Gene therapy for obsessive–compulsive disorder: Basic research and clinical prospects

Abstract

Background: Obsessive-Compulsive Disorder (OCD) is a prevalent psychiatric condition known for its resistance to conventional treatments. Despite available pharmacological and psychotherapeutic interventions, a significant number of patients do not respond adequately to these approaches. Recent genome-wide association studies (GWAS) have identified genetic links to OCD, sparking interest in exploring gene therapy as an alternative treatment method. Main body: Gene therapy involves correcting or replacing defective genes to target the root cause of the disorder. Preliminary studies have shown promising results, focusing on genes such as Brain Derived Neurotrophic Factor (BDNF), oxytocin receptor (OXTR), SLITRK5, and SLC6A4. Continued exploration of genes like SHANK3 and IMOOD, as well as animal models like SLITRK5 knockout mice, offer insights into potential therapeutic targets. However, ethical and technical challenges must be addressed before wider implementation can occur. Ethical considerations include the multifactorial nature of psychiatric disorders, the need for comprehensive treatment, and issues surrounding informed consent, particularly in cases where patients lack insight into their condition. Technical challenges involve safe gene delivery to the brain, potential off-target effects, and achieving optimal gene expression levels. Conclusions: Gene therapy for OCD is still in the early stages of research and development. While current research is still in its infancy, the identification of specific genes and pathways associated with OCD offers a foundation for future therapeutic interventions. Despite the ethical and technical challenges that remain, advancements in genetic engineering and the establishment of animal models provide a hopeful outlook for the development of effective gene therapy strategies. As the field progresses, Further research is essential to fully realize the potential of gene therapy in managing OCD and related psychiatric conditions. © 2025 Elsevier Inc.