The COMT Val158Met polymorphism is associated with novelty seeking in czech methamphetamine abusers: Preliminary results

Abstract

Attempts have been made to obtain indicators of the abuse of illicit drugs. Many techniques are expensive and/or time-consuming. Others have limitations due to the focus on specific populations. The recent outbreak of fentanyl deaths in Chicago and Detroit related to fentanyl-laced heroin suggest that mortality is a valuable indicator of a drug's presence and prevalence in a community. Drug mortality statistics are accessible from Medical Examiner/Coroner offices. It is possible that including deaths both intentional and non-intentional will give the best overall indication of trends in drug use. By following death rates, it may be possible to provide a ''canary in the coal mine'' for drugs of abuse. We've studied data from the Florida Department of Law Enforcement for cocaine related deaths. Data from 2005 showed 1,943 deaths compared to 1,034 cocaine related deaths in 2000, a 90% increase. Data from the first 6 months of 2006 reveals a continuing increasing trend with an increase of 10.8% compared to 2005. Supporting data from a survey of students at the University of Florida showed an increase of cocaine use in the previous year from 4.0% in 1991 to 7.1% in 2004. There appears to be a renewed epidemic of cocaine abuse in Florida. Interventions are required to prevent progression of this alarming trend.

Methamphetamine Induces Long-Term Alterations in Reactivity to Environmental Stimuli: Correlation with Dopaminergic and Serotonergic Toxicity

“…Accordingly, our data are consistent with previous evidence showing that METH induces emotional alterations (Comer et al 2001;Looby and Earleywine 2007), reduces novelty-seeking behavior (Misslin and Ropartz 1981) and decreases novelty-induced exploration due to non-specific effects on arousal (Berlyne et al 1966). METH abusers and addicts express a variable degree of novelty-seeking behavior, probably in relationship to their premorbid characteristics and specific genetic polymorphisms (Hosák et al 2006). However, they have been reported to display apathy and avolition (Tomiyama 1990;Ashizawa et al 1996), as well as persistent lack of motivation and anhedonia after several months from METH discontinuation (Wang et al 2004).…”

Association of DRD4 and COMT Polymorphisms with Disgust Sensitivity in Healthy Volunteers

“…Although there has been little research on a direct relationship between dopamine-related genes and disgust sensitivity, association studies between the COMT Val158Met gene polymorphism and other personality traits related to disgust sensitivity provide indirect evidence for their possible association. Novelty-seeking behavior, conceived as the opposite of disgust sensitivity, is related to a need to stimulate the nucleus accumbens [25,26] . The low-activity Met allele of COMT increases prefrontal dopamine levels and decreases dopaminergic neurotransmission in the nucleus accumbens, thereby leading to a decreased need for an enhanced level of dopaminergic activity to stimulate it [26] .…”

“…Novelty-seeking behavior, conceived as the opposite of disgust sensitivity, is related to a need to stimulate the nucleus accumbens [25,26] . The low-activity Met allele of COMT increases prefrontal dopamine levels and decreases dopaminergic neurotransmission in the nucleus accumbens, thereby leading to a decreased need for an enhanced level of dopaminergic activity to stimulate it [26] . Also, the COMT gene has been reported to be potentially associated with harm avoidance temperament, which is known to be related to disgust sensitivity [27] .…”

Genetic association studies of methamphetamine use disorders: A systematic review and synthesis

“…Although the precise pathways and mechanisms by which BDNF acts are unclear, demonstrations of BDNF's role in survival and differentiation of dopamine neurons [Hyman et al, 1991;Spina et al, 1992] has suggested a putative role of BDNF in the addiction process [Bolanos and Nestler, 2004;Tsai, 2007]. COMT is a major mammalian enzyme involved in the metabolic degradation of dopamine released in the brain and has been linked to neurocognition [Malhotra et al, 2002;Rosa et al, 2004;Bruder et al, 2005], novelty seeking [Hosak et al, 2006;Golimbet et al, 2007], amphetamine response [Mattay et al, 2003], and psychiatric disorders [Karayiorgou et al, 1997;Egan et al, 2001;Glatt et al, 2003;Qian et al, 2003] in addition to drug abuse [Vandenbergh et al, 1997;Horowitz et al, 2000]. DRD4 is one of three dopamine receptors (D2 and D3 are the others) that constitute the D2 receptor family, and is involved in a variety of functions such as cognition, locomotor activity, emotion, food intake, positive reinforcement and endocrine regulation [Missale et al, 1998].…”