Epigenetics and Pharmacoepigenetics of Neurodevelopmental and Neuropsychiatric Disorders

Neuropsychiatric disorders (NPDs) are the third major problem of health in developed countries. Epigenetics is a fundamental process in brain development (neurogenesis, differentiation, specialization, neuronal identity); however, our present knowledge on neuroepigenetics, though quantitatively important, is very limited in terms of organization and systematization of data. In addition to epigenetic Mendelian disorders caused by mutations in components of the epigenetic machinery, a large number of neurodevelopmental disorders exhibit epigenetic aberrations (differential DNA methylation in CpG islands, chromatin remodeling, histone modifications, miRNA dysregulation) that might be involved in their pathogenesis. Phenotypes associated with NPDs can be transmitted to progeny by epigenetics-related transgenerational inheritance. Most brain tumors, in their diverse manifestations, are decorated with epigenetic signatures that can be potentially used as biomarkers for diagnosis, prognosis, and drug monitoring. The pharmacoepigenetics of NPDs related to antidepressants, neuroleptics, anxiolytics, anticonvulsants, hypnotics, and other psychotropic drugs is still in its infancy, and no epigenetic drugs have been used as potential candidate treatments for NPDs, with the exception of valproic acid in epilepsy. Some technical problems might limit the future use of epigenetic drugs in NPDs as a result of the difficulties that present molecules pose for brain penetration, diffusibility, and toxicity.