P300 in alcohol dependence: Effects of TaqI-A genotype

Background and Objectives: TaqI-A polymorphism, related to D2 dopamine receptor (DRD2), and event-related P300 potentials have been considered markers of alcohol dependence. The effect of alcohol use variables and TaqI-A on P300 in a single sample have been hardly analysed previously. This study examined changes in P300 parameters after six months of abstinence in alcohol-dependent subjects classified by their TaqI-A genotype. Methods: 102 men with alcohol dependence were studied at baseline and at 6 months of continued abstinence. P300 was recorded using an auditory paradigm. TaqI-A polymorphism was genotyped: 34.3% of sample was classified as A1[TaqI-A1/TaqI-A1and TaqI-A1/TaqI-A2] and 65.7% as A2 [TaqI-A2/TaqI-A2]. The association between P300 and TaqI-A and the correlation with age and alcohol consumption were considered. Results: The abstinence period was not associated to differences in neither P300 latency (F[1, 99] = 1.154 p = 0.285) nor amplitude (F[1, 99] = 1.453, p = 0.231). A1 subgroup was related to a longer latency (F[1, 99] = 5.055 p = 0.027), an early abuse age onset (F[1, 100] = 14.552 p < 0.001) and close to be significant to an early dependence age onset (F[1, 100] = 3.868 p = 0.052). Other drinking pattern variables were not associated to p300 measures. Family history for alcoholism and TaqI-A were not related (X[1] = 0.327 p = 0.568) and no association was found with p300 measures. Current age correlated positively with P300 latency (F[1, 99] = 26.082, p < 0,001) and negatively with amplitude (F[1, 99] = 5.297 p = 0.023). P300 amplitude was not influenced by alcohol use variables nor TaqI-A polymorphism. Conclusions: P300 latency could be a biological marker of vulnerability to alcohol dependence related to TaqI-A1 polymorphism, irrespective of alcohol use variables. Received: 11 November 2008 Revised: 10 August 2009 Accepted: 14 September 2009 Background and Objectives P300 is a positive electrical deflection recorded at maximal amplitudes over the midline centroparietal scalp in response to rare attended events within a sequence of similar, but discriminate, stimuli. Although the functional significance of P300 is still debated1, 2, its amplitude indexes the allocation of resources for the evaluation of stimuli and its sensitivity to instrumental manipulation indicates that it reflects a neural substrate of controlled information processing strategies3. Reduced P300 amplitude has been reported in many psychiatric disorders, including schizophrenia4, depression5, and alcoholism6. Various studies have related the presence of lower P300 amplitude or longer P300 latency with alcoholism7-10. Many of these studies have been carried out on children of alcoholics, so P300 alterations have been considered a genetic marker of vulnerability to alcoholism11 or an endophenotype of an alcoholism subtype12-15. The brain dopaminergic system, which is centrally involved in reward and learning, has been widely studied in substance use disorders. The TaqI-A single-nucleotide polymorphism (SNP) (rs1800497) located near the 3 ́region of the dopamine D2 receptor gene (DRD2; chromosome 11q22–q23) has been considered a genetic marker of alcoholism1619. TaqI-A SNP consists of the substitution of C > T, also called the A2 and A1 alleles, respectively, which affects a previously unidentified protein kinase gene called ANKK1 (ankyrin repeat and kinase domain containing 1)20. There is no consensus about the role of the A1 allele and A1 genotype (heterozygous or homozygous for A1 allele) in addictive behaviour, but three meta-analyses have shown a robust association between TaqI-A SNP and alcoholism21, 22. In addition, the P300 wave has been associated with dopaminergic activity23 and TaqI-A polymorphism has been associated with P300-wave changes. The relationship between P300 wave and TaqI-A has been examined in non alcoholic sons of alcoholics. Longer latencies24 and amplitude attenuation have been observed in A1 subjects25, 26. We found that A1 alcohol-dependent males had longer P300 latencies than A2 alcohol dependents and healthy controls27. Nonetheless, other studies have not found any differences between the A1 and A2 subgroups28. To further examine P300 capability to measure possible differences associated to the TaqI A1 and A2 subgroups and to ethanol toxic effect in alcohol dependence, we studied changes in the P300 wave after a period of abstinence in a sample of alcohol-dependent males classified by TaqI-A genotype. There have been published several works that had taken into account an abstinency period and the influence of family history for alcoholism on P300wave measures but not the TaqI A polymorphism29-32.