Epigenetic and pharmacoepigenomic studies of major psychoses and potentials for therapeutics

被引:31
作者
Abdolmaleky, Hamid Mostafavi [1 ,2 ,3 ,4 ,5 ]
Zhou, Jing-Rong [1 ]
Thiagalingam, Sam [3 ]
Smith, Cassandra L. [2 ]
机构
[1] Harvard Univ, Sch Med, Lab Nutr & Metab, BIDMC, Boston, MA 02115 USA
[2] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA
[3] Boston Univ, Sch Med, Dept Med Genet & Genom, Boston, MA 02215 USA
[4] Iran Univ Med Sci, Dept Psychiat, Tehran, Iran
[5] Iran Univ Med Sci, Tehran Psychiat Inst, Tehran, Iran
关键词
bipolar disorder; brain; chromatin; DNA methylation; epigenetics; nutrition; pharmacoepigenomics; pharmacogenomics; psychiatry; schizophrenia;
D O I
10.2217/14622416.9.12.1809
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:1809 / 1823
页数:15
相关论文
共 154 条
  • [1] Hypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and bipolar disorder
    Abdolmaleky, Hamid Mostafavi
    Cheng, Kuang-hung
    Faraone, Stephen V.
    Wilcox, Marsha
    Glatt, Stephen J.
    Gao, Fangming
    Smith, Cassandra L.
    Shafa, Rahim
    Aeali, Batol
    Carnevale, Julie
    Pan, Hongjie
    Papageorgis, Panagiotis
    Ponte, Jose F.
    Sivaraman, Vadivelu
    Tsuang, Ming T.
    Thiagalingam, Sam
    [J]. HUMAN MOLECULAR GENETICS, 2006, 15 (21) : 3132 - 3145
  • [2] Genetics and epigenetics in major psychiatric disorders - Dilemmas, achievements, applications, and future scope
    Abdolmaleky, HM
    Thiagalingam, S
    Wilcox, M
    [J]. AMERICAN JOURNAL OF PHARMACOGENOMICS, 2005, 5 (03) : 149 - 160
  • [3] Hypermethylation of the reelin (RELN) promoter in the brain of schizophrenic patients:: A preliminary report
    Abdolmaleky, HM
    Cheng, KH
    Russo, A
    Smith, CL
    Faraone, SV
    Wilcox, M
    Shafa, R
    Glatt, SJ
    Nguyen, G
    Ponte, JF
    Thiagalingam, S
    Tsuang, MT
    [J]. AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2005, 134B (01) : 60 - 66
  • [4] Methylomics in psychiatry: Modulation of gene-environment interactions may be through DNA methylation
    Abdolmaleky, HM
    Smith, CL
    Faraone, SV
    Shafa, R
    Stone, W
    Glatt, SJ
    Tsuang, MT
    [J]. AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2004, 127B (01): : 51 - 59
  • [5] The neurobiology of Rett syndrome
    Akbarian, S
    [J]. NEUROSCIENTIST, 2003, 9 (01) : 57 - 63
  • [6] The molecular pathology of Rett syndrome - Synopsis and update
    Akbarian, Schahram
    Jiang, Yan
    Laforet, Genevieve
    [J]. NEUROMOLECULAR MEDICINE, 2006, 8 (04) : 485 - 494
  • [7] ALLIS CD, 2007, EPIGENETICS, P191
  • [8] Allis CD, 2007, EPIGENETICS
  • [9] ALLIS CD, 2007, EPIGENETICS, P357
  • [10] [Anonymous], 2005, PSYCHIAT GENETICS RE