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Key Points

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  • Disease summary:

    • Nicotine dependence (ND) is a complex psychiatric disorder determined by both genetics and environment, as well as gene-gene and gene-environment interactions.

    • About 20% of US adults use tobacco (primarily cigarettes); 70% of smokers want to quit, but only 4% to 7% are successful on a long-term basis without assistance.

    • Tobacco use is the leading preventable cause of morbidity and death in the United States.

    • It is the most common cause of cancer-related deaths in many countries, including cancers of the lung, larynx, esophagus, oral tissues, and bladder.

    • Tobacco use is also a leading cause of coronary artery disease, myocardial infarction, peripheral vascular disease, stroke, and chronic obstructive pulmonary disease (COPD).

    • Tobacco use is directly responsible for more than 443,000 premature deaths annually in the United States, with direct and indirect healthcare costs exceeding $193 billion.

    • Extensive research documents the relation between tobacco use and psychiatric conditions, particularly depression, anxiety disorders, substance abuse, and schizophrenia. Nicotine-dependent individuals appear more likely to develop depressive and anxiety disorders, and quitting partially reduces that risk. Tobacco users with psychiatric disorders are less likely to quit and are at risk for a substantially shortened life spans. Tobacco use prevalence rates for those with psychotic, depressive, or anxiety disorders or for those who are alcohol dependent is much higher than for the general population. In addition, nicotine alters the metabolism of many medications, including psychotropics, requiring close monitoring and dosage adjustment.

  • Monogenic forms:

    • No single-gene cause of ND is known.

  • Family history:

    • Initiation of smoking is two to four times more likely for adolescents whose parents and siblings smoke.

  • Twin studies:

    • Monozygotic twins have a significantly higher concordance rate for ND than dizygotic twins. For example, one study revealed the concordance rate for ND in monozygotic twins to be 72% versus 28% for dizygotic twins.

  • Environmental factors:

    • Many factors such as peers, friends, and family members who smoke, low socioeconomic status, or stressful environments are implicated as environmental triggers for ND.

  • Association studies:

    • Many studies, including candidate gene-based association and genome-wide association (GWA) studies, have been conducted. Genetic variants associated with ND provide insight into the etiology of ND; however, testing for single-nucleotide polymorphisms (SNPs) is not yet clinically validated to diagnose or guide the management of ND.

  • Pharmacogenomics:

    • There are reproducible and clinically significant associations of a phenotypic biomarker of nicotine metabolism rate (and CYP2A6 enzyme activity) with smoking cessation and response to nicotine replacement therapies. Although there is promising evidence for a role in smoking cessation for SNPs in the nicotinic receptor subunit genes β2, α5, and α3, effects are small and not consistently replicated.

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Diagnostic Criteria and Clinical Characteristics

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Diagnostic Criteria for ND

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DSM-IV diagnosis of ND requires an individual to meet at least three of the following criteria during a 12-month period:

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  • Tolerance: the need for a markedly increased amount of nicotine to produce the desired effect ...

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