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Single nucleotide polymorphism near CREB1, rs7591784, is associated with pretreatment methamphetamine use frequency and outcome of outpatient treatment for methamphetamine use disorder.

ABSTRACT: Although stimulant dependence is highly heritable, few studies have examined genetic influences on methamphetamine dependence. We performed a candidate gene study of 52 SNPs and pretreatment methamphetamine use frequency among 263 methamphetamine dependent Hispanic and Non-Hispanic White participants of several methamphetamine outpatient clinical trials in Los Angeles. One SNP, rs7591784 was significantly associated with pretreatment methamphetamine use frequency following Bonferroni correction (p < 0.001) in males but not females. We then examined rs7591784 and methamphetamine urine drug screen results during 12 weeks of outpatient treatment among males with treatment outcome data available (N = 94) and found rs7591784 was significantly associated with methamphetamine use during treatment controlling for pretreatment methamphetamine use. rs7591784 is near CREB1 and in a linkage disequilibrium block with rs2952768, previously shown to influence CREB1 expression. The CREB signaling pathway is involved in gene expression changes related to chronic use of multiple drugs of abuse including methamphetamine and these results suggest that variability in CREB signaling may influence pretreatment frequency of methamphetamine use as well as outcomes of outpatient treatment. Medications targeting the CREB pathway, including phosphodiesterase inhibitors, warrant investigation as pharmacotherapies for methamphetamine use disorders.

SUBMITTER: Heinzerling KG

PROVIDER: S-EPMC5053101 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Project description:BackgroundAlexithymia, which is characterized by difficulty identifying and describing feelings, is a stable personality trait and it has been associated with early life experiences. Methamphetamine dependence patients with high level of alexithymia may be particularly vulnerable to engaging in more frequent methamphetamine use. Therefore, we aimed to evaluate whether alexithymia was associated with frequency of methamphetamine use. Additionally, the current study sought to examine early-life factors associated with the development of alexithymia, i.e., parental rearing styles.MethodParticipants were 108 non-injecting methamphetamine dependent patients from a male compulsory detoxification center. The level of alexithymia was assessed by Toronto Alexithymia Scale-20(TAS-20). In addition, we applied Egna Minneu av. Bardndosnauppforstran (EMBU) to assess the parental rearing styles, including the dimensions of warmth, rejection, punishment/strictness, overinvolvement, overprotection, and favoring.ResultsThe total score of TAS-20 was positively correlated with frequency of methamphetamine use (r = 0.26, p < 0.01). Specifically, except for externally oriented thinking, difficulty identifying feelings (r = 0.23, p < 0.05) and difficulty describing feelings (r = 0.25, p < 0.05) were positively correlated with frequency of methamphetamine use. Multiple linear regression showed that more maternal rejection (B = 0.59, p = 0.002), or less maternal warmth (B = -0.22, p = 0.004) was associated with higher levels of alexithymia. Ordinal logistic regression showed that for every 1 score increase in the total score of TAS-20, there was a 1.06 times risk of a one level increase in the level of methamphetamine use frequency (OR = 1.06, p = 0.01).ConclusionsThese results have major implications for understanding the role of alexithymia in craving and addiction, while providing a further and explicit entry point for addiction treatment. Moreover, more attention should be focused on parenting in relation to early experiences.

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Single nucleotide polymorphism near CREB1, rs7591784, is associated with pretreatment methamphetamine use frequency and outcome of outpatient treatment for methamphetamine use disorder.

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