# Presentation: 045164

## 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*

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

## 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.

## “Persons with a current mental disorder consumed approximately 44.3% of cigarettes smoked by the U.S. population.”

							(Lasser et al., 2000, JAMA)

- 							(Lasser et al., 2000, JAMA)

## 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.

## Lifetime History of Daily Smoking

- “Did you ever smoke daily for one month or more?”

## 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.

## Lifetime Comorbidity of Daily Smoking

| Anxiety disorders | OR  (95% CI) |
| --- | --- |
| GAD | 2.4  (1.5, 3.7) |
| Panic disorder | 1.7  (1.1, 2.5) |
| Agoraphobia | 1.6  (1.1, 2.4) |
| Social phobia | 1.4  (1.1, 1.7) |
| Simple phobia | 1.6  (1.2, 2.0) |

- All significant at p<0.05 			      (NCS; n=4414)

## Lifetime Comorbidity of Daily Smoking

| Affective disorders | OR  (95% CI) |
| --- | --- |
| Depression | 1.7  (1.3, 2.2) |
| Dysthymia | 1.7  (1.2, 2.4) |

- All significant at p<0.05			   (NCS; n=4414)

## Lifetime Comorbidity of Daily Smoking

- All significant at p<0.05	 		      (NCS; n=4414)

| Substance disorders | OR  (95% CI) |
| --- | --- |
| Alcohol abuse | 3.3  (2.6, 4.1) |
| Alcohol dependence | 4.0  (3.0, 5.4) |
| Drug abuse | 2.6  (1.5, 4.3) |
| Drug dependence | 3.4  (2.4, 4.9) |

## Lifetime Comorbidity of Daily Smoking

| Other disorders | OR  (95% CI) |
| --- | --- |
| Conduct disorder | 2.2  (1.7, 3.0) |
| ASPD* | 4.3  (2.2, 8.4) |

- All significant at p<0.05			       (NCS; n=4414)*ASPD, antisocial personality disorder

## Lifetime Comorbidity of Daily Smoking

| Psychiatric disorders | OR  (95% CI) |
| --- | --- |
| Any anxiety dx | 1.5  (1.3, 1.8)   |
| Any affective dx | 1.8  (1.4, 2.2) |
| Any substance dx | 3.2  (2.6, 4.0) |

- All significant at p<0.05	   		            (NCS; n=4414)

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

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

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

## Associations of Psychiatric Disorders in Dependent and Non-dependent Smokers

|  | Dependent smokers
OR (95% CI) | Non-dependent 
OR (95% CI)  |
| --- | --- | --- |
| Alcohol dependence | 2.7  (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 dependence | 11.8  (4.3, 32.2)* |     6.5  (2.2, 19.5)* |
| Major depression | 2.9  (1.9, 4.5)* | 1.1  (0.6, 1.8) |
| Any anxiety | 2.4  (1.7, 3.5)* | 1.4  (1.0, 2.0) |

- *p <0.05 		                                            (Southeast Michigan; n = 1007)  (Breslau, 1995)
- Reference group:  never daily smokers

## 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.

## 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

## These three hypotheses are subsumed under the notion of “self medication.”

Accordingly, smoking begins as a successful attempt to relieve painful feelings.

- Accordingly, smoking begins as a successful attempt to relieve painful feelings.

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

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

-           smoking substances	      effect on brain
-        b. Smoking	          lung function (panic dx)

## 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)

- 	a.  Low self esteem
- 	b.  Associating with peers who smoke
- 		  and have behavior problems
- 	c.  Shared genetic predisposition
- 	 	  (e.g. for  impulsivity)

## Causality in observational studies?

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

- postulated cause and an outcome.
- (A necessary condition)

## 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.

- (e.g. smoking) _does not_ predict subsequent “outcome” (e.g. depression) can be used to rule out a causal explanation.

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

##      Time 1					 Time 2

      Cause				 	Outcome
    (smoking)				     (depression)

Confounding
(e.g. heritability)

-       Cause				 	Outcome
-     (smoking)				     (depression)
- Confounding
- (e.g. heritability)

## 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dependence | Persistence |
| --- | --- | --- | --- |
| Major depression | 1.5* |  2.0* | 0.8 |
| Dysthymia | 1.6* | 0.9 | 0.5 |

## Preexisting Disorders & Risk for Daily Smoking, Nicotine Dependence, & Persistence (vs. quitting): Odds Ratios

- *p<0.05						                                     (NCS; n = 4414)

*Preexisting Disorders* & Risk for Daily Smoking, Nicotine Dependence, & Persistence (vs. quitting): Odds Ratios

|  | Daily smoking | Nicotine dependence | Persistence |
| --- | --- | --- | --- |
| Agoraphobia | 1.3 |  1.8* | 1.8 |
| GAD |  1.9* | 1.8 | 0.8 |
| Simple phobia |  1.6* |  1.8* | 1.4 |
| Social phobia |  1.5* |  1.8* | 1.3 |
| Panic disorder | 0.9 | 1.8 | 0.3 |
| PTSD |  2.1* |  1.7* | 0.9 |

## 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dependence | Persistence |
| --- | --- | --- | --- |
| Alcohol A/D | 1.4* |  1.8* | 0.7 |
| Drug A/D | 1.6* |  1.7* | 0.9 |

## 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.

## 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.

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

## Daily Smoking and the Subsequent Onset of Disorders

| Subsequent disorder | OR (95% CI) |
| --- | --- |
| Major depression | 3.2 (1.6, 6.5)* |
| Dysthymia | 3.6 (1.8, 7.5)* |

- Adjusted for race, sex, education, age           (Breslau et al., 2004, *Psychol. Med.*)
- *p<0.05				                                        (NCS; n = 4414)

## Daily Smoking and the Subsequent Onset of Disorders

| Subsequent disorder | OR (95% CI) |
| --- | --- |
| Panic disorder |   2.6 (1.2, 5.4)* |
| Agoraphobia |   4.4 (2.3, 8.2)* |
| Simple phobia | 1.4 (0.7, 2.8) |
| Social phobia | 1.1 (0.5, 2.4) |
| GAD | 2.7 (0.9, 8.1) |
| PTSD | 1.3 (0.6, 2.9) |

- Adjusted for race, sex, education, age	            (Breslau et al., 2004, *Psychol. Med.)*
- *p<0.05                                                                                                (NCS; n = 4414)

## Daily Smoking and the Subsequent Onset of Disorders

| Subsequent disorder | OR (95% CI) |
| --- | --- |
| Alcohol A/D | 3.0 (2.1, 4.4)* |
| Drug A/D | 3.4 (2.1, 5.4)* |

- Adjusted for race, sex, education, age           (Breslau et al., 2004, *Psychol. Med.*)
- *p<0.05				                                        (NCS; n = 4414)

## Proximity of Exposure

|  | Risk for dxs in active vs. past smokers | Years sincequitting |
| --- | --- | --- |
| Major Depression | Not significant | Not significant |
| Dysthymia | Not significant | Not significant |
| Panic disorder | p<0.05 | p<0.05 |
| Agoraphobia | p<0.05 | p<0.05 |
| Alcohol A/D | p<0.05 | Not significant |
| Drug A/D | p<0.05 | Not significant |

- Adjusted for race, sex, education, age		          (Breslau et al., 2004, *Psychol. Med.*)
- 					                                          (NCS; n = 4414)

## 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).

-     	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

## 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.

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

## 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.

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

## 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

## 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