CRISPR-Cas9 gene editing in neuropsychiatric disorders: Challenges and promising avenues

• CRISPR-Cas9 technology provides unprecedented precision in decoding the genetic complexities of neuropsychiatric disorders, including schizophrenia, bipolar disorder, major depressive disorder, ASD, and ADHD. • Specific CRISPR applications target and modify implicated genes, offering unique insights into the elusive genetic factors underlying these conditions. • Ethical considerations, particularly regarding germline editing and safety concerns, underscore the importance of a cautious and responsible approach. This review explores the transformative potential of CRISPR-Cas9 gene editing technology in neuropsychiatric disorders. Neuropsychiatric conditions, marked by genetic and environmental factors, pose significant global health challenges. Traditional treatments often address symptoms, leaving underlying genetic anomalies untouched. CRISPR-Cas9, renowned for its unparalleled precision, presents an opportunity to unravel the complex genetic architecture contributing to disorders like schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). The review explores specific applications of CRISPR technology, showcasing studies targeting genes associated with these disorders and exploring alternative splicing mechanisms, microexon involvement, and the role of master regulators. Despite the revolutionary promise of CRISPR, challenges and limitations must be addressed. Technical challenges, such as achieving allele-specific modifications and minimising off-target effects, require ongoing research. Safety concerns, ethical considerations regarding germline editing, and potential unintended consequences emphasise the need for cautious implementation. Ongoing research aims to refine CRISPR techniques, enhance precision, and overcome current challenges. Collaboration between scientists, ethicists, clinicians, and patient advocacy groups is pivotal for responsible implementation. Identifying specific genes or pathways for therapeutic targeting holds promise for personalised and precise interventions. This review envisions a future where the responsible integration of CRISPR technology transforms the understanding and treatment of neuropsychiatric disorders, providing a multidimensional approach that balances scientific innovation with ethical considerations.