Neurocircuit-based investigation of obsessive-compulsive disorder: a contribution to the study of disease mechanisms and the development of new treatments

• Grant number: 23/11569-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2023
• End date: September 30, 2026
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Roseli Gedanke Shavitt
• Grantee: Acácio Moreira Neto
• Host Institution: Instituto de Psiquiatria Doutor Antonio Carlos Pacheco e Silva (IPq). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 19/27250-3 - Neurocircuit-based investigation of obsessive-compulsive disorder: a contribution to the study of disease mechanisms and the development of new treatments, AP.TEM

Abstract

The aim of this proposal is to investigate the involvement of specific neurocircuits, selected based on evidence from neuroimaging and neuropsychological studies, in Obsessive-Compulsive Disorder (OCD). We will test their relationship with distinct phenotypes and their engagement with two first-line treatments. To achieve this, we will characterize the phenotype of adults with OCD and study the structure, activity, connectivity, and metabolism of the fronto-limbic circuits, implicated in fear and emotional regulation experiences, and the sensorimotor circuits, implicated in sensory experiences. Data acquisition will occur at baseline and after treatment with sertraline hydrochloride or cognitive-behavioral therapy.The pre-treatment data analysis will aim to identify the functioning of the selected circuits and their association with the phenotype. The longitudinal analysis will allow us to verify whether the circuits of interest were engaged as therapeutic targets. The same circuits will also be evaluated in treatment-resistant OCD patients undergoing radiosurgery, and we will conduct a longitudinal investigation of microRNAs possibly associated with the circuits of interest. In parallel, we will test the feasibility of an innovative treatment for OCD, f-NIRS neurofeedback.Thus, we will generate unprecedented data linking specific brain circuits with the phenotype and the mechanisms of the disease, contributing to the development of treatments targeted at more specific brain targets and enabling the advancement of a new taxonomy based on neurocircuits.