CYP2A6 Effects on Subjective Reactions to Initial Smoking Attempt.

INTRODUCTION: In very novice smokers, CYP2A6 genotypes that reduce nicotine metabolism to an intermediate rate may increase smoking risk, relative to both normal and slow rates. The present study examined the hypothesis that intermediate metabolism variants are associated with greater pleasurable effects of the initial smoking attempt than either normal or slow metabolism variants. METHODS: Participants were novice smokers (N = 261, 65% female) of European descent. Predicted nicotine metabolic rate based on CYP2A6 diplotypes (CYP2A6 Diplotype Predicted Rate [CDPR]) was partitioned into Normal, Intermediate, and Slow categories using a metabolism metric. Subjective reactions to the initial smoking attempt were assessed by the Pleasurable Smoking Experiences (PSE) scale, which was collected within 3 years of the initial smoking attempt. The effect of CDPR on PSE was tested using a generalized linear model in which CDPR was dummy coded and Intermediate CDPR was the reference condition. Gender was included in the model as a control for higher PSE scores by males. RESULTS: Lower PSE scores were associated with Normal CDPR, ß = -0.34, P = .008, and Slow CDPR, ß = -0.52, P = .001, relative to Intermediate CDPR. CONCLUSIONS: Intermediate CDPR-enhanced pleasurable effects of the initial smoking attempt relative to other CYP2A6 variants. This finding is consistent with the hypothesis that the risk effect of Intermediate CDPR on early smoking is a function of optimal pleasurable effects. IMPLICATIONS: This study supports our recent hypothesis that CYP2A6 diplotypes that encode intermediate nicotine metabolism rate are associated with enhanced pleasurable events following the initial smoking attempt, compared with diplotypes that encode either normal or slow metabolism. This hypothesis was offered to account for our unexpected previous finding of enhanced smoking risk in very novice smokers associated with intermediate metabolism rate. Our new finding encourages further investigation of time-dependent relations between CYP2A6 effects and smoking motives, and it encourages laboratory study of the mechanisms underlying the initial smoking enhancement in novice smokers associated with intermediate metabolism.

CYP2A6 Longitudinal Effects in Young Smokers.

INTRODUCTION: The present study sought to identify time-dependent within-participant effects of CYP2A6 genotypes on smoking frequency and nicotine dependence in young smokers. METHODS: Predicted nicotine metabolic rate based on CYP2A6 diplotypes (CYP2A6 diplotype predicted rate [CDPR]) was partitioned into Normal, Intermediate, and Slow categories using a metabolism metric. Growth-curve models characterized baseline and longitudinal CDPR effects with data from eight longitudinal assessments during a 6-year period (from approximately age 16-22) in young smokers of European descent (N = 296, 57% female) who had smoked less than 100 cigarettes lifetime at baseline and more than that amount by Year 6. Phenotypes were number of days smoked during the previous 30 days and a youth version of the Nicotine Dependence Syndrome Scale (NDSS). A zero-inflated Poisson growth-curve model was used to account for the preponderance of zero days smoked. RESULTS: At baseline, Intermediate CDPR was a risk factor relative to both Normal and Slow CDPR for smoking frequency and the NDSS. Slow CDPR was associated with the highest probability of smoking discontinuation at baseline. However, due to CDPR time trend differences, by young adulthood these baseline effects had been reordered such that the greatest risks for smoking frequency and the NDSS were associated with Normal CDPR. CONCLUSIONS: Reduced metabolism CYP2A6 genotypes are associated with both risk and protective effects in novice smokers. However, differences in the time-by-CDPR effects result in a reordering of genotype effects such that normal metabolism becomes the risk variant by young adulthood, as has been reliably reported in older smokers.

The "backbone" of stigma: identifying the global core of public prejudice associated with mental illness.

OBJECTIVES: We used the Stigma in Global Context-Mental Health Study to assess the core sentiments that represent consistent, salient public health intervention targets. METHODS: Data from 16 countries employed a nationally representative sampling strategy, international collaboration for instrument development, and case vignettes with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition depression and schizophrenia criteria. We measured knowledge and prejudice with existing questions and scales, and employed exploratory data analysis to examine the public response to 43 items. RESULTS: Across countries, levels of recognition, acceptance of neurobiological attributions, and treatment endorsement were high. However, a core of 5 prejudice items was consistently high, even in countries with low overall stigma levels. The levels were generally lower for depression than schizophrenia, and exclusionary sentiments for more intimate venues and in authority-based roles showed the greatest stigma. Negative responses to schizophrenia and depression were highly correlated across countries. CONCLUSIONS: These results challenge researchers to reconfigure measurement strategies and policymakers to reconsider efforts to improve population mental health. Efforts should prioritize inclusion, integration, and competences for the reduction of cultural barriers to recognition, response, and recovery.

The Theory of Industrial Society and Cultural Schemata: Does the "Cultural Myth of Stigma" Underlie the WHO Schizophrenia Paradox?

The WHO's International Studies of Schizophrenia conclude that schizophrenia may have a more benign course in "developing" societies than in the West. The authors focus on this finding's most common corollary: cultural schemata are shaped by the transition from agrarian to industrial society. Developing societies are viewed as traditional, gemeinschaft cultures lacking the stigmatizing beliefs about persons with mental illness held in modern, gesellschaft cultures of developed societies. The Stigma in Global Context-Mental Health Study formalized the cultural myth of public stigma (CMPS) with propositions linking level of development to intolerant, exclusionary, and individualistic attitudes. In 17 countries, the authors find no support for the corollary; where support is found, the findings are opposite expectations, with developed societies reporting lower stigma levels. Reconceptualizing of the cultural landscape on more specific dimensions also produces null or contrary findings. This correction to nostalgic myths of cultural context in developing societies thwarts misguided treatment, policy, and stigma-reduction efforts.

"A disease like any other"? A decade of change in public reactions to schizophrenia, depression, and alcohol dependence.

OBJECTIVE: Clinicians, advocates, and policy makers have presented mental illnesses as medical diseases in efforts to overcome low service use, poor adherence rates, and stigma. The authors examined the impact of this approach with a 10-year comparison of public endorsement of treatment and prejudice. METHOD: The authors analyzed responses to vignettes in the mental health modules of the 1996 and 2006 General Social Survey describing individuals meeting DSM-IV criteria for schizophrenia, major depression, and alcohol dependence to explore whether more of the public 1) embraces neurobiological understandings of mental illness; 2) endorses treatment from providers, including psychiatrists; and 3) reports community acceptance or rejection of people with these disorders. Multivariate analyses examined whether acceptance of neurobiological causes increased treatment support and lessened stigma. RESULTS: In 2006, 67% of the public attributed major depression to neurobiological causes, compared with 54% in 1996. High proportions of respondents endorsed treatment, with general increases in the proportion endorsing treatment from doctors and specific increases in the proportions endorsing psychiatrists for treatment of alcohol dependence (from 61% in 1996 to 79% in 2006) and major depression (from 75% in 1996 to 85% in 2006). Social distance and perceived danger associated with people with these disorders did not decrease significantly. Holding a neurobiological conception of these disorders increased the likelihood of support for treatment but was generally unrelated to stigma. Where associated, the effect was to increase, not decrease, community rejection. CONCLUSIONS: More of the public embraces a neurobiological understanding of mental illness. This view translates into support for services but not into a decrease in stigma. Reconfiguring stigma reduction strategies may require providers and advocates to shift to an emphasis on competence and inclusion.