Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Patterns of gene expression in the limbic system of suicides with and without major depression

Abstract

The limbic system has consistently been associated with the control of emotions and with mood disorders. The goal of this study was to identify new molecular targets associated with suicide and with major depression using oligonucleotide microarrays in the limbic system (amygdala, hippocampus, anterior cingulate gryus (BA24) and posterior cingulate gyrus (BA29)). A total of 39 subjects were included in this study. They were all male subjects and comprised 26 suicides (depressed suicides=18, non depressed suicides=8) and 13 matched controls. Brain gene expression analysis was carried out on human brain samples using the Affymetrix HG U133 chip set. Differential expression in each of the limbic regions showed group-specific patterns of expression, supporting particular neurobiological mechanisms implicated in suicide and depression. Confirmation of genes selected based on their significance and the interest of their function with reverse transcriptase-polymerase chain reaction showed consistently correlated signals with the results obtained in the microarray analysis. Gene ontology analysis with differentially expressed genes revealed an overrepresentation of transcription and metabolism-related genes in the hippocampus and amygdala, whereas differentially expressed genes in BA24 and BA29 were more generally related to RNA-binding, regulation of enzymatic activity and protein metabolism. Limbic expression patterns were most extensively altered in the hippocampus, where processes related to major depression were associated with altered expression of factors involved with transcription and cellular metabolism. Additionally, our results confirm previous evidence pointing to global alteration of gabaergic neurotransmission in suicide and major depression, offering new avenues in the study and possibly treatment of such complex disorders. Overall, these data suggest that specific patterns of expression in the limbic system contribute to the etiology of depression and suicidal behaviors and highlight the role of the hippocampus in major depression.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

References

  1. Diekstra RFW . The epidemiology of suicide and parasuicide. Acta Psychiatrica Scandinavica 1993; 371: 9–20.

    Article  CAS  PubMed  Google Scholar 

  2. Lesage AD, Boyer R, Grunberg F, Vanier C, Morisette R, Ménard-Buteau C et al. Suicide and mental disorders: a case-control study of young men. Am J Psychiat 1994; 151: 1063–1068.

    Article  CAS  PubMed  Google Scholar 

  3. Mann JJ . The neurobiology of suicide. Nat Med 1998; 4: 25–30.

    Article  CAS  PubMed  Google Scholar 

  4. Gross-Isseroff R, Biegon A, Voet H, Weizman A . The suicide brain: a review of postmortem receptor/transporter binding studies. Neurosci Biobehav Rev 1998; 22: 653–661.

    Article  CAS  PubMed  Google Scholar 

  5. Turecki G . Suicidal behavior: is there a genetic predisposition? Bipolar Disord 2001; 3: 335–349.

    Article  CAS  PubMed  Google Scholar 

  6. Drevets WC . Neuroimaging abnormalities in the amygdala in mood disorders. Ann NY Acad Sci 2003; 985: 420–444.

    Article  PubMed  Google Scholar 

  7. Mervaala E, Fohr J, Kononen M, Valkonen-Korhonen M, Vainio P, Partanen K et al. Quantitative MRI of the hippocampus and amygdala in severe depression. Psychol Med 2000; 30: 117–125.

    Article  CAS  PubMed  Google Scholar 

  8. Sheline YI, Gado MH, Price JL . Amygdala core nuclei volumes are decreased in recurrent major depression. Neuroreport 1998; 9: 2023–2028.

    Article  CAS  PubMed  Google Scholar 

  9. Hastings RS, Parsey RV, Oquendo MA, Arango V, Mann JJ . Volumetric analysis of the prefrontal cortex, amygdala, and hippocampus in major depression. Neuropsychopharmacology 2004; 29: 952–959.

    Article  PubMed  Google Scholar 

  10. Rosso IM, Cintron CM, Steingard RJ, Renshaw PF, Young AD, Yurgelun-Todd DA . Amygdala and hippocampus volumes in pediatric major depression. Biol Psychiat 2005; 57: 21–26.

    Article  PubMed  Google Scholar 

  11. Bremner JD, Narayan M, Anderson ER, Staib LH, Miller HL, Charney DS . Hippocampal volume reduction in major depression. Am J Psychiat 2000; 157: 115–118.

    Article  CAS  PubMed  Google Scholar 

  12. Frodl T, Meisenzahl E, Zetzsche T, Bottlender R, Born C, Groll C et al. Enlargement of the amygdala in patients with a first episode of major depression. Biol Psychiat 2002; 51: 708–714.

    Article  PubMed  Google Scholar 

  13. Frodl T, Meisenzahl EM, Zetzsche T, Born C, Jager M, Groll C et al. Larger amygdala volumes in first depressive episode as compared to recurrent major depression and healthy control subjects. Biol Psychiat 2003; 53: 338–344.

    Article  PubMed  Google Scholar 

  14. Lange C, Irle E . Enlarged amygdala volume and reduced hippocampal volume in young women with major depression. Psychol Med 2004; 34: 1059–1064.

    Article  CAS  PubMed  Google Scholar 

  15. Frodl T, Meisenzahl EM, Zetzsche T, Born C, Groll C, Jager M et al. Hippocampal changes in patients with a first episode of major depression. Am J Psychiat 2002; 159: 1112–1118.

    Article  PubMed  Google Scholar 

  16. Sheline YI, Sanghavi M, Mintun MA, Gado MH . Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neurosci 1999; 19: 5034–5043.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sheline YI, Wang PW, Gado MH, Csernansky JG, Vannier MW . Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci USA 1996; 93: 3908–3913.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Steffens DC, Byrum CE, McQuoid DR, Greenberg DL, Payne ME, Blitchington TF et al. Hippocampal volume in geriatric depression. Biol Psychiat 2000; 48: 301–309.

    Article  CAS  PubMed  Google Scholar 

  19. Vythilingam M, Heim C, Newport J, Miller AH, Anderson E, Bronen R et al. Childhood trauma associated with smaller hippocampal volume in women with major depression. Am J Psychiat 2002; 159: 2072–2080.

    Article  PubMed  Google Scholar 

  20. MacQueen GM, Campbell S, McEwen BS, Macdonald K, Amano S, Joffe RT et al. Course of illness, hippocampal function, and hippocampal volume in major depression. Proc Natl Acad Sci USA 2003; 100: 1387–1392.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ashtari M, Greenwald BS, Kramer-Ginsberg E, Hu J, Wu H, Patel M et al. Hippocampal/amygdala volumes in geriatric depression. Psychol Med 1999; 29: 629–638.

    Article  CAS  PubMed  Google Scholar 

  22. Vakili K, Pillay SS, Lafer B, Fava M, Renshaw PF, Bonello-Cintron CM et al. Hippocampal volume in primary unipolar major depression: a magnetic resonance imaging study. Biol Psychiat 2000; 47: 1087–1090.

    Article  CAS  PubMed  Google Scholar 

  23. Vythilingam M, Vermetten E, Anderson GM, Luckenbaugh D, Anderson ER, Snow J et al. Hippocampal volume, memory, and cortisol status in major depressive disorder: effects of treatment. Biol Psychiat 2004; 56: 101–112.

    Article  CAS  PubMed  Google Scholar 

  24. Botteron KN, Raichle ME, Drevets WC, Heath AC, Todd RD . Volumetric reduction in left subgenual prefrontal cortex in early onset depression. Biol Psychiat 2002; 51: 342–344.

    Article  PubMed  Google Scholar 

  25. Bremner JD, Vythilingam M, Vermetten E, Nazeer A, Adil J, Khan S et al. Reduced volume of orbitofrontal cortex in major depression. Biol Psychiat 2002; 51: 273–279.

    Article  PubMed  Google Scholar 

  26. Drevets WC . Prefrontal cortical-amygdalar metabolism in major depression. Ann NY Acad Sci 1999; 877: 614–637.

    Article  CAS  PubMed  Google Scholar 

  27. Kegeles LS, Malone KM, Slifstein M, Ellis SP, Xanthopoulos E, Keilp JG et al. Response of cortical metabolic deficits to serotonergic challenge in familial mood disorders. Am J Psychiat 2003; 160: 76–82.

    Article  PubMed  Google Scholar 

  28. Mayberg HS, Liotti M, Brannan SK, McGinnis S, Mahurin RK, Jerabek PA et al. Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. Am J Psychiat 1999; 156: 675–682.

    CAS  PubMed  Google Scholar 

  29. Buchsbaum MS, Wu J, Siegel BV, Hackett E, Trenary M, Abel L et al. Effect of sertraline on regional metabolic rate in patients with affective disorder. Biol Psychiat 1997; 41: 15–22.

    Article  CAS  PubMed  Google Scholar 

  30. Goodwin GM, Austin MP, Dougall N, Ross M, Murray C, O’Carroll RE et al. State changes in brain activity shown by the uptake of 99mTc-exametazime with single photon emission tomography in major depression before and after treatment. J Affect Disord 1993; 29: 243–253.

    Article  CAS  PubMed  Google Scholar 

  31. Goldapple K, Segal Z, Garson C, Lau M, Bieling P, Kennedy S et al. Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy. Arch Gen Psychiatry 2004; 61: 34–41.

    Article  PubMed  Google Scholar 

  32. Swaab DF, Bao AM, Lucassen PJ . The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev 2005; 4: 141–194.

    Article  CAS  PubMed  Google Scholar 

  33. Pandey GN, Dwivedi Y, Rizavi HS, Ren X, Pandey SC, Pesold C et al. Higher expression of serotonin 5-HT(2A) receptors in the postmortem brains of teenage suicide victims. Am J Psychiat 2002; 159: 419–429.

    Article  PubMed  Google Scholar 

  34. Dwivedi Y, Rao JS, Rizavi HS, Kotowski J, Conley RR, Roberts RC et al. Abnormal expression and functional characteristics of cyclic adenosine monophosphate response element binding protein in postmortem brain of suicide subjects. Arch Gen Psychiatry 2003; 60: 273–282.

    Article  CAS  PubMed  Google Scholar 

  35. Dwivedi Y, Rizavi HS, Roberts RC, Conley RC, Tamminga CA, Pandey GN . Reduced activation and expression of ERK1/2 MAP kinase in the post-mortem brain of depressed suicide subjects. J Neurochem 2001; 77: 916–928.

    Article  CAS  PubMed  Google Scholar 

  36. Pandey GN, Dwivedi Y, Rizavi HS, Ren X, Conley RR . Decreased catalytic activity and expression of protein kinase C isozymes in teenage suicide victims: a postmortem brain study. Arch Gen Psychiatry 2004; 61: 685–693.

    Article  CAS  PubMed  Google Scholar 

  37. Rosel P, Arranz B, Urretavizcaya M, Oros M, San L, Navarro MA . Altered 5-HT2A and 5-HT4 postsynaptic receptors and their intracellular signalling systems IP3 and cAMP in brains from depressed violent suicide victims. Neuropsychobiology 2004; 49: 189–195.

    Article  CAS  PubMed  Google Scholar 

  38. Mann JJ, Brent DA, Arango V . The neurobiology and genetics of suicide and attempted suicide: a focus on the serotonergic system. Neuropsychopharmacology 2001; 24: 467–477.

    Article  CAS  PubMed  Google Scholar 

  39. Baldessarini RJ, Hennen J . Genetics of suicide: an overview. Harv Rev Psychiatry 2004; 12: 1–13.

    PubMed  Google Scholar 

  40. Swift RG, Sadler DB, Swift M . Psychiatric findings in Wolfram syndrome homozygotes. The Lancet 1990; 336: 667–669.

    Article  CAS  Google Scholar 

  41. Swift M, Swift RG . Wolframin mutations and hospitalization for psychiatric illness. Mol Psychiat 2005; 10: 799–803.

    Article  CAS  Google Scholar 

  42. Sequeira A, Kim C, Seguin M, Lesage A, Chawky N, Desautels A et al. Wolfram syndrome and suicide: Evidence for a role of WFS1 in suicidal and impulsive behavior. Am J Med Genet B Neuropsychiatr Genet 2003; 119: 108–113.

    Article  Google Scholar 

  43. Kunugi H, Hashimoto R, Yoshida M, Tatsumi M, Kamijima K . A missense polymorphism (S205L) of the low-affinity neurotrophin receptor p75NTR gene is associated with depressive disorder and attempted suicide. Am J Med Genet B Neuropsychiatr Genet 2004; 129: 44–46.

    Article  Google Scholar 

  44. Zhang S, Amstein T, Shen J, Brush FR, Gershenfeld HK . Molecular correlates of emotional learning using genetically selected rat lines. Genes Brain Behav 2005; 4: 99–109.

    Article  CAS  PubMed  Google Scholar 

  45. Simard LR, Prescott G, Rochette C, Morgan K, Lemieux B, Mathieu J et al. Linkage disequilibrium analysis of childhood-onset spinal muscular atrophy (SMA) in the French-Canadian population. Hum Mol Genet 1994; 3: 459–463.

    Article  CAS  PubMed  Google Scholar 

  46. Kim CD, Seguin M, Therrien N, Riopel G, Chawky N, Lesage AD et al. Familial aggregation of suicidal behavior: a family study of male suicide completers from the general population. Am J Psychiat 2005; 162: 1017–1019.

    Article  PubMed  Google Scholar 

  47. Dennis Jr G, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC et al. DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol 2003; 4: R60.

    Article  PubMed Central  Google Scholar 

  48. Kakiuchi C, Iwamoto K, Ishiwata M, Bundo M, Kasahara T, Kusumi I et al. Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder. Nat Genet 2003; 35: 171–175.

    Article  CAS  PubMed  Google Scholar 

  49. Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P et al. Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 1999; 286: 735–741.

    Article  CAS  PubMed  Google Scholar 

  50. Sequeira A, Gwadry FG, Ffrench-Mullen JM, Canetti L, Gingras Y, Casero Jr RA et al. Implication of SSAT by gene expression and genetic variation in suicide and major depression. Arch Gen Psychiatry 2006; 63: 35–48.

    Article  CAS  PubMed  Google Scholar 

  51. Sibille E, Arango V, Galfalvy HC, Pavlidis P, Erraji-Benchekroun L, Ellis SP et al. Gene expression profiling of depression and suicide in human prefrontal cortex. Neuropsychopharmacology 2004; 29: 351–361.

    Article  CAS  PubMed  Google Scholar 

  52. Malberg JE, Eisch AJ, Nestler EJ, Duman RS . Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 2000; 20: 9104–9110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 2003; 301: 805–809.

    Article  CAS  PubMed  Google Scholar 

  54. Campbell S, Marriott M, Nahmias C, MacQueen GM . Lower hippocampal volume in patients suffering from depression: a meta-analysis. Am J Psychiat 2004; 161: 598–607.

    Article  PubMed  Google Scholar 

  55. Duman RS . Synaptic plasticity and mood disorders. Mol Psychiatry 2002; 7 (Suppl 1): S29–S34.

    Article  CAS  PubMed  Google Scholar 

  56. Manji HK, Drevets WC, Charney DS . The cellular neurobiology of depression. Nat Med 2001; 7: 541–547.

    Article  CAS  PubMed  Google Scholar 

  57. Duman RS, Heninger GR, Nestler EJ . A molecular and cellular theory of depression. Arch Gen Psychiatry 1997; 54: 597–606.

    Article  CAS  PubMed  Google Scholar 

  58. Dwivedi Y, Rao JS, Rizavi HS, Kotowski J, Conley RR, Roberts RC et al. Abnormal expression and functional characteristics of cyclic adenosine monophosphate response element binding protein in postmortem brain of suicide subjects. Arch Gen Psychiatry 2003; 60: 273–282.

    Article  CAS  PubMed  Google Scholar 

  59. Dwivedi Y, Rizavi HS, Shukla PK, Lyons J, Faludi G, Palkovits M et al. Protein kinase A in postmortem brain of depressed suicide victims: altered expression of specific regulatory and catalytic subunits. Biol Psychiat 2004; 55: 234–243.

    Article  CAS  PubMed  Google Scholar 

  60. Aston C, Jiang L, Sokolov BP . Microarray analysis of postmortem temporal cortex from patients with schizophrenia. J Neurosci Res 2004; 77: 858–866.

    Article  CAS  PubMed  Google Scholar 

  61. Aston C, Jiang L, Sokolov BP . Transcriptional profiling reveals evidence for signaling and oligodendroglial abnormalities in the temporal cortex from patients with major depressive disorder. Mol Psychiatry 2005; 10: 309–322.

    Article  CAS  PubMed  Google Scholar 

  62. Choudary PV, Molnar M, Evans SJ, Tomita H, Li JZ, Vawter MP et al. Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression. Proc Natl Acad Sci USA 2005; 102: 15653–15658.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Evans SJ, Choudary PV, Neal CR, Li JZ, Vawter MP, Tomita H et al. Dysregulation of the fibroblast growth factor system in major depression. Proc Natl Acad Sci USA 2004; 101: 15506–15511.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Iwamoto K, Kakiuchi C, Bundo M, Ikeda K, Kato T . Molecular characterization of bipolar disorder by comparing gene expression profiles of postmortem brains of major mental disorders. Mol Psychiatry 2004; 9: 406–416.

    Article  CAS  PubMed  Google Scholar 

  65. Iwamoto K, Bundo M, Kato T . Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis. Hum Mol Genet 2005; 14: 241–253.

    Article  CAS  PubMed  Google Scholar 

  66. Katsel P, Davis KL, Gorman JM, Haroutunian V . Variations in differential gene expression patterns across multiple brain regions in schizophrenia. Schizophr Res 2005; 77: 241–252.

    Article  CAS  PubMed  Google Scholar 

  67. Katsel P, Davis KL, Haroutunian V . Variations in myelin and oligodendrocyte-related gene expression across multiple brain regions in schizophrenia: a gene ontology study. Schizophr Res 2005; 79: 157–173.

    Article  PubMed  Google Scholar 

  68. Altshuler LL, Casanova MF, Goldberg TE, Kleinman JE . The hippocampus and parahippocampus in schizophrenia, suicide, and control brains. Arch Gen Psychiatry 1990; 47: 1029–1034.

    Article  CAS  PubMed  Google Scholar 

  69. Ongur D, Drevets WC, Price JL . Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci USA 1998; 95: 13290–13295.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Sapolsky RM . The possibility of neurotoxicity in the hippocampus in major depression: a primer on neuron death. Biol Psychiat 2000; 48: 755–765.

    Article  CAS  PubMed  Google Scholar 

  71. Dwivedi Y, Rizavi HS, Conley RR, Roberts RC, Tamminga CA, Pandey GN . Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects. Arch Gen Psychiat 2003; 60: 804–815.

    Article  CAS  PubMed  Google Scholar 

  72. Dwivedi Y, Rizavi HS, Conley RR, Pandey GN . ERK MAP kinase signaling in post-mortem brain of suicide subjects: differential regulation of upstream Raf kinases Raf-1 and B-Raf. Mol Psychiatry 2006; 11: 86–98.

    Article  CAS  PubMed  Google Scholar 

  73. Pandey GN, Dwivedi Y, Ren X, Rizavi HS, Roberts RC, Conley RR et al. Altered expression and phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) in postmortem brain of suicide victims with or without depression. J Psychiatr Res 2003; 37: 421–432.

    Article  PubMed  Google Scholar 

  74. Isometsa ET, Henriksson MM, Aro HM, Heikkinen ME, Kuoppasalmi KI, Lonnqvist JK . Suicide in major depression. Am J Psychiatr 1994; 151: 530–536.

    Article  CAS  PubMed  Google Scholar 

  75. Dhossche DM . Toxicology of suicide: touchstone for suicide prevention? Med Sci Monit 2003; 9: SR9–SR19.

    CAS  PubMed  Google Scholar 

  76. Benes FM, Matzilevich D, Burke RE, Walsh J . The expression of proapoptosis genes is increased in bipolar disorder, but not in schizophrenia. Mol Psychiatry 2006; 11: 241–251.

    Article  CAS  PubMed  Google Scholar 

  77. Welle S, Brooks AI, Delehanty JM, Needler N, Thornton CA . Gene expression profile of aging in human muscle. Physiol Genomics 2003; 14: 149–159.

    Article  CAS  PubMed  Google Scholar 

  78. Tusher VG, Tibshirani R, Chu G . Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA 2001; 98: 5116–5121.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Bland JM, Altman DG . Multiple significance tests: the Bonferroni method. BMJ 1995; 310: 170.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Konradi C . Gene expression microarray studies in polygenic psychiatric disorders: Applications and data analysis. Brain Res Brain Res Rev 2005; 50: 142–155.

    Article  CAS  PubMed  Google Scholar 

  81. Konradi C, Eaton M, MacDonald ML, Walsh J, Benes FM, Heckers S . Molecular evidence for mitochondrial dysfunction in bipolar disorder. Arch Gen Psychiatr 2004; 61: 300–308.

    Article  CAS  PubMed  Google Scholar 

  82. Vawter MP, Tomita H, Meng F, Bolstad B, Li J, Evans S et al. Mitochondrial related gene expression changes are sensitive to agonal-pH state. Mol Psychiatry 2006; 11: 663–679.

    Article  CAS  Google Scholar 

  83. Mimmack ML, Ryan M, Baba H, Navarro-Ruiz J, Iritani S, Faull RL et al. Gene expression analysis in schizophrenia: reproducible up-regulation of several members of the apolipoprotein L family located in a high-susceptibility locus for schizophrenia on chromosome 22. Proc Natl Acad Sci USA 2002; 99: 4680–4685.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Mirnics K, Middleton FA, Marquez A, Lewis DA, Levitt P . Molecular characterization of schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex. Neuron 2000; 28: 53–67.

    Article  CAS  PubMed  Google Scholar 

  85. Benes FM, Burke RE, Walsh J, Berretta S, Matzilevich D, Minns M et al. Acute amygdalar activation induces an upregulation of multiple monoamine G protein coupled pathways in rat hippocampus. Mol Psychiatry 2004; 9: 932–945, 895.

    Article  CAS  PubMed  Google Scholar 

  86. Yang G, Gong YD, Gong K, Jiang WL, Kwon E, Wang P et al. Reduced synaptic vesicle density and active zone size in mice lacking amyloid precursor protein (APP) and APP-like protein 2. Neurosci Lett 2005; 384: 66–71.

    Article  CAS  PubMed  Google Scholar 

  87. Pastorino L, Ikin AF, Lamprianou S, Vacaresse N, Revelli JP, Platt K et al. BACE (beta-secretase) modulates the processing of APLP2 in vivo. Mol Cell Neurosci 2004; 25: 642–649.

    Article  CAS  PubMed  Google Scholar 

  88. Ferguson GD, Herschman HR, Storm DR . Reduced anxiety and depression-like behavior in synaptotagmin IV (-/-) mice. Neuropharmacology 2004; 47: 604–611.

    Article  CAS  PubMed  Google Scholar 

  89. Ferguson GD, Wang H, Herschman HR, Storm DR . Altered hippocampal short-term plasticity and associative memory in synaptotagmin IV (-/-) mice. Hippocampus 2004; 14: 964–974.

    Article  CAS  PubMed  Google Scholar 

  90. Rahman S, Li PP, Young LT, Kofman O, Kish SJ, Warsh JJ . Reduced [3H]Cyclic AMP binding in postmortem brain from subjects with Bipolar Affective Disorder. J Neurochem 1997; 68: 297–304.

    Article  CAS  PubMed  Google Scholar 

  91. Abdulla YH, Hamadah K . 3′, 5′ cyclic adenosine monophosphate in depression and mania. The Lancet 1970; 1: 378–381.

    Article  CAS  Google Scholar 

  92. Reiach JS, Li PP, Warsh JJ, Kish SJ, Young LT . Reduced adenylyl cyclase immunolabeling and activity in postmortem temporal cortex of depressed suicide victims. J Affect Disord 1999; 56: 141–151.

    Article  CAS  PubMed  Google Scholar 

  93. Dowlatshahi D, MacQueen GM, Wang JF, Reiach JS, Young LT . G Protein-coupled cyclic AMP signaling in postmortem brain of subjects with mood disorders: effects of diagnosis, suicide, and treatment at the time of death. J Neurochem 1999; 73: 1121–1126.

    Article  CAS  PubMed  Google Scholar 

  94. Odagaki Y, Garcia-Sevilla JA, Huguelet P, La Harpe R, Koyama T, Guimon J . Cyclic AMP-mediated signaling components are upregulated in the prefrontal cortex of depressed suicide victims. Brain Res 2001; 898: 224–231.

    Article  CAS  PubMed  Google Scholar 

  95. Merali Z, Du L, Hrdina P, Palkovits M, Faludi G, Poulter MO 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: 1478–1485.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Petroff OA . GABA and glutamate in the human brain. Neuroscientist 2002; 8: 562–573.

    Article  CAS  PubMed  Google Scholar 

  97. Brambilla P, Perez J, Barale F, Schettini G, Soares JC . GABAergic dysfunction in mood disorders. Mol Psychiatry 2003; 8: 721–737, 715.

    Article  CAS  PubMed  Google Scholar 

  98. Sanacora G, Mason GF, Rothman DL, Behar KL, Hyder F, Petroff OA et al. Reduced cortical gamma-aminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy. Arch Gen Psychiatr 1999; 56: 1043–1047.

    Article  CAS  PubMed  Google Scholar 

  99. Bustin SA, Nolan T . Pitfalls of quantitative real-time reverse-transcription polymerase chain reaction. J Biomol Tech 2004; 15: 155–166.

    PubMed  PubMed Central  Google Scholar 

  100. Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 2002; 3: 1–12.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to G Turecki.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sequeira, A., Klempan, T., Canetti, L. et al. Patterns of gene expression in the limbic system of suicides with and without major depression. Mol Psychiatry 12, 640–655 (2007). https://doi.org/10.1038/sj.mp.4001969

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.mp.4001969

Keywords

This article is cited by

Search

Quick links