Associations between experimental substance use, faah-gene variations, impulsivity and sensation seeking / Asociaciones entre el uso experimental de sustancias, variaciones del gen FAAH, impulsividad y búsqueda de sensaciones

Background: Experimental substance use among young people is related to individual factors including personality traits such as impulsivity and sensation seeking, and genetic variations such as single nucleotide polymorphisms (SNPs) in the fatty acid amide hydrolase (FAAH) gene. The objective of this study is to analyze the relationship between these three sets of variables. Methods: Volunteer undergraduate students (N = 861, 76% female, M = 20.7 years) completed an ad hoc questionnaire on variables related to their consumption of alcohol, tobacco, cannabis, synthetic drugs and cocaine. In addition, 591 of them completed the Barratt Impulsiveness Scale-11 (BIS-11) and the Sensation Seeking Scale-V (SSS-V). All participants were genotyped in FAAH C385A SNP and its proxy variant rs12075550. Results: Consistent with previous data, both impulsivity and sensation seeking were associated with most of the variables related to experimental substance use. In addition, we found the first evidence of an association between the rs12075550 SNP and some of these consumption phenotypes. However, no significant association was found between either of the two SNPs and impulsivity or sensation seeking. Conclusions: The results highlight the importance of considering both personality and genetic differences, together with contextual factors, in the analysis of substance use

Antecedentes: el uso experimental de sustancias en los jóvenes está relacionada con factores individuales que incluyen rasgos de personalidad, como impulsividad o búsqueda de sensaciones, y variaciones genéticas, como polimorfismos de un solo nucleótido (SNPs) del gen amida hidrolasa de ácidos grasos (FAAH). El objetivo de este estudio es analizar la relación entre estos tres conjuntos de variables. Método: estudiantes universitarios voluntarios (N = 861, 76% mujeres, M = 20,7 años) rellenaron un cuestionario ad hoc de variables relacionadas con el consumo de alcohol, tabaco, cannabis, drogas sintéticas y cocaína. Además, 591 de ellos rellenaron las escalas BIS-11 y SSS-V. Se genotipó a todos ellos en SNP FAAH C385A y su variante proxy rs12075550. Resultados: como se esperaba, la impulsividad y la búsqueda de sensaciones estuvieron asociadas con la mayor parte de las variables relativas al uso experimental de sustancias. Además, encontramos por primera vez evidencia de una asociación entre rs12075550 y algunos de estos fenotipos de consumo. Sin embargo, no encontramos asociaciones significativas entre SNPs e impulsividad o búsqueda de sensaciones. Conclusiones: los resultados resaltan la importancia de tener en cuenta las diferencias genéticas y las de personalidad, junto con los factores contextuales, al analizar el uso de sustancias

Associations between experimental substance use, FAAH-gene variations, impulsivity and sensation seeking.

BACKGROUND: Experimental substance use among young people is related to individual factors including personality traits such as impulsivity and sensation seeking, and genetic variations such as single nucleotide polymorphisms (SNPs) in the fatty acid amide hydrolase (FAAH) gene. The objective of this study is to analyze the relationship between these three sets of variables. METHODS: Volunteer undergraduate students (N = 861, 76% female, M = 20.7 years) completed an ad hoc questionnaire on variables related to their consumption of alcohol, tobacco, cannabis, synthetic drugs and cocaine. In addition, 591 of them completed the Barratt Impulsiveness Scale-11 (BIS-11) and the Sensation Seeking Scale-V (SSS-V). All participants were genotyped in FAAH C385A SNP and its proxy variant rs12075550. RESULTS: Consistent with previous data, both impulsivity and sensation seeking were associated with most of the variables related to experimental substance use. In addition, we found the first evidence of an association between the rs12075550 SNP and some of these consumption phenotypes. However, no significant association was found between either of the two SNPs and impulsivity or sensation seeking. CONCLUSIONS: The results highlight the importance of considering both personality and genetic differences, together with contextual factors, in the analysis of substance use.

The ANKK1/DRD2 locus is a genomic substrate for affective priming and recognition of angry faces.

INTRODUCTION: Ankyrin repeat and kinase domain containing I (ANKK1) and dopamine D2 receptor (DRD2) genes have been associated with psychopathic traits in clinical samples. On the other hand, individuals high in psychopathy show reduced affective priming and deficits in facial expression recognition. We have hypothesized that these emotion-related cognitive phenomena are associated with Taq IA (rs18000497) SNP (single nucleotide polymorphism) of the ANKK1 gene and with C957T (rs6277) SNP of the DRD2 gene. METHODS: We performed a genetic association analysis in 94 self-reported Caucasian healthy volunteers. The participants completed 144 trials of an affective priming task, in which primes and targets were emotional words. They also had to recognize 64 facial expressions of happiness, sadness, anger, and fear in an expression recognition task. Regarding the genetic analyses, Taq IA and C957T SNPs were genotyped. RESULTS: We found that the C957T SNP TT genotype was associated with a stronger priming effect and a better recognition of angry expressions. No associations were found for the Taq IA SNP. In addition, in silico analysis demonstrated that C957T SNP is a marker of a regulatory sequence at the 5' UTR of ANKK1 gene, thus suggesting the involvement of the whole ANKK1/DRD2 locus in cognitive-emotional processing. CONCLUSIONS: These results suggest that affective priming and recognition of angry facial expressions are endophenotypes that lie on the pathway between the ANKK1/DRD2 locus and some deviant phenotypes.

Risky alcohol consumption in young people is associated with the fatty acid amide hydrolase gene polymorphism C385A and affective rating of drug pictures.

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.

Cuestionario de Fallos de Memoria de la Vida Cotidiana (MFE). Análisis de factores con población española / Memory failures of Everyday (MFE): Factor Analysis with Spanish population

Uno de los instrumentos más utilizados para valorar los olvidos cotidianos es el Cuestionario de Fallos de Memoria de la Vida Cotidiana (MFE). Los objetivos del presente estudio fueron: a) examinar la estructura factorial del MFE, b) explorar las relaciones de los factores resultantes con el rendimiento objetivo de memoria (Listas de Palabras y Escenas de la Es-cala de Memoria de Wechsler - III), el estado de ánimo y la ansiedad (Escala de Depresión y Ansiedad de Goldberg) y con dos preguntas generales sobre quejas de memoria. Los datos se recogieron de una muestra de 647 adultos jóvenes (19-64 años). Los resultados mostraron la existencia de una estructura de tres factores, que explicaban el 29.3 % de la varianza: Recuerdo de Actividades, Monitorización de la Comunicación y Reconocimiento. Los dos primeros factores mostraron una correlación positiva más alta en-tre ellos y una asociación mayor con el estado de ánimo y las quejas genera-les de memoria. Por el contrario, el factor Reconocimiento presentó una correlación positiva más alta con la edad y negativa con el rendimiento objetivo de memoria

One of the most frequently used instruments to study everyday memory failures is the Memory Failures of Everyday Questionnaire (MFE). The objectives of the present study were: a) to examine the factor structure of the MFE, and b) to explore the relationship of the resulting factors with performance in tests of objective memory (Word Lists and Family Pictures of the Wechsler Memory Scale-III) and mood state (Goldberg Depression and Anxiety Scale), as well as with two general questions about memory complaints. Data were collected from a sample of 647 young adults (19-64 years). Factor analysis revealed three factors which explained 29.3 % of the total variance: Activities Recall, Communication Monitoring, and Recognition. The first two factors showed a higher positive correlation between them and a higher association with mood state and general memory complaints. In contrast, the recognition factor shows positive correlation with age and negative with objective memory performance

Association of perceived health and depression with older adults' subjective memory complaints: contrasting a specific questionnaire with general complaints questions.

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.

Relación de las quejas de memoria con el rendimiento de memoria, el estado de ánimo y variables sociodemográficas en adultos jóvenes / Relationship between memory complaints and memory performance, mood and sociodemographic variables in young adults

Introducción. Las consultas en neurología por quejas de memoria se han incrementado en los últimos años, tanto en mayores como en jóvenes. Se han realizado pocos estudios sobre las variables que influyen en las quejas en adultos jóvenes. Objetivo. Analizar en esta población la relación de las quejas con el rendimiento objetivo de memoria, con la depresión y la ansiedad, con la edad, el sexo y el nivel de estudios. Sujetos y métodos. Muestra de 582 individuos trabajadores sin deterioro cognitivo y edad de 2-64 años. Los materiales utilizados fueron listas de palabras y escenas de familia de la escala de memoria de Wechsler, tercera edición, cuestionario de fallos de memoria de la vida diaria (MFE), y escala de depresión y ansiedad de Goldberg. Resultados. No se encontró asociación estadísticamente significativa entre la valoración subjetiva de la memoria y el rendimiento objetivo inmediato o demorado, ni en la memoria visual ni en la verbal. La depresión y la ansiedad fueron las variables con mayor correlación con la puntuación global del MFE. En el análisis de regresión, las variables significativas fueron: la depresión, con el mayor tamaño de efecto, la edad, los estudios universitarios y el sexo. Conclusión. Las personas jóvenes que manifestaron más olvidos cotidianos no presentaron un rendimiento menor en las pruebas objetivas de memoria. Las variables más importantes que intervinieron en las quejas fueron la depresión y la ansiedad. Las personas más jóvenes, las que tenían estudios universitarios y los varones manifestaron menos quejas de memoria (AU)

Introduction. Neurological consultations due to memory complaints have increased in recent years in both older and younger people. Few investigations have studied the variables related to memory complaints in young adults. Aim. To analyze, in a sample of young adults, the relationship between memory complaints and objective memory performance, depressive and anxiety symptoms, age, sex and level of studies. Subjects and methods. The study included 582 healthy workers, without cognitive impairment, aged 22-64 years. Assessment: Word List and Family Scenes of Wechsler Memory Scale-III, Memory Failures of Everyday Questionnaire (MFE) and Goldberg Anxiety and Depression Scale. Results. We did not find any significant association between subjective assessment of memory and objective performance, both immediate and delayed in verbal and visual memory. Depression and anxiety had the highest correlation with MFE. The significant variables in the multiple regression analysis were: depression, with the largest effect size, age, college studies and sex. Conclusion. In young adults, those which had a greater perception of daily forgetfulness were not those with lesser memory performance. The most important variables involved in memory complaints were depression and anxiety. Younger people, people with college education and men reported less memory complaints (AU)

[Relationship between memory complaints and memory performance, mood and sociodemographic variables in young adults]. / Relacion de las quejas de memoria con el rendimiento de memoria, el estado de animo y variables sociodemograficas en adultos jovenes.

INTRODUCTION: Neurological consultations due to memory complaints have increased in recent years in both older and younger people. Few investigations have studied the variables related to memory complaints in young adults. AIM: To analyze, in a sample of young adults, the relationship between memory complaints and objective memory performance, depressive and anxiety symptoms, age, sex and level of studies. SUBJECTS AND METHODS: The study included 582 healthy workers, without cognitive impairment, aged 22-64 years. ASSESSMENT: Word List and Family Scenes of Wechsler Memory Scale-III, Memory Failures of Everyday Questionnaire (MFE) and Goldberg Anxiety and Depression Scale. RESULTS: We did not find any significant association between subjective assessment of memory and objective performance, both immediate and delayed in verbal and visual memory. Depression and anxiety had the highest correlation with MFE. The significant variables in the multiple regression analysis were: depression, with the largest effect size, age, college studies and sex. CONCLUSION: In young adults, those which had a greater perception of daily forgetfulness were not those with lesser memory performance. The most important variables involved in memory complaints were depression and anxiety. Younger people, people with college education and men reported less memory complaints.

TITLE: Relacion de las quejas de memoria con el rendimiento de memoria, el estado de animo y variables sociodemograficas en adultos jovenes.Introduccion. Las consultas en neurologia por quejas de memoria se han incrementado en los ultimos años, tanto en mayores como en jovenes. Se han realizado pocos estudios sobre las variables que influyen en las quejas en adultos jovenes. Objetivo. Analizar en esta poblacion la relacion de las quejas con el rendimiento objetivo de memoria, con la depresion y la ansiedad, con la edad, el sexo y el nivel de estudios. Sujetos y metodos. Muestra de 582 individuos trabajadores sin deterioro cognitivo y edad de 22-64 años. Los materiales utilizados fueron listas de palabras y escenas de familia de la escala de memoria de Wechsler, tercera edicion, cuestionario de fallos de memoria de la vida diaria (MFE), y escala de depresion y ansiedad de Goldberg. Resultados. No se encontro asociacion estadisticamente significativa entre la valoracion subjetiva de la memoria y el rendimiento objetivo inmediato o demorado, ni en la memoria visual ni en la verbal. La depresion y la ansiedad fueron las variables con mayor correlacion con la puntuacion global del MFE. En el analisis de regresion, las variables significativas fueron: la depresion, con el mayor tamaño de efecto, la edad, los estudios universitarios y el sexo. Conclusion. Las personas jovenes que manifestaron mas olvidos cotidianos no presentaron un rendimiento menor en las pruebas objetivas de memoria. Las variables mas importantes que intervinieron en las quejas fueron la depresion y la ansiedad. Las personas mas jovenes, las que tenian estudios universitarios y los varones manifestaron menos quejas de memoria.

Aversive priming: cognitive processing of threatening stimuli is facilitated by aversive primes.

It would be reasonable to expect that our previous experience regarding a stimulus that predicts harm would make the subsequent identification of that stimulus easier when harm happens again. Forty-eight volunteers were submitted to both phases of this sequence of events: learning of the predictive relationship and later priming. A face with neutral expression (CS+) was paired with a moderately aversive electric shock and another (CS-) with a neutral tone. Subsequently, these two faces, as well as other known and new faces, were presented for familiarity judgments. Both the CS+ and the CS- faces were preceded by an aversive stimulus (aversive prime) in one occasion and by a neutral stimulus (neutral prime) in another. The familiarity judgment regarding the CS+ was faster after the aversive prime than after the neutral prime, but there was no difference regarding the CS-. The differential effect of the aversive prime over the CS+ and the CS- showed a significant but small correlation with the differential skin conductance response to CS+ and CS- (signal learning), and with the differential evaluation of those stimuli in terms of like-dislike (evaluative learning). The scope of these results, as well as the usefulness of this methodological model, is discussed.

Aversive priming: cognitive processing of threatening stimuli is facilitated by aversive primes

It would be reasonable to expect that our previous experience regarding a stimulus that predicts harm would make the subsequent identification of that stimulus easier when harm happens again. Forty-eight volunteers were submitted to both phases of this sequence of events: learning of the predictive relationship and later priming. A face with neutral expression (CS+) was paired with a moderately aversive electric shock and another (CS-) with a neutral tone. Subsequently, these two faces, as well as other known and new faces, were presented for familiarity judgments. Both the CS+ and the CS- faces were preceded by an aversive stimulus (aversive prime) in one occasion and by a neutral stimulus (neutral prime) in another. The familiarity judgment regarding the CS+ was faster after the aversive prime than after the neutral prime, but there was no difference regarding the CS-. The differential effect of the aversive prime over the CS+ and the CS- showed a significant but small correlation with the differential skin conductance response to CS+ and CS- (signal learning), and with the differential evaluation of those stimuli in terms of like-dislike (evaluative learning). The scope of these results, as well as the usefulness of this methodological model, is discussed (AU)

Cabe esperar que nuestra experiencia previa respecto a un estímulo predictor de un daño facilite la identificación posterior de ese estímulo cuando el daño ocurre de nuevo. Se sometió a 48 voluntarios a ambas fases de esta secuencia de hechos: aprendizaje de la relación predictiva y facilitación posterior. Se emparejó una cara con expresión neutra (EC+) con una descarga eléctrica moderadamente aversiva y otra (EC-) con un tono neutro. Posteriormente se sometieron esas dos caras, mezcladas con otras antiguas y nuevas, a juicios de familiaridad. Tanto la cara EC+ como la cara EC- iban precedidas de un estímulo aversivo (prime aversivo) en una ocasión y de un estimulo neutro (prime neutro) en otra. El juicio de familiaridad respecto al EC+ fue más rápido tras el prime aversivo que tras el prime neutro, pero no hubo diferencia en el caso del EC-. El efecto diferencial del prime aversivo sobre el EC+ y el EC- mostró una correlación significativa, aunque pequeña, con la respuesta de conductancia de la piel diferencial al EC+ y al EC- (aprendizaje de señal), y con la evaluación diferencial en términos de agrado-desagrado de uno y otro estímulo (aprendizaje evaluativo). Se discute el alcance de estos resultados y la utilidad del modelo metodológico (AU)

Cocaine reverses the naltrexone-induced reduction in operant ethanol self-administration: the effects on immediate-early gene expression in the rat prefrontal cortex.

Naltrexone is a clinically approved medication for alcoholism. We aimed to investigate the effectiveness of naltrexone co-administered with cocaine and the association of these substances with immediate-early gene expression in the rat prefrontal cortex. We used chronic operant ethanol self-administration and oral treatments prescribed for alcoholism and available in pharmacies to maximise the predictive validity in humans. We performed real-time PCR analysis to determine gene expression levels in the prefrontal cortex. Only the highest dose of naltrexone (1, 3, and 10 mg/kg, p.o.) reduced the response to ethanol. Cocaine increased ethanol self-administration in a dose-dependent manner (2.5, 10, 20 mg/kg, i.p.) and reversed the naltrexone-induced reduction. Naltrexone failed to prevent the cocaine-induced increase in locomotor activity observed in these animals. Chronic self-administration of ethanol reduced the expression of the C-fos gene 4- to 12-fold and increased expression of the COX-2 (up to 4-fold) and Homer1a genes in the rat prefrontal cortex. Chronic ethanol self-administration is prevented by naltrexone, but cocaine fully reverses this effect. This result suggests that cocaine may overcome naltrexone's effectiveness as a treatment for alcoholism. The ethanol-induced reduction in C-fos gene expression in the prefrontal cortex reveals an abnormal activity of these neurons, which may be relevant in the compulsive consumption of ethanol, the control of reward-related areas and the behavioural phenotype of ethanol addiction.