Epigenetic Basis of Mental Illness

被引:236
作者
Nestler, Eric J. [1 ,2 ]
Pena, Catherine J. [1 ,2 ]
Kundakovic, Marija [1 ,2 ]
Mitchell, Amanda [1 ,2 ]
Akbarian, Schahram [1 ,2 ]
机构
[1] Icahn Sch Med Mt Sinai, Friedman Brain Inst, Dept Neurosci, New York, NY 10029 USA
[2] Icahn Sch Med Mt Sinai, Friedman Brain Inst, Dept Psychiat, New York, NY 10029 USA
关键词
depression; schizophrenia; bipolar disorder; histone acetylation; histone methylation; DNA methylation; microRNA; 3D chromatin structure; DNA METHYLATION STATUS; EARLY-LIFE EXPERIENCE; RECEPTOR GENE NR3C1; BIPOLAR DISORDER; PSYCHIATRIC-DISORDERS; PREFRONTAL CORTEX; MATERNAL-CARE; GLUCOCORTICOID-RECEPTOR; HISTONE METHYLATION; HUMAN BRAIN;
D O I
10.1177/1073858415608147
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Psychiatric disorders are complex multifactorial illnesses involving chronic alterations in neural circuit structure and function as well as likely abnormalities in glial cells. While genetic factors are important in the etiology of most mental disorders, the relatively high rates of discordance among identical twins, particularly for depression and other stress-related syndromes, clearly indicate the importance of additional mechanisms. Environmental factors such as stress are known to play a role in the onset of these illnesses. Exposure to such environmental insults induces stable changes in gene expression, neural circuit function, and ultimately behavior, and these maladaptations appear distinct between developmental versus adult exposures. Increasing evidence indicates that these sustained abnormalities are maintained by epigenetic modifications in specific brain regions. Indeed, transcriptional dysregulation and the aberrant epigenetic regulation that underlies this dysregulation is a unifying theme in psychiatric disorders. Here, we provide a progress report of epigenetic studies of the three major psychiatric syndromes, depression, schizophrenia, and bipolar disorder. We review the literature derived from animal models of these disorders as well as from studies of postmortem brain tissue from human patients. While epigenetic studies of mental illness remain at early stages, understanding how environmental factors recruit the epigenetic machinery within specific brain regions to cause lasting changes in disease susceptibility and pathophysiology is revealing new insight into the etiology and treatment of these conditions.
引用
收藏
页码:447 / 463
页数:17
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