The TaqI-A of the ANKK1 gene and the C957T of the DRD2 gene are epistatically associated with psychopathic traits in alcohol-dependent patients.

Drug addiction is a complex disease with overlapping stages and influenced by multiple environmental and genetic factors. In addition to neurobiological changes, repeated drug exposure modulates affective responses to drug stimuli including visual cues. Here, we made a preliminary screening among ten Single Nucleotide Polymorphisms (SNP) of the CNR1 (rs806368, rs1049353, rs6454674, rs7766029), FAAH (rs324420, rs12075550), DRD2 (rs6277), ANKK1 (rs1800497), COMT (rs4680), and OPRM1 (rs1799971) genes to identify that SNPs that were more directly associated with alcohol, tobacco and/or cannabis consumption in young individuals (n = 91). Also, affective rating for alcohol-, tobacco- and cannabis-related pictures was examined in each individual. Our results make it possible to select the rs324420 SNP (C385A) of the FAAH gene for further analysis. Increasing the sample size up to n = 185 we found that the homozygous CC C385A SNP genotype was associated with risky alcohol use (p = 0.006, odds ratio 2.38). Subsequently, we replicated this genetic association with risky alcohol use using another independent sample. Risky drinkers (mean 166.8 g pure alcohol) and smokers (more than 15 cigarettes) rated drug pictures more positively (p < 0.001) and they showed a strong positive correlation with drug use during weekends, which is the period in which the first problematic experiences with alcohol and other drugs appear (initial stages of the drug addiction process). As conclusion, because drug addiction is a multi-step process and a preventable disease, our results indicate that the FAAH C385A SNP is one of the most promising candidates for individuals who are at higher risk for alcohol problems.

The objectives of this paper were to evaluate the association of subjective memory complaints (SMC) with perceived state of health, mood and episodic memory (associative and everyday memory). We studied these areas using two different complaint assessment methods (three general questions and a validated scale). The study included 269 older adults (aged 65-87) with age-related memory changes, but without cognitive impairment. They were evaluated with Mini-cognitive Exam, Rivermead Behavioural Memory Test (a test of everyday memory), Paired Associates Learning Test, Memory Failures of Everyday Questionnaire, three memory complaints questions, Nottingham Health Profile and Geriatric Depression Scale. The results indicated that memory for everyday performance, mood and perceived health were independent predictors of SMC, with mood and perceived health being stronger predictors than actual memory performance. Age was not associated with subjective memory and, with regard to level of education, only the illiterate level was associated with SMC. A specific questionnaire on subjective memory was found to be preferable to an aggregate of complaints questions on self-reported memory; only health profile was found to predict the outcomes on memory complaints questions. Our conclusion is that a group of underlying factors other than everyday memory were playing a role in SMC; these SMC of subjects with age-related memory changes were mainly associated with subjective evaluations of their health.

Polymorphisms of DRD2 and ANKK1 have been associated with psychiatric syndromes where there is believed to be an underlying learning process deficit such as addiction, post-traumatic stress disorder and psychopathy. We investigated the effects of the DRD2 C957T and ANKK1 TaqIA single nucleotide polymorphism (SNP), which have been associated with psychopathic traits in alcoholic patients, on fear conditioning and aversive priming in healthy volunteers. We found that the DRD2 C957T SNP, but not the ANKK1 TaqIA SNP, was associated with both differential conditioning of the skin conductance response and the aversive priming effect. There were no differences between the genotype groups with respect to the extinction of the skin-conductance conditioned response. These results suggest that the C957T SNP could be related to learning differences associated with the risk of developing psychiatric disorders in individuals that are carriers of the C homozygous genotype. Our genetic data raise the possibility that the dopaminergic system functional variations determined by this SNP could affect fear learning.

Genetic variants that are related to the dopaminergic system have been frequently found to be associated with various neurological and mental disorders. Here, we studied the relationships between some of these genetic variants and some cognitive and psychophysiological processes that are implicated in such disorders. Two single nucleotide polymorphisms were chosen: one in the dopamine D2 receptor gene (rs6277-C957T) and one in the catechol-O-methyltransferase gene (rs4680-Val158Met), which is involved in the metabolic degradation of dopamine. The performance of participants on two long-term memory tasks was assessed: free recall (declarative memory) and mirror drawing (procedural motor learning). Heart rate (HR) was also monitored during the initial trials of the mirror-drawing task, which is considered to be a laboratory middle-stress generator (moderate stress), and during a rest period (low stress). Data were collected from 213 healthy Caucasian university students. The C957T C homozygous participants showed more rapid learning than the T allele carriers in the procedural motor learning task and smaller differences in HR between the moderate-and the low-stress conditions. These results provide useful information regarding phenotypic variance in both healthy individuals and patients.