Scholarship 23/13554-6 - Transtornos relacionados ao uso de álcool, Imagem por ressonância magn - BV FAPESP
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Methylation pattern and morphofunctional analysis of decision making neural network in individuals with alcohol use disorder

Grant number: 23/13554-6
Support Opportunities:Scholarships abroad - Research Internship - Post-doctor
Start date until: January 01, 2024
End date until: May 31, 2024
Field of knowledge:Health Sciences - Medicine - Psychiatry
Principal Investigator:Isabel Cristina Céspedes
Grantee:Laís da Silva Pereira Rufino
Supervisor: João Ricardo Nickenig Vissoci
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Institution abroad: Duke University, United States  
Associated to the scholarship:21/13092-7 - METHYLATION PATTERN ANALYSIS AND MORPHOFUNCTIONAL ALTERATIONS IN DECISION MAKING CONTROL NEURAL NETWORKS IN INDIVIDUALS WITH ALCOHOL USE DISORDERS, BP.PD

Abstract

Alcohol use disorder (AUD) is a worldwide and frequent problem with multifactorial characteristics influenced by genetic and environmental factors. AUD was ranked as the seventh largest risk factor for death, with an average consumption of 6,4 liters of pure alcohol and a total of 132.6 million disability-adjusted life years (DALYs) in 2016. Alcohol causes neuroplastic effects on the central nervous system in important structures associated with reward, stress, and cognition and in systems of neurotransmitters such as dopamine and glutamate. The glutamatergic mobilization and the activation of their receptors have been considered important elements in alcohol's these alcohol-induced neuroplastic processes. In AUD, the hyperglutamatergic state causes important behavioral changes and affects cognition, precisely decision making, which is a target of alcohol deleterious effects and that leads to the maintenance of behaviors substance seeking. Cognitive control mainly decision making involves many neural areas and circuits, with the prefrontal cortex being considered the most important structure in these tasks. The prefrontal cortex plays an important function in cognitive, executive, and motivational processes and its morphofunctional alterations can be observed by functional magnetic resonance imaging (f MRI). This study aims to analyze the impact of chronic alcohol use on cognitive abilities (mainly decision-making), through the evaluation of cognitive, emotional, genetic, and neurofunctional (neural networks) aspects. It has been performed on 50 volunteers diagnosed with AUD as well as 50 control volunteers They answered cognitive tests (Iowa Gambling Task, Rey's word list, and Stroop Test) and emotional tests inventory of Beck for depression and T race State anxiety inventory). Blood samples were collected for analysis of methylation patterns of the glutamatergic genes (epigenetic effects) by the Infinium® HumanMethylation450 BeadChip The f MRI images will be analyzed from neuronal connectivity of the decision-making networks. We will do complex and sophisticated mathematical modulations and statistical analyses between epigenetic, fMRI, and behavioral (cognitive and emotional) data. The results of this project have the potential to provide a better understanding of the mechanism underlying the abuse of alcohol and the decline of decision-making, establishing clearer parameters on the origin and level of impairment of this cognitive ability and guiding the diagnostic resources and therapeutic measures available today for AUD treatment. (AU)

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