Differentiation of induced pluripotent stem cells into dopaminergic neurons using a sample of individuals at high risk for psychosis

• Grant number: 24/04919-3
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2025
• End date: March 31, 2027
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Alexandre Andrade Loch
• Grantee: Alexandre Andrade Loch
• 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

Abstract

Schizophrenia (ESZ) is a debilitating mental disorder that affects millions of individuals worldwide, with significant implications across various domains. It is postulated that ESZ presents clinical and biological manifestations even before the onset of the disorder itself, characterizing what is commonly referred to as ultra high-risk individuals for psychosis (UHR). However, not all UHR individuals convert to psychosis or other psychiatric disorder, underscoring the critical need to identify biological markers that predict conversion more accurately. In this regard, it has already been observed that UHR individuals exhibit alterations in dopaminergic transmission characteristic of those with psychosis. Therefore, the aim of this study is to identify potential morphological variations in this pathway, specifically in D2 receptor density among UHR individuals who convert to psychosis compared to those who do not convert or healthy controls. For this purpose, dopaminergic neurons differentiated from induced pluripotent stem cell (iPSC) lines obtained from the peripheral blood of these individuals will be analyzed. Given that the structural effects under investigation may represent crucial aspects underlying psychiatric disorders, particularly ESZ, the findings from this study may provide valuable insights into its pathophysiology, as well as identify novel preventive, diagnostic and therapeutic targets. (AU)