A comprehensive update on genetic inheritance, epigenetic factors, associated pathology, and recent therapeutic intervention by gene therapy in schizophrenia

• Published in: Chemical biology & drug design 2024-01, Vol.103 (1), p.e14374-n/a
• Main Authors: R, Rachana, Devtalla, Harshit, Rana, Karishma, Panda, Siva Prasad, Agrawal, Arushi, Kadyan, Shreya, Jindal, Divya, Pancham, Pranav, Yadav, Deepshikha, Jha, Niraj Kumar, Jha, Saurabh Kumar, Gupta, Vivek, Singh, Manisha
• Format: Article
• Language: English
• Subjects: Brain - metabolism; CRISPR technology; DNA Copy Number Variations; Epigenesis, Genetic; Genome-Wide Association Study; genome‐wide association studies; Humans; nanotechnology; Polymorphism, Single Nucleotide; schizophrenia; Schizophrenia - genetics; Schizophrenia - metabolism; Schizophrenia - therapy; single nucleotide polymorphism; siRNA and miRNA technology
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/cbdd.14374

Schizophrenia is a severe psychological disorder in which reality is interpreted abnormally by the patient. The symptoms of the disease include delusions and hallucinations, associated with extremely disordered behavior and thinking, which may affect the daily lives of the patients. Advancements in technology have led to understanding the dynamics of the disease and the identification of the underlying causes. Multiple investigations prove that it is regulated genetically, and epigenetically, and is affected by environmental factors. The molecular and neural pathways linked to the regulation of schizophrenia have been extensively studied. Over 180 Schizophrenic risk loci have now been recognized due to several genome‐wide association studies (GWAS). It has been observed that multiple transcription factors (TF) binding‐disrupting single nucleotide polymorphisms (SNPs) have been related to gene expression responsible for the disease in cerebral complexes. Copy number variation, SNP defects, and epigenetic changes in chromosomes may cause overexpression or underexpression of certain genes responsible for the disease. Nowadays, gene therapy is being implemented for its treatment as several of these genetic defects have been identified. Scientists are trying to use viral vectors, miRNA, siRNA, and CRISPR technology. In addition, nanotechnology is also being applied to target such genes. The primary aim of such targeting was to either delete or silence such hyperactive genes or induce certain genes that inhibit the expression of these genes. There are challenges in delivering the gene/DNA to the site of action in the brain, and scientists are working to resolve the same. The present article describes the basics regarding the disease, its causes and factors responsible, and the gene therapy solutions available to treat this disease. Dopaminergic pathways influence positive and negative symptoms. Upregulation of the D1 receptor in the striatal region results in positive signs, while downregulation of the D2 receptor in PFC results in negative symptoms.