Neurotoxicity Research

, Volume 18, Issue 3–4, pp 347–366 | Cite as

Epigenetics and Biomarkers in the Staging of Neuropsychiatric Disorders

  • Trevor Archer
  • Richard J. Beninger
  • Tomas Palomo
  • Richard M. Kostrzewa


Epigenetics, or alterations in the phenotype or gene expression due to mechanisms other than changes in the underlying DNA sequence, reflects the sensitivity and responsiveness of human and animal brains in constantly varying circumstances regulating gene expression profiles that define the biomarkers and present the ultimate phenotypical outcomes, such as cognition and emotion. Epigenetics is associated with functionally relevant alterations to the genome in such a fashion that under the particular conditions of early, adolescent, and adult life, environmental signals may activate intracellular pathways that remodel the “epigenome,” triggering changes in gene expression and neural function. Thus, genetic influences in neuropsychiatric disorders that are subject to clinical staging, epigenetics in schizophrenia, epigenetic considerations in the expression of sensorimotor gating resulting from disease conditions, biomarkers of drug use and addiction, current notions on the role of dopamine in schizophrenia spectrum disorders, and the discrete interactions of biomarkers in persistent memory were to greater or lesser extents reflected upon. The relative contributions of endophenotypes and epistasis for mediating epigenetic phenomena and the outcomes as observed in the analysis of biomarkers appear to offer a multitude of interactive combinations to further complicate the labyrinthine machinations of diagnosis, intervention, and prognosis.


Epigenetics Biomarkers Brain disorder Schizophrenia Gating Addiction Cognition Staging 


  1. Abdolmaleky HM, Faraone SV, Glatt SJ, Tsuang MT (2004) Meta-analysis of association between the T102C polymorphism of the 5HT2A receptor gene and schizophrenia. Schizophr Res 67:53–62PubMedGoogle Scholar
  2. Abdolmaleky HM, Cheng KH, Russo A, Smith CL, Faraone SV, Wilcox M, Shafa R, Glatt SJ, Nguyen G, Ponte JF, Thiagalingam S, Tsuang MT (2005) Hypermethylation of the reelin (RELN) promoter in the brain of schizophrenic patients: a preliminary report. Am J Med Genet B 134:60–66Google Scholar
  3. Abel K, Waikar M, Pedro B, Hemsley D, Geyer M (1998) Repeated testing of prepulse inhibition and habituation of the startle reflex: a study in healthy human controls. J Psychopharmacol 12:330–337PubMedGoogle Scholar
  4. Abi-Dargham A, Gil R, Krystal J, Baldwin RM, Seibyl JP, Bowers M, van Dyck CH, Charney DS, Innis RB, Laruelle M (1998) Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort. Am J Psychiatry 155:761–767PubMedGoogle Scholar
  5. Abi-Dargham A, Rodenhiser J, Printz D, Zea-Ponce Y, Gil R, Kegeles LS, Weiss R, Cooper TB, Mann JJ, Van Heertum RL, Gorman JM, Laruelle M (2000) Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort. Am J Psychiatry 155:761–767Google Scholar
  6. Abi-Dargham A, van de Giessen E, Slifstein M, Kegeles LS, Laruelle M (2009) Baseline and amphetamine-stimulated dopamine activity are related in drug-naive schizophrenic subjects. Biol Psychiatry 65:1091–1093PubMedGoogle Scholar
  7. Abi-Dargham A, Kegeles LS, Slifstein M, Laruelle M (2010) Antipsychotic induced changes in striatal D2 receptors in schizophrenia: in vivo evidence from dopamine depletion studies. Neurotox Res (in press)Google Scholar
  8. Al-Amin HA, Weinberger DR, Lipska BK (2000) exaggerated MK-801-induced motor hyperactivity in rats with neonatal lesion of the ventral hippocampus. Behav Pharmacol 11:269–278PubMedGoogle Scholar
  9. Al-Amin HA, Saade NE, Khani M, Atweh SF, Jaber M (2003) Effects of chronic dizocilpine on acute pain and on mRNA expression of neuropeptides and the dopamine and glutamate receptors. Brain Res 981:99–107PubMedGoogle Scholar
  10. Allen NC, Bagade S, McQueen MB, Ioannidis JP, Kavvoura FK, Khoury MJ, Tanzi RE, Bertram L (2008) Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. Nat Genet 40:827–834PubMedGoogle Scholar
  11. Alvarez S, Mas S, Gassó P, Bernardo M, Parellada E, Lafuente A (2009) Lack of association between schizophrenia and polymorphisms in dopamine metabolism and transport genes. Fundam Clin Pharmacol. Dec 23. PMID:20041956Google Scholar
  12. Anokhin AP, Heath AC, Myers E, Ralano A, Wood S (2003) Genetic influences of prepulse inhibition of startle reflex in humans. Neurosci Lett 353:45–48PubMedGoogle Scholar
  13. Archer T, Kostrzewa RM, Beninger RJ, Archer TA (2008) Cognitive symptoms facilitatory for diagnoses in neuropsychiatric disorders: executive function and locus of control. Neurotox Res 14:205–225PubMedGoogle Scholar
  14. Archer T, Kostrzewa RM, Palomo T, Beninger RJ (2010a) Clinical staging in the pathophysiology of psychotic and affective disorders: facilitation of prognosis and treatment. Neurotoxicity Res (in press)Google Scholar
  15. Archer T, Kostrzewa RM, Beninger RJ, Palomo T (2010b) Staging perspectives in neurodevelopmental aspects of neuropsychiatry: agents, phases and ages at expression. Neurotoxicity Res (in press)Google Scholar
  16. Arion D, Horváth S, Lewis DA, Mirnics K (2010) Infragranular gene expression disturbances in the prefrontal cortex in schizophrenia: signature of altered neural development? Neurobiol Dis 37:738–746PubMedGoogle Scholar
  17. Asensio S, Romero MJ, Romero FJ, Wong C, Alia-Klein N, Tomasi D, Wang GJ, Telang F, Volkow ND, Goldstein RZ (2009) Striatal dopamine D2 receptor availability predicts the thalamic and medial prefrontal responses to reward in cocaine abusers three years later. Synapse 64:397–402Google Scholar
  18. Badner JA, Gershon ES (2002) Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Mol Psychiatry 7:405–411PubMedGoogle Scholar
  19. Bahi A, Boyer F, Chandrasekar V, Dreyer JL (2008) Role of accumbens BDNF and TrkB in cocaine-induced psychomotor sensitization, conditioned-place preference, and reinstatement in rats. Psychopharmacology 199:169–182PubMedGoogle Scholar
  20. Barkus C, McHugh SB, Sprengel R, Seeburg PH, Rawlins JN, Bannerman DM (2009) Hippocampal NMDA receptors and anxiety: at the interface between cognition and emotion. Eur J Pharmacol 626:49–56PubMedGoogle Scholar
  21. Bekinschtein P, Katche C, Slipczuk L, Gonzalez C, Dorman G, Cammarota M, Izquierdo I, Medina JH (2010) Persistence of long-term memory storage: new insights into its molecular signatures in the hippocampus and related structures. Neurotox Res (in press). PMID:20151243Google Scholar
  22. Bell H, Chenoweth B, Wilson DA (2008) Neurobehavioral consequences of cortical adaptation disruption during ontogeny. Neurosci Lett 445:47–52PubMedGoogle Scholar
  23. Belsky J, Steinberg L, Houts RM, Halpern-Felsher BL, NICHD Early Child Care Research Network (2010) The development of reproductive strategy in females: early maternal harshness --> earlier menarche --> increased sexual risk taking. Dev Psychol 46:120–128PubMedGoogle Scholar
  24. Benabid AL, Benazzous A, Pollak P (2002) Mechanisms of deep brain stimulation. Mov Disord 17(Suppl 3):S73–S74PubMedGoogle Scholar
  25. Beninger RJ (2006) Dopamine and incentive learning: a framework for considering antipsychotic medication effects. Neurotox Res 10:199–209PubMedGoogle Scholar
  26. Beninger RJ, Wasserman JI, Zanibbi K, Charbonneau D, Mangels J, Beninger BV (2003) Typical and atypical antipsychotic medications differentially affect two nondeclarative memory tasks in schizophrenic patients: a double dissociation. Schizophr Bull 61:281–292Google Scholar
  27. Beninger RJ, Wasserman JI, Delva NJ (2009) Probabilistic classification and gambling in medicated schizophrenic patients: comparison of olanzepine, risperidone, clozapine and typical antipsychotics. Abstract 9th world congress of biological psychiatry [28 June–02 July], Paris. doi:10.3284/wfsbp.2009.1
  28. Beninger RJ, Baker TW, Florczynski MM, Banasikowski TJ (2010) Regional differences in the action of antipsychotic drugs: implications for cognitive effects in schizophrenic patients. Neurotox Res (in press)Google Scholar
  29. Bernier PM, Burle B, Vidal F, Hasbroucq T, Blouin J (2009) Direct evidence for cortical suppression of somatosensory afferents during visuomotor adaptation. Cereb Cortex 19:2106–2113PubMedGoogle Scholar
  30. Bertrand JB, Langlois JB, Bégou M, Volle J, Brun P, d’Amato T, Saoud M, Suaud-Chagny MF (2010) Longitudinal MRI monitoring of brain damage in the neonatal ventral hippocampal lesion rat model of schizophrenia. Hippocampus 20:264–278PubMedGoogle Scholar
  31. Best JA, Nijhout HF, Reed MC (2009) Homeostatic mechanisms in dopamine synthesis and release: a mathematical model. Theor Biol Med Model 6:21PubMedGoogle Scholar
  32. Bickel S, Javitt DC (2009) Neurophysiological and neurochemical animal models of schizophrenia: focus on glutamate. Behav Brain Res 204:352–362PubMedGoogle Scholar
  33. Bird MK, Lawrence AJ (2009) Group I metabotropic glutamate receptors: involvement in drug-seeking and drug-induced plasticity. Curr Mol Pharmacol 2:83–94PubMedGoogle Scholar
  34. Bitsios P, Giakoumaki SG (2005) Relationship of prepulse inhibition of the startle reflex to attentional and executive mechanisms in man. Int J Psychophysiol 55:229–241PubMedGoogle Scholar
  35. Bitsios P, Giakoumaki SG, Theou K, Frangou S (2006) Increased prepulse inhibition of the acoustic startle response is associated with better strategy formation and execution times in healthy males. Neuropsychologia 44:2494–2499PubMedGoogle Scholar
  36. Blum K, Noble EP, Sheridan PJ, Montgomery A, Ritchie T, Jagadeeswaran P, Nogami H, Briggs AH, Cohn JB (1990) Allelic association of human dopamine D2 receptor gene in alcoholism. JAMA 263:2055–2060PubMedGoogle Scholar
  37. Blum K, Noble EP, Sheridan PJ, Montgomery A, Ritchie T, Ozkaragoz T, Fitch RJ, Wood R, Finley O, Sadlack F (1993) Genetic predisposition in alcoholism: association of the D2 dopamine receptor TaqI B1 RFLP with severe alcoholics. Alcohol 10:59–67PubMedGoogle Scholar
  38. Brady AM (2009) Neonatal ventral hippocampal lesions disrupt set-shifting ability in adult rats. Behav Brain Res 205:294–298PubMedGoogle Scholar
  39. Braff DL, Freedman R (2008) Clinically responsible genetic testing in neuropsychiatric patients: a bridge too far and too soon. Am J Psychiatry 165:952–955PubMedGoogle Scholar
  40. Braff DL, Light GA (2004) Preattentional and attentional cognitive deficits as targets for treating schizophrenia. Psychopharmacology 174:75–85PubMedGoogle Scholar
  41. Braff DL, Light GA (2005) The use of neurophysiological endophenotypes to understand the genetic basis of schizophrenia. Dialogues Clin Neurosci 7:125–135PubMedGoogle Scholar
  42. Braff DL, Grillon C, Geyer MA (1992) Gating and habituation of the startle reflex in schizophrenic patients. Arch Gen Psychiatry 49:206–215PubMedGoogle Scholar
  43. Braff DL, Geyer MA, Swerdlow NR (2001a) Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology 156:234–258PubMedGoogle Scholar
  44. Braff DL, Geyer MA, Light GA, Sprock J, Perry W, Cadenhead KS, Swerdlow NR (2001b) Impact of prepulse characteristics on the detection of sensorimotor gating deficits in schizophrenia. Schizophr Res 49:171–178PubMedGoogle Scholar
  45. Braff DL, Greenwood TA, Swerdlow NR, Light GA, Schork NJ, The Investigators of the Consortium on the Genetics of Schizophrenia (2008) Advances in endophenotyping schizophrenia. Schizophr Res 103:218–228PubMedGoogle Scholar
  46. Brand S, Angst J, Holsboer-Trachsler E (2009) Is the increase of hypomanic stages during adolescence related to gender and developmental tasks? World J Biol Psychiatry. 2010 Jan 14. PMID:20073548Google Scholar
  47. Brauch H, Jordan VC (2009) Targeting of tamoxifen to enhance antitumour action for the treatment and prevention of breast cancer: the ‘personalised’ approach? Eur J Cancer 45:2274–2283PubMedGoogle Scholar
  48. Breier A, Su TP, Saunders R, Carson RE, Kolachana BS, de Bartolomeis A, Weinberger DR, Weisenfeld N, Malhotra AK, Eckelman WC, Pickar D (1997) Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proc Natl Acad Sci USA 94:2569–2574PubMedGoogle Scholar
  49. Cadenhead KS, Perry W, Shafer K, Braff DL (1999) Cognitive functions in schizotypal personality disorder. Schizophr Res 37:123–132PubMedGoogle Scholar
  50. Cadenhead KS, Light GA, Geyer MA, McDowell JE, Braff DL (2002) Neurobiological measures of schizotypal personality disorder: defining an inhibitory endophenotype? Am J Psychiatry 159:869–871PubMedGoogle Scholar
  51. Carlsson B (2008) SNPs—a shortcut to personalized medicine. Genet Eng Biotech News,  p 12Google Scholar
  52. Caselles A, Micó JC, Amigó S (2009) Cocaine addiction and personality: a mathematical model. Br J Math Stat Psychol. Dec 23. PMID:20030966Google Scholar
  53. Castellanos FX, Fine EJ, Kaysen D, Marsh WL, Rapoport JL, Hallett M (1996) Sensorimotor gating in boys with Tourette’s syndrome and ADHD: preliminary results. Biol Psychiatry 39:33–41PubMedGoogle Scholar
  54. Cauffman E, Shulman EP, Steinberg L, Claus E, Banich MT, Graham S, Woolard J (2010) Age differences in affective decision making as indexed by performance on the Iowa Gambling Task. Dev Psychol 46:193–207PubMedGoogle Scholar
  55. Centers for Disease Control and Prevention (CDC) (2010) “Choking game” awareness and participation among 8th graders—Oregon, 2008. MMWR Morb Mortal Wkly Rep 59:1–5Google Scholar
  56. Champagne FA, Curley JP (2009) Epigenetic mechanisms mediating the long-term effects of maternal care on development. Neurosci Biobehav Rev 33:593–600PubMedGoogle Scholar
  57. Chandler VL (2007) Paramutation: from maize to mice. Cell 128:641–645PubMedGoogle Scholar
  58. Chen J, Lipska BK, Halim N, Ma QD, Matsumoto M, Melhem S, Kolachana BS, Hyde TM, Hernan MM, Apud J, Egan MF, Kleinman JE, Weinberger DR (2004) Functional analysis of genetic variation in catechol-o-methyltransferase (COMT): effects on mRNA protein, and enzyme activity in postmortem human brain. Am J Hum Genet 75:807–821PubMedGoogle Scholar
  59. Cichewicz RH (2010) Epigenome manipulation as a pathway to new natural product scaffolds and their congeners. Nat Prod Rep 27:11–22PubMedGoogle Scholar
  60. Colantuoni C, Hyde TM, Mitkus S, Joseph A, Sartorius L, Aguirre C, Creswell J, Johnson E, Deep-Soboslay A, Herman MM, Lipska BK, Weinberger DR, Kleinman JE (2008) Age-related changes in the expression of schizophrenia susceptibility genes in the human prefrontal cortex. Brain Struct Funct 213:255–271PubMedGoogle Scholar
  61. Conner BT, Hellemann GS, Ritchie TL, Noble EP (2010) Genetic, personality, and environmental predictors of drug use in adolescents. J Subst Abuse Treat 38:178–190PubMedGoogle Scholar
  62. Conrod PJ, Castellanos-Ryan N, Strang J (2010) Brief, personality-targeted coping skills interventions and survival as a non-drug user over a 2-year period during adolescence. Arch Gen Psychiatry 67:85–93PubMedGoogle Scholar
  63. Cornish K, Munir F, Wilding J (2001) A neurophysiological and behavioural profile of attention deficits in fragile X syndrome. Rev Neurol 33(Suppl 1):S24–S29PubMedGoogle Scholar
  64. Corvin AP, Morris DW, McGhee K, Schwaiger S, Scully P, Quinn J, Meagher D, Clair DS, Waddington JL, Gill M (2004) Confirmation and refinement of an “at-risk” haplotype for schizophrenia suggests the EST cluster, Hs.97362, as a potential susceptibility gene at the neuregulin-1 locus. Mol Psychiatry 9:208–213PubMedGoogle Scholar
  65. Curley JP, Rock V, Moynihan AM, Bateson P, Keverne B, Champagne FA (2010) Developmental shifts in the behavioral phenotypes of inbred mice: the role of postnatal and juvenile social experiences. Behav Genet 40:220–232PubMedGoogle Scholar
  66. Dawson M, Schell A, Hazlett E, Nuechterlein K, Filion D (2000) On the clinical and cognitive meaning of impaired sensorimotor gating in schizophrenia. Psychiatry Res 96:187–197PubMedGoogle Scholar
  67. Dean B, Pavey G, Opeskin K (1997) [H-3]raclopride binding to brain tissue from subjects with schizophrenia: methodological aspects. Neuropharmacology 36:779–786PubMedGoogle Scholar
  68. DelPezzo E, Hoffman H (1980) Attentional factors in the inhibition of a reflex by a visual stimulus. Science 210:673–674PubMedGoogle Scholar
  69. Doehring A, Kirchhof A, Lötsch J (2009a) Genetic diagnostics of functional variants of the human dopamine D2 receptor gene. Psychiatr Genet 19:259–268PubMedGoogle Scholar
  70. Doehring A, Hentig N, Graff J, Salamat S, Schmidt M, Geisslinger G, Harder S, Lötsch J (2009b) Genetic variants altering dopamine D2 receptor expression or function modulate the risk of opiate addiction and the dosage requirements of methadone substitution. Pharmacogenet Genomics 19:407–414PubMedGoogle Scholar
  71. Dolinoy DC, Weldman JR, Waterland RA, Jirtle RL (2006) Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome. Environ Health Perspect 114:567–572PubMedGoogle Scholar
  72. Donohoe G, Walters J, Morris DW, Quinn EM, Judge R, Norton N, Giegling I, Hartmann AM, Möller HJ, Muglia P, Williams H, Moskvina V, Peel R, O’Donoghue T, Owen MJ, O’Donovan MC, Gill M, Rujescu D, Corvin A (2009) Influence of NOS1 on verbal intelligence and working memory in both patients with schizophrenia and healthy control subjects. Arch Gen Psychiatry 66:1045–1054PubMedGoogle Scholar
  73. Dulloo AG (2006) Regulation of fat storage via suppressed thermogenesis: a thrifty phenotype that predisposes individuals with catch-up growth to insulin resistance and obesity. Horm Res 65(Suppl 3):90–97PubMedGoogle Scholar
  74. Eastwood SL, Harrison PJ (2003) Interstitial white matter neurons express less reelin and are abnormally distributed in schizophrenia: towards an integration of molecular and morphologic aspects of the neurodevelopmental hypothesis. Mol Psychiatry 5:654–663Google Scholar
  75. Elden A, Flaten MA (2002) The relationship of automatic and controlled processing to prepulse inhibition. J Psychophysiol 16:46–55Google Scholar
  76. El-Rawas R, Saade NE, Thiriet N, Atweh S, Jaber M, Al-Amin HA (2009) Developmental changes in the mRNA expression of neuropeptides and dopamine and glutamate receptors in neonates and adult rats after ventral hippocampal lesions. Schizophr Res 113:298–307PubMedGoogle Scholar
  77. Fatemi SH, Earle JA, McMenomy T (2000) Reduction in reelin immunoreactivity in hippocampus of subjects with schizophrenia, bipolar disorder and major depression. Mol Psychiatry 5:654–663PubMedGoogle Scholar
  78. Feifel D (1999) Indiffidual differences in prepulse inhibition of startle as a measure of individual dopamine function. Behav Neurosci 113:1020–1029PubMedGoogle Scholar
  79. Feifel D, Minassian A, Perry W (2009) Prepulse inhibition of startle in adults with ADHD. J Psychiatr Res 43:484–489PubMedGoogle Scholar
  80. Fendt M, Li L, Yeomans JS (2001) Brain stem circuits mediating prepulse inhibition of startle reflex. Psychopharmacology 156:216–224PubMedGoogle Scholar
  81. Fiedorowicz JG, Epping EA, Flaum M (2008) Toward defining schizophrenia as a more useful clinical concept. Curr Psychiatry Rep 10:344–351PubMedGoogle Scholar
  82. Filion D, Poje A (2003) Selective and nonselective attention effects on prepulse inhibition of startle: a comparison of task and no-task protocols. Biol Psychol 64:283–296PubMedGoogle Scholar
  83. Flores G, Silva-Gomez AB, Ibanez O, Quirion R, Srivastava LK (2005) Comparative behavioral changes in postpubertal rats after neonatal excitotoxic lesions of the ventral hippocampus and the prefrontal cortex. Synapse 56:147–153PubMedGoogle Scholar
  84. François J, Ferrandon A, Koning E, Angst MJ, Sandner G, Nehlig A (2009) Selective reorganization of GABAergic transmission in neonatal ventral hippocampal-lesioned rats. Int J Neuropsychopharmacol 12:1097–1110PubMedGoogle Scholar
  85. Frankland PW, Wang Y, Rosner B, Shimizu T, Balleine BW, Dykens EM, Ornitz EM, Silva AJ (2004) Sensorigating abnormalities in young males with fragile X syndrome and Fmr1-knockout mice. Mol Psychiatry 9:417–425PubMedGoogle Scholar
  86. Franklin TB, Mansuy IM (2009) Epigenetic inheritance in mammals: evidence for the impact of adverse environmental effects. Neurobiol Dis. Nov 27. PMID:19931614Google Scholar
  87. Friston KJ (1998) The disconnection hypothesis. Schizophr Res 30:115–125PubMedGoogle Scholar
  88. Frost DO, Page SC, Carroll C, Kolb B (2010) Early exposure to haloperidol or olanzapine induces long-term alterations of dendritic form. Synapse 64:191–199PubMedGoogle Scholar
  89. Furini CR, Rossato JI, Bitencourt LL, Medina JH, Izquierdo I, Cammarota M (2009) Beta-adrenergic receptors link NO/sGC/PKG signaling to BDNF expression during the consolidation of object recognition long-term memory. Hippocampus. Jun 16. PMID:19533679Google Scholar
  90. Galvez R, Greenough WT (2005) Sequence of abnormal dendritic spine development in primary somatosensory cortex of a mouse model of the fragile X mental retardation syndrome. Am J Med Genet A 135A:155–160Google Scholar
  91. Gao H, Granka JM, Feldman MW (2009) On the classification of epistatic interactions. Genetics. Dec 21. PMID:20026678Google Scholar
  92. Gefvert O, Lindström LH, Waters N, Waters S, Carlsson A, Tedroff J (2003) Different corticostriatal patterns of l-DOPA utilization in patients with untreated schizophrenia and patients treated with classical antipsychotics or clozapine. Scand J Psychol 44:289–292PubMedGoogle Scholar
  93. Gelernter J, Southwick S, Goodson S, Morgan A, Nagy L, Charney DS (1999) No association between D2 dopamine receptor (DRD2) “A” system alleles, or DRD2 haplotypes, and posttraumatic stress disorders. Biol Psychiatry 45:620–625PubMedGoogle Scholar
  94. Geyer MA (2006) The family of sensorimotor gating disorders: comorbidities or diagnostic overlaps? Neurotox Res 10:211–220PubMedGoogle Scholar
  95. Geyer MA, Krebs-Thompson K, Braff DL, Swerdlow NR (2001) Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology 156:117–154PubMedGoogle Scholar
  96. Giakoumaki SG, Roussos P, Rogdaki M, Karli C, Bitsios P, Frangou S (2007) Evidence of disrupted prepulse inhibition in unaffected siblings of bipolar disorder patients. Biol Psychiatry 62:1418–1422PubMedGoogle Scholar
  97. Giakoumaki SG, Bitsios P, Frangou S (2008) The level of prepulse inhibition in healthy individuals may index cortical modulation of early information processing. Brain Res 1078:168–170Google Scholar
  98. Girgenti MJ, Nisenbaum LK, Bymaster F, Terwilliger R, Duman RS, Newton SS (2010) Antipsychotic induced gene regulation in multiple brain regions. J Neurochem. Jan 13. PMID:20070869Google Scholar
  99. Gomes MV, Waterland RA (2008) Individual epigenetic variation: when, why, and so what? Nestle Nutr Workshop Ser Pediatr Program 62:141–150PubMedGoogle Scholar
  100. Goos LM, Ragsdale G (2008) Genomic imprinting and human psychology: cognition, behavior and pathology. Adv Exp Med Biol 626:71–88PubMedGoogle Scholar
  101. Goto Y, Yang CR, Otani S (2010) Functional and dysfunctional synaptic plasticity in prefrontal cortex: roles in psychiatric disorders. Biol Psychiatry 67:199–207PubMedGoogle Scholar
  102. Gottesman II, Gould TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160:636–645PubMedGoogle Scholar
  103. Gould TD, Gottesman II (2006) Psychiatric endophenotypes and the development of valid animal models. Genes Brain Behav 5:113–119PubMedGoogle Scholar
  104. Grace AA (2004) Developmental dysregulation of the dopamine system and the pathophysiology of schizophrenia. In: Keshavan MS, Kennedy JL, Murray RM (eds) Neurodevelopment and schizophrenia. Cambridge University Press, Cambridge, pp 273–294Google Scholar
  105. Grace AA (2010) Dopamine system dysregulation as the common pathophysiological basis for schizophrenia psychosis, psychostimulant abuse, and stress. Neurotox Res (in press). PMID:20043199Google Scholar
  106. Gragnoli C (2010) PSMD9 gene in the NIDDM2 locus is linked to type 2 diabetes in Italians. J Cell Physiol 222:265–267PubMedGoogle Scholar
  107. Graham FK (1975) Presidential address, 1974. The more or less startling effects of weak prestimulation. Psychophysiology 12:238–248PubMedGoogle Scholar
  108. Grayson DR, Jia X, Chen Y, Sharma RP, Mitchell CP, Guidotti A, Costa E (2005) Reelin promoter hypermethylation in schizophrenia. Proc Natl Acad Sci USA 102:9341–9346PubMedGoogle Scholar
  109. Greenwood TA, Braff DL, Light GA, Cadenhead KS, Calkins ME, Dobie DJ, Freedman R, Green MF, Gur RE, Gur RC, Mintz J, Nuechterlein KH, Olincy A, Radant AD, Seidman LJ, Siever LJ, Silverman JM, Stone WS, Swerdlow NR, Tsuang DW, Tsuang MT, Turetsky BI, Schork NJ (2007) Initial heritability analyses of endophenotypic measures for schizophrenia: the consortium on the genetics of schizophrenia. Arch Gen Psychiatry 64:1242–1250PubMedGoogle Scholar
  110. Guillin O, Abi-Dargham A, Laruelle M (2007) Neurobiology of dopamine in schizophrenia. Int Rev Neurobiol 78:1–39PubMedGoogle Scholar
  111. Hadamitzky M, Harich S, Koch M, Schwabe K (2007) Deficient prepulse inhibition induced by selective breeding of rats can be restored by the dopamine D2 antagonist. Behav Brain Res 177:364–367PubMedGoogle Scholar
  112. Harrison PJ, Weinberger DR (2005) Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry 10:40–68PubMedGoogle Scholar
  113. Hashimoto T, Volk DW, Eggan SM, Mirnics K, Pierri JN, Sun Z, Sampson AR, Lewis DA (2003) Gene expression deficits in a subclass of GAGA neurons in the prefrontal cortex of subjects with schizophrenia. J Neurosci 23:6315–6326PubMedGoogle Scholar
  114. Hashimoto T, Bergen SE, Nguyen QL, Xu B, Monteggia LM, Pierri JN, Sun Z, Sampson AR, Lewis DA (2005) Relationship of brain-derived neurotrophic factor and its receptor TrkB to altered inhibitory prefrontal circuitry in schizophrenia. J Neurosci 25:372–383PubMedGoogle Scholar
  115. Hashimoto T, Arion D, Unger T, Maldonado-Aviles JG, Morris HM, Volk DW, Mirnics K, Lewis DA (2008) Alterations in GABA-related transcriptome in the dorsolateral prefrontal cortex of subjects with schizophrenia. Mol Psychiatry 13:147–161PubMedGoogle Scholar
  116. Heimer L, Zahm DS, Churchill L, Kalivas PW, Wohltmann C (1991) Specificity in the projection patterns of accumbal core and shell in the rat. Neuroscience 41:89–125PubMedGoogle Scholar
  117. Hessl D, Berry-Kravis E, Cordeiro L, Yuhas J, Ornitz EM, Campbell A, Chruscinski E, Hervey C, Long JM, Hagerman RJ (2009) Prepulse inhibition in fragile X syndrome: feasibility, reliability, and implications for treatment. Am J Med Genet B 150B:545–553Google Scholar
  118. Hietala J, Syvalahti E, Vilkman H, Vourio K, Rakkolainen V, Bergnan J, Haaparanta M, Solin O, Kuoppamäki M, Eronen E, Ruotsalainen U, Salokangas RK (1999) Depressive symptoms and presynaptic dopamine function in neuroleptic-naive schizophrenia. Schizophr Res 35:41–50PubMedGoogle Scholar
  119. Higo N, Nishimura Y, Murata Y, Oishi T, Yoshino-Saito K, Takahashi M, Tsuboi F, Isa T (2009) Increased expression of the growth-associated protein 43 gene in the sensorimotor cortex of the macaque monkey after lesioning the lateral corticospinal tract. J Comp Neurol 516:493–506PubMedGoogle Scholar
  120. Hitzemann R, Malmanger B, Belknap J, Darakjian P, McWeeney S (2008) Short-term selective breeding for high and low prepulse inhibition of the acoustic startle response: pharmacological characterization and QTL mapping in the selected lines. Pharmacol Biochem Behav 90:525–533PubMedGoogle Scholar
  121. Ho DH, Burggren WW (2010) Epigenetics and transgenerational transfer: a physiological perspective. J Exp Biol 213:3–16PubMedGoogle Scholar
  122. Hoeft F, Hernandez A, Parthasarathy S, Watson CL, Hall SS, Reiss AL (2007) Fronto-striatal dysfunction and potential compensatory mechanisms in male adolescents with fragile X syndrome. Hum Brain Mapp 28:543–554PubMedGoogle Scholar
  123. Hoenicka J, Aragues M, Ponce G, Rodriguez-Jimenez R, Jimenez-Arriero MA, Palomo T (2007) From dopaminergic genes to psychiatric disorders. Neurotox Res 11:61–72PubMedGoogle Scholar
  124. Hoenicka J, Quiñones-Lombraña A, España-Serrano L, Alvira-Botero X, Kremer L, Pérez-González R, Rodríguez-Jiménez R, Jiménez-Arriero MA, Ponce G, Palomo T (2010) The ANKK1 gene associated with addictions is expressed in astroglial cells and upregulated by apomorphine. Biol Psychiatry 67:3–11PubMedGoogle Scholar
  125. Hoenig K, Hochrein A, Quednow BB, Maier W, Wagner M (2005) Impaired prepulse inhibition of acoustic startle in obsessive-compulsive disorder. Biol Psychiatry 57:1153–1158PubMedGoogle Scholar
  126. Holliday R (1990) Mechanisms for the control of gene activity during development. Biol Rev Camb Philos Soc 65:431–471PubMedGoogle Scholar
  127. Hon G, Wang W, Ren B (2009) Discovery and annotation of functional chromatin signatures in the human genome. PLoS Comput Biol 5:e1000566PubMedGoogle Scholar
  128. Horan WP, Green MF, Knowlton BJ, Wynn JK, Mintz J, Nuechterlein KH (2008) Impaired implicit learning in schizophrenia. Neuropsychology 22:606–617PubMedGoogle Scholar
  129. Irwin SA, Galvez R, Greenough WT (2000) Dendritic spine structural anomalies in fraglie X mental retardation syndrome. Cereb Cortex 10:1038–1044PubMedGoogle Scholar
  130. Ito H, Takano H, Takahashi H, Arakawa R, Miyoshi M, Kodaka F, Okumura M, Otsuka T, Suhara T (2009) Effects of the antipsychotic risperidone on dopamine synthesis in human brain measured by positron emission tomography with L-[beta-11C]DOPA: a stabilizing effect for dopaminergic neurotransmission? J Neurosci 29:13730–13734PubMedGoogle Scholar
  131. Izquierdo I, Medina JH, Cammarota M (2010) Disquisitions about the effect of age and dopamine on memory processes. Neurotox Res (in press)Google Scholar
  132. Jablonka E, Raz G (2009) Transgenerational epigenetic inheritance: prevalence, mechanisms, and implications for the study of heredity and evolution. Q Rev Biol 84:131–176PubMedGoogle Scholar
  133. Joo EJ, Lee KY, Jeong SH, Roh MS, Kim SH, Ahn YM, Kim YS (2009) AKT1 gene polymorphisms and obstetric complications in the patients with schizophrenia. Psychiatr Investig 6:102–107Google Scholar
  134. Joober R, Zarate JM, Rouleau GA, Skamene E, Boksa P (2002) Provisional mapping of quantitative trait loci modulating the acoustic startle response and prepulse inhibition of acoustic startle. Neuropsychopharmacology 27:765–781PubMedGoogle Scholar
  135. Katche C, Bekinschtein P, Slipczuk L, Goldin A, Izquierdo IA, Cammarota M, Medina JH (2010) Delayed wave of c-Fos expression in the dorsal hippocampus involved specifically in persistence of long-term memory storage. Proc Natl Acad Sci USA 107:349–354PubMedGoogle Scholar
  136. Kauer JA, Malenka RC (2007) Synaptic plasticity and addiction. Nat Rev Neurosci 8:844–858PubMedGoogle Scholar
  137. Kegeles LS, Slifstein M, Frankle WG, Xu X, Hackett E, Bae SA, Gonzales R, Kim JH, Alvarez B, Gil R, Laruelle M, Abi-Dargham A (2008) Dose-occupancy study of striatal and extrastriatal dopamine D2 receptors by aripiprazole in schizophrenia with PET and [18F]fallypride. Neuropsychopharmacology 33:3111–3125PubMedGoogle Scholar
  138. Keuroghlian AS, Knudsen EI (2007) Adaptive auditory plasticity in developing and adult animals. Prog Neurobiol 82:109–121PubMedGoogle Scholar
  139. Keverne EB (2010) Epigenetically regulated imprinted genes and foetal programming. Neurotox Res (in press)Google Scholar
  140. Kiang M, Braff DL, Sprock J, Light GA (2009) The relationship between preattentive sensory processing deficits and age in schizophrenia patients. Clin Neurophysiol 120:1949–1957PubMedGoogle Scholar
  141. Koch M (1999) The neurobiology of startle. Prog Neurobiol 59:107–128 PubMedGoogle Scholar
  142. Koch M, Fendt M (2000) Startle response modulation as a behavioral tool in neuropharmacology. Curr Neuropharmacol 1:175–185Google Scholar
  143. Kodsi MH, Swerdlow NR (1995) Prepulse inhibition in the rat is regulated by ventral and caudodorsal striato-pallidal circuitry. Behav Neurosci 109:912–928PubMedGoogle Scholar
  144. Kretschmer BD, Koch M (1998) The ventral pallidum mediates disruption of prepulse inhibition of the acoustic startle response induced by dopamine agonists, but not by NMDA antagonists. Brain Res 798:204–210PubMedGoogle Scholar
  145. Kuehn BM (2009) Scientists target cocaine addiction. JAMA 302:2641–2642PubMedGoogle Scholar
  146. Laakso A, Vilkman H, Bergman J, Haaparanta M, Solin O, Syvälahti E, Salokangas RK, Hietala J (2002) Sex differences in striatal presynaptic dopamine synthesis capacity in healthy subjects. Biol Psychiatry 52:759–763PubMedGoogle Scholar
  147. Launay JM, Del Pino M, Chironi G, Callebert J, Peoc’h K, Mégnien JL, Mallet J, Simon A, Rendu F (2009) Smoking induces long-lasting effects through a monoamine-oxidase epigenetic regulation. PLoS One 4:e7959PubMedGoogle Scholar
  148. Lenz B, Klafki HW, Hillemacher T, Killisch N, Schaller G, Frieling H, Clepce M, Gossler A, Thuerauf N, Winterer G, Kornhuber J, Bleich S (2010) Smoking behaviour is associated with expression and phosphorylation of CREB in human buffy coat. Int J Neuropsychopharmacol 5:1–9Google Scholar
  149. Leussis MP, Frayne ML, Saito M, Berry EM, Aldinger KA, Rockwell GN, Hammer RP Jr, Baskin-Hill AE, Singer JB, Nadeau JH, Sklar P, Petryshen TL (2009) Genomic survey of prepulse inhibition in mouse chromosome substitution strains. Genes Brain Behav 8:806–816PubMedGoogle Scholar
  150. Lewis DA, Glantz LA, Pierri JN, Sweet RA (2003) Altered cortical glutamate neurotransmission in schizophrenia: evidence from morphological studies of pyramidal neurons. Ann NY Acad Sci 1003:102–112PubMedGoogle Scholar
  151. Lewis DA, Hashimoto T, Volk DW (2005) Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci 6:312–324PubMedGoogle Scholar
  152. Lewis DA, Hashimoto T, Morris HM (2008) Cell and receptor type-specific alterations in markers of GABA neurotransmission in the prefrontal cortex of subjects with schizophrenia. Neurotox Res 14:1–12Google Scholar
  153. Lindström LH, Gefvert O, Hagberg G, Lundberg T, Bergström M, Hartvig P, Långström B (1999) Increased dopamine synthesis rate in medial prefrontal cortex and striatum in schizophrenia indicated by L-(beta-11C) DOPA and PET. Biol Psychiatry 46:681–688PubMedGoogle Scholar
  154. Lipska BK, Al-Amin HA, Weinberger DR (1998) Excitotoxic lesions of the medial prefrontal cortex. Effects on abnormal behaviors associated with neonatal hippocampal damage. Neuropsychopharmacology 19:451–464PubMedGoogle Scholar
  155. Lisman JE, Coyle JT, Green RW, Javitt DC, Benes FM, Heckers S, Grace AA (2008) Circuit-based framework for understanding neurotransmitter and gene interactions in schizophrenia. Trends Neurosci 31:234–242PubMedGoogle Scholar
  156. Lodge DJ, Grace AA (2007) Aberrant hippocampal activity underlies the dopamine dysregulation in an animal model of schizophrenia. J Neurosci 27:11424–11430PubMedGoogle Scholar
  157. Lodge DJ, Grace AA (2008) Amphetamine activation of hippocampal drive of mesolimbic dopamine neurons: a mechanism of behavioral sensitization. J Neurosci 28:7876–7882PubMedGoogle Scholar
  158. Lodge DJ, Behrens MM, Grace AA (2009) A loss of parvalbumin-containing interneurons is associated with diminished oscillatory activity in an animal model of schizophrenia. J Neurosci 29:2344–2354PubMedGoogle Scholar
  159. Lomeña F, Catafau AM, Parellada E, Bernardo M, Font M, Gutiérrez F, Pavía J (2004) Striatal dopamine D2 receptor density in neuroleptic-naive and in neuroleptic-free schizophrenic patients: an 123I-IBZM-SPECT study. Psychopharmacology 172:165–169PubMedGoogle Scholar
  160. Macedo CE, Angst MJ, Guiberteau T, Brasse D, O’Brien TJ, Sandner G (2009) Acoustic hypersensitivity in adult rats after neonatal ventral hippocampus lesions. Behav Brain Res 207:161–168PubMedGoogle Scholar
  161. Maier W, Mössner R, Quednow BB, Wagner M, Hurlemann R (2008) From genes to psychoses and back: the role of the 5HT2α receptor and prepulse inhibition in schizophrenia. Eur Arch Psychiatry Clin Neurosci 258(Suppl 5):40–43PubMedGoogle Scholar
  162. Martinez-Gras I, Rubio G, del Manzano BA, Rodriguez-Jimenez R, Garcia-Sanchez F, Bagney A, Leza JC, Borrell J (2009) The relationship between prepulse inhibition and general psychopathology in patients with schizophrenia treated with long-acting risperidone. Schizophr Res 115:215–221PubMedGoogle Scholar
  163. McAlonan GM, Daly E, Kumari V, Critchley HD, van Amelsvoort T, Suckling J, Simmons A, Sigmundsson T, Greenwood K, Russell A, Schmitz N, Happe F, Howlin P, Murphy DG (2002) Brain anatomy and sensorimotor gating in Asperger’s syndrome. Brain 125(Pt 7):1594–1606PubMedGoogle Scholar
  164. McElligott ZA, Winder DG (2009) Modulation of glutamatergic synaptic transmission in the bed nucleus of the stria terminalis. Prog Neuropsychopharmacol Biol Psychiatry 33:1329–1335PubMedGoogle Scholar
  165. McGowan S, Lawrence AD, Sales T, Quested D, Grasby P (2004) Presynaptic dopaminergic dysfunction in schizophrenia: a positron emission tomographic [18F]fluorodopa study. Arch Gen Psychiatry 61:134–142PubMedGoogle Scholar
  166. Meisenzahl EM, Schmitt GJ, Scheuerecker J, Möller HJ (2007) The role of dopamine for the pathophysiology of schizophrenia. Int Rev Psychiatry 19:337–345PubMedGoogle Scholar
  167. Melkersson K, Hulting AL (2009) Serotonin receptor 2A gene polymorphisms and schizophrenia: association with family history, diagnostic subtype and height in patients. Neuro Endocrinol Lett 30:343–351PubMedGoogle Scholar
  168. Mercaldo V, Descalzi G, Zhuo M (2009) Fragile X mental retardation protein in learning-related synaptic plasticity. Mol Cells 28:501–507PubMedGoogle Scholar
  169. Montag C, Hartmann P, Merz M, Burk C, Reuter M (2008) D2 receptor density and prepulse inhibition in humans: negative findings from a molecular genetic approach. Behav Brain Res 187:428–432PubMedGoogle Scholar
  170. Montag C, Weber B, Jentgens E, Elger C, Reuter M (2010) An epistasis effect of functional variants on the BDNF and DRD2 genes modulates gray matter volume of the anterior cingulate cortex in healthy humans. Neuropsychologia 48:1016–1021PubMedGoogle Scholar
  171. Morgan DK, Whitelaw E (2009) The role of epigenetics in mediating environmental effects on phenotype. Nestle Nutr Workshop Ser Pediatr Program 63:109–117PubMedGoogle Scholar
  172. Moriwaki M, Kishi T, Takahashi H, Hashimoto R, Kawashima K, Okochi T, Kitajima T, Furukawa O, Fujita K, Takeda M, Iwata N (2009) Prepulse inhibition of the startle response with chronic schizophrenia: a replication study. Neurosci Res 65:259–262PubMedGoogle Scholar
  173. Mössner R, Schuhmacher A, Kühn KU, Cvetanovska G, Rujescu D, Zill P, Quednow BB, Rietschel M, Wölwer W, Gaebel W, Wagner M, Maier W (2009a) Functional serotonin 1A receptor variant influences treatment response to atypical antipsychotics in schizophrenia. Pharmacogenet Genomics 19:91–94PubMedGoogle Scholar
  174. Mössner R, Schuhmacher A, Wagner M, Quednow BB, Frommann I, Kühn KU, Schwab SG, Rietschel M, Falkai P, Wölwer W, Ruhrmann S, Bechdolf A, Gaebel W, Klosterkötter J, Maier W (2009b) DAOA/G72 predicts the progression of prodromal syndromes to first episode psychosis. Eur Arch Psychiatry Clin Neurosci. Sep 10. PMID:19763662Google Scholar
  175. Mouri A, Noda Y, Enomoto T, Nabeshima T (2007) Phencyclidine animal models of schizophrenia: approaches from abnormality of glutamatergic neurotransmission and neurodevelopment. Neurochem Int 51:173–184PubMedGoogle Scholar
  176. Munafo MR, Matheson IJ, Flint J (2007) Association of the DRD2 gene Taq1A polymorphism and alcoholism: a meta-analysis of case–control and evidence of publication bias. Mol Psychiatry 12:454–461PubMedGoogle Scholar
  177. Nadeau JH (2009) Transgenerational genetic effects on phenotypic variation and disease risk. Hum Mol Genet 18:R202–R210PubMedGoogle Scholar
  178. Nagarajan RP, Costello JF (2009) Molecular epigenetics and genetics in neuro-oncology. Neurotherapeutics 6:436–446PubMedGoogle Scholar
  179. Nicodemus KK, Callicott JH, Higier RG, Luna A, Nixon DC, Lipska BK, Vakkalanka R, Giegling I, Rujescu D, Clair DS, Muglia P, Shugart YY, Weinberger DR (2010) Evidence of statistical epistasis between DISC1, CIT and NDEL1 impacting risk for schizophrenia: biological validation with functional neuroimaging. Hum Genet. Jan 19. PMID:20084519Google Scholar
  180. Noble EP (2009) D2 dopamine receptor gene in psychiatric and neurologic disorders and its phenotypes. Am J Med Genet B 116:103–125Google Scholar
  181. Noble EP, Blum K (1993) Alcoholism and the D2 dopamine receptor gene. JAMA 270:1547–1548PubMedGoogle Scholar
  182. Nunokawa A, Watanabe Y, Kaneko N, Sugai T, Yazaki S, Arinami T, Ujike H, Inada T, Iwata N, Kunugi H, Sasaki T, Itokawa M, Ozaki N, Hashimoto R, Someya T (2009) The dopamine D3 receptor (DRD3) gene and risk of schizophrenia: case–control studies and an updated meta-analysis. Schizophr Res 116:61–67Google Scholar
  183. Oberle E, Schonert-Reichl KA, Thomson KC (2009) Understanding the link between social and emotional well-being and peer relations in early adolescence: gender-specific predictors of peer acceptance. J Youth Adolesc. Nov 29. PMID:20091211Google Scholar
  184. Otto SP, Whitlock MC (2009) The impact of epistatic selection on the genomic traces of selection. Mol Ecol 18:4985–4987PubMedGoogle Scholar
  185. Palomo T, Kostrzewa RM, Beninger RJ, Archer T (2008) Schizopsychotic symptom-profiles and biomarkers: beacons in diagnostic labyrinths. Neurotox Res 14:79–96PubMedGoogle Scholar
  186. Pascual MM, Pastor V, Bernabeu RO (2009) Nicotine-conditioned place preference induced CREB phosphorylation and Fos expression in the adult rat brain. Psychopharmacology 207:57–71PubMedGoogle Scholar
  187. Perry W (2009) Beyond the numbers: expanding the boundaries of neuropsychology. Arch Clin Neuropsychol 24:21–29PubMedGoogle Scholar
  188. Perry W, Geyer M, Braff DL (1999) Sensorimotor gating and thought disturbance measured in close temporal proximity in schizophrenic patients. Arch Gen Psychiatry 56:277–281PubMedGoogle Scholar
  189. Perry W, Minassian A, Feifel D, Braff DL (2001) Sensorimotor deficits in bipolar disorder patients with acute psychotic mania. Biol Psychiatry 50:418–424PubMedGoogle Scholar
  190. Perry W, Minassian A, Lopez B, Maron L, Lincoln A (2007) Sensorimotor gating deficits in adults with autism. Biol Psychiatry 61:82–486Google Scholar
  191. Pezzi S, Checa N, Alberch J (2005) The vulnerability of striatal projection neurons and interneurons to excitotoxicity is differentially regulated by dopamine during development. Int J Dev Neurosci 23:343–349PubMedGoogle Scholar
  192. Phillips TJ, Reed C, Burkhart-Kasch S, Li N, Hitzemann R, Yu CH, Brown LL, Helms ML, Crabbe JC, Belknap JK (2010) A method for mapping intralocus interactions influencing excessive alcohol drinking. Mamm Genome 21:39–51PubMedGoogle Scholar
  193. Ponce G, Jimenez-Arriero MA, Rubio G, Hoenicka J, Ampuero I, Ramos JA, Palomo T (2003) The A1 allele of the DRD2 gene (TaqI A polymorphisms) is associated with antisocial personality in a sample of alcohol-dependent patients. Eur Psychiatry 18:356–360PubMedGoogle Scholar
  194. Ponce G, Pérez-González R, Aragüés M, Palomo T, Rodríguez-Jiménez R, Jiménez-Arriero MA, Hoenicka J (2009) The ANKK1 kinase gene and psychiatric disorders. Neurotox Res 16:50–59PubMedGoogle Scholar
  195. Post RM (2010) Mechanisms of illness progression in the recurrent affective disorders. Neurotox Res (in press)Google Scholar
  196. Pothuizen HHJ, Jongen-Relo AL, Feldon J (2005) The effect of temporary inactivation of the core and shell subregions of the nucleus accumbens on prepulse inhibition of the acoustic startle reflex and activity in rats. Neuropsychopharmacology 30:683–696PubMedGoogle Scholar
  197. Powell SB, Zhou X, Geyer MA (2009) Prepulse inhibition and genetic mouse models of schizophrenia. Behav Brain Res 204:282–294PubMedGoogle Scholar
  198. Prentice AM (2005) Early influences on human energy regulation: thrifty genotypes and thrifty phenotypes. Physiol Behav 86:640–645PubMedGoogle Scholar
  199. Price KL, McRae-Clark AL, Saladin ME, Maria MM, DeSantis SM, Back SE, Brady KT (2009) D-cycloserine and cocaine cue reactivity: preliminary findings. Am J Drug Alcohol Abuse 35:434–438PubMedGoogle Scholar
  200. Quednow BB, Wagner M, Mossner R, Maier W, Kuhn KU (2008) Sensorimotor gating of schizophrenia patients depends on catechol-o-methyltransferase Val158Met polymorphism. Schizophr Bull. Jul 17. PMID:18635674Google Scholar
  201. Quincozes-Santos A, Bobermin LD, Tonial RP, Bambini-Junior V, Riesgo R, Gottfried C (2009) Effects of atypical (risperidone) and typical (haloperidol) antipsychotic agents on astroglial functions. Eur Arch Psychiatry Clin Neurosci. Dec 30. PMID:20041330Google Scholar
  202. Rabin RA, Sacco KA, George TP (2009) Correlation of prepulse inhibition and Wisconsin card sorting test in schizophrenia and controls: effects of smoking status. Schizophr Res 114:91–97PubMedGoogle Scholar
  203. Reik W (2007) Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 447:425–432PubMedGoogle Scholar
  204. Reiss AL, Dant CC (2003) The behavioral neurogenetics of fragile X syndrome: analyzing gene-brain-behavior relationships in child developmental psychopathologies. Dev Psychopathol 15:927–968PubMedGoogle Scholar
  205. Reser JE (2006) Evolutionary neuropathology & congenital mental retardation: environmental cues predictive of maternal deprivation influence the fetus to minimize cerebral metabolism in order to express bioenergetic thrift. Med Hypotheses 67:529–544PubMedGoogle Scholar
  206. Ribasés M, Bosch R, Hervás A, Ramos-Quiroga JA, Sánchez-Mora C, Bielsa A, Gastaminza X, Guijarro-Domingo S, Nogueira M, Gómez-Barros N, Kreiker S, Gross-Lesch S, Jacob CP, Lesch KP, Reif A, Johansson S, Plessen KJ, Knappskog PM, Haavik J, Estivill X, Casas M, Bayés M, Cormand B (2009) Case–control study of six genes asymmetrically expressed in the two cerebral hemispheres: association of BAIAP2 with attention-deficit/hyperactivity disorder. Biol Psychiatry 66:926–934PubMedGoogle Scholar
  207. Rich BA, Vinton D, Grillon C, Bhangoo RK, Leibenluft E (2005) An investigation of prepulse inhibition in pediatric bipolar disorder. Bipolar Disord 7:198–203PubMedGoogle Scholar
  208. Richards EJ (2006) Inherited epigenetic variation—revisiting soft inheritance. Nat Rev Genet 7:395–401PubMedGoogle Scholar
  209. Ridge JP, Dodd PR (2009) Cortical NMDA receptor expression in human chronic alcoholism: influence of the TaqIA allele of ANKK1. Neurochem Res 34:1775–1782PubMedGoogle Scholar
  210. Robinson GE, Fernald RD, Clayton DF (2008) Genes and social behavior. Science 322:896–900PubMedGoogle Scholar
  211. Rossato JL, Bevilaqua LR, Izquierdo I, Medina JH, Cammarota M (2009) Dopamine controls persistence of long-term memory storage. Science 325:1017–1020PubMedGoogle Scholar
  212. Roussos P, Giakoumaki SG, Bitsios P (2008a) The dopamine D(3) receptor Ser9Gly polymorphism modulates prepulse inhibition of the acoustic startle reflex. Biol Psychiatry 64:235–240PubMedGoogle Scholar
  213. Roussos P, Giakoumaki SG, Rogmaki M, Pavlakis S, Frangou S, Bitsios P (2008b) Prepulse inhibition of the startle response depends on the catechol-o-methyltransferase Val158Met gene polymorphism. Psychol Med 38:1651–1658PubMedGoogle Scholar
  214. Roussos P, Giakoumaki SG, Bitsios P (2009) Tolcapone effects on gating, working memory, and mood interact with the synonymous catechol-O-methyltransferase rs4818c/g polymorphism. Biol Psychiatry 66:997–1004PubMedGoogle Scholar
  215. Russo VEA, Martienssen RA, Riggs AD (1996) Epigenetic mechanisms of gene regulation. Cold Spring Harbor Laboratory Press, PlainviewGoogle Scholar
  216. Saunders BT, Robinson TE (2009) A cocaine cue acts as an incentive stimulus in some but not others: implications for addiction. Biol Psychiatry. Dec 31. PMID:20045508Google Scholar
  217. Savitz JB, Solms M, Ramesar RS (2005) Neurocognitive function as an endophenotype for genetic studies of bipolar affective disorder. Neuromol Med 7:275–286Google Scholar
  218. Schabe K, Polikashvili N, Krauss JK (2009) Deficient sensorimotor gating induced by selective breeding in rats is improved by entopenduncular nucleus lesions. Neurobiol Dis 34:351–356Google Scholar
  219. Schlagenhauf F, Wüstenberg T, Schmack K, Dinges M, Wrase J, Koslowski M, Kienast T, Bauer M, Gallinat J, Juckel G, Heinz A (2008) Switching schizophrenia patients from typical neuroleptics to olanzapine: effects on BOLD response during attention and working memory. Eur Neuropsychopharmacol 18:589–599PubMedGoogle Scholar
  220. Schmitt GJ, Frodl T, Dresel S, la Fougère C, Bottlender R, Koutsouleris N, Hahn K, Möller HJ, Meisenzahl EM (2006) Striatal dopamine transporter availability is associated with the productive psychotic state in first episode, drug-naive schizophrenic patients. Eur Arch Psychiatry Clin Neurosci 256:115–121PubMedGoogle Scholar
  221. Schmitt GJ, Meisenzahl EM, Frodl T, La Fougère C, Hahn K, Möller HJ, Dresel S (2009) Increase of striatal dopamine transmission in first episode drug-naive schizophrenic patients as demonstrated by [(123)I]IBZM SPECT. Psychiatry Res 173:183–189PubMedGoogle Scholar
  222. Scholes KE, Martin-Iverson MT (2009a) Disturbed prepulse inhibition in patients with schizophrenia is consequential to dysfunction of selective attention. Psychophysiology. Oct 12. PMID:19824951Google Scholar
  223. Scholes KE, Martin-Iverson MT (2009b) Alterations to pre-pulse inhibition (PPI) in chronic cannabis users are secondary to sustained attention deficits. Psychopharmacology (Berl) 207:469–484Google Scholar
  224. Scholes KE, Martin-Iverson MT (2009c) Relationships between prepulse inhibition and cognition are mediated by attentional processes. Behav Brain Res 205:456–467PubMedGoogle Scholar
  225. Schuhmacher A, Mössner R, Quednow BB, Kühn KU, Wagner M, Cvetanovska G, Rujescu D, Zill P, Möller HJ, Rietschel M, Franke P, Wölwer W, Gaebel W, Maier W (2009) Influence of 5-HT3 receptor subunit genes HTR3A, HTR3B, HTR3C, HTR3D and HTR3E on treatment response to antipsychotics in schizophrenia. Pharmacogenet Genomics. Sep 29. PMID:19794330Google Scholar
  226. Seeman P, Bzowej NH, Guan HC, Bergeron C, Reynolds GP, Bird ED, Riederer P, Jellinger K, Tourtelotte WW (1987) Human brain D1 and D2 dopamine receptors in schizophrenia, Alzheimer’s, Parkinson’s, and Huntington’s diseases. Neuropsychopharmacology 1:5–15PubMedGoogle Scholar
  227. Sesack SR, Grace AA (2010) Cortico-basal ganglia reward network: microcircuitry. Neuropsychopharmacology 35:27–47PubMedGoogle Scholar
  228. Sharma A, Hoeffer CA, Takayasu Y, Miyawaki T, McBride SM, Klann E, Zukin RS (2009) Dysregulation of mTOR signaling in fragile X syndrome. J Neurosci 30:694–702Google Scholar
  229. Shen YC, Chen SF, Chen CH, Lin CC, Chen SJ, Chen YJ, Luu SU (2009) Effects of DRD2/ANKK1 gene variations and clinical factors on aripiprazole efficacy in schizophrenic patients. J Psychiatr Res 43:600–606PubMedGoogle Scholar
  230. Slifstein M, Kegeles LS, Xu X, Thompson JL, Urban N, Castrillon J, Hackett E, Bae SA, Laruelle M, Abi-Dargham A (2009) Striatal and extrastriatal dopamine release measured with PET and [(18)F] fallypride. Synapse 64:350–362Google Scholar
  231. Slipczuk L, Bekinschtein P, Katche C, Cammarota M, Izquierdo I, Medina JH (2009) BDNF activates mTOR to regulate GluR1 expression required for memory formation. PLoS One 4:e6007PubMedGoogle Scholar
  232. Slotkin RA, Martienssen R (2007) Transposable elements and the epigenetic regulation of the genome. Nat Rev Genet 8:272–285PubMedGoogle Scholar
  233. Smillie LD, Cooper AJ, Proitsi P, Powell JF, Pickering AD (2009) Variation in DRD2 dopamine gene predicts Extraverted personality. Neurosci Lett 468:234–237PubMedGoogle Scholar
  234. Smith L, Watson M, Gates S, Ball D, Foxcroft D (2008) Meta-analysis of the association of the Taq1A polymorphism with the risk of alcohol dependency: a HuGE gene-disease association review. Am J Epidemiol 167:125–138PubMedGoogle Scholar
  235. Srivastava V, Deshpande SN, Thelma BK (2009) Dopaminergic pathway gene polymorphisms and genetic susceptibility to schizophrenia among north Indians. Neuropsychobiology 61:64–70PubMedGoogle Scholar
  236. Stelzel C, Basten U, Montag C, Reuter M, Fiebach CJ (2009) Effects of dopamine-related gene-gene interactions on working memory component processes. Eur J Neurosci 29:1056–1063PubMedGoogle Scholar
  237. Stephan KE, Baldeweg T, Friston KJ (2006) Synaptic plasticity and dysconnection in schizophrenia. Biol Psychiatry 59:929–939PubMedGoogle Scholar
  238. Stoddart CW, Noonan J, Martin-Iversen MT (2008) Stimulus quality affects expression of the acoustic startle response and prepulse inhibition in mice. Behav Neurosci 122:516–526PubMedGoogle Scholar
  239. Stone JM, Morrison PD, Pilowsky LS (2007) Glutamate and dopamine dysregulation in schizophrenia—a synthesis and selective review. J Psychopharmacol 21:440–452PubMedGoogle Scholar
  240. Swerdlow NR, Geyer MA (1998) Using an animal model of deficient sensorimotor gating to study the pathophysiology and new treatments of schizophrenia. Schizophr Bull 24:285–301PubMedGoogle Scholar
  241. Swerdlow NR, Benbow CH, Zisook S, Geyer M, Braff DL (1993) A preliminary assessment of sensorimotor gating in patients with obsessive compulsive disorder. Biol Psychiatry 33:298–301PubMedGoogle Scholar
  242. Swerdlow NR, Hartman PL, Auerbach PP (1997) Changes in sensorimotor inhibition across the menstrual cycle: implications for neuropsychiatric disorders. Biol Psychiatry 41:452–460PubMedGoogle Scholar
  243. Swerdlow NR, Sprock J, Light GA, Cadenhead K, Calkins ME, Dobie DJ, Freedman R, Green MF, Greenwood TA, Gur RE, Mintz J, Olincy A, Nuechterlein KH, Radant AD, Schork NJ, Seidman LJ, Siever LJ, Silverman JM, Stone WS, Tsuang DW, Tsuang MT, Turetsky BI, Braff DL (2007) Multi-site studies of acoustic startle and prepulse inhibition in humans: initial experience and methodological considerations based on studies by the consortium on the genetics of schizophrenia. Schizophr Res 92:237–251PubMedGoogle Scholar
  244. Swerdlow NR, Weber M, Qu Y, Light GA, Braff DL (2008) Realistic expectations of prepulse inhibition in translational models for schizophrenia research. Psychopharmacology 199:331–338PubMedGoogle Scholar
  245. Szyf M (2009) The early life environment and the epigenome. Biochim Biophys Acta 1790:878–885PubMedGoogle Scholar
  246. Szyf M, Weaver I, Meaney MJ (2007) Maternal care, the epigenome and phenotypic differences in behavior. Reprod Toxicol 24:9–19PubMedGoogle Scholar
  247. Szyf M, McGowan P, Meaney MJ (2008) The social environment and the epigenome. Environ Mol Mutagen 49:46–60PubMedGoogle Scholar
  248. Tajima K, Fernández H, López-Ibor J, Carrasco J, Díaz-Marsá M (2009) Schizophrenia treatment. Critical review on the drugs and mechanisms of action of antipsychotics. Actas Esp Psiquiatr 37:330–342PubMedGoogle Scholar
  249. Tam GW, Redon R, Carter NP, Grant SG (2009) The role of DNA copy number variation in schizophrenia. Biol Psychiatry 66:1005–1012PubMedGoogle Scholar
  250. Tamanini F, Willemsen R, van Unen L, Bontekoe C, Galjaard H, Oostra BA, Hoogeven AT (1997) Differential expression of FMR1, FXR1 and FXR2 proteins in human brain and testis. Hum Mol Genet 6:1315–1322PubMedGoogle Scholar
  251. Tandon R, Nasrallah HA, Keshavan MS (2009) Schizophrenia, “just the facts” 4. Clinical features and conceptualization. Schizophr Res 110:1–23PubMedGoogle Scholar
  252. Tang JX, Chen WY, He G, Zhou J, Gu NF, Feng GY, He L (2004) Polymorphism within 5′ end of the neureglin 1 gene are genetically associated with schizophrenia in the Chinese population. Mol Psychiatry 9:11–12PubMedGoogle Scholar
  253. Tarazi FI, Florijn WJ, Creese I (1997) Differential regulation of dopamine receptors after chronic typical and atypical antipsychotic drug treatment. Neuroscience 78:985–996PubMedGoogle Scholar
  254. Thorne G, Dawson M, Schell A (2005) Attention and prepulse inhibition: the effects of task-relevant, irrelevant, and no task conditions. Int J Psychophysiol 56:121–128PubMedGoogle Scholar
  255. Thorne GL, Dawson ME, Schell AM (2006) Effects of perceptual load on startle reflex modification at a long lead interval. Psychophysiology 43:498–503PubMedGoogle Scholar
  256. Tisch S, Silberstein P, Limousin-Dowsey P, Jahanshahi M (2004) The basal ganglia: anatomy, physiology, and pharmacology. Psychiatr Clin North Am 27:757–799PubMedGoogle Scholar
  257. Toda M, Abi-Dargham A (2007) Dopamine hypothesis of schizophrenia: making sense of it all. Curr Psychiatry Rep 9:329–336PubMedGoogle Scholar
  258. Tseng KY, Lewis BL, Lipska BK, O’Donnell P (2007) Post-pubertal disruption of medial prefrontal cortex dopamine-glutamate interactions in a developmental animal model of schizophrenia. Biol Psychiatry 62:730–738PubMedGoogle Scholar
  259. Tsutsumi A, Kanazawa T, Kikuyama H, Okugawa G, Uenishi H, Miyamoto T, Matsumoto N, Koh J, Shinosaki K, Kishimoto T, Yoneda H, Kinoshita T (2009) Genetic polymorphisms in dopamine- and serotonin-related genes and treatment responses to risperidone and perospirone. Psychiatr Investig 6:222–225Google Scholar
  260. Turetsky BI, Greenwood TA, Olincy A, Radant AD, Braff DL, Cadenhead KS, Dobie DJ, Freedman R, Green MF, Gur RE, Gur RC, Light GA, Mintz J, Nuechterlein KH, Schork NJ, Seidman LJ, Siever LJ, Silverman JM, Stone WS, Swerdlow NR, Tsuang DW, Tsuang MT, Calkins ME (2008) Abnormal auditory N100 amplitude: a heritable endophenotype in first-degree relatives of schizophrenia probands. Biol Psychiatry 64:1051–1059PubMedGoogle Scholar
  261. Valenti O, Grace AA (2008) Acute and repeated stress induce a pronounced and sustained activation of VTA DA neuron population activity. Program no. 47911. Neuroscience Meet, Washington, DC, Society for NeuroscienceGoogle Scholar
  262. Valenti O, Grace AA (2009) Antipsychotic drug-induced increases in ventral tegmental area dopamine neuron population activity via activation of the nucleus accumbens-ventral pallidum pathway. Int J Neuropsychopharmacol 15:1–16Google Scholar
  263. van den Buuse M (2009) Modeling the positive symptoms of schizophrenia in genetically modified mice: pharmacology and methodology aspects. Schizophr Bull. Nov 9. PMID:19900963Google Scholar
  264. Van den Oever MC, Spijker S, Smit AB, De Vries TJ (2009) Prefrontal cortex plasticity mechanisms in drug seeking and relapse. Neurosci Biobehav Rev (in press). PMID:19932711Google Scholar
  265. van Winkel R, Stefanis NC, Myin-Germeys I (2008) Psychosocial stress and psychosis. A review of the neurobiological mechanisms and the evidence for gene–stress interaction. Schizophr Bull 34:1095–1105PubMedGoogle Scholar
  266. Vandegehuchte MB, Vandenbrouck T, Coninck DD, De Coen WM, Janssen CR (2009) Can metal stress induce transferable changes in gene transcription in Daphnia magna? Aquat Toxicol. Jul 25. PMID:19683351Google Scholar
  267. Vasanthi D, Mishra RK (2008) Epigenetic regulation of genes during development: a conserved theme from flies to mammals. J Genet Genomics 35:413–429PubMedGoogle Scholar
  268. Veldic M, Kadriu B, Maloku E, Agis-Balboa RC, Guidotti A, Davis JM, Costa E (2007) Epigenetic mechanisms expressed in basal ganglia GABAergic neurons differentiate schizophrenia from bipolar disorder. Schizophr Res 91:51–61PubMedGoogle Scholar
  269. Vohs JL, Chambers RA, Krishnan GP, O’Donnell BF, Hetrick WP, Kaiser ST, Berg S, Morzorati SL (2009) Auditory sensory gating in the neonatal ventral hippocampal lesion model of schizophrenia. Neuropsychobiology 60:12–22PubMedGoogle Scholar
  270. Waddington CH (1942) The epigenotype. Endeavour 1:18–20Google Scholar
  271. Watanabe A, Toyota T, Owada Y, Hayashi T, Iwayama Y, Matsumata M, Ishitsuka Y, Nakaya A, Maekawa M, Ohnishi T, Arai R, Sakurai K, Yamada K, Kondo H, Hashimoto K, Osumi N, Yoskikawa T (2007) Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype. PLoS Biol 5:e297PubMedGoogle Scholar
  272. Waterland RA (2009a) Early environmental effects on epigenetic regulation in humans. Epigenetics 4(8):523–525PubMedGoogle Scholar
  273. Waterland RA (2009b) Is epigenetics an important link between early life events and adult disease? Horm Res 71(Suppl 1):13–16PubMedGoogle Scholar
  274. Waterland RA, Jirtle RL (2003) Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol 25:5293–5300Google Scholar
  275. Waterland RA, Dolinoy DC, Lin JR, Smith CA, Shi X, Tahiliani KG (2006) Maternal methyl supplements increase offspring DNA methylation at axin fused. Genesis 44:401–406PubMedGoogle Scholar
  276. Weiss LA (2009) Autism genetics: emerging data from genome-wide copy-number and single nucleotide polymorphism scans. Expert Rev Mol Diagn 9:795–803PubMedGoogle Scholar
  277. Wells JC (2003) The thrifty phenotype hypothesis: thrifty offspring or thrifty mother? J Theor Biol 221:143–161PubMedGoogle Scholar
  278. Wells JC (2007) The thrifty phenotype as an adaptive maternal effect. Biol Rev Camb Philos Soc 82:143–172PubMedGoogle Scholar
  279. White MJ, Morris CP, Lawford BR, Young RM (2009) Behavioral phenotypes of impulsivity related to the ANKK1 gene are independent of an acute stressor. Behav Brain Funct 4:54Google Scholar
  280. Whitlock JR, Heynen AJ, Shuler MG, Bear MF (2006) Learning induces long-term potentiation in the hippocampus. Science 313:1093–1097PubMedGoogle Scholar
  281. Wolf ME (2010) Progressive dysregulation of glutamate synapses in addiction. Neurotox Res (in press)Google Scholar
  282. Wolf ME, Ferrario (2010) AMPA receptor plasticity after cocaine withdrawal. Neurosci Biobehav Rev (in press). PMID:20109488Google Scholar
  283. Wolf ME, Sun X, Mangiavacchi S, Chao SZ (2004) Psychomotor stimulants and neuronal plasticity. Neuropharmacology 47:61–79PubMedGoogle Scholar
  284. Wolff GL, Kodell RL, Moore SR, Cooney CA (1998) Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/a mice. FASEB J 12:949–957PubMedGoogle Scholar
  285. Woo TU, Walsh JP, Benes FM (2004) Density of glutamic acid decarboxylase 67 messenger RNA-containing neurons that express the N-methyl-d-aspartate receptor subunit NR2A in the anterior cingulated cortex in schizophrenia and bipolar disorder. Arch Gen Psychiatry 61:649–657PubMedGoogle Scholar
  286. Wood GK, Quirion R, Srivastava LK (2003) Early environment contributes to developmental disruption of MPFC after neonatal ventral hippocampal lesions in rats. Synapse 50:223–232PubMedGoogle Scholar
  287. Woodcock KA, Oliver C, Humphreys GW (2009a) A specific pathway can be identified between genetic characteristics and behaviour profiles in Prader–Willi syndrome via cognitive, environmental and physiological mechanisms. J Intellect Disabil Res 53:493–500PubMedGoogle Scholar
  288. Woodcock KA, Oliver C, Humphreys GW (2009b) Task-switching deficits and repetitive behaviour in genetic neurodevelopmental disorders: data from children with Prader–Willi syndrome chromosome 15 q11–q13 deletion and boys with Fragile X syndrome. Cogn Neuropsychol 26:172–194PubMedGoogle Scholar
  289. Woodcock KA, Oliver C, Humphreys GW (2009c) Associations between repetitive questioning, resistance to change, temper outbursts and anxiety in Prader–Willi and Fragile-X syndromes. J Intellect Disabil Res 53:265–278PubMedGoogle Scholar
  290. Wu CC, Shete S (2005) Analysis of genes for alcoholism using two-disease-locus models. BMC Genet 6(Suppl 1):S149PubMedGoogle Scholar
  291. Wu SN, Gao R, Xing QH, Li HF, Shen YF, Gu NF, Feng GY, He L (2006) Association of DRD2 polymorphisms and chlorpromazine-induced extrapyramidal syndrome in Chinese schizophrenic patients. Acta Pharmacol Sin 27:966–970PubMedGoogle Scholar
  292. Xu K, Lichtermann D, Lipsky RH, Franke P, Liu X, Hu Y, Cao L, Schwab SG, Wildenauer DB, Bau CH, Ferro E, Astor W, Finch T, Terry J, Taubman J, Maier W, Goldman D (2004) Association of specific haplotypes of D2 dopamine receptor gene with vulnerability to heroin dependence in 2 distinct populations. Arch Gen Psychiatry 61:597–606PubMedGoogle Scholar
  293. Xu B, Woodroffe A, Rodriguez-Murillo L, Roos JL, van Rensburg EJ, Abecasis GR, Gogos JA, Karayiorgou M (2009) Elucidating the genetic architecture of familial schizophrenia using rare copy number variant and linkage scans. Proc Natl Acad Sci USA 106:16746–16751PubMedGoogle Scholar
  294. Yagnik CS (2006) Waist-hip ratio: a thrifty phenotype? Natl Med J India 19:200–201PubMedGoogle Scholar
  295. Yang JZ, Si TM, Ruan Y, Ling YS, Han YH, Wang XL, Zhou M, Zhang HY, Kong QM, Liu C, Ju GZ, Shu L, Ma DL, Zhang D (2003) Association study of neureglin 1 gene with schizophrenia. Mol Psychiatry 8:706–709PubMedGoogle Scholar
  296. Yang BZ, Kranzler HR, Zhao H, Gruen JR, Luo X, Gelernter J (2008) Haplotypic variants in DRD2, ANKK1, TTC12, and NCAM1 are associated with comorbid alcohol and drug dependence. Alcohol Clin Exp Res 32:2117–2127PubMedGoogle Scholar
  297. Zahm DS, Heimer L (1993) Specificity in the efferent projections of the nucleus accumbens in the rat: comparison of the rostral pole projection patterns with those of the core and shell. J Comp Neurol 327:220–232PubMedGoogle Scholar
  298. Zavitsanou K, Cranney J, Richardson R (1999) Dopamine antagonists in the orbital prefrontal cortex reduce prepulse inhibition of the acoustic startle response in the rat. Pharmacol Biochem Behav 63:55–61PubMedGoogle Scholar
  299. Zhang TY, Meaney MJ (2010) Epigenetics and the environmental regulation of the genome and its function. Annu Rev Psychol 61:439–466PubMedGoogle Scholar
  300. Zhou W (2010) Normalizing drug-induced neuronal plasticity in nucleus accumbens weakens enduring drug-seeking behavior. Neuropsychopharmacology 35:352–353PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Trevor Archer
    • 1
  • Richard J. Beninger
    • 2
  • Tomas Palomo
    • 3
  • Richard M. Kostrzewa
    • 4
  1. 1.Department of PsychologyUniversity of GothenburgGothenburgSweden
  2. 2.Departments of Psychology and PsychiatryQueen’s UniversityKingstonCanada
  3. 3.Servicio PsiquitricoHospital UniversitarioMadridSpain
  4. 4.Department of Pharmacology, Quillen College of MedicineEast Tennessee State UniversityJohnson CityUSA

Personalised recommendations