Genes associated with the use/abuse of cocaine and crack cocaine: Systematic review and biological networks analysis.

• Grant number: 24/16550-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2024
• End date: September 30, 2025
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Caroline Perez Camilo
• Grantee: Vinícius Aguiar Rosa
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The use of cocaine and its smoked form, "crack," has significantly increased over the past thirty years, emerging as a major public health concern. Cocaine and crack cocaine dependence are influenced by both environmental factors, including socioeconomic status, social adversity, quality of life, stress, and comorbidity with other psychiatric disorders, and genetic alterations. Some studies showed an estimated heritability for cocaine abuse ranging from 0.32 to 0.79, along with a contribution of common genetic risk factors specific to cocaine between 92-93%. Over the past twenty years, efforts have been made to identify genes, genetic variants, and, more recently, epigenetic modifications associated with vulnerability to cocaine and crack cocaine use, abuse, and dependence. In this context, the present project aims to perform a systematic literature review to identify, synthesize, and update existing knowledge on genes associated with cocaine and crack use and abuse. This systematic review will be conducted in accordance with the PRISMA guidelines, utilizing the following databases: PubMed, EMBASE, Scopus, and Web of Science. The inclusion criteria, defined using Boolean expressions, will encompass: (i) observational epidemiological studies (cohort, prospective, retrospective, and case-control studies) in humans published up to April 2024; (ii) studies identifying genes associated with cocaine and crack use/abuse; (iii) studies with a clear phenotype definition; (iv) studies in Portuguese, English, or Spanish. Exclusion criteria will include experimental studies lacking control groups, studies involving animal models, as well as dissertations, books, book reviews, editorials, narrative reviews or opinions, case series, and case reports. Article selection will be performed independently by two reviewers in two stages: 1) screening of titles and abstracts; and 2) full-text review. Data extraction will be carried out using a standardized form, tailored to address the key questions of the review. Data synthesis will be performed either quantitatively or narratively, depending on the homogeneity of the selected studies. Finally, the genes identified through the systematic review will be analyzed in protein-protein interaction (PPI) networks and functional enrichment assessments using the STRING database. The synthesis of these findings is expected to enhance our understanding of the biological mechanisms underlying cocaine and crack dependence.