Showing papers by "Gabriel Rubio published in 2009"

Modulation of impulsivity by topiramate: implications for the treatment of alcohol dependence.

Abstract: Topiramate (TP), an anticonvulsant drug, has been widely used in the treatment of disorders characterized by impulsivity symptoms, so it goes to reason that it might be useful in addictive disorders. Recently, TP has been used to treat alcohol dependence, but it is still not known whether the effects of TP on alcohol consumption are related with its action on impulsivity. The aim of this preliminary study was to investigate which dimension of behavioral impulsivity is associated with the effects of TP. A 12-week, double-blind, placebo-controlled pilot study of TP for the treatment of alcohol dependence was conducted. Subjects were men recruited from alcoholism treatment units (TP = 31; placebo = 32). Diagnoses were made using the Structured Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Behavioral inhibition was assessed using the continuous performance test (CPT) and the stop-signal task. Differential reinforcement for low-rate responding (DRLR) was used to evaluate the delay-discounting dimension. Alcohol craving and alcohol consumption during the study were evaluated. Patients treated with TP presented lower rates of alcohol consumption in the number of drinks per drinking day (P < 0.05) and the number of heavy drinking days (P < 0.001). Scores on alcohol craving scales decreased significantly, and there was more improvement on the continuous performance test (total omissions and total commissions) and on the stop-signal task in the TP group than in the control group. Improved alcohol consumption behavior was associated with performance on the behavioral inhibition paradigm. The results of this study indicate that TP reduces drinking and that the mechanisms underlying this effect may involve, at least in part, modulation of the behavioral inhibition paradigm.

Gender‐specific COMT Val158Met polymorphism association in Spanish schizophrenic patients

Abstract: The functional Val158Met polymorphism (rs4680) located at the gene that codes for the catechol-O-methyltransferase (COMT) has been extensively investigated in schizophrenia although current data are still controversial. Since COMT activity is sexually dimorphic, we carried out two independent studies in homogeneous samples of male and female Spanish schizophrenic patients. In males, we found an association between the homozygous Val genotype and the disorder, which resembled a recessive model (P = 0.022; odds ratio [OR] = 1.67). This Val homozygotes overrepresentation is produced at the expense of the heterozygous individuals decrease, whilst the Met homozygotes showed no differences when compared controls and patients. As a consequence, the heterozygous genotype in this sample had a protective effect (P = 0.03; OR = 0.65) and a strong deviation from Hardy–Weinberg equilibrium in male cases was observed (P = 0.006). In addition, a 2-SNP haplotype analysis (rs4818-Val158Met) confirmed there is an overrepresentation of the different homozygous Val genotypes in the male schizophrenic sample. Regarding females, we did not find any statistically significant association between COMT SNP and schizophrenia. In the light of this we suggest that the Val158Met SNP is involved in risk and protective genotypes for the vulnerability to schizophrenia in Spanish male population. © 2009 Wiley-Liss, Inc.

Experience with injectable long-acting risperidone in long-term therapy after an acute episode of schizophrenia: the SPHERE Study.

Abstract: Background: Risperidone long-acting injectable (RLAI) is the first long-acting formulation of an atypical antipsychotic introduced into clinical practice. RLAI combines the benefits of atypical antipsychotic agents with an extended duration of activity and is intended for long-term management of schizophrenia. This study evaluated the use of RLAI as part of a long-term management strategy in patients with an acute episode of schizophrenia. Objectives: The primary objective was to determine clinicians’ approaches to the use of RLAI in patients with an acute exacerbation of schizophrenia by examining the prescribing patterns of antipsychotic and other psychotropic medications. Other objectives were to evaluate the overall safety of switching patients to RLAI from previous antipsychotic therapy and to determine patients’, caregivers’ and relatives’ attitudes towards RLAI treatment. Methods: The Safety and Profile of Handling and Employing of Risperdal® Consta® in Emergency/Acute Care Settings (SPHERE) study ...

Alcohol craving scale based on three factors.

Abstract: Background: Alcohol craving is a central aspect of alcoholism about which various explanatory theories and assessment questionnaires, based on such craving, have been developed How

Opioid and cannabinoid systems as therapeutic targets for the treatment of alcohol dependence: From animal models to clinical practice

Abstract: The development of alcohol dependence is the result of a combination of various factors. Psychosocial and psychiatric conditions, together with functional alterations of the brain or genetic traits, contribute to the development of problems related to alcohol use or alcohol dependence. Clinical studies using neuroimaging techniques (PET, fMRI) and preclinical studies using different animal models of problems related to ethanol consumption have improved our knowledge of the neurochemical mechanisms involved in alcohol dependence. These studies have served to identify peptides or receptors modified by ethanol consumption, which are functionally altered in strains of rats or mice highly vulnerable to ethanol consumption. Such peptides or receptors may be interesting targets for the treatment of alcoholism. Among the different targets studied in recent years, the opioid and cannabinoid systems meet a number of conditions for eligibility as candidates for the treatment of alcohol dependence. The � -opioid receptor and cannabinoid CB1 receptor, in particular, are affected by ethanol consumption. In clinical studies, genetic polymorphisms of the � -opioid and CB1 receptors have been associated with increased vulnerability to alcohol consumption. Similarly, functional alterations in � - opioid and cannabinoid receptors have been identified in specific strains of rats or mice with high preference to ethanol consumption. Furthermore, several studies have shown that the manipulation of these receptors using agonists or antagonists may increase or decrease ethanol consumption, which confirms the validity of these receptors as targets for the treatment of alcohol dependence. In this review, we analyzed the genetic traits and psychiatric and/or psychosocial conditions that affect vulnerability to and the pharmacologic treatment of alcohol dependence, with special emphasis on the role of opioid and cannabinoid receptors. The use of animal models as important tools for identifying neurochemical mechanisms relevant to understanding and treating alcohol use problems was evaluated.

P300 in alcohol dependence: Effects of TaqI-A genotype

Abstract: 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.