Tomas Palomo
Universidad Complutense de Madrid, PSYCHIATRY, Faculty Member
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Alcoholism is a major public health problem. Although its prevalence is higher in men, the clinical and social repercussions of alcoholism in women are also of great concern, as they have differential characteristics in different... more
Alcoholism is a major public health problem. Although its prevalence is higher in men, the clinical and social repercussions of alcoholism in women are also of great concern, as they have differential characteristics in different vulnerability, and thus therapeutic implications. In recent years, we have seen an increase of the percentages of women with problems related to alcohol consumption in Spain. Several pharmacological treatments as the antagonist of the opioid receptors naltrexone have demonstrated efficacy in the treatment of dehabituation of alcoholism in males, however, there are no studies in the female population. This report is the first randomized study about the efficacy of naltrexone in the treatment of dehabituation in women with alcohol dependence disorder. In a 12 week, single-blind, randomized trial, we studied 100 women with alcohol dependence disorder (DSM-IV), evaluating the efficacy of adding naltrexone as adjunctive treatment to the dehabituation treatment. The naltrexone group showed a lower rate of alcohol relapse during the follow-up period (76 % vs. 46%; chi2=8.239; p=0.004), and significantly lower dropout rates (16% vs. 38 %; chi2=5.074; p=0.024). We also found a lower number of days of intoxication (2.88 vs. 14.64; t=2.732; p=0.011). Naltrexone shows efficacy as adjunctive treatment to maintain abstinence in women with alcohol dependence disorder. Further studies are needed to confirm the efficacy of this treatment and to find specific predictors of good outcome in women.
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Previous studies have generally found a relationship between negative and cognitive symptoms in schizophrenia. The present study investigated the relationship between the 5 PANSS factors of a recent consensus model developed by NIMH... more
Previous studies have generally found a relationship between negative and cognitive symptoms in schizophrenia. The present study investigated the relationship between the 5 PANSS factors of a recent consensus model developed by NIMH researchers, and cognitive performance as assessed with the MATRICS Consensus Cognitive Battery (MCCB) in 80 patients with schizophrenia using correlation and regression analyses. The PANSS Cognitive factor showed a small to moderate significant association with MCCB Speed of processing, Working memory, Verbal learning, the Neurocognitive composite score, and the Overall composite score. Notably, however, no relationship was found between the PANSS Negative factor and any of the MCCB scores. The Positive, Excited and Depressed factors also did not show associations with the MCCB. These results highlight the need for refined assessment instruments and support the relative independence of cognition from other domains of psychopathology, including negative symptoms, in patients with schizophrenia.
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The ankyrin repeat and kinase domain containing 1 (ANKK1) TaqIA polymorphism has been extensively studied as a marker of the gene for dopamine receptor D2 (DRD2) in addictions and other dopamine-associated traits. In vitro mRNA and... more
The ankyrin repeat and kinase domain containing 1 (ANKK1) TaqIA polymorphism has been extensively studied as a marker of the gene for dopamine receptor D2 (DRD2) in addictions and other dopamine-associated traits. In vitro mRNA and protein studies have shown a potential connection between ANKK1 and the dopaminergic system functioning. Here, we have investigated whether Ankk1 expression in the brain is regulated by treatment with dopaminergic agonists. We used quantitative RT-PCR of total brain and Western blots of specific brain areas to study Ankk1 in murine brain after dopaminergic treatments. We found that Ankk1 mRNA was upregulated after activation of D1R-like dopamine receptors with SKF38393 (2.660 ± 1.035-fold; t: 4.066, df: 11, P = 0.002) and apomorphine (2.043 ± 0.595-fold; t: 3.782, df: 8, P = 0.005). The D2R-like agonist quinelorane has no effect upon Ankk1 mRNA (1.004 ± 0.580-fold; t: 0.015, df: 10, P = 0.9885). In contrast, mice treatment with the D2R-like agonists 7-OH-DPAT and aripiprazole caused a significant Ankk1 mRNA downregulation (0.606 ± 0.057-fold; t: 2.786, df: 10, P = 0.02 and 0.588 ± 0.130-fold; t: 2.394, df: 11, P = 0.036, respectively). With respect the Ankk1 proteins profile, no effects were found after SKF38393 (t: 0.54, df: 2, P = 0.643) and Quinelorane (t: 0.286, df: 8, P = 0.782) treatments. In contrast, the D2R-like agonist 7-OH-DPAT (±) caused a significant increment of Ankk1 in the striatum (t: 2.718, df: 7; P = 0.03) when compared to the prefrontal cortex. The activation of D1R-like and D2-R-like leads to opposite transcriptional regulation of Ankk1 by specific pathways.
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Research Interests: Cognitive Science, Psychiatry, Schizophrenia, Magnetic Resonance Imaging, Prefrontal Cortex, and 19 moreBrain Mapping, Linear Model, Cerebrospinal Fluid, Humans, Chronic Disease, Female, Male, Follow-up studies, Recurrence, Clinical Sciences, Middle Aged, Atrophy, Adult, First Year, Disease Progression, Reference Values, Neurosciences, Gray Matter, and Expected Value
Research Interests: Electrophysiology, Schizophrenia, Nonparametric Statistics, Magnetic Resonance Imaging, MRI, and 16 moreElectroencephalography, Morphometry, Brain Mapping, Humans, Female, Roi, Male, Middle Aged, Longitudinal Studies, Adult, Clinical Data, Biological Process, Sensitivity and Specificity, Treatment Response, Nuclear Magnetic Resonance Imaging, and Biological Data
Anticonvulsant drugs have been used in the treatment of alcohol addiction with relatively good results. The purpose of the present study was to evaluate tolerance and safety of topiramate in patients presenting alcohol dependence. We... more
Anticonvulsant drugs have been used in the treatment of alcohol addiction with relatively good results. The purpose of the present study was to evaluate tolerance and safety of topiramate in patients presenting alcohol dependence. We studied 24 patients that fulfilled alcohol-dependence criteria (DSM-IV) and presented other psychiatric disorders for which the use of topiramate was indicated. During the 12 weeks of the study, the patients received topiramate (262 mg/day) plus the psychoactive drugs they were taking for the other disorders. Carbohydrate-deficient transferrin (CDT) values and measures of craving and alcohol use were taken every 2 weeks. Baseline rating of amount and frequency of craving and alcohol use decreased significantly by week 2, and CDT values decreased from week 6. Topiramate was well tolerated, and there were only three dropouts due to adverse events. Topiramate is safe and well tolerated, and may be beneficial in the treatment of alcohol dependence. A placebo-controlled study would be of interest.
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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... more
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.
Research Interests: Polymorphism, Humans, Sequence alignment, Neurotoxicity, dopamine receptor D4, and 13 moreClinical Sciences, Cell nucleus, Single Nucleotide Polymorphism, Linkage Disequilibrium, Protein Expression, Genetic Polymorphism, Transfection, In Silico, Cytoplasm, Neurosciences, Apomorphine, Biochemistry and cell biology, and Gene Expression Regulation
Tardive dyskinesia (TD) is a severe and potential irreversible side effect of antipsychotic treatment. Treatment of established TD is often unsuccessful. In this article, we report three cases of psychogeriatric patients who suffered from... more
Tardive dyskinesia (TD) is a severe and potential irreversible side effect of antipsychotic treatment. Treatment of established TD is often unsuccessful. In this article, we report three cases of psychogeriatric patients who suffered from TD as a side effect of long-term treatment with haloperidol that resolved after switching treatment to aripiprazole. Potential psychopharmacological mechanisms explaining this finding are briefly discussed.
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Research Interests: Multiple sclerosis, Chronic Pain, Movement disorders, Brain, Humans, and 15 moreAnimals, Neurotoxicity, Analgesia, Central Nervous System, Mental Disorders, Feeding Behavior, Clinical Sciences, Cognitive impairment, Pharmaceutical Preparation, Endocannabinoids, Therapeutic Use, Neurosciences, Cognition disorders, Biochemistry and cell biology, and Cannabinoid Receptor
Research Interests: Adolescent, Spain, Antisocial Personality Disorder, DNA, Humans, and 15 moreAlcoholism, Personality Disorder, Male, Neurotoxicity, Clinical Sciences, Aged, Middle Aged, Alcohol dependence, Genotype, Adult, Single Nucleotide Polymorphism, Clinical Study, Genetic Analysis, Neurosciences, and Biochemistry and cell biology
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The cannabinoid receptor 1 gene (CNR1) has been associated with addictive disorders and schizophrenia in different studies. We have compared the frequencies of the alleles for the... more
The cannabinoid receptor 1 gene (CNR1) has been associated with addictive disorders and schizophrenia in different studies. We have compared the frequencies of the alleles for the 3'-UTR CNR1 microsatellite in a sample of 113 Spanish schizophrenic patients, including 68 with comorbid substance abuse, and 111 healthy controls. We report that the frequency of the allele 4 of this microsatellite is significantly lower in schizophrenia patients when compared with controls (chi(2) = 7.858; df 1; P = 0.005). No differences have been found with respect to substance abuse.Thus, the allele 4 represents, in our sample, a protective factor against schizophrenia (odds ratio 0.468, 95% confidence interval (CI) 0.27-0.79). The population attributable genetic risk for the allele 4 absence is 30% (95% CI = 17-41%) and the attributable risk for the allele 4 absence in those with schizophrenia is 53% (95% CI = 20-73%). Our results suggest that, independent of substance abuse, differences in the cannabinoid system function could be involved in the vulnerability to schizophrenia in Spanish population.