Epigenetic and pharmacoepigenomic studies of major psychoses and potentials for therapeutics.
Individuals with neuropsychiatric diseases have epigenetic programming disturbances, both in the brain, which is the primary affected organ, and in secondary tissues. Epigenetic modulations are molecular modifications made to DNA, RNA and proteins that fine-tune genotype into phenotype and do not include DNA base changes. For instance, gene-expression modulation is linked to epigenetic codes in chromatin that consist of post-replication DNA methylation and histone protein modifications (e.g., methylation, acetylation and so on), particularly in gene-promoter regions. Epigenetic coding is modulated globally, and in a gene-specific manner by environmental exposures that include nutrition, toxins, drugs and so on. Analysis of epigenetic aberrations in diseases helps to identify dysfunctional genes and pathways, establish more robust cause-effect relationships than genetic studies alone, and identify new pharmaceutical targets and drugs, including nucleic acid reagents such as inhibitory RNAs. The emerging science of pharmacoepigenomics can impact the treatment of psychiatric and other complex diseases. In fact, some therapeutics now in use target epigenetic programming. In the near future, epigenetic interventions should help stabilize affected individuals and lead to prevention strategies.
Abdolmaleky
Hamid Mostafavi
HM
Laboratory of Nutrition and Metabolism at BIDMC, Harvard Medical School, Boston, MA, USA. sabdolma@bidmc.harvard.edu
Zhou
Jin-Rong
JR
Thiagalingam
Sam
S
Smith
Cassandra L
CL
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015870:Gene Expression / Q000187:drug effects; D006657:Histones / Q000235:genetics; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000235:genetics
D014150:Antipsychotic Agents; D006657:Histones