Person: Rubio Valladolid, Gabriel
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First Name
Gabriel
Last Name
Rubio Valladolid
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Medicina Legal, Psiquiatría y Patología
Area
Psiquiatría
Identifiers
4 results
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Item Plasma concentrations of oleoylethanolamide and other acylethanolamides are altered in alcohol-dependent patients: effect of length of abstinence(Addiction Biology, 2016) García Marchena, N; Pavon, Francisco J.; Pastor, A; Araos, P; Pedraz, M; Romero Sanchiz, P; Calado, M; Suárez, J; Castilla Ortega, E; Orio Ortiz, Laura; Boronat, A; Torrens, M; Rubio Valladolid, Gabriel; Rubio, G; de la Torre, Rafael; Rodríguez de Fonseca, F; Serrano, AAcylethanolamides are a family of endogenous lipid mediators that are involved in physiological and behavioral processes associated with addiction. Recently, oleoylethanolamide (OEA) has been reported to reduce alcohol intake and relapse in rodents but the contribution of OEA and other acylethanolamides in alcohol addiction in humans is unknown. The present study is aimed to characterize the plasma acylethanolamides in alcohol dependence. Seventy-nine abstinent alcohol-dependent subjects (27 women) recruited from outpatient treatment programs and age-/sex-/body mass-matched healthy volunteers (28 women) were clinically assessed with the diagnostic interview PRISM according to the DSM-IV-TR after blood extraction for quantification of acylethanolamide concentrations in the plasma. Our results indicate that all acylethanolamides were significantly increased in alcohol-dependent patients compared with control subjects (p < 0.001). A logistic model based on these acylethanolamides was developed to distinguish alcohol-dependent patients from controls and included OEA, arachidonoylethanolamide (AEA) and docosatetraenoylethanolamide (DEA), providing a high discriminatory power according to area under the curve [AUC = 0.92 (95%CI: 0.87–0.96), p < 0.001]. Additionally, we found a significant effect of the duration of alcohol abstinence on the concentrations of OEA, AEA and DEA using a regression model (p < 0.05, p < 0.01 and p < 0.001, respectively), which was confirmed by a negative correlation (rho = −0.31, −0.40 and −0.44, respectively). However, acylethanolamides were not influenced by the addiction alcohol severity, duration of problematic alcohol use or diagnosis of psychiatric comorbidity. Our results support the preclinical studies and suggest that OEA, AEA and DEA are altered in alcohol-dependence during abstinence and that might act as potential markers for predicting length of alcohol abstinence.Item Decreased plasma concentrations of BDNF and IGF-1 in abstinent patients with alcohol use disorders(Plos One, 2017) García Marchena, Nuria; Martín Velasco, Ana Isabel; Villanúa Bernués, María Ángeles; Rubio Valladolid, Gabriel; Pavón Moron, Francisco JoséThe identification of growth factors as potential biomarkers in alcohol addiction may help to understand underlying mechanisms associated with the pathogenesis of alcohol use disorders (AUDs). Previous studies have linked growth factors to neural plasticity in neurocognitive impairment and mental disorders. In order to further clarify the impact of chronic alcohol consumption on circulating growth factors, a cross-sectional study was performed in abstinent AUD patients (alcohol group, N = 91) and healthy control subjects (control group, N = 55) to examine plasma concentrations of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1) and IGF-1 binding protein-3 (IGFBP-3). The association of these plasma peptides with relevant AUD-related variables and psychiatric comorbidity was explored. The alcohol group was diagnosed with severe AUD and showed an average of 13 years of problematic use and 10 months of abstinence at the moment of participating in the study. Regarding common medical conditions associated with AUD, we observed an elevated incidence of alcohol-induced liver and pancreas diseases (18.7%) and psychiatric comorbidity (76.9%). Thus, AUD patients displayed a high prevalence of dual diagnosis (39.3%) [mainly depression (19.9%)] and comorbid substance use disorders (40.7%). Plasma BDNF and IGF-1 concentrations were significantly lower in the alcohol group than in the control group (p<0.001). Remarkably, there was a negative association between IGF-1 concentrations and age in the control group (r = -0.52, p<0.001) that was not found in the alcohol group. Concerning AUD-related variables, AUD patients with liver and pancreas diseases showed even lower concentrations of BDNF (p<0.05). In contrast, the changes in plasma concentrations of these peptides were not associated with abstinence, problematic use, AUD severity or lifetime psychiatric comorbidity. These results suggest that further research is necessary to elucidate the role of BDNF in alcohol-induced toxicity and the biological significance of the lack of correlation between age and plasma IGF-1 levels in abstinent AUD patients.Item Pro-/Anti-inflammatory Dysregulation in Patients With First Episode of Psychosis: Toward an Integrative Inflammatory Hypothesis of Schizophrenia(Schizophrenia Bulletin, 2014) García Bueno, Borja; Mac-Dowell Mata, Karina Soledad; Rodríguez Jiménez, Roberto; Rubio Valladolid, Gabriel; Leza Cerro, Juan CarlosBackground: Schizophrenia is a chronic syndrome of unknown etiology, predominantly defined by signs of psychosis. The onset of the disorder occurs typically in late adolescence or early adulthood. Efforts to study pathophysiological mechanisms in early stages of the disease are crucial in order to prompt intervention. Methods: Case-control study of first-episode psychotic (FEP) patients and matched controls. We recruited 117 patients during the first year after their FEP according to the DSM-IV criteria and recruited 106 gender-, race-, and age-matched controls between September 2010 and June 2011. Results: Biochemical studies carried out in peripheral mononuclear blood cells (PMBC) and plasma evidence a significant increase in intracellular components of a main proinflammatory pathway, along with a significant decrease in the anti-inflammatory ones. Multivariate logistic regression analyses identified the expression of inducible isoforms of nitric oxide synthase and cyclooxygenase in PMBC and homocysteine plasma levels as the most reliable potential risk factors and the inhibitor of the inflammatory transcription factor NFκB, IκBα, and the anti-inflammatory prostaglandin 15d-PGJ2 as potential protection factors. Discussion: Taken as a whole, the results of this study indicate robust phenotypical differences at the cellular machinery level in PMBC of patients with FEP. Although more scientific evidence is needed, the determination of multiple components of pro- and anti-inflammatory cellular pathways including the activity of nuclear receptors has interesting potential as biological markers and potential risk/protective factors for FEP. Due to its soluble nature, a notable finding in this study is that the anti-inflammatory mediator 15d-PGJ2 might be used as plasmatic biomarker for first episodes of psychosis.Item Alcohol-induced cognitive deficits are associated with decreased circulating levels of the neurotrophin BDNF in humans and rats(Addiction Biology, 2019) Silva Peña, Daniel; Martín Velasco, Ana Isabel; Villanúa Bernués, María Ángeles; Rubio Valladolid, Gabriel; Rodríguez De Fonseca, Fernando Antonio; Suárez Pérez, JuanChronic alcohol consumption is associated with neurocognitive and memory deficits, dramatically affecting plasticityand connectivity, with maximal expression as dementia. Neurotrophic factors may contribute to alcohol-related cogni-tive decline. For further investigation, a cross-sectional study was performed to evaluate the association of cognitiveimpairment, by using frontal assessment battery, and memory loss, using memory failures everyday, with the circulat-ing levels of the neurotrophin brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) in abstinent sub-jects with alcohol use disorders (AUDs,N= 58, average of 17.9 years of problematic use and 4.3 months of abstinence)compared with healthy control subjects (N= 22). This association was also explored in a pre-clinical model of adoles-cent rats chronically exposed to alcohol up to adulthood (~77 days old) in a three-bottle free-choice (5–10–20 per-cent), repeated abstinence and relapse paradigm. AUD subjects had low educational level and cognitive impairmentassociated with teenage consumption and lower circulating levels of BDNF and NT-3. Only BDNF concentrationshowed a positive correlation with frontal assessment battery in AUD patients. In the ethanol-exposed rats, the plasmalevels of BDNF and NT-3 were also decreased, and a negative correlation between hippocampalBdnfmRNA levels andrecognition memory was found. The ethanol-exposed rat hippocampus showed a decrease in the mRNA levels of neu-rotrophic (BdnfandNtf-3) and neurogenic (Mki67,Sox2,Dcx,Ncam1andCalb1) factors, associated to a deactivation ofthe neurogenic regulator mitogen-activated protein kinase extracellular signal-regulated kinase. Results suggest a rel-evant role of BDNF/extracellular signal-regulated kinase 2 signaling in alcohol-induced cognitive impairment and sug-gest that early alcohol exposure-derived effects on cognition are associated with neurotrophin signaling deficits.