Evaluación de biomarcadores en adicción a la coaína y comorbilidad psiquiátrica

Résumé

The present doctoral thesis has as main objective to study the effects of the pathological use of cocaine on biological variables measured in plasma. As additional objective, it has been analyzed the relationship of these biological variables with the presence of psychiatric comorbidity, as well as their dependence of sex and time of drug exposure. The identification of biological markers is relevant to improve the diagnosis and stratification of patients, improving the appropriate application of therapeutic interventions and considering as risk factor the presence of psychiatric comorbidity associated with addiction. The present study is the result of an intense research in a multidisciplinary working group, who has characterized the interactions among multiple factors (physiological, clinical, molecular factors¿) in patients affected by cocaine addiction. Exhaustive psychiatric interviews have been performed to gather information from participants referred to sociodemographic data, patterns of consumption of substances and diagnosis of comorbid psychiatric disorders. For this purpose, it has been used the psychiatric semistructured interview PRISM. In addition, blood samples from each subject were also collected for the quantification of potential biomarkers in these patients as well as in age, sex and body mass index-matched healthy controls. In the first study, we evaluated plasma profile of pro-inflammatory cytokines and chemokines in abstinent patients with a history of pathological use of cocaine. These immunological signals were considered as potential biomarkers of pathological use of cocaine, cocaine symptom severity and psychiatric comorbidity. The results show that plasma concentrations of inflammatory mediators are altered in abstinent cocaine users. Among these molecules, we have found that the concentrations of TNF¿, MCP-1 and SDF-1 are altered in cocaine users compared with healthy controls. In addition, the concentrations of IL-1ß, fractalkine and SDF-1 correlate positively with cocaine symptom severity abuse and dependence (DSM-IV TR) and they are suggested as potential biomarkers of severity of cocaine addiction. In the second study, we evaluated the plasma concentrations of neurotrophic factors and a binding protein, IGFBP-3, in relation to the pathological use of cocaine in abstinent subjects. The results show that plasma concentrations of BDNF, IGF-1 and IGFBP-3 are not influenced by the pathological cocaine use. However, BDNF is affected by the presence of comorbid mood and anxiety disorders (both cocaine-induced and primary disorders). In the third study, we evaluated the influence of sex differences and cocaine use on the plasma concentrations of inflammatory mediators and circulating fatty acid derivatives. The present results show that sex plays a critical role in the plasma concentrations of certain molecules and the effects observed by cocaine use. In fact, it has been reported differences in the concentrations of cytokines in women (pro and anti-inflammatory cytokines IL1BETA, IL6, IL10 and TNF) and these changes are not observed in addict women. However, the acylethanolamide POEA that is not altered by sex in the control group is found increased in addict women.The present results confirm that sex acts as a determinant factor in the study of potentials biomarkers of the cocaine addiction and the presence of psychiatric comorbidity. In this population, addicted women show significantly higher dominance of psychiatric comorbidity (mood, anxiety and psychotic disorders) while addicted men show higher psychiatric disorders because of the use of other substances of abuse.AS final conclusion, the present results emphasize the importance of identifying biomarkers to a better understanding of the underlying processes in cocaine addiction. This scientific knowledge is extremely important in order to improve the diagnosis and treatment in cocaine addiction.