Epigenetic mediation of environmental influences in major psychotic disorders.
The major psychotic disorders schizophrenia and bipolar disorder are etiologically complex involving both heritable and nonheritable factors. The absence of consistently replicated major genetic effects, together with evidence for lasting changes in gene expression after environmental exposures, is consistent with the concept that the biologic underpinnings of these disorders are epigenetic in form rather than DNA sequence based. Psychosis-associated environmental exposures, particularly at key developmental stages, may result in long-lasting epigenetic alterations that impact on the neurobiological processes involved in pathology. Although direct evidence for epigenetic dysfunction in both schizophrenia and bipolar disorder is still limited, methodological technologies in epigenomic profiling have advanced. This means that we are at the exciting stage where it is feasible to start investigating molecular modifications to DNA and histones and examine the mechanisms by which environmental factors can act upon the genome to bring about epigenetic changes in gene expression involved in the etiology of these disorders. Given the dynamic nature of the epigenetic machinery and potential reversibility of epigenetic modifications, the understanding of such mechanisms is of key relevance for clinical psychiatry and for identifying new targets for prevention and/or intervention.
Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Maastricht University Medical Centre, European Graduate School of Neuroscience, South Limburg Mental Health Research and Teaching Network, Vijverdalseweg 1, Maastricht 6226 NB, The Netherlands. b.rutten@np.unimaas.nl
Bart P F
BP
Rutten
Jonathan
J
Mill
D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics* / Q000523:psychology*; D002648:Child; D002649:Child Abuse / Q000523:psychology; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics; D004200:Diseases in Twins / Q000235:genetics / Q000523:psychology; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D013287:Illicit Drugs / Q000633:toxicity; D016487:Parenting / Q000523:psychology; D010641:Phenotype; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000523:psychology; D011605:Psychoses, Substance-Induced / Q000235:genetics / Q000523:psychology; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics*; D012565:Schizophrenic Psychology; D012931:Social Environment; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D013287:Illicit Drugs; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid