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On the Identification of Drugs Modulating Epigenetic Mechanisms in Depression

Pathways to Restoring Synapses After Childhood Abuse Leading to Depression

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Virginia Woolf and Neuropsychiatry

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Abstract

Two important facts about suicide rates need to be highlighted. First, the rates of suicide in the United States and Australia are about the same, and considerably greater than that in the United Kingdom. It is clearly of the first importance to determine why there are such differences in English-speaking countries with such common heritage and values. Claims made along the lines that countries like the United States and Australia ‘developed from pioneering European origins (Cantor et al. 1996) where toughness, independence and industriousness were central to the male-dominated cultures’ leading to ‘hard working, violence and firearms’ of a kind not associated with the United Kingdom seem wholly inadequate. Clearly deep epidemiological and sociological studies are called for to assess how these very different suicide rates arise and so identify what can possibly be done to bring down the rates to those comparable in the United Kingdom.

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References

  • Abel T, Zukin RS (2008) Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders. Curr Opin Pharmacol 8:57–64

    Article  PubMed  CAS  Google Scholar 

  • Andersen SL, Tomada A, Vincow ES, Valente E, Polcari A, Teicher MH (2008) Preliminary evidence for sensitive periods in the effect of childhood sexual abuse on regional brain development. J Neuropsychiatry Clin Neurosci 20:292–301

    Article  PubMed  Google Scholar 

  • Balasubramanian S, Verner E, Buggy JJ (2009) Isoform-specific histone deacetylase inhibitors: the next step? Cancer Lett 280:211–221

    Article  PubMed  CAS  Google Scholar 

  • Bensley LS, van Eenwyk J, Spieker SJ, Schoder J (1999) Self-reported abuse history and adolescent problem behaviors I. Antisocial and suicidal behaviors. J Adolesc Health 24:163–172

    Article  PubMed  CAS  Google Scholar 

  • Braquehais MD, Oquendo MA, Baca-Garcia E, Sher L (2010) Is impulsivity a link between childhood abuse and suicide? Compr Psychiatry 51:121–129

    Article  PubMed  Google Scholar 

  • Brent DA, Mann JJ (2006) Familial pathways to suicidal behavior–understanding and preventing suicide among adolescents. N Engl J Med 355:2719–2721

    Article  PubMed  Google Scholar 

  • Brent DA, Johnson BA, Perper J, Connolly J, Bridge J, Bartle S, Rather C (1994) Personality disorder, personality traits, impulsive violence, and completed suicide in adolescents. J Am Acad Child Adolesc Psychiatry 33:1080–1086

    Article  PubMed  CAS  Google Scholar 

  • Brent DA, Bridge J, Johnson BA, Connolly J (1996) Suicidal behavior runs in families. A controlled family study of adolescent suicide victims. Arch Gen Psychiatry 53:1145–1152

    Article  PubMed  CAS  Google Scholar 

  • Brezo J, Paris J, Barker ED, Tremblay R, Vitaro F, Zoccolillo M, Hebert M, Turecki G (2007) Natural history of suicidal behaviors in a population-based sample of young adults. Psychol Med 37:1563–1574

    PubMed  Google Scholar 

  • Cantor CH, Leenaars AA, Lester D, Slater PJ, Wolanowski AM, O’Toole B (1996) Suicide trends in eight predominantly English-speaking countries 1960–1989. Soc Psychiatry Psychiatr Epidemiol 31:364–373

    Article  PubMed  CAS  Google Scholar 

  • Carrion VG, Weems CF, Watson C, Eliez S, Menon V, Reiss AL (2009) Converging evidence for abnormalities of the prefrontal cortex and evaluation of midsagittal structures in pediatric posttraumatic stress disorder: an MRI study. Psychiatry Res 172:226–234

    Article  PubMed  Google Scholar 

  • Cohen JA (2005) Treating traumatized children: current status and future directions. J Trauma Dissociation 6:109–121

    Article  PubMed  Google Scholar 

  • Cohen BM, Mannarino AP (1996) Child centred therapy treatment manual. Pittsburg: MCP Hahnemann University School of Medicine

    Google Scholar 

  • Cohen JA, Deblinger E, Mannarino AP, Steer RA (2004) A multisite, randomized controlled trial for children with sexual abuse-related PTSD symptoms. J Am Acad Child Adolesc Psychiatry 43:393–402

    Article  PubMed  Google Scholar 

  • Copeland WE, Keeler G, Angold A, Costello EJ (2007) Traumatic events and posttraumatic stress in childhood. Arch Gen Psychiatry 64:577–584

    Article  PubMed  Google Scholar 

  • Currier D, Mann JJ (2008) Stress, genes and the biology of suicidal behavior. Psychiatr Clin North Am 31:247–269

    Article  PubMed  Google Scholar 

  • Curtis T, Larsen FB, Helweg-Larsen K, Bjerregaard P (2002) Violence, sexual abuse and health in Greenland. Int J Circumpolar Health 61:110–122

    PubMed  Google Scholar 

  • Davidson JR (2000) Pharmacotherapy of posttraumatic stress disorder: treatment options, long-term follow-up, and predictors of outcome. J Clin Psychiatry 61 (Suppl 5): 52–6; discussion 57–9

    Google Scholar 

  • de Bellis MD, Keshavan MS, Frustaci K, Shifflett H, Iyengar S, Beers SR, Hall J (2002) Superior temporal gyrus volumes in maltreated children and adolescents with PTSD. Biol Psychiatry 51:544–552

    Article  PubMed  Google Scholar 

  • de Ruijter AJ, van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB (2003) Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 370:737–749

    Article  PubMed  Google Scholar 

  • Deblinger E, Heflin AH (1996) Treating sexually abused children and their non-offending parents: a cognitive behavioral approach. Sage Publications, Thousand Oaks

    Google Scholar 

  • Deblinger E, Steer RA, Lippmann J (1999) Two-year follow-up study of cognitive behavioral therapy for sexually abused children suffering post-traumatic stress symptoms. Child Abuse Negl 23:1371–1378

    Article  PubMed  CAS  Google Scholar 

  • Deblinger E, Mannarino AP, Cohen JA, Steer RA (2006) A follow-up study of a multisite, randomized, controlled trial for children with sexual abuse-related PTSD symptoms. J Am Acad Child Adolesc Psychiatry 45:1474–1484

    Article  PubMed  Google Scholar 

  • Diaconu G, Turecki G (2009) Family history of suicidal behavior predicts impulsive-aggressive behavior levels in psychiatric outpatients. J Affect Disord 113:172–178

    Article  PubMed  Google Scholar 

  • Dumais A, Lesage AD, Alda M, Rouleau G, Dumont M, Chawky N, Roy M, Mann JJ, Benkelfat C, Turecki G (2005) Risk factors for suicide completion in major depression: a case–control study of impulsive and aggressive behaviors in men. Am J Psychiatry 162:2116–2124

    Article  PubMed  CAS  Google Scholar 

  • Evans E, Hawton K, Rodham K (2005) Suicidal phenomena and abuse in adolescents: a review of epidemiological studies. Child Abuse Negl 29:45–58

    Article  PubMed  Google Scholar 

  • Fairbank JA, Fairbank DW (2009) Epidemiology of child traumatic stress. Curr Psychiatry Rep 11:289–295

    Article  PubMed  Google Scholar 

  • Fergusson DM, Horwood LJ, Lynskey MT (1996) Childhood sexual abuse and psychiatric disorder in young adulthood: II. Psychiatric outcomes of childhood sexual abuse. J Am Acad Child Adolesc Psychiatry 35:1365–1374

    Article  PubMed  CAS  Google Scholar 

  • Fiori LM, Turecki G (2010) Gene expression profiling of suicide completers. Eur Psychiatry 25:287–290

    Article  PubMed  CAS  Google Scholar 

  • Glowinski AL, Bucholz KK, Nelson EC, Fu Q, Madden PA, Reich W, Heath AC (2001) Suicide attempts in an adolescent female twin sample. J Am Acad Child Adolesc Psychiatry 40:1300–1307

    Article  PubMed  CAS  Google Scholar 

  • Grayson DR, Kundakovic M, Sharma RP (2010) Is there a future for histone deacetylase inhibitors in the pharmacotherapy of psychiatric disorders? Mol Pharmacol 77:126–135

    Article  PubMed  CAS  Google Scholar 

  • Haddad PM, Das A, Ashfaq M, Wieck A (2009) A review of valproate in psychiatric practice. Expert Opin Drug Metab Toxicol 5:539–551

    Article  PubMed  CAS  Google Scholar 

  • Hamm CA, Costa FF (2011) The impact of epigenomics on future drug design and new therapies. Drug Discov Today 16:626–635

    Article  PubMed  CAS  Google Scholar 

  • Hauke J, Riessland M, Lunke S, Eyupoglu IY, Blumcke I, El-Osta A, Wirth B, Hahnen E (2009) Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition. Hum Mol Genet 18:304–317

    Article  PubMed  CAS  Google Scholar 

  • Hess-Stumpp H, Bracker TU, Henderson D, Politz O (2007) MS-275, a potent orally available inhibitor of histone deacetylases–the development of an anticancer agent. Int J Biochem Cell Biol 39:1388–1405

    Article  PubMed  CAS  Google Scholar 

  • Hetrick SE, Purcell R, Garner B, Parslow R (2010) Combined pharmacotherapy and psychological therapies for post traumatic stress disorder (PTSD). Cochrane Database Syst Rev 7:CD007316

    PubMed  Google Scholar 

  • Johnstone RW (2002) Histone-deacetylase inhibitors: novel drugs for the treatment of cancer. Nat Rev Drug Discov 1:287–299

    Article  PubMed  CAS  Google Scholar 

  • Kazantsev AG, Thompson LM (2008) Therapeutic application of histone deacetylase inhibitors for central nervous system disorders. Nat Rev Drug Discov 7:854–868

    Article  PubMed  CAS  Google Scholar 

  • Kazdin AE, Bass D, Siegel T, Thomas C (1989) Cognitive-behavioral therapy and relationship therapy in the treatment of children referred for antisocial behavior. J Consult Clin Psychol 57:522–535

    Article  PubMed  CAS  Google Scholar 

  • Keller S, Sarchiapone M, Zarrilli F, Videtic A, Ferraro A, Carli V, Sacchetti S, Lembo F, Angiolillo A, Jovanovic N, Pisanti F, Tomaiuolo R, Monticelli A, Balazic J, Roy A, Marusic A, Cocozza S, Fusco A, Bruni CB, Castaldo G, Chiariotti L (2010) Increased BDNF promoter methylation in the Wernicke area of suicide subjects. Arch Gen Psychiatry 67:258–267

    Article  PubMed  CAS  Google Scholar 

  • Kendall PC (1994) Treating anxiety disorders in children: results of a randomized clinical trial. J Consult Clin Psychol 62:100–110

    Article  PubMed  CAS  Google Scholar 

  • Kilpatrick DG, Ruggiero KJ, Acierno R, Saunders BE, Resnick HS, Best CL (2003) Violence and risk of PTSD, major depression, substance abuse/dependence, and comorbidity: results from the National Survey of Adolescents. J Consult Clin Psychol 71:692–700

    Article  PubMed  Google Scholar 

  • Kim CD, Seguin M, Therrien N, Riopel G, Chawky N, Lesage AD, Turecki G (2005) Familial aggregation of suicidal behavior: a family study of male suicide completers from the general population. Am J Psychiatry 162:1017–1019

    Article  PubMed  Google Scholar 

  • la Vecchia C, Lucchini F, Levi F (1994) Worldwide trends in suicide mortality, 1955–1989. Acta Psychiatr Scand 90:53–64

    Article  PubMed  Google Scholar 

  • Luo F, Florence CS, Quispe-Agnoli M, Ouyang L, Crosby AE (2011) Impact of business cycles on US suicide rates, 1928–2007. Am J Public Health 101:1139–1146

    Article  PubMed  Google Scholar 

  • Macdonald GM, Higgins JP, Ramchandani P (2006) Cognitive-behavioural interventions for children who have been sexually abused. Cochrane Database Syst Rev 4:CD001930

    PubMed  Google Scholar 

  • Machado-Vieira R, Ibrahim L, Zarate CA JR (2011) Histone deacetylases and mood disorders: epigenetic programming in gene-environment interactions. CNS Neurosci Ther 17:699–704

    Article  PubMed  CAS  Google Scholar 

  • Mann JJ (2003) Neurobiology of suicidal behaviour. Nat Rev Neurosci 4:819–828

    Article  PubMed  CAS  Google Scholar 

  • Mann JJ, Apter A, Bertolote J, Beautrais A, Currier D, Haas A, Hegerl U, Lonnqvist J, Malone K, Marusic A, Mehlum L, Patton G, Phillips M, Rutz W, Rihmer Z, Schmidtke A, Shaffer D, Silverman M, Takahashi Y, Varnik A, Wasserman D, Yip P, Hendin H (2005) Suicide prevention strategies: a systematic review. JAMA 294:2064–2074

    Article  PubMed  CAS  Google Scholar 

  • Mazza D, Dennerstein L, Garamszegi CV, Dudley EC (2001) The physical, sexual and emotional violence history of middle-aged women: a community-based prevalence study. Med J Aust 175:199–201

    PubMed  CAS  Google Scholar 

  • McGirr A, Seguin M, Renaud J, Benkelfat C, Alda M, Turecki G (2006) Gender and risk factors for suicide: evidence for heterogeneity in predisposing mechanisms in a psychological autopsy study. J Clin Psychiatry 67:1612–1617

    Article  PubMed  Google Scholar 

  • McGirr A, Paris J, Lesage A, Renaud J, Turecki G (2007) Risk factors for suicide completion in borderline personality disorder: a case–control study of cluster B comorbidity and impulsive aggression. J Clin Psychiatry 68:721–729

    Article  PubMed  Google Scholar 

  • McGowan PO, Sasaki A, Huang TC, Unterberger A, Suderman M, Ernst C, Meaney MJ, Turecki G, Szyf M (2008) Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain. PLoS One 3:e2085

    Article  PubMed  Google Scholar 

  • Mill J, Tang T, Kaminsky Z, Khare T, Yazdanpanah S, Bouchard L, Jia P, Assadzadeh A, Flanagan J, Schumacher A, Wang SC, Petronis A (2008) Epigenomic profiling reveals DNA-methylation changes associated with major psychosis. Am J Hum Genet 82:696–711

    Article  PubMed  CAS  Google Scholar 

  • Milner A, McClure R, Sun J, de Leo D (2011) Globalisation and suicide: an empirical investigation in 35 countries over the period 1980–2006. Health Place 17:996–1003

    Article  PubMed  Google Scholar 

  • Murgatroyd C, Patchev AV, Wu Y, Micale V, Bockmuhl Y, Fischer D, Holsboer F, Wotjak CT, Almeida OF, Spengler D (2009) Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nat Neurosci 12:1559–1566

    Article  PubMed  CAS  Google Scholar 

  • Oecd (2009) Country statistical profiles 2009 [Online]. Available: http://stats.oecd.org/Index.aspx?DataSetCode=csp2009. Accessed June 2012

  • Poulter MO, Du L, Weaver IC, Palkovits M, Faludi G, Merali Z, Szyf M, Anisman H (2008) GABAA receptor promoter hypermethylation in suicide brain: implications for the involvement of epigenetic processes. Biol Psychiatry 64:645–652

    Article  PubMed  CAS  Google Scholar 

  • Riessland M, Brichta L, Hahnen E, Wirth B (2006) The benzamide M344, a novel histone deacetylase inhibitor, significantly increases SMN2 RNA/protein levels in spinal muscular atrophy cells. Hum Genet 120:101–110

    Article  PubMed  CAS  Google Scholar 

  • Roy A, Segal NL, Centerwall BS, Robinette CD (1991) Suicide in twins. Arch Gen Psychiatry 48:29–32

    Article  PubMed  CAS  Google Scholar 

  • Roy A, Segal NL, Sarchiapone M (1995) Attempted suicide among living co-twins of twin suicide victims. Am J Psychiatry 152:1075–1076

    PubMed  CAS  Google Scholar 

  • Russell DE (1983) The incidence and prevalence of intrafamilial and extrafamilial sexual abuse of female children. Child Abuse Negl 7:133–146

    Article  PubMed  CAS  Google Scholar 

  • Schroeder FA, Lin CL, Crusio WE, Akbarian S (2007) Antidepressant-like effects of the histone deacetylase inhibitor, sodium butyrate, in the mouse. Biol Psychiatry 62:55–64

    Article  PubMed  CAS  Google Scholar 

  • Schroeder M, Krebs MO, Bleich S, Frieling H (2010) Epigenetics and depression: current challenges and new therapeutic options. Curr Opin Psychiatry 23:588–592

    Article  PubMed  Google Scholar 

  • Schulsinger F, Kety SS, Rosenthal D, Wender PH (1979) A family study of suicide. In: Schou M, Stromgren E (eds) Origins, prevention and treatment of affective disorders. Academic, Orlando

    Google Scholar 

  • Seguin M, Lesage A, Turecki G, Bouchard M, Chawky N, Tremblay N, Daigle F, Guy A (2007) Life trajectories and burden of adversity: mapping the developmental profiles of suicide mortality. Psychol Med 37:1575–1583

    Article  PubMed  Google Scholar 

  • Simonini MV, Camargo LM, Dong E, Maloku E, Veldic M, Costa E, Guidotti A (2006) The benzamide MS-275 is a potent, long-lasting brain region-selective inhibitor of histone deacetylases. Proc Natl Acad Sci U S A 103:1587–1592

    Article  PubMed  CAS  Google Scholar 

  • Spaeth-Rublee B, Pincus HA, Huynh PT (2010) Measuring quality of mental health care: a review of initiatives and programs in selected countries. Can J Psychiatry 55:539–548

    PubMed  Google Scholar 

  • Spokas M, Wenzel A, Stirman SW, Brown GK, Beck AT (2009) Suicide risk factors and mediators between childhood sexual abuse and suicide ideation among male and female suicide attempters. J Trauma Stress 22:467–470

    Article  PubMed  Google Scholar 

  • Statham DJ, Heath AC, Madden PA, Bucholz KK, Bierut L, Dinwiddie SH, Slutske WS, Dunne MP, Martin NG (1998) Suicidal behaviour: an epidemiological and genetic study. Psychol Med 28:839–855

    Article  PubMed  CAS  Google Scholar 

  • Straus MA, Gelles RJ, Steinmetz SK (1980) Behind closed doors: violence in the American family. Doubleday/Anchor, New York

    Google Scholar 

  • Svedin CG, Back C, Soderback SB (2002) Family relations, family climate and sexual abuse. Nord J Psychiatry 56:355–362

    Article  PubMed  Google Scholar 

  • Thomas K, Chang SS, Gunnell D (2011) Suicide epidemics: the impact of newly emerging methods on overall suicide rates - a time trends study. BMC Public Health 11:314

    Article  PubMed  Google Scholar 

  • Tomoda A, Navalta CP, Polcari A, Sadato N, Teicher MH (2009) Childhood sexual abuse is associated with reduced gray matter volume in visual cortex of young women. Biol Psychiatry 66:642–648

    Article  PubMed  Google Scholar 

  • Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ (2006) Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci 9:519–525

    Article  PubMed  CAS  Google Scholar 

  • Tupler LA, de Bellis MD (2006) Segmented hippocampal volume in children and adolescents with posttraumatic stress disorder. Biol Psychiatry 59:523–529

    Article  PubMed  Google Scholar 

  • Wender PH, Kety SS, Rosenthal D, Schulsinger F, Ortmann J, Lunde I (1986) Psychiatric disorders in the biological and adoptive families of adopted individuals with affective disorders. Arch Gen Psychiatry 43:923–929

    Article  PubMed  CAS  Google Scholar 

  • Widom CS, Dumont K, Czaja SJ (2007) A prospective investigation of major depressive disorder and comorbidity in abused and neglected children grown up. Arch Gen Psychiatry 64:49–56

    Article  PubMed  Google Scholar 

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  1. Brain and Mind Research Institute, Camperdown, NSW, Australia

    Maxwell Bennett

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Bennett, M. (2013). On the Identification of Drugs Modulating Epigenetic Mechanisms in Depression. In: Virginia Woolf and Neuropsychiatry. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5748-6_8

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