Epigenetic effects of childhood adversity in the brain and suicide risk

The Neurobiological Basis of Suicide

Volumn , Issue , 2012, Pages 275-296

  Labonté, Benoit ^a   Turecki, Gustavo ^a  

^a DOUGLAS MENTAL HEALTH UNIVERSITY INSTITUTE   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85052305255     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1201/b12215     Document Type: Chapter

References (147)

1. Kessler, D., D. Sharp, and G. Lewis, Screening for depression in primary care. Br J Gen Pract, 2005; 55(518): 659-660.
2. Kessler, R.C. et al., Prevalence, severity, and comorbidity of 12-month DSM-IV dis-orders in the National Comorbidity Survey Replication. Arch Gen Psychiatry, 2005; 62(6): 617-627.
3. Regier, D.A. et al., The NIMH Depression Awareness, Recognition, and Treatment Program: Structure, aims, and scientific basis. Am J Psychiatry, 1988; 145(11): 1351-1357.
4. Robins, L.N. and R.K. Price, Adult disorders predicted by childhood conduct problems: Results from the NIMH Epidemiologic Catchment Area project. Psychiatry, 1991; 54(2): 116-132.
5. Weissman, M.M., K.K. Kidd, and B.A. Prusoff, Variability in rates of affective disor-ders in relatives of depressed and normal probands. Arch Gen Psychiatry, 1982; 39(12): 1397-1403.
6. Lopez, A.D. and C.C. Murray, The global burden of disease, 1990-2020. Nat Med, 1998; 4(11): 1241-1243.
7. Arsenault-Lapierre, G., C. Kim, and G. Turecki, Psychiatric diagnoses in 3275 suicides: A meta-analysis. BMC Psychiatry, 2004; 4: 37.
8. Cavanagh, J.T. et al., Psychological autopsy studies of suicide: A systematic review. Psychol Med, 2003; 33(3): 395-405.
9. Angst, F. et al., Mortality of patients with mood disorders: Follow-up over 34-38 years. J Affect Disord, 2002; 68(2-3): 167-181.
10. Angst, J., F. Angst, and H.H. Stassen, Suicide risk in patients with major depressive disorder. J Clin Psychiatry, 1999; 60(Suppl 2): 57-62; discussion 75-76, 113-116.
11. Angst, J., M. Degonda, and C. Ernst, The Zurich Study: XV. Suicide attempts in a cohort from age 20 to 30. Eur Arch Psychiatry Clin Neurosci, 1992; 242(2-3): 135-141.
12. Blair-West, G.W. et al., Lifetime suicide risk in major depression: Sex and age determi-nants. J Affect Disord, 1999; 55(2-3): 171-178.
13. Turecki, G., Dissecting the suicide phenotype: The role of impulsive-aggressive behaviours. J Psychiatry Neurosci, 2005; 30(6): 398-408.
14. McGirr, A. and G. Turecki, The relationship of impulsive aggressiveness to suicidality and other depression-linked behaviors. Curr Psychiatry Rep, 2007; 9(6): 460-466.
15. Yen, S. et al., Personality traits as prospective predictors of suicide attempts. Acta Psychiatr Scand, 2009; 120(3): 222-229.
16. Kwok, S.Y. and D.T. Shek, Socio-demographic correlates of suicidal ideation among Chinese adolescents in Hong Kong. Int J Adolesc Med Health, 2008; 20(4): 463-472.
17. Ang, R.P. and Y.P. Ooi, Impact of gender and parents’ marital status on adolescents’ suicidal ideation. Int J Soc Psychiatry, 2004; 50(4): 351-360.
18. Santa Mina, E.E. and R.M. Gallop, Childhood sexual and physical abuse and adult self-harm and suicidal behaviour: A literature review. Can J Psychiatry, 1998; 43(8): 793-800.
19. Evans, E., K. Hawton, and K. Rodham, Suicidal phenomena and abuse in adolescents: A review of epidemiological studies. Child Abuse Negl, 2005; 29(1): 45-58.
20. Fliege, H. et al., Risk factors and correlates of deliberate self-harm behavior: A system-atic review. J Psychosom Res, 2009; 66(6): 477-493.
21. Brezo, J., T. Klempan, and G. Turecki, The genetics of suicide: A critical review of molecular studies. Psychiatr Clin North Am, 2008; 31(2): 179-203.
22. Ernst, C., N. Mechawar, and G. Turecki, Suicide neurobiology. Prog Neurobiol, 2009; 89: 315-333.
23. Szyf, M., The early life environment and the epigenome. Biochim Biophys Acta, 2009; 1790(9): 878-85. Epub February 3, 2009.
24. McGowan, P.O., M.J. Meaney, and M. Szyf, Diet and the epigenetic (re)programming of phenotypic differences in behavior. Brain Res, 2008; 1237: 12-24.
25. Arnow, B.A., Relationships between childhood maltreatment, adult health and psy-chiatric outcomes, and medical utilization. J Clin Psychiatry, 2004; 65(Suppl 12): 10-15.
26. Molnar, B.E., L.F. Berkman, and S.L. Buka, Psychopathology, childhood sexual abuse and other childhood adversities: Relative links to subsequent suicidal behaviour in the US. Psychol Med, 2001; 31(6): 965-977.
27. Dinwiddie, S. et al., Early sexual abuse and lifetime psychopathology: A co-twin-control study. Psychol Med, 2000; 30(1): 41-52.
28. Gladstone, G.L. et al., Implications of childhood trauma for depressed women: An anal-ysis of pathways from childhood sexual abuse to deliberate self-harm and revictimiza-tion. Am J Psychiatry, 2004; 161(8): 1417-1425.
29. Jaffee, S.R. et al., Differences in early childhood risk factors for juvenile-onset and adult-onset depression. Arch Gen Psychiatry, 2002; 59(3): 215-222.
30. Bensley, L.S. et al., Self-reported abuse history and adolescent problem behaviors. I. Antisocial and suicidal behaviors. J Adolesc Health, 1999; 24(3): 163-172.
31. Ystgaard, M. et al., Is there a specific relationship between childhood sexual and physi-cal abuse and repeated suicidal behavior? Child Abuse Negl, 2004; 28(8): 863-875.
32. Spinhoven, P. et al., Childhood sexual abuse differentially predicts outcome of cog-nitive-behavioral therapy for deliberate self-harm. J Nerv Ment Dis, 2009; 197(6): 455-457.
33. Akyuz, G. et al., Reported childhood trauma, attempted suicide and self-mutilative behavior among women in the general population. Eur Psychiatry, 2005; 20(3): 268-273.
34. Hawton, K. et al., Deliberate self harm in adolescents: Self report survey in schools in England. Br Med J, 2002; 325(7374): 1207-1211.
35. Brezo, J. et al., Predicting suicide attempts in young adults with histories of childhood abuse. Br J Psychiatry, 2008; 193(2): 134-139.
36. Fergusson, D.M., J.M. Boden, and L.J. Horwood, Exposure to childhood sexual and physical abuse and adjustment in early adulthood. Child Abuse Negl, 2008; 32(6): 607-619.
37. Andover, M.S., C. Zlotnick, and I.W. Miller, Childhood physical and sexual abuse in depressed patients with single and multiple suicide attempts. Suicide Life Threat Behav, 2007; 37(4): 467-474.
38. Joiner, T.E., Jr. et al., Childhood physical and sexual abuse and lifetime number of sui-cide attempts: A persistent and theoretically important relationship. Behav Res Ther, 2007; 45(3): 539-547.
39. McHolm, A.E., H.L. MacMillan, and E. Jamieson, The relationship between childhood physical abuse and suicidality among depressed women: Results from a community sample. Am J Psychiatry, 2003; 160(5): 933-938.
40. Klose, R.J. and A.P. Bird, Genomic DNA methylation: The mark and its mediators. Trends Biochem Sci, 2006; 31(2): 89-97.
41. Kouzarides, T., Chromatin modifications and their function. Cell, 2007; 128(4): 693-705.
42. Schratt, G., microRNAs at the synapse. Nat Rev Neurosci, 2009; 10(12): 842-849.
43. Schratt, G., Fine-tuning neural gene expression with microRNAs. Curr Opin Neurobiol, 2009; 19(2): 213-219.
44. Maunakea, A.K. et al., Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature, 2010; 466(7303): 253-257.
45. Pariante, C.M. and S.L. Lightman, The HPA axis in major depression: Classical theories and new developments. Trends Neurosci, 2008; 31(9): 464-468.
46. Heim, C. et al., The link between childhood trauma and depression: Insights from HPA axis studies in humans. Psychoneuroendocrinology, 2008; 33(6): 693-710.
47. Nemeroff, C.B. and W.W. Vale, The neurobiology of depression: Inroads to treatment and new drug discovery. J Clin Psychiatry, 2005; 66(Suppl 7): 5-13.
48. Heim, C. et al., Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. JAMA, 2000; 284(5): 592-597.
49. Heim, C. et al., The dexamethasone/corticotropin-releasing factor test in men with major depression: Role of childhood trauma. Biol Psychiatry, 2008; 63(4): 398-405.
50. Francis, D. et al., Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science, 1999; 286(5442): 1155-1158.
51. Liu, D. et al., Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science, 1997; 277(5332): 1659-1662.
52. McGowan, P.O. et al., Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci, 2009; 12(3): 342-348.
53. Mitchell, J.B., L.J. Iny, and M.J. Meaney, The role of serotonin in the development and environmental regulation of type II corticosteroid receptor binding in rat hippocampus. Brain Res Dev Brain Res, 1990; 55(2): 231-235.
54. Smythe, J.W., W.B. Rowe, and M.J. Meaney, Neonatal handling alters serotonin (5-HT) turnover and 5-HT2 receptor binding in selected brain regions: Relationship to the han-dling effect on glucocorticoid receptor expression. Brain Res Dev Brain Res, 1994; 80(1-2): 183-189.
55. Meaney, M.J., D.H. Aitken, and R.M. Sapolsky, Thyroid hormones influence the development of hippocampal glucocorticoid receptors in the rat: A mechanism for the effects of postnatal handling on the development of the adrenocortical stress response. Neuroendocrinology, 1987; 45(4): 278-283.
56. Laplante, P., J. Diorio, and M.J. Meaney, Serotonin regulates hippocampal glucocorti-coid receptor expression via a 5-HT7 receptor. Brain Res Dev Brain Res, 2002; 139(2): 199-203.
57. Meaney, M.J. et al., Postnatal handling increases the expression of cAMP-inducible transcription factors in the rat hippocampus: The effects of thyroid hormones and serotonin. J Neurosci, 2000; 20(10): 3926-3935.
58. McCormick, J.A. et al., 5′-Heterogeneity of glucocorticoid receptor messenger RNA is tissue specific: Differential regulation of variant transcripts by early-life events. Mol Endocrinol, 2000; 14(4): 506-517.
59. Turner, J.D. and C.P. Muller, Structure of the glucocorticoid receptor (NR3C1) gene 5′ untranslated region: Identification, and tissue distribution of multiple new human exon 1. J Mol Endocrinol, 2005; 35(2): 283-292.
60. Meaney, M.J., Maternal care, gene expression, and the transmission of individual differ-ences in stress reactivity across generations. Annu Rev Neurosci, 2001; 24: 1161-1192.
61. Turner, J.D. et al., Highly individual methylation patterns of alternative glucocorticoid receptor promoters suggest individualized epigenetic regulatory mechanisms. Nucleic Acids Res, 2008; 36(22): 7207-7218.
62. Weaver, I.C. et al., Epigenetic programming by maternal behavior. Nat Neurosci, 2004; 7(8): 847-854.
63. Alt, S.R. et al., Differential expression of glucocorticoid receptor transcripts in major depressive disorder is not epigenetically programmed. Psychoneuroendocrinology, 2010; 35(4): 544-556.
64. Weaver, I.C. et al., The transcription factor nerve growth factor-inducible protein a mediates epigenetic programming: Altering epigenetic marks by immediate-early genes. J Neurosci, 2007; 27(7): 1756-1768.
65. Kee, B.L., J. Arias, and M.R. Montminy, Adaptor-mediated recruitment of RNA poly-merase II to a signal-dependent activator. J Biol Chem, 1996; 271(5): 2373-2375.
66. Kim, T.K. et al., Widespread transcription at neuronal activity-regulated enhancers. Nature, 465(7295): 182-187.
67. Murgatroyd, C. et al., Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nat Neurosci, 2009; 12(12): 1559-1566.
68. Gainer, H., R.L. Fields, and S.B. House, Vasopressin gene expression: Experimental models and strategies. Exp Neurol, 2001; 171(2): 190-199.
69. Chen, W.G. et al., Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science, 2003; 302(5646): 885-889.
70. Zhou, Z. et al., Brain-specific phosphorylation of MeCP2 regulates activity-dependent BDNF transcription, dendritic growth, and spine maturation. Neuron, 2006; 52(2): 255-269.
71. Rhee, H.J., E.J. Kim, and J.K. Lee, Physiological polyamines: Simple primordial stress molecules. J Cell Mol Med, 2007; 11(4): 685-703.
72. Fiori, L.M. and G. Turecki, Implication of the polyamine system in mental disorders. J Psychiatry Neurosci, 2008; 33(2): 102-110.
73. Gilad, G.M. and V.H. Gilad, Overview of the brain polyamine-stress-response: Regulation, development, and modulation by lithium and role in cell survival. Cell Mol Neurobiol, 2003; 23(4-5): 637-649.
74. Gilad, G.M. et al., Developmental regulation of the brain polyamine-stress-response. Int J Dev Neurosci, 1998; 16(3-4): 271-278.
75. Minguet, E.G. et al., Evolutionary diversification in polyamine biosynthesis. Mol Biol Evol, 2008; 25(10): 2119-2128.
76. Moinard, C., L. Cynober, and J.P. de Bandt, Polyamines: Metabolism and implications in human diseases. Clin Nutr, 2005; 24(2): 184-197.
77. Genedani, S. et al., Influence of SAMe on the modifications of brain polyamine levels in an animal model of depression. Neuroreport, 2001; 12(18): 3939-3942.
78. Sequeira, A. et al., Implication of SSAT by gene expression and genetic variation in suicide and major depression. Arch Gen Psychiatry, 2006; 63(1): 35-48.
79. Sequeira, A. et al., Patterns of gene expression in the limbic system of suicides with and without major depression. Mol Psychiatry, 2007; 12(7): 640-655.
80. Dahel, K.A., N.M. Al-Saffar, and K.A. Flayeh, Polyamine oxidase activity in sera of depressed and schizophrenic patients after ECT treatment. Neurochem Res, 2001; 26(4): 415-418.
81. Halaris, A. et al., Plasma agmatine and platelet imidazoline receptors in depression. Ann N Y Acad Sci, 1999; 881: 445-451.
82. Zomkowski, A.D. et al., Agmatine produces antidepressant-like effects in two models of depression in mice. Neuroreport, 2002; 13(4): 387-391.
83. Zomkowski, A.D., A.R. Santos, and A.L. Rodrigues, Putrescine produces antidepres-sant-like effects in the forced swimming test and in the tail suspension test in mice. Prog Neuropsychopharmacol Biol Psychiatry, 2006; 30(8): 1419-1425.
84. Gong, Z.H. et al., Anxiolytic effect of agmatine in rats and mice. Eur J Pharmacol, 2006; 550(1-3): 112-116.
85. Fiori, L.M. and G. Turecki, Genetic and epigenetic influences on expression of sperm-ine synthase and spermine oxidase in suicide completers. Int J Neuropsychopharmacol, 2010; 13(6): 725-736.
86. Brunoni, A.R., M. Lopes, and F. Fregni, A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: Implications for the role of neuroplasticity in depression. Int J Neuropsychopharmacol, 2008; 11(8): 1169-1180.
87. Dwivedi, Y. et al., Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects. Arch Gen Psychiatry, 2003; 60(8): 804-815.
88. Pandey, G.N. et al., Brain-derived neurotrophic factor and tyrosine kinase B receptor sig-nalling in post-mortem brain of teenage suicide victims. Int J Neuropsychopharmacol, 2008; 11(8): 1047-1061.
89. Chen, B. et al., Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiatry, 2001; 50(4): 260-265.
90. Sen, S., R. Duman, and G. Sanacora, Serum brain-derived neurotrophic factor, depres-sion, and antidepressant medications: Meta-analyses and implications. Biol Psychiatry, 2008; 64(6): 527-532.
91. Matrisciano, F. et al., Changes in BDNF serum levels in patients with major depression disorder (MDD) after 6 months treatment with sertraline, escitalopram, or venlafaxine. J Psychiatr Res, 2009; 43(3): 247-254.
92. Chan, J.P. et al., Examination of behavioral deficits triggered by targeting BDNF in fetal or postnatal brains of mice. Neuroscience, 2006; 142(1): 49-58.
93. Gronli, J. et al., Chronic mild stress inhibits BDNF protein expression and CREB activa-tion in the dentate gyrus but not in the hippocampus proper. Pharmacol Biochem Behav, 2006; 85(4): 842-849.
94. Duric, V. and K.E. McCarson, Hippocampal neurokinin-1 receptor and brain-derived neurotrophic factor gene expression is decreased in rat models of pain and stress. Neuroscience, 2005; 133(4): 999-1006.
95. Duric, V. and K.E. McCarson, Effects of analgesic or antidepressant drugs on pain- or stress-evoked hippocampal and spinal neurokinin-1 receptor and brain-derived neurotrophic factor gene expression in the rat. J Pharmacol Exp Ther, 2006; 319(3): 1235-1243.
96. Rogoz, Z., G. Skuza, and B. Legutko, Repeated treatment with mirtazepine induces brain-derived neurotrophic factor gene expression in rats. J Physiol Pharmacol, 2005; 56(4): 661-671.
97. Xu, H. et al., Synergetic effects of quetiapine and venlafaxine in preventing the chronic restraint stress-induced decrease in cell proliferation and BDNF expression in rat hippocampus. Hippocampus, 2006; 16(6): 551-559.
98. Tsankova, N.M. et al., Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci, 2006; 9(4): 519-525.
99. Roth, T.L. et al., Lasting epigenetic influence of early-life adversity on the BDNF gene. Biol Psychiatry, 2009; 65(9): 760-769.
100. Aid, T. et al., Mouse and rat BDNF gene structure and expression revisited. J Neurosci Res, 2007; 85(3): 525-535.
101. Schroeder, F.A. et al., Antidepressant-like effects of the histone deacetylase inhibitor, sodium butyrate, in the mouse. Biol Psychiatry, 2007; 62(1): 55-64.
102. Covington, H.E., 3rd et al., Antidepressant actions of histone deacetylase inhibitors. J Neurosci, 2009; 29(37): 11451-11460.
103. Keller, S. et al., Increased BDNF promoter methylation in the Wernicke area of suicide subjects. Arch Gen Psychiatry, 2010; 67(3): 258-267.
104. Pruunsild, P. et al., Dissecting the human BDNF locus: Bidirectional transcription, com-plex splicing, and multiple promoters. Genomics, 2007; 90(3): 397-406.
105. Duman, R.S. and L.M. Monteggia, A neurotrophic model for stress-related mood disor-ders. Biol Psychiatry, 2006; 59(12): 1116-1127.
106. Kim, Y.K. et al., Low plasma BDNF is associated with suicidal behavior in major depression. Prog Neuropsychopharmacol Biol Psychiatry, 2007; 31(1): 78-85.
107. Dwivedi, Y. et al., Neurotrophin receptor activation and expression in human postmor-tem brain: Effect of suicide. Biol Psychiatry, 2009; 65(4): 319-328.
108. Aston, C., L. Jiang, and B.P. Sokolov, Transcriptional profiling reveals evidence for signaling and oligodendroglial abnormalities in the temporal cortex from patients with major depressive disorder. Mol Psychiatry, 2005; 10(3): 309-322.
109. Nakatani, N. et al., Genome-wide expression analysis detects eight genes with robust alterations specific to bipolar I disorder: Relevance to neuronal network perturbation. Hum Mol Genet, 2006; 15(12): 1949-1962.
110. Mercier, G. et al., MAP kinase activation by fluoxetine and its relation to gene expres-sion in cultured rat astrocytes. J Mol Neurosci, 2004; 24(2): 207-216.
111. Rose, C.R. et al., Truncated TrkB-T1 mediates neurotrophin-evoked calcium signalling in glia cells. Nature, 2003; 426(6962): 74-78.
112. Ernst, C. et al., Alternative splicing, methylation state, and expression profile of tropo-myosin-related kinase B in the frontal cortex of suicide completers. Arch Gen Psychiatry, 2009; 66(1): 22-32.
113. Ernst, C., E.S. Chen, and G. Turecki, Histone methylation and decreased expression of TrkB.T1 in orbital frontal cortex of suicide completers. Mol Psychiatry, 2009; 14(9): 830-832.
114. Haltiner, M.M., S.T. Smale, and R. Tjian, Two distinct promoter elements in the human rRNA gene identified by linker scanning mutagenesis. Mol Cell Biol, 1986; 6(1): 227-235.
115. Learned, R.M. et al., Human rRNA transcription is modulated by the coordinate binding of two factors to an upstream control element. Cell, 1986; 45(6): 847-857.
116. Ghoshal, K. et al., Role of human ribosomal RNA (rRNA) promoter methylation and of methyl-CpG-binding protein MBD2 in the suppression of rRNA gene expression. J Biol Chem, 2004; 279(8): 6783-6793.
117. Santoro, R. and I. Grummt, Molecular mechanisms mediating methylation-dependent silencing of ribosomal gene transcription. Mol Cell, 2001; 8(3): 719-725.
118. Brown, S.E. and M. Szyf, Epigenetic programming of the rRNA promoter by MBD3. Mol Cell Biol, 2007; 27(13): 4938-4952.
119. McGowan, P.O. et al., Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain. PLoS One, 2008; 3(5): e2085.
120. Cronholm, B. et al., Suicidal behaviour syndrome with low CSF 5-HIAA. Br Med J, 1977; 1(6063): 776.
121. Bhagwagar, Z. and P.J. Cowen, ‘It’s not over when it’s over’: Persistent neurobiological abnormalities in recovered depressed patients. Psychol Med, 2008; 38(3): 307-313.
122. Du, L. et al., Serotonergic genes and suicidality. Crisis, 2001; 22(2): 54-60.
123. Turecki, G. et al., Prediction of level of serotonin 2A receptor binding by serotonin receptor 2A genetic variation in postmortem brain samples from subjects who did or did not commit suicide. Am J Psychiatry, 1999; 156(9): 1456-1458.
124. Du, L. et al., Association of polymorphism of serotonin 2A receptor gene with suicidal ideation in major depressive disorder. Am J Med Genet, 2000; 96(1): 56-60.
125. De Luca, V. et al., Differential expression and parent-of-origin effect of the 5-HT2A receptor gene C102T polymorphism: Analysis of suicidality in schizophrenia and bipo-lar disorder. Am J Med Genet B Neuropsychiatr Genet, 2007; 144B(3): 370-374.
126. Polesskaya, O.O., C. Aston, and B.P. Sokolov, Allele C-specific methylation of the 5-HT2A receptor gene: Evidence for correlation with its expression and expression of DNA methylase DNMT1. J Neurosci Res, 2006; 83(3): 362-373.
127. De Luca, V. et al., Methylation and QTDT analysis of the 5-HT2A receptor 102C allele: Analysis of suicidality in major psychosis. J Psychiatr Res, 2009; 43(5): 532-537.
128. Klempan, T.A. et al., Altered expression of genes involved in ATP biosynthesis and GABAergic neurotransmission in the ventral prefrontal cortex of suicides with and with-out major depression. Mol Psychiatry, 2009; 14(2): 175-189.
129. Merali, Z. et al., Dysregulation in the suicide brain: mRNA expression of corticotropin-releasing hormone receptors and GABA(A) receptor subunits in frontal cortical brain region. J Neurosci, 2004; 24(6): 1478-1485.
130. Torrey, E.F. et al., Neurochemical markers for schizophrenia, bipolar disorder, and major depression in postmortem brains. Biol Psychiatry, 2005; 57(3): 252-260.
131. Guidotti, A. et al., Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: A postmortem brain study. Arch Gen Psychiatry, 2000; 57(11): 1061-1069.
132. Akbarian, S. et al., Gene expression for glutamic acid decarboxylase is reduced with-out loss of neurons in prefrontal cortex of schizophrenics. Arch Gen Psychiatry, 1995; 52(4): 258-266.
133. Heckers, S. et al., Differential hippocampal expression of glutamic acid decarboxylase 65 and 67 messenger RNA in bipolar disorder and schizophrenia. Arch Gen Psychiatry, 2002; 59(6): 521-529.
134. Volk, D.W. et al., Decreased glutamic acid decarboxylase67 messenger RNA expression in a subset of prefrontal cortical gamma-aminobutyric acid neurons in subjects with schizophrenia. Arch Gen Psychiatry, 2000; 57(3): 237-245.
135. Veldic, M. et al., DNA-methyltransferase 1 mRNA is selectively overexpressed in tel-encephalic GABAergic interneurons of schizophrenia brains. Proc Natl Acad Sci USA, 2004; 101(1): 348-353.
136. Kundakovic, M. et al., DNA methyltransferase inhibitors coordinately induce expres-sion of the human reelin and glutamic acid decarboxylase 67 genes. Mol Pharmacol, 2007; 71(3): 644-653.
137. Grayson, D.R. et al., Reelin promoter hypermethylation in schizophrenia. Proc Natl Acad Sci USA, 2005; 102(26): 9341-9346.
138. Tamura, Y. et al., Epigenetic aberration of the human REELIN gene in psychiatric disor-ders. Mol Psychiatry, 2007; 12(6): 519, 593-600.
139. Zhang, T.Y. et al., Maternal care and DNA methylation of a glutamic acid decarboxylase 1 promoter in rat hippocampus. J Neurosci, 2010; 30(39): 13130-13137.
140. Poulter, M.O. et al., GABAA receptor promoter hypermethylation in suicide brain: Implications for the involvement of epigenetic processes. Biol Psychiatry, 2008; 64(8): 645-652.
141. Ebersole, T.A. et al., The quaking gene product necessary in embryogenesis and myelin-ation combines features of RNA binding and signal transduction proteins. Nat Genet, 1996; 12(3): 260-265.
142. Zhao, L. et al., QKI binds MAP1B mRNA and enhances MAP1B expression during oligodendrocyte development. Mol Biol Cell, 2006; 17(10): 4179-4186.
143. Aberg, K. et al., Human QKI, a new candidate gene for schizophrenia involved in myelination. Am J Med Genet B Neuropsychiatr Genet, 2006; 141B(1): 84-90.
144. Aston, C., L. Jiang, and B.P. Sokolov, Microarray analysis of postmortem temporal cor-tex from patients with schizophrenia. J Neurosci Res, 2004; 77(6): 858-866.
145. Li, Z.Z. et al., Expression of Hqk encoding a KH RNA binding protein is altered in human glioma. Jpn J Cancer Res, 2002; 93(2): 167-177.
146. Siomi, H. et al., The pre-mRNA binding K protein contains a novel evolutionarily con-served motif. Nucleic Acids Res, 1993; 21(5): 1193-1198.
147. Klempan, T.A. et al., Characterization of QKI gene expression, genetics, and epi-genetics in suicide victims with major depressive disorder. Biol Psychiatry, 2009; 66(9): 824-831.