Neurotransmission-related genetic polymorphisms, negative affectivity traits, and gender predict tobacco abstinence symptoms across 44 days with and without nicotine patch.

Abstract

Genetic and personality trait moderators of tobacco abstinence-symptom trajectories were assessed in a highly controlled study. Based on evidence suggesting their importance in stress reactivity and smoking, moderators studied were serotonin transporter gene (5-HTTLPR) and dopamine D2 receptor gene (DRD2) polymorphisms, and negative affect-related personality traits. Smokers were randomly assigned to quit smoking with nicotine or placebo patches. Financial incentives resulted in 80% verified abstinence across the 44-day study. Individuals with one or two short alleles of 5-HTTLPR (S carriers) experienced larger increases in negative affect (NA) symptoms than those without a short allele. Nicotine replacement therapy (NRT) alleviated anxiety only in S carriers. NRT reduced NA to a greater extent in DRD2 A1 carriers than in A2A2 individuals during the first two weeks of treatment (when on the 21 mg patch); however, A1 carriers experienced a renewal of NA symptoms when switched to the 7mg patch and when off patch, while A2A2 individuals continued to benefit from NRT. The results suggest that the effects of genotype and treatment may vary across different durations of abstinence, treatment doses, and genotypes.Differences in genetic makeup are a potentially important, yet little studied factor that may help explain individual differences in negative affect (NA)-related tobacco abstinence symptoms (TAS) (reviewed by Pergadia, Heath, Martin, & Madden, 2006). The large individual differences in the severity and time course of NA-related TAS (Piasecki, Jorenby, Smith, Fiore, & Baker, 2003a, 2003b, 2003c appear to be important because relapse to smoking occurs more often in those experiencing high levels of NA (Shiffman & Waters, 2004). However, the factors that predict severity and nature of NA-related TAS have only been partially characterized. While NA-related personality traits (NATs) and history of major NArelated psychiatric disorder have been found to predict both severity of NA during abstinence and relapse (Covey, Glassman, & Stetner, 1990;Gilbert et al., 2002; Gilbert, Crauthers, Mooney, McClernon, & Jensen, 1999;Zvolensky, Lejuez, Kahler, Correspondence concerning this article should be addressed to David G. Gilbert, Department of Psychology, Southern Illinois University, Mailcode 6502, Carbondale, Illinois, 62901-6502. Electronic mail may be sent to dgilbert@siu.edu. Publisher's Disclaimer:The following manuscript is the final accepted manuscript. It has not been subjected to the final copyediting, fact-checking, and proofreading required for formal publication. It is not the definitive, publisher-authenticated version. The American Psychological Association and its Council of Editors disclaim any responsibility or liabilities for errors or omissions of this manuscript version, any version derived from this manuscript by NIH, or other third parties. The published version is available at www.apa.org/journals/abn. & Brown, 2004), these factors and degree of nicotine dependence (Gilbert et al., 2002;Pi...

DRD2 -related TaqIA polymorphism modulates motivation to smoke

“…Specifi cally, a two-level model was fi tted, where a level-1 submodel describes how each individual ' s craving changed across 15 monitoring sessions over time and a level-2 submodel relates interindividual differences in craving trajectories to predictors including individual genotypes, treatment, sex, the interaction of genotypes and treatment, the interaction of genotypes and sex, and other control personal variables such as age, FTND scores, and prequit craving levels. To obtain a more parsimonious representation from each multilevel model, level-2 fi xed effect parameters that were not signifi cant according to the single parameter hypothesis test ( z -statistic but labeled as t ratio in HLM) or did not account for signifi cant variance according to the model deviance statistic were removed sequentially from the initial model (for more details about this approach, see Supplementary Material and Gilbert et al, 2009 ). Because of statistical power limitations associated with the small sample size of the smoke group, we limited analysis at this step to the two abstinence groups ( n = 129).…”

“…This is an important possibility that deserves further investigation. It should be noted that nicotine patch treatment signifi cantly reduced negative affective symptoms during smoking cessation in this study ( Gilbert et al, 2009 ), indicating that other factors could have attenuated the craving-suppressing effects of NRT.…”

“…Individuals with at least one A1 allele appear to have up to 40% fewer striatal DRD2 receptors relative to those carrying the A2/A2 allele ( Noble, Blum, Ritchie, Montgomery, & Sheridan, 1991 ;Ritchie and Noble, 2003 ). Compared with A2/A2 genotype, TaqIA A1 variant has been associated with an increased electroencephalography slowing during smoking abstinence ( Gilbert et al, 2004 ), with less improvement in negative affect withdrawal symptoms by antidepressants ( Cinciripini et al, 2004 ;David et al, 2003 ), and with more short-lived attenuation of affective symptoms by nicotine replacement therapy (NRT; Gilbert et al, 2009 ). In contrast, comprehensive reviews of many studies suggest that main effects of this genotype on smoking cessation have been elusive ( Munafò, Timpson, David, Ebrahim, & Lawlor, 2009 ;Munafò et al, 2004 ).…”

“…Detailed description of subjects participating in the study was reported in a separate paper ( Gilbert et al, 2009 ). In brief, smokers wanting to quit were recruited in a Midwestern university community from 1998 through 2004.…”

Sigara Bagimliliginin Genetigi

“…[46] 5HTTLPR geninin sigara bırakma tedavisi ile ilişkisini araştıran çalışmalar, kısa allelin nikotin replasman tedavisi ile önemli bir ilişkisi olduğu, kısa allel taşıyanların sigarayı bırakmada daha başarısız olduğu saptanmıştır. [47] David ve arkadaşları ise çalışmalarında sigara bırakma tedavisinin etkinliğinin, tedavi esnasında çıkan yoksunluk belirtilerinin şiddetinin, kullanılan ilaçların tedavi dozlarının, genotiplerin farklılıklarına göre değişebileceğini öne sürmüş-lerdir. [48] Japon toplumunda yapılan bir çalışmanın bazı sonuçlarına göre, 5-HTTLPR geninin L allelinin uzunluğunun sigara içimi ile ilişkili olduğunu varsayan bir nörokimyasal hipotez öne sürülmüştür.…”