Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2016 Jul 19.
Published in final edited form as: Am J Med Genet B Neuropsychiatr Genet. 2015 Oct 15;171(4):521–524. doi: 10.1002/ajmg.b.32385

Nicotine dependence and psychosis in Bipolar disorder and Schizoaffective disorder, Bipolar Type

Elena Estrada a, Sarah Hartz b, Jeffrey Tran a, Donald Hilty a; GPCC, Pamela Sklar c, Jordan W Smoller d, Carlos N Pato a, Michele T Pato a,*
PMCID: PMC4950843  NIHMSID: NIHMS769769  PMID: 26467098

Abstract

Objective

Patients with Bipolar disorder smoke more than the general population. Smoking negatively impacts mortality and clinical course in Bipolar disorder patients. Prior studies have shown contradictory results regarding the impact of psychosis on smoking behavior in Bipolar disorder. We analyzed a large sample of Bipolar disorder and Schizoaffective disorder, Bipolar Type patients and predicted those with a history of psychosis would be more likely to be nicotine dependent.

Methods

Data from subjects and controls were collected from the Genomic Psychiatry Cohort (GPC). Subjects were diagnosed with Bipolar disorder without psychosis (N=610), Bipolar disorder with psychosis (N=1591), and Schizoaffective Disorder, Bipolar Type (N=1544). Participants were classified with or without nicotine dependence. Diagnostic groups were compared to controls (N=10065) using logistic regression.

Results

Among smokers (N=6157), those with Bipolar disorder had an increased risk of nicotine dependence (OR=2.5; p<0.0001). Patients with Bipolar disorder with psychosis were more likely to be dependent than Bipolar disorder patients without psychosis (OR=1.3; p=0.03). Schizoaffective disorder, Bipolar Type patients had more risk of nicotine dependence when compared to Bipolar disorder patients with or without psychosis (OR=1.2; p=0.02).

Conclusions

Bipolar disorder patients experiencing more severity of psychosis have more risk of nicotine dependence.

Keywords: smoking, severe mental illness, cigarettes

Introduction

Smoking kills the mentally ill 13–30 years earlier then the general population (Colton and Manderscheid 2006) and has been identified as the single greatest modifiable risk factor for decreasing mortality in the mentally ill (Parks et al. 2006). Smoking also contributes to psychiatric morbidity in Bipolar disorder patients (Goldstein et al. 2008; Waxmonsky et al. 2005). Bipolar disorder patients who smoke experience worse outcomes in mania treatment (Berk et al. 2008), earlier age of first manic episode (Ostacher et al. 2006), and more lifetime suicide attempts (Goldstein et al. 2008) than Bipolar patients who do not smoke.

Severely mentally ill patients, including those with Bipolar disorder and Schizoaffective disorder, are eight times more likely than the general population to smoke cigarettes (Hartz et al. 2014). The impact of psychosis on smoking has been investigated in past with contradictory results. Waxmonsky et al 2005 found an association between history of psychosis with smoking severity in a large sample of Bipolar disorder patients (N=1904). Corvin et al 2001 found a similar association in a small sample of Bipolar disorder patients (N=92). However, Kreinin et al 2012 was not able to reproduce an association between smoking severity and psychosis in Bipolar disorder patients (N=102). Cassidy et al 2002 also failed to find the same association between psychosis severity and smoking in 67 Bipolar disorder patients.

We investigated the impact of psychosis on nicotine dependence in a large sample of patients with Bipolar disorder and Schizoaffective disorder, Bipolar type per the Diagnostic and Statistical Manual of Mental Disorders IV Text Revision (American Psychiatric Association. Task Force on DSM-IV. 1994). Furthermore, we separated patients with Bipolar disorder into those with and without psychosis. While multiple studies have shown that those with Bipolar disorder smoke more then those without mental illness (Hartz et al. 2014; Lasser et al. 2000; Parks et al. 2006) fewer studies have controlled for psychosis within their Bipolar disorder and Schizoaffective disorder, Bipolar type samples (Cassidy et al. 2002; Corvin et al. 2001; Kreinin et al. 2012; Vanable et al. 2003). Given that the DSM IV criteria for Bipolar disorder includes but does not require psychosis, a study that separates Bipolar disorder patients into those with and without psychosis can further demonstrate the relationship between smoking and psychosis in the severely mentally ill. We separated Bipolar disorder patients into those with and without a history of psychosis and further included a sample of Schizoaffective disorder, Bipolar type patients to analyze the effects of psychosis on smoking behavior. Controls were screened negative for mania and psychosis.

Methods

Diagnostic Instruments

Subjects were diagnosed using the Diagnostic Interview for Psychosis and Affective Disorders (DIPAD) which is an instrument based on the Diagnostic Interview for Genetic Studies (DIGS) (Nurnberger et al. 1994) and is consistent with the DSM-IV-TR. Nicotine dependence was defined using the CAGE questionnaire subtly modified for nicotine use (Kitchens 1994; Rustin 2000). Smokers were defined as individuals who endorsed smoking 100 cigarettes in their lifetime. Nicotine dependence was defined as smokers who had difficult quitting, and who immediately smoke upon waking. This definition of nicotine dependence was compared with the database National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) and showed PPV=70% and NPV=79%.

Sample and Analyses

Subjects and control data were attained from the Genomic Psychiatry Cohort (GPC) (Pato et al. 2013). Subjects were diagnosed with Bipolar disorder with psychosis (N=1591), Bipolar disorder without psychosis (N=610) or Schizoaffective disorder, Bipolar type (N=1544). Controls (N=10065) screened negative for mania and psychosis. Caucasians, African American, and Hispanic participants were included. Logistic regression analysis results were performed modeling the association between nicotine dependence and psychiatric diagnosis, adjusted for age, sex, race and ethnicity.

Results

Table 2 shows logistic regression results for nicotine dependence among smokers (N=6,157) adjusted for age, sex, race, ethnicity. Odds ratio for having psychotic features is the additional risk of being a dependent smoker beyond the bipolar diagnosis. Odds ratio for schizoaffective disorder bipolar subtype is the additional risk of being a dependent smoker above both having bipolar disorder and having psychotic features. When comparing Bipolar disorder patients psychosis to those without psychosis, those with psychosis were found at higher risk for nicotine dependence (OR=1.3; p=0.03). Schizoaffective disorder, Bipolar type patients showed higher risk for nicotine dependence than Bipolar patients with or without psychosis (OR=1.2; p=0.02).

Table 2.

Logistic regression analysis for nicotine dependence among smokers, adjusted for age, sex, race and ethnicity. Age was positively associated with nicotine dependence (p=0.01); no other covariates were statistically significant.

Odds ratio p-value
Bipolar disorder* 2.5 <0.0001
Psychotic Features** 1.3 0.03
Schizoaffective disorder, Bipolar type 1.2 0.02
Open in a new tab

Discussion

Patients with severe mental illness smoke to a greater extent than the general population (Hartz et al. 2014; Parks et al. 2006). Smoking is especially harmful to the clinical course of Bipolar disorder patients (Berk et al. 2008; Goldstein et al. 2008). Smoking effectively lowers circulating doses of psychotropic medication by inducing cytochrome P450 which complicates the treatment of Bipolar disorder (Desai, Seabolt and Jann 2001). Smoking has also been found to be associated with manic cycling, mixed episodes, and greater episode severity in Bipolar disorder patients (Waxmonsky et al. 2005).

This study demonstrated the impact of psychosis on risk of nicotine dependence. In smokers, Bipolar disorder diagnoses increased the risk of nicotine dependence (OR=2.5; p<0.0001). Within the Bipolar disorder sample, those patients with psychotic features were more likely to be nicotine dependent than Bipolar disorder patients without psychotic features (OR=1.3; p=0.03). Lastly, the Schizoaffective disorder, Bipolar type sample demonstrated more risk of nicotine dependence compared the Bipolar disorder sample with or without psychosis (OR=1.2; p=0.02). Our study shows that patients who are more severely psychotic are more likely to be nicotine dependent then those with less severe symptoms.

Schizoaffective disorder has been discussed as a sub type of Schizophrenia (DSM-I 1952; Williams and McGlashan 1987), a psychotic mood disorder (Lake and Hurwitz 2006), part of the psychotic spectrum of diagnoses (Keshavan et al. 2011; Tamminga et al. 2013), or a separate diagnostic entity (Mitsuda 1965). Several studies have used clinical and demographic data to show Schizoaffective disorder patients fall between Bipolar and Schizophrenic patients on either ends of a psychosis spectrum (Mancuso et al. 2014; Pagel et al. 2013). This study investigates nicotine dependence in a sample of Schizoaffective disorder, Bipolar type and Bipolar patients with and without psychosis. Our findings support the theory of a psychosis spectrum by showing greater risk of nicotine dependence in patients experiencing a greater degree of psychosis.

Limitations of this study include an inability to quantify smoking severity or to assess withdrawal and tolerance. This study would have also benefited from the inclusion of Schizophrenic patients to further compare the association between psychosis and smoking across diagnostic groups. This is the largest study to date investigating psychosis and nicotine in Bipolar disorder patients and further includes a sample with and without psychotic features. We found that among the severely mentally ill, those with psychotic features demonstrated greater risk of nicotine dependence.

Table 1.

Sample characteristics

Bipolar without psychosis Bipolar with psychosis Schizoaffective Disorder, Bipolar type Controls
N 610 1,591 1,544 10,065
% Female 61% 52% 42% 56%
Average Age (SD) 43 (14) 43 (13) 43 (11) 38 (15)
% Caucasian 68% 64% 55% 48%
% African American 15% 18% 25% 17%
% Hispanic 17% 18% 20% 35%
% Smokers* 72% 76% 84% 35%
% Nicotine dependent** 41% 48% 56% 12%
Open in a new tab
*

Smokers defined as individuals who have smoked 100 cigarettes lifetime

**

Nicotine dependence is defined as smokers who have difficulty quitting and smoke immediately upon waking

Acknowledgments

This work was supported in part by National Institutes of Health grants R01 MH085542 and R01 MH08554.

The Genomic Psychiatry Cohort Consortium (GPCC) investigators are Helena Medeiros1, Janet L. Sobell1, Colony Abbott1, Maria Helena Azevedo2, Antonio Macedo2, Evelyn J. Bromet3, Peter F. Buckley4, Michael A. Escamilla5, Ayman H. Fanous6, Laura J. Fochtmann3, Douglas S. Lehrer8, Fabio Macciardi9, Dolores Malaspina10, Stephen R. Marder11, Christopher P. Morley13, Humberto Nicolini14, Diana O. Perkins15, Jeffrey J Rakofsky7, Mark H. Rapaport7, Steven A. McCarroll12. Becky Kincaid7, James A. Knowles1, Marquis Vawter9. NESARC data were obtained from the NIAAA (http://niaaa.census.gov).

Footnotes

1

Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine of the University of Southern California, Los Angeles, CA

2

Department of Psychiatry, University of Coimbra, Coimbra, Portugal

3

Department of Psychiatry and Behavioral Science, State University of New York, Stony Brook, NY

4

Department of Psychiatry, Georgia Regents University Medical Center, Augusta, GA

5

Department of Psychiatry, Texas Tech University Health Sciences Center, El Paso, TX

6

Department of Psychiatry, Veterans Administration Medical Center, Washington, DC

7

Department of Psychiatry and Behavioral Science, Emory University, Atlanta, GA

8

Department of Psychiatry, Wright State University, Dayton, OH

9

Department of Psychiatry, University of California, Irvine, CA

10

Department of Psychiatry, New York University, New York, NY

11

Department of Psychiatry, University of California, Los Angeles, CA

12

Department of Genetics, Harvard Medical School, Boston, MA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA

13

Departments of Family Medicine, Public Health & Preventive Medicine, and Psychiatry & Behavioral Sciences, State University of New York, Upstate Medical Center, Syracuse, NY

14

Center for Genomic Sciences, Universidad Autónoma de la Ciudad de México, Mexico City, Mexico and Carracci Medical Group, Mexico City, MX

15

Department of Psychiatry, University of North Carolina, Chapel Hill, NC

References

  1. American Psychiatric Association., and American Psychiatric Association. Task Force on DSM-IV. Diagnostic and statistical manual of mental disorders : DSM-IV. Washington, DC: American Psychiatric Association; 1994. [Google Scholar]
  2. Berk M, Ng F, Wang WV, Tohen M, Lubman DI, Vieta E, Dodd S. Going up in smoke: tobacco smoking is associated with worse treatment outcomes in mania. J Affect Disord. 2008;110(1–2):126–34. doi: 10.1016/j.jad.2008.01.018. [DOI] [PubMed] [Google Scholar]
  3. Cassidy F, McEvoy JP, Yang YK, Wilson WH. Smoking and psychosis in patients with bipolar I disorder. Compr Psychiatry. 2002;43(1):63–4. doi: 10.1053/comp.2002.29847. [DOI] [PubMed] [Google Scholar]
  4. Colton CW, Manderscheid RW. Congruencies in increased mortality rates, years of potential life lost, and causes of death among public mental health clients in eight states. Prev Chronic Dis. 2006;3(2):A42. [PMC free article] [PubMed] [Google Scholar]
  5. Corvin A, O’Mahony E, O’Regan M, Comerford C, O’Connell R, Craddock N, Gill M. Cigarette smoking and psychotic symptoms in bipolar affective disorder. Br J Psychiatry. 2001;179:35–8. doi: 10.1192/bjp.179.1.35. [DOI] [PubMed] [Google Scholar]
  6. Desai HD, Seabolt J, Jann MW. Smoking in patients receiving psychotropic medications: a pharmacokinetic perspective. CNS Drugs. 2001;15(6):469–94. doi: 10.2165/00023210-200115060-00005. [DOI] [PubMed] [Google Scholar]
  7. DSM-I. Diagnostic and Statistical Manual of Mental Disorders. Washington, DC: American Psychiatric Press Inc; 1952. [Google Scholar]
  8. Goldstein BI, Birmaher B, Axelson DA, Goldstein TR, Esposito-Smythers C, Strober MA, Hunt J, Leonard H, Gill MK, Iyengar S, Grimm C, Yang M, Ryan ND, Keller MB. Significance of cigarette smoking among youths with bipolar disorder. Am J Addict. 2008;17(5):364–71. doi: 10.1080/10550490802266151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hartz SM, Pato CN, Medeiros H, Cavazos-Rehg P, Sobell JL, Knowles JA, Bierut LJ, Pato MT Genomic Psychiatry Cohort Consortium. Comorbidity of severe psychotic disorders with measures of substance use. JAMA Psychiatry. 2014;71(3):248–54. doi: 10.1001/jamapsychiatry.2013.3726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Keshavan MS, Morris DW, Sweeney JA, Pearlson G, Thaker G, Seidman LJ, Eack SM, Tamminga C. A dimensional approach to the psychosis spectrum between bipolar disorder and schizophrenia: the Schizo-Bipolar Scale. Schizophr Res. 2011;133(1–3):250–4. doi: 10.1016/j.schres.2011.09.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kitchens JM. Does this patient have an alcohol problem? JAMA. 1994;272(22):1782–7. [PubMed] [Google Scholar]
  12. Kreinin A, Novitski D, Rabinowitz D, Weizman A, Grinshpoon A. Association between tobacco smoking and bipolar affective disorder: clinical, epidemiological, cross-sectional, retrospective study in outpatients. Compr Psychiatry. 2012;53(3):269–74. doi: 10.1016/j.comppsych.2011.04.063. [DOI] [PubMed] [Google Scholar]
  13. Lake CR, Hurwitz N. Schizoaffective disorders are psychotic mood disorders; there are no schizoaffective disorders. Psychiatry Res. 2006;143(2–3):255–87. doi: 10.1016/j.psychres.2005.08.012. [DOI] [PubMed] [Google Scholar]
  14. Lasser K, Boyd JW, Woolhandler S, Himmelstein DU, McCormick D, Bor DH. Smoking and mental illness: A population-based prevalence study. JAMA. 2000;284(20):2606–10. doi: 10.1001/jama.284.20.2606. [DOI] [PubMed] [Google Scholar]
  15. Mancuso SG, Morgan VA, Mitchell PB, Berk M, Young A, Castle DJ. A comparison of schizophrenia, schizoaffective disorder, and bipolar disorder: Results from the Second Australian national psychosis survey. J Affect Disord. 2014;172C:30–37. doi: 10.1016/j.jad.2014.09.035. [DOI] [PubMed] [Google Scholar]
  16. Mitsuda H. The concept of “atypical psychoses” from the aspect of clinical genetics. Acta Psychiatr Scand. 1965;41(3):372–7. doi: 10.1111/j.1600-0447.1965.tb04996.x. [DOI] [PubMed] [Google Scholar]
  17. Nurnberger JI, Blehar MC, Kaufmann CA, York-Cooler C, Simpson SG, Harkavy-Friedman J, Severe JB, Malaspina D, Reich T. Diagnostic interview for genetic studies. Rationale, unique features, and training. NIMH Genetics Initiative. Arch Gen Psychiatry. 1994;51(11):849–59. doi: 10.1001/archpsyc.1994.03950110009002. discussion 863–4. [DOI] [PubMed] [Google Scholar]
  18. Ostacher MJ, Nierenberg AA, Perlis RH, Eidelman P, Borrelli DJ, Tran TB, Marzilli Ericson G, Weiss RD, Sachs GS. The relationship between smoking and suicidal behavior, comorbidity, and course of illness in bipolar disorder. J Clin Psychiatry. 2006;67(12):1907–11. doi: 10.4088/jcp.v67n1210. [DOI] [PubMed] [Google Scholar]
  19. Pagel T, Baldessarini RJ, Franklin J, Baethge C. Characteristics of patients diagnosed with schizoaffective disorder compared with schizophrenia and bipolar disorder. Bipolar Disord. 2013;15(3):229–39. doi: 10.1111/bdi.12057. [DOI] [PubMed] [Google Scholar]
  20. Parks Joe, Svendsen Dale, Patricia Singer, Foti Mary Ellen. NASMHPD Medical Directors Council Publications and Reports. Alexandria, VA: National Association of State Mental Health Program Directors Medical Directors Council; 2006. Morbidity and Mortality in People with Serious Mental Illness; p. 87. [Google Scholar]
  21. Pato MT, Sobell JL, Medeiros H, Abbott C, Sklar BM, Buckley PF, Bromet EJ, Escamilla MA, Fanous AH, Lehrer DS, Macciardi F, Malaspina D, McCarroll SA, Marder SR, Moran J, Morley CP, Nicolini H, Perkins DO, Purcell SM, Rapaport MH, Sklar P, Smoller JW, Knowles JA, Pato CN and Genomic Psychiatry Cohort Consortium. The genomic psychiatry cohort: partners in discovery. Am J Med Genet B Neuropsychiatr Genet. 2013;162B(4):306–12. doi: 10.1002/ajmg.b.32160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rustin TA. Assessing nicotine dependence. Am Fam Physician. 2000;62(3):579–84. 591–2. [PubMed] [Google Scholar]
  23. Tamminga CA, Ivleva EI, Keshavan MS, Pearlson GD, Clementz BA, Witte B, Morris DW, Bishop J, Thaker GK, Sweeney JA. Clinical phenotypes of psychosis in the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) Am J Psychiatry. 2013;170(11):1263–74. doi: 10.1176/appi.ajp.2013.12101339. [DOI] [PubMed] [Google Scholar]
  24. Vanable PA, Carey MP, Carey KB, Maisto SA. Smoking among psychiatric outpatients: relationship to substance use, diagnosis, and illness severity. Psychol Addict Behav. 2003;17(4):259–65. doi: 10.1037/0893-164X.17.4.259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Waxmonsky JA, Thomas MR, Miklowitz DJ, Allen MH, Wisniewski SR, Zhang H, Ostacher MJ, Fossey MD. Prevalence and correlates of tobacco use in bipolar disorder: data from the first 2000 participants in the Systematic Treatment Enhancement Program. Gen Hosp Psychiatry. 2005;27(5):321–8. doi: 10.1016/j.genhosppsych.2005.05.003. [DOI] [PubMed] [Google Scholar]
  26. Williams PV, McGlashan TH. Schizoaffective psychosis. I. Comparative long-term outcome. Arch Gen Psychiatry. 1987;44(2):130–7. doi: 10.1001/archpsyc.1987.01800140032005. [DOI] [PubMed] [Google Scholar]

RESOURCES