Motion estimation of subcellular structures from fluorescence microscopy images.

We present an automatic image processing framework to study moving intracellular structures from live cell fluorescence microscopy. The system includes the identification of static and dynamic structures from time-lapse images using data clustering as well as the identification of the trajectory of moving objects with a probabilistic tracking algorithm. The method has been successfully applied to study mitochondrial movement in neurons. The approach provides excellent performance under different experimental conditions and is robust to common sources of noise including experimental, molecular and biological fluctuations.

The ANKK1 protein associated with addictions has nuclear and cytoplasmic localization and shows a differential response of Ala239Thr to apomorphine.

The TaqIA single-nucleotide polymorphism (SNP), which is the most widely studied genetic polymorphism in addictions, is located at the gene that encodes the RIP kinase ANKK1 near the gene for dopamine receptor D2. The TaqIA SNP is in strong linkage disequilibrium with the SNP rs7118900, which changes the alanine at position 239 to threonine in the ANKK1 protein (Ala239/A2; Thr239/A1). In silico analysis has predicted that this polymorphic substitution creates an additional phosphorylation site in the kinase domain of ANKK1. To investigate the contribution of ANKK1 to the pathophysiology of TaqIA-associated phenotypes, we analyzed transfected HEK293T cells with the human ANKK1-kinase(Ala239) and ANKK1-kinase(Thr239) variants tagged with GFP. We observed that the ANKK1-kinase is located in both the nucleus and the cytoplasm, suggesting that there is nucleocytoplasmic shuttling of this putative signal transducer. In addition, we found that the Ala239Thr ANKK1-kinase polymorphism exhibited strong expression differences in both the nucleus and the cytoplasm at basal level and when stimulated with the dopamine agonist apomorphine. Specifically, the ANKK1-kinase(Thr239) variant showed the highest level of basal protein expression, while ANKK1-kinase(Ala239) was 0.64-fold lower. After treatment with apomorphine, ANKK1-kinase(Ala239) showed a 2.4-fold increment in protein levels, whereas a 0.67-fold reduction was observed in ANKK1-kinase(Thr239). Thus, here we provide the first evidence of functional ANKK1 differences that are marked by TaqIA and could be associated with vulnerability to addiction.

High frequency of childhood ADHD history in women with fibromyalgia.

Fibromyalgia and ADHD share some clinical features, and a reduced dopamine function has been proposed for both disorders. Here we found, in a large sample of fibromyalgia female patients, a higher frequency of childhood ADHD antecedent when compared with healthy women. Our data suggest that Fibromyalgia and ADHD have some common etiopathological mechanism.

The D2 dopamine receptor gene variant C957T affects human fear conditioning and aversive priming.

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.

P300 in alcohol dependence: Effectsof TaqI-A genotype

Background and Objectives: TaqI-A polymorphism, related to D2dopamine receptor (DRD2), and event-related P300 potentials have been consideredmarkers of alcohol dependence. The effect of alcohol use variables and TaqI-A on P300 ina single sample have been hardly analysed previously. This study examined changes inP300 parameters after six months of abstinence in alcohol-dependent subjects classifiedby their TaqI-A genotype.Methods: 102 men with alcohol dependence were studied at baseline and at 6 monthsof continued abstinence. P300 was recorded using an auditory paradigm. TaqI-A polymorphismwas genotyped: 34.3% of sample was classified as A1[TaqI-A1/TaqI-A1andTaqI-A1/TaqI-A2] and 65.7% as A2 [TaqI-A2/TaqI-A2]. The association between P300and 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 relatedto 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. Familyhistory for alcoholism and TaqI-A were not related (X[1] = 0.327 p = 0.568) and no associationwas 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 amplitudewas not influenced by alcohol use variables nor TaqI-A polymorphism.Conclusions: P300 latency could be a biological marker of vulnerability to alcohol dependencerelated to TaqI-A1 polymorphism, irrespective of alcohol use variables (AU)

DRD2 and ANKK1 genotype in alcohol-dependent patients with psychopathic traits: association and interaction study.

BACKGROUND: The TaqI-A polymorphism of the ANKK1 gene, adjacent to the DRD2 gene, has been associated with alcoholism and other psychiatric conditions, although other DRD2 gene variants, such as the C957T polymorphism, could be related to these phenotypic traits. AIMS: To investigate the contribution of the TaqI-A and the C957T polymorphisms to the presence of psychopathic traits in patients with alcoholism. METHOD: We performed association and interaction analyses of the polymorphisms in 150 controls and 176 male alcohol-dependent patients assessed for the presence of dissocial personal disorder, using the Psychopathy Checklist-Revised (PCL-R). RESULTS: There was a significant association of the TaqI-A and C957T polymorphisms when both genotypes were present, with PCL-R scores of F(1-171=0.13) (P=0.01) and a frequency of dissocial personal disorder OR=10.52, P<0.001. CONCLUSIONS: The TaqI-A of the ANKK1 gene and the C957T of the DRD2 gene are epistatically associated with psychopathic traits in alcohol-dependent patients.

Psychopathology and Wisconsin Card Sorting Test performance in male schizophrenic patients: influence of dual diagnosis.

BACKGROUND: Different neuropsychological studies have shown schizophrenic patients to have executive function deficits, as illustrated by their performance in neuropsychological tasks such as the Wisconsin Card Sorting Test (WCST); certain studies have described a relationship between these deficits and negative symptoms. Schizophrenic patients also exhibit a high lifetime prevalence (40-50%) of comorbid substance use disorders (SUDs). However, little attention has been paid to this comorbidity (dual diagnosis) in studies associating executive functions and negative symptoms. SAMPLING AND METHODS: Our objective is to investigate the relationship between performance in the WCST and psychopathology as measured by the Positive and Negative Syndrome Scale (PANSS) in a sample of 65 male schizophrenic patients with a history of SUDs (Sch SUD+) and in a sample of 48 male schizophrenic patients without such history (Sch SUD-). RESULTS: In the Sch SUD- group, patients who completed 4 or more categories in the WCST ('good performers') obtained a mean score of 21.2 +/- 8.8 on the negative subscale of the PANSS, compared with a mean score of 27.8 +/- 8.6 in those who completed 3 or less ('poor performers'); these differences were statistically significant (p = 0.015). In the Sch SUD+ group, however, no association was found between WCST performance and the PANSS negative subscale score. CONCLUSIONS: The presence of a history of comorbid SUDs should be taken into consideration in studies investigating executive functions and negative symptoms in schizophrenia.

C957T DRD2 polymorphism is associated with schizophrenia in Spanish patients.

OBJECTIVE: The objective was to confirm whether a homozygous genotype for the C957 allele of the C957T DRD2 gene single nucleotide polymorphism (SNP) is associated with schizophrenia in an independent study population. METHOD: We examined the genotypic distribution of this SNP in a set of clinically ascertained schizophrenic patients (n = 131) and age-matched control subjects (n = 364). Individuals were genotyped using automated analysis of fluorescently labeled PCR products. RESULTS: The distribution of grouped genotypes for the C957T DRD2 SNP (CC vs. CT, TT) showed that C homozygote genotype was over-represented in our patient sample when compared with control subjects. This difference reaches the statistical significance (chi(2) = 7.0; df = 1; P = 0.008; OR = 2.05; % CI 1.2-3.4). CONCLUSION: The findings of this study provide additional evidence that genetic variation at the DRD2 gene plays an important role in the vulnerability to schizophrenia.

Impulsivity and sustained attention in pathological gamblers: influence of childhood ADHD history.

Pathological gambling (PG) has been associated to both impulsiveness and attention deficit/hyperactivity disorder (ADHD) in different studies. Our objective was to compare different impulsivity and sustained attention variables, using both behavioural tasks and self-administered questionnaires, in a group of pathological gamblers with a history of childhood ADHD (PG-ADHD; n = 16), a group of pathological gamblers without this history (PG-non-ADHD; n = 39), and a control group (n = 40). As instruments of measure, we used the stop signal task (to evaluate inhibitory control/impulsivity), the differential reinforcement of Low Rate Responding Task (delay of gratification/impulsivity) and the Continuous Performance Test (sustained attention). The Barratt Impulsivity Scale (BIS-11) was used as a self-administered questionnaire to measure impulsiveness. Our results show that patients in the PG-ADHD group exhibit a significantly lower capacity to delay gratification than those in the PG-non-ADHD and control groups, and less inhibitory control than patients in the PG-non-ADHD group. On self-administered questionnaires such as the BIS-11 the PG-ADHD group obtained higher scores than the PG-non-ADHD and control groups. However, no differences were found with respect to sustained attention using the CPT. Our results suggest a possible selective implication of the prefrontal cortex in PG, which would be especially evident in those with a childhood history of ADHD.

[Genes in Alzheimer's disease]. / Genes de la enfermedad de Alzheimer.

INTRODUCTION: Alzheimer's disease (AD) is the most frequent degenerative dementia among the elderly population. Families that have an autosomal dominant pattern for AD constitute about 13% of early cases (< or = 65 years) and less than 0.01% of the total number of patients. DEVELOPMENT: Molecular analysis of families with early onset AD has made it possible to identify mutations in three different genes that are responsible for the disease: the gene encoding for the amyloid precursor protein peptide (APP), and the presenilin 1 (PSEN1) and presenilin 2 (PSEN2) genes. Yet, these genes are involved in less than 5% of the total number of cases of AD. The remaining AD patients are mostly cases of late or familial onset, where the disease appears as a result of a complex interaction among environmental factors and individual predisposing genetic traits. A large number of molecular genetics studies have clearly implicated the APOE epsilon4 allele as a proven risk factor for the late form of AD in almost all the populations that have been studied. CONCLUSIONS: Although the APOE epsilon4 allele is the only proven genetic risk factor for the late form of the disease, genetic epidemiological studies suggest that other loci are also involved.

TaqI-A polymorphism linked to the DRD2 gene and P300 in alcoholic patients

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Background and Objetives: Different studies carried out mainly in young non-consuming children of alcoholics show an association of P300 abnormalities with alcoholism and with the TaqI-A1 allele. Since the relationship between P300 and the TaqI-A1 allele has not been specifically studied in alcoholic patients, our objective was to investigate whether the association exits in this population. Methods: Our sample consisted of 176 recently detoxified male alcohol-dependent patients. These patients had been alcohol dependent from a mean age of 22.6 years and consumed on average 164.63 (± 142.99) cm3 of alcohol daily. P300 was studied using an auditory paradigm. TaqI-A polymorphism genotyping was performed. The association between P300 and TaqI-A, and correlation with age and alcohol consumption, was studied. Results: The TaqI-A1 allele was found in 38.6 percents of our patients (n = 68). The latency and amplitude of P300 were 361.64 milliseconds and 17.53 microvolts, respectively. P300 wave latency in alcoholic patients was longer than the reference value obtained from a sample of healthy men of the Event-Related Potentials Unit (p < 0.001). Alcoholic patients who carried the TaqI-A1 allele showed more prolonged P300 latency than non-carriers, and these in turn more than the control subjects. P300 characteristics varied according to age, but an association with amount of alcohol or number of years consuming was not found. Conclusions: There is a relationship between the TaqI-A polymorphism and P300 wave characteristics in alcoholic patients. Further investigations need to be carried out in non-consuming alcoholic patients and in healthy control subjects to confirm this association and to clarify the possible influence of the neurotoxic effects of alcohol on P300 physiology (AU)

Genes de la enfermedad de Alzheimer / Genes in alzheimer’s disease

Introducción. La enfermedad de Alzheimer (EA) es la demencia degenerativa más frecuente entre la población anciana. Las familias que presentan un patrón autosómico dominante para la EA constituyen alrededor de un 13% de los casos precoces (£ 65 años) y menos del 0,01% del total de los pacientes. Desarrollo. El análisis molecular de familias afectadas de EA de comienzo precoz, ha permitido la identificación de mutaciones en tres genes diferentes que son las responsables de la enfermedad: el gen que codifica la proteína precursora del péptido amiloide (APP), el gen de la presenilina 1 (PSEN1) y el de la presenilina 2 (PSEN2). Sin embargo, estos genes están implicados en menos de un 5% de los casos totales de EA. El resto de los pacientes con EA son en su mayoría de presentación tardía o familiar, donde la enfermedad aparece como resultado de una interacción compleja entre factores ambientales y rasgos genéticos de predisposición individual. Una gran cantidad de estudios de genética molecular han implicado claramente al alelo ε4 del gen APOE como un factor de riesgo comprobado para la forma tardía de la EA en casi todas las poblaciones estudiadas. Conclusión. Aunque el alelo ε4 del gen APOE es el único factor de riesgo genético comprobado para la forma tardía de la enfermedad, los estudios de epidemiología genética sugieren que otros loci también están implicados (AU)

Introduction. Alzheimer's disease (AD) is the most frequent degenerative dementia among the elderly population. Families that have an autosomal dominant pattern for AD constitute about 13% of early cases (≤ 65 years) and less than 0.01% of the total number of patients. Development. Molecular analysis of families with early onset AD has made it possible to identify mutations in three different genes that are responsible for the disease: the gene encoding for the amyloid precursor protein peptide (APP), and the presenil in 1 (PSEN1) and presenil in 2 (PSEN2) genes. Yet, these genes are involved in less than 5% of the total number of cases of AD. The remaining AD patients are mostly cases of late or familial onset, where the disease appears as a result of a complex interaction among environmental factors and individual predisposing genetic traits. A large number of molecular genetics studies have clearly implicated the APOE ε4 allele as a proven risk factor for the late form of AD in almost all the populations that have been studied. Conclusions. Although the APOE ε4allele is the only proven genetic risk factor for the late form of the disease, genetic epidemiological studies suggest that other loci are also involved (AU)

The TaqIA polymorphism linked to the DRD2 gene is related to lower attention and less inhibitory control in alcoholic patients.

The TaqIA polymorphism linked to the DRD2 gene has been associated with alcoholism. The aim of this work is to study attention and inhibitory control as per the continuous performance test and the stop task in a sample of 50 Spanish male alcoholic patients split into two groups according to the presence of the TaqIA1 allele in their genotype. Our results show that alcoholics carrying the TaqIA1 allele present lower sustained attention and less inhibitory control than those patients without such allele.

Performance in the Wisconsin Card Sorting Test and the C957T polymorphism of the DRD2 gene in healthy volunteers.

INTRODUCTION: Previous studies have associated a decreased striatal D2 dopamine receptor (DRD2) binding with impaired performance in cognitive tasks. In vivo studies have found a lower DRD2 binding associated with the CC genotype of the C957T single nucleotide polymorphism (SNP) of the DRD2 gene. OBJECTIVE: The aim of this study was to investigate the relationship between executive functions and the C957T DRD2 SNP. We hypothesized that the CC genotype would be associated with a poorer executive functioning. METHODS: Our sample consisted of 83 healthy volunteers (28 males and 55 females; mean age 25.2, SD 1.7 years). To assess executive functions, the Wisconsin Card Sorting Test was used, considering the variables perseverative errors, perseverative responses, and number of categories achieved. The genotype distribution was 13 CC, 41 CT, and 29 TT, satisfying Hardy-Weinberg equilibrium. RESULTS: Carriers of the CC genotype, compared with carriers of the CT/TT genotypes, achieved significantly fewer categories (5.00 vs. 5.81; p = 0.004), made a greater number of perseverative errors (13.46 vs. 8.39; p = 0.018), and had a greater number of perseverative responses (14.92 vs. 8.94; p = 0.014). CONCLUSIONS: Our results support the hypothesis that the C957T DRD2 SNP may influence cognitive performance through its repercussions on central dopaminergic function.

Clinical predictors of response to naltrexone in alcoholic patients: who benefits most from treatment with naltrexone?

AIMS: To determine the clinically ascertained variables that are related to satisfactory response to naltrexone (NTX) treatment of alcohol dependence after detoxification. METHODS: The use of intake and outcome variables were measured in a randomized 3-month open-controlled trial comparing the effects of naltrexone plus psychotherapy treatment versus psychotherapy treatment alone on the maintenance of abstinence in the final 28 days (n = 336, all male). RESULTS: Predictors of a positive response to NTX treatment were family history of alcoholism (P = 0.010), early age at onset of drinking problems (P = 0.014) and comorbid use of other drugs of abuse (P < 0.001). Among the subjects not treated with NTX, the greater the number of predictor variables, the lower the final 28 days abstinence rates (P = 0.00003), but this was not the case in patients treated with NTX (P = 0.844). CONCLUSIONS: Patients with these features, suggesting biological vulnerability overall have poorer outcomes, but this can be reduced with NTX treatment. The type of alcoholism should be considered before deciding on the pharmacological strategy.

Depression in Parkinson's disease is related to a genetic polymorphism of the cannabinoid receptor gene (CNR1).

Depression is a common symptom in Parkinson's disease (PD) and it is present in up to 40% of the patients. The cause of depression in PD is thought to be related to disturbance of monoamine neurotransmission. The endogenous cannabinoid system mediates different brain processes that play a role in the control of behaviour and emotions. Cannabinoid function may be altered in neuropsychiatry diseases, directly or through interactions with monoamine, GABA and glutamate systems. For this reason, we have investigated whether there is a genetic risk factor for depression in PD linked to the polymorphisms of CB1 receptor gene. Depression was more frequent in patients with PD than in controls with osteoarthritis. The presence of depression did not correlate with the stage of the disease but it was more frequent in patients with pure akinetic syndrome than in those with tremoric or mixed type PD. The CB1 receptor gene polymorphism (AAT)n is considered to modify the transcription of the gene and, therefore, it may have functional relevance. We analysed the length of the polymorphic triplet (AAT)n of the gene that encodes CB1 (CNR1) receptor in 89 subjects (48 PD patients and 41 controls). In patients with PD, the presence of two long alleles, with more than 16 repeated AAT trinucleotides in the CNR1 gene, was associated with a reduced prevalence of depression (Fisher's exact test: P=0.003). This association did not reach significant differences in the control group, but the number of control individuals with depression was too small to allow for statistical analysis. Since the alleles with long expansions may have functional impact in cannabinoid neurotransmission, our data suggest that the pharmacological manipulation of cannabinoid neurotransmission could open a new therapeutic approach for the treatment of depression in PD and possibly in other conditions.

IDRD2 TaqIA polymorphism is associated with urinary homovanillic acid levels in a sample of Spanish male alcoholic patients.

The TaqIA1 allele of the dopamine receptor gene D2 (DRD2) has been associated with alcoholism, as well as with other addictive behaviours. The exact nature of how the presence of this allele can be a vulnerability factor in the development of alcoholism remains unclear. In this study we found that the presence in the DRD2 genotype of the TaqIA1 allele in Spanish alcoholics is associated with higher levels of urine homovanillic acid (HVA) when compared to patients homozygous for the TaqIA2 allele. A sample of 142 Spanish male alcoholic patients was split into 2 groups on the basis of the presence or absence of the A1 allele in their genotype. The urine sample was analyzed by high performance liquid cromatography (HPLC), and the concentration of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and vanilylmandelic acid (VMA) was determined. We found a statistical difference in the concentration of HVA between the groups, that suggests this polymorphism could be related to the variance of urine HVA levels.

The A1 allele of the DRD2 gene (TaqI A polymorphisms) is associated with antisocial personality in a sample of alcohol-dependent patients.

BACKGROUND: Presence of A1 allele of the DRD2 gene has been associated with a predisposition for alcoholism although there are limited data about its phenotypic expression in alcoholism. OBJECTIVES: To determine the importance of the A1 allele in clinical variables of alcohol dependence. METHODOLOGY: A sample of 103 alcohol-dependent males was studied. All patients were recruited consecutively from the general hospital and community settings. The diagnostics were made with the structured clinical interview for DSM-III-R (SCID); and the International Personality Disorder Examination (IPDE). Diagnosis of family alcoholism was made by direct interview or with the Research Diagnostic Criteria-Family History (RDC-FH). The Addiction Severity Index (ASI) and the Severity of Alcohol Dependence Scale (SADS) were used to assess alcohol dependence severity. Genotyping was done by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. RESULTS: Approximately 39% of the sample carried the A1 allele (A1+ group). This group had higher prevalences of antisocial personality disorder (60% vs. 15.9%); and alcoholism family history (72.5% vs. 52.4%). Also A1+ had early onset alcohol abuse and more drinking problems. The presence of A1+ was the main factor to explain the diagnosis of antisocial personality disorder, but the weight of this factor was not sufficient to explain the complications assessed by the ASI. CONCLUSIONS: Our results support the existence of an association between the A1 allele and factors resulting from dopaminergic deficiency, otherwise denominated reward deficiency syndrome.

Unique origin and low penetrance of the 946delGAG mutation in Valencian DYT1 families.

Mutations in the DYT1 gene cause idiopathic torsion dystonia (ITD) transmitted in families as an autosomal dominant trait with incomplete penetrance. The most common mutation, 946delGAG, has been observed in populations with different ethnic and geographic origins. We have investigated 40 individuals from 22 unrelated families with ITD originating from the Land of Valencia, Spain, for the presence of this mutation and we found 5 patients and 6 unaffected subjects from 4 families who were carriers of the mutation. This finding indicates that 18% of families may be diagnosed as DYT1 and that penetrance is reduced. We detected two different geographic and linguistic origins of the Valencian families. However, by haplotype analysis using D9S1260, D9S1261, D9S63 and D9S1262 as flanking markers, we demonstrated that all affected and unaffected carriers shared a common chromosome confirming identical origin of the mutation in the four families. We postulate a unique origin for the 946delGAG mutation in the Land of Valencia and, based on linguistic criterion, we propose that the mutation might have occurred at the beginning of the second millennium. Genetic analysis of another family from Castilla-La Mancha showed a different haplotype segregating with the disease, suggesting that at least two distinct mutational events for the 946delGAG mutation have occurred in Spain.

Aspectos genéticos del alcoholismo / Genetic aspects of alcoholism

Objetivo: El alcoholismo es un conjunto heterogéneo de trastornos que comparten su relación con la ingesta de etanol. La importancia de los factores genéticos en el desarrollo del alcoholismo está avalada por una amplia serie de investigaciones llevadas a cabo desde hace años. Los estudios de familia, en gemelos y de adopción indican que los hijos de padres alcohólicos tienen un marcado riesgo para el trastorno. En la actualidad, el avance de las técnicas moleculares ha aportado un nuevo enfoque al estudio de la asociación entre genética y alcoholismo. Material y métodos: Se revisan los aspectos genéticos del alcoholismo. Resultados: Los efectos producidos por el alcohol, van a depender de la actividad de las enzimas encargadas de su degradación. Los individuos que presenten polimorfismos para alguno de sus genes, que impliquen una alteración en la eliminación del etanol, contribuirán a la variabilidad genética en su consumo y en sus efectos sobre el organismo. Por otro lado, sabemos que la capacidad adictiva del alcohol y otras drogas se basa en su capacidad para potenciar la transmisión dopaminérgica en el sistema mesolímbico, centro fundamental del sistema de recompensa, que se encuentra modulado por diferentes sistemas de neurotransmisores como el opioide y el serotoninérgico. La existencia de variantes genéticas para las proteínas clave de estos sistemas, podrán estar también relacionadas con su consumo. Conclusiones: El adecuado conocimiento de la importancia de los factores genéticos en el alcoholismo, y de su interrelación con otros factores fisiológicos y psicosociales, resulta fundamental para alcanzar un acercamiento más adecuado a los distintos trastornos relacionados con el alcohol para su correcta comprensión y manejo, y también para actuar, de forma preventiva, sobre los elementos que supongan un aumento en la vulnerabilidad a padecerlos. (AU)