title: Latent class typology of nicotine withdrawal: genetic contributions and association with failed smoking cessation and psychiatric disorders.
abstract: BACKGROUND
  Nicotine withdrawal is associated with failed smoking cessation and thus contributes to continuance of the habit and increases risk of smoking-related illnesses. Withdrawal is also associated with psychiatric disorders such as depression and alcoholism. However, relatively little is known about how to characterize the severity of withdrawal, including whether withdrawal subtypes exist in male smokers. If so, do these subtypes represent quantitative or qualitative differences?
  
  
  METHODS
  Smoking and withdrawal data were obtained from 4112 male-male twin pairs of the Vietnam Era Twin Registry during a 1992 administration of the Diagnostic Interview Schedule. Latent Class Analysis (LCA) was used to derive significantly different nicotine withdrawal profiles, and their association with psychiatric disorders was assessed. Genetic and environmental contributions and the correlation between these contributions were evaluated using bivariate biometrical modeling of the withdrawal phenotype and failed smoking cessation.
  
  
  RESULTS
  The LCA model which best fit the data was a four-class severity continuum. Psychiatric disorders were significantly associated with more severe classes and the magnitude of the association increased as withdrawal severity increased. Genetics accounted for 31% and 51% of the variance in risk for withdrawal and failed cessation, respectively. The genetic contributions were significantly correlated (r = 0.37).
  
  
  CONCLUSIONS
  Nicotine withdrawal classes are characterized by quantitative differences. The strong association between psychiatric disorders and withdrawal severity and the significant genetic correlation between withdrawal and cessation highlight the importance of withdrawal severity. Further refinement of the DSM definition of withdrawal to incorporate severity ratings may be warranted.
authors.affiliation: Department of Internal Medicine, Division of General Medical Sciences, Washington University School of Medicine, St Louis, MO, USA. hxian@im.wustl.edu
authors.forename: Hong
authors.initials: H
authors.lastname: Xian
authors.forename: Jeffrey F
authors.initials: JF
authors.lastname: Scherrer
authors.forename: Pamela A F
authors.initials: PA
authors.lastname: Madden
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lyons
authors.forename: Ming
authors.initials: M
authors.lastname: Tsuang
authors.forename: William R
authors.initials: WR
authors.lastname: True
authors.forename: Seth A
authors.initials: SA
authors.lastname: Eisen
mesh_terms: D000328:Adult; D005260:Female; D005731:Ganglionic Stimulants / Q000009:adverse effects* / Q000494:pharmacology*; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000150:complications / Q000235:genetics; D008875:Middle Aged; D009538:Nicotine / Q000009:adverse effects* / Q000494:pharmacology*; D012307:Risk Factors; D012720:Severity of Illness Index; D016540:Smoking Cessation; D013375:Substance Withdrawal Syndrome / Q000235:genetics* / Q000523:psychology*; D014029:Tobacco Use Disorder / Q000235:genetics* / Q000523:psychology* / Q000628:therapy; D016896:Treatment Outcome
chemical_list: D005731:Ganglionic Stimulants; D009538:Nicotine