Disorders relating to use of substances: epigenetic, neurotrophic, morphometric and neural network effects on decision-making

• Grant number: 19/25423-8
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2020
• End date: August 31, 2023
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Isabel Cristina Céspedes
• Grantee: Isabel Cristina Céspedes
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Ana Maria Ferreira de Sousa Sebastião ; Diego Robles Mazzotti ; Henrique Carrete Junior ; João Ricardo Sato ; Maria Lucia Oliveira de Souza Formigoni

Abstract

According to the latest surveys, about 2.3 billion people used licit drugs and 275 million used illicit drugs worldwide in 2015. The disability adjusted life years (DALYs) estimate indicated a loss of 132.6 million years due to licit drug use and 28 million years due to illicit drug use in 2015. The multifactorial character of substance use disorders includes genetic, psychosocial factors and the effects of the drug itself on the body. Drugs of abuse are associated with changes in several neural systems, with emphasis on the dopaminergic and glutamatergic systems, neuroplastic, morphometric and behavioral changes. These changes can affect important cognitive functions such as decision making. This impaired ability influences and sustains drug search and exposure behaviors. The aim of this paper is to compare cognitive abilities, with emphasis on decision making, of healthy volunteers with individuals with substance use disorders (alcohol, marijuana, cocaine and crack) and to study their association with epigenetic marks in genes that encode glutamatergic system elements, with variations in BDNF neurotrophic factor concentration, neuromorphometric data, and the pattern of connectivity between neural networks associated with decision making (areas: prefrontal cortex, amygdala, and nucleus accumbens). Volunteers diagnosed with substance use disorder and controls will undergo cognitive (Iowa Gambling Task, Rey Auditory Verbal Learning Test - RAVLT and Stroop Color) and emotional (Beck Inventory for Depression and State-Trait Anxiety Inventory) tests. Blood samples will be collected to measure plasma BDNF concentration and methylation of candidate genes. Resting state functional magnetic resonance images will be acquired for connectivity analysis of networks involved in decision making, as well as volumetric data for calculating volume and integrity of nervous tissue using stereology and tractography techniques. We hope to be able to assess the degree of impairment in cognitive skills, especially decision-making ability, in individuals with substance use disorders (alcohol, marijuana, cocaine and crack) through cognitive testing. Associate this possible degree of decision-making impairment with affective disorders, epigenetic marks, neurotrophic changes, morphometric patterns and neural connectivity. Thus, understand the mechanisms behind these cognitive changes for better diagnosis and control of these effects. (AU)