Estudio post-mortem de las alteraciones en la expresión de RNA en el cerebro de pacientes suicidas

Despite individuals with substance use disorder (SUD) have a high suicide risk, most of gene expression studies in suicide have excluded individuals with this disorder. Thus, little is known about the gene expression profile in suicides with SUD. The identification of altered biological processes in the brain of suicides with SUD is crucial in the comprehension of the SUD and suicidal behavior comorbidity. This dissertation describes the evaluation of gene expression differences in the dorsolateral prefrontal cortex of suicides and non-suicides with and without SUD.Sixty-six brain tissue samples were collected and classified in the following groups: i) 23 suicides with SUD, ii) 20 suicides without SUD, iii) 9 non-suicides with SUD and iv) 14 non-suicides without SUD. The results of this study suggest that suicides with SUD have a gene expression profile in the prefrontal cortex different from that of individuals with only one of these conditions, presenting differences in the expression of genes involved in cell proliferation and glutamatergic neurotransmission.We performed a re-analysis of the gene expression data of 38 suicides focused on dual diagnosis and suicide. Dual diagnosis is the concurrence of at least one SUD and one or more mental disorders in a given individual. Although this comorbidity is highly prevalent and is associated with adverse clinical outcomes, its neurobiology has not been elucidated. In addition, patients with dual pathology have a higher suicide risk compared to patients with only one disorder.The objective of this re-analysis was to evaluate the differences in the gene expression profile in the prefrontal cortex of suicides with dual pathology compared to suicides with a single disorder. Our results suggest an alteration in the expression of genes involved in glutamatergic neurotransmission, GABAergic neurotransmission and neurogenesis in suicides with dual diagnosis compared to suicides with a single disorder and suicides without mental comorbidities.The observed differences in gene expression in the prefrontal cortex between suicides with and without SUD, as well as suicides with dual diagnosis and a single disorder may contribute to the phenotypic and clinical discrepancies observed among these patients. The identification of molecular characteristics in the brain of individuals with suicidal behavior and psychiatric comorbidities will allow the design of preventive and therapeutic measures aimed at the adequate treatment of each comorbidity.