% CI) Non-dependent OR (95% CI) Alcohol dependence2.7 (1.8, 4.0)* 2.1 (1.4, 3.2)* Cannabis dependence 8.0 (4.3, 14.8)* 4.3 (2.2, 8.2)* Cocaine dependence11.8 (4.3, 32.2)* 6.5 (2.2, 19.5)* Major depression2.9 (1.9, 4.5)*1.1 (0.6, 1.8) Any anxiety2.4 (1.7, 3.5)*1.4 (1.0, 2.0) Associations of Psychiatric Disorders in Dependent and Non-dependent Smokers *p <0.05 (Southeast Michigan; n = 1007) (Breslau, 1995) Reference group: never daily smokers

17. Potential Explanations for Smoking-Mental Illness Association 1. Mental illness as ‘cause’ of smoking. 2. Smoking as ‘cause’ of mental illness. 3. Common predispositions to both smoking and mental illness.

18. 1. Mental illness as ‘cause’ of smoking a. Mental illness smoking initiation b. Mental illness progression to regular smoking and dependence c. Mental illness reduced capacity to quit

19. These three hypotheses are subsumed under the notion of “self medication.” Accordingly, smoking begins as a successful attempt to relieve painful feelings.

20. Vulnerable persons find the effects of nicotine powerfully reinforcing; this occurs before they develop physiologic dependence;dependent smokers smoke to avoid withdrawal.

21. 2. Smoking as cause of mental illness a. Nicotine & other pharmacologic smoking substances effect on brain b. Smoking lung function (panic dx)

22. 3. Correlated liabilities for both smoking & disorder a. Low self esteem b. Associating with peers who smoke and have behavior problems c. Shared genetic predisposition (e.g. for impulsivity)

23. Causality in observational studies?

24. Temporal order between a postulated cause and an outcome. (A necessary condition)

25. Evidence that a postulated “cause” (e.g. smoking) does not predict subsequent “outcome” (e.g. depression) can be used to rule out a causal explanation.

26. However, evidence that the postulated “cause” predicts increased risk for subsequent onset of outcome is often equivocal.

27. Time 1 Time 2 Cause Outcome (smoking) (depression) Confounding (e.g. heritability)

28. Preexisting Disorders & Risk for Daily Smoking, Nicotine Dependence, & Persistence (vs. quitting): Odds Ratios Adjusted for race, sex, education, age (Breslau et al., 2004, Biol. Psych. ) *p<0.05 (NCS; n = 4414) Daily smoking Nicotine dependencePersistence Major depression1.5* 2.0*0.8 Dysthymia1.6*0.90.5

29. Adjusted for race, sex, education, age (Breslau et al., 2004, Biol. Psych. ) *p<0.05 (NCS; n = 4414) Preexisting Disorders & Risk for Daily Smoking, Nicotine Dependence, & Persistence (vs. quitting): Odds Ratios Daily smoking Nicotine dependencePersistence Agoraphobia1.3 1.8*1.8 GAD 1.9*1.80.8 Simple phobia 1.6* 1.8*1.4 Social phobia 1.5* 1.8*1.3 Panic disorder0.91.80.3 PTSD 2.1* 1.7*0.9

30. Preexisting Disorders & Risk for Daily Smoking, Nicotine Dependence, & Persistence (vs. quitting): Odds Ratios Adjusted for race, sex, education, age (Breslau et al., 2004, Biol. Psych. ) *p<0.05 (NCS; n = 4414) Daily smoking Nicotine dependencePersistence Alcohol A/D1.4* 1.8*0.7 Drug A/D1.6* 1.7*0.9

31. The role of psychiatric disorders varied across stages of smoking; it played a role in onset of daily smoking and progression to dependence, but not in quitting.

32. Active vs. Past (remitted) Disorders The majority of preexisting disorders, when active, predicted the subsequent onset of daily smoking and smokers’ progression to dependence. In contrast, remitted disorders did not predict subsequent smoking.

33. Does smoking increase the risk for subsequent onset of specific psychiatric disorders?

34. Daily Smoking and the Subsequent Onset of Disorders Subsequent disorderOR (95% CI) Major depression3.2 (1.6, 6.5)* Dysthymia3.6 (1.8, 7.5)* Adjusted for race, sex, education, age (Breslau et al., 2004, Psychol. Med. ) *p<0.05 (NCS; n = 4414)

35. Daily Smoking and the Subsequent Onset of Disorders Subsequent disorderOR (95% CI) Panic disorder 2.6 (1.2, 5.4)* Agoraphobia 4.4 (2.3, 8.2)* Simple phobia1.4 (0.7, 2.8) Social phobia1.1 (0.5, 2.4) GAD2.7 (0.9, 8.1) PTSD1.3 (0.6, 2.9) Adjusted for race, sex, education, age (Breslau et al., 2004, Psychol. Med.) *p<0.05 (NCS; n = 4414)

36. Daily Smoking and the Subsequent Onset of Disorders Subsequent disorderOR (95% CI) Alcohol A/D3.0 (2.1, 4.4)* Drug A/D3.4 (2.1, 5.4)* Adjusted for race, sex, education, age (Breslau et al., 2004, Psychol. Med. ) *p<0.05 (NCS; n = 4414)

37. Risk for dxs in active vs. past smokers Years since quitting Major DepressionNot significant DysthymiaNot significant Panic disorderp<0.05 Agoraphobiap<0.05 Alcohol A/Dp<0.05Not significant Drug A/Dp<0.05Not significant Adjusted for race, sex, education, age (Breslau et al., 2004, Psychol. Med. ) (NCS; n = 4414) Proximity of Exposure

38.  Treatment of smoking is unlikely to reduce onset of depression: past smokers do not differ from active smokers.  Smoking is unlikely to cause depression.  Depression and smoking are likely to be linked by common predisposition (genetic evidence). Smoking and Depression

39. Smoking and Panic Disorder  Evidence of risk only in one direction (smoking panic disorder)  Active smoking, but not past smoking, increases risk.  In past smokers, there is a decreased risk for panic onset with passage of time since quitting.

40. Active smoking may be a marker for other substance use disorders.

41. These results are based on retrospective data, using statistical methods that take into account information on age of onset of disorders and age of onset of smoking.

42. Evidence from prospective studies of smaller samples (not national) support these findings.

43. Summary 1.Little evidence for influence of depression on smoking initiation. 2.Support for progression to daily smoking/nicotine dependence. 3.No support for reduced quitting. 1.Increased risk in smokers. 2.Potential role for respiratory problems. Depression as cause Panic dx as outcome

44. Summary 1. Smoking and/or alcohol precede(s) use of illicit drugs. 2. The smoking-illicit drug sequence is more common in females. Smoking, alcohol & illicit drugs