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Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances

Molecular Psychiatry volume 13, pages 786–799 (2008)Cite this article

Abstract

Hyperactivity of corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus (PVN) of the hypothalamus is a prominent feature in depression and may be important in the etiology of this disease. The activity of the CRF neurons in the stress response is modulated by a number of factors that stimulate or inhibit CRF expression, including (1) corticosteroid receptors and their chaperones, heat shock proteins 70 and 90, (2) sex hormone receptors, (3) CRF receptors 1 (CRFR1) and 2, (4) cytokines interleukin 1-β and tumor necrosis factor-α, (5) neuropeptides and receptors, vasopressin (AVP), AVP receptor 1a (AVPR1A) and oxytocin and (6) transcription factor cAMP-response element-binding protein. We hypothesized that, in depression, the transcript levels of those genes that are involved in the activation of the hypothalamo–pituitary–adrenal (HPA) axis are upregulated, whereas the transcript levels of the genes involved in the inhibition of the HPA axis are downregulated. We performed laser microdissection and real-time PCR in the PVN and as a control in the supraoptic nucleus. Snap-frozen post-mortem hypothalami of seven depressed and seven matched controls were used. We found significantly increased CRF mRNA levels in the PVN of the depressed patients. This was accompanied by a significantly increased expression of four genes that are involved in the activation of CRF neurons, that is, CRFR1, estrogen receptor-α, AVPR1A and mineralocorticoid receptor, while the expression of the androgen receptor mRNA involved in the inhibition of CRF neurons was decreased significantly. These findings raise the possibility that a disturbed balance in the production of receptors may contribute to the activation of the HPA axis in depression.

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References

  1. Bao AM, Meynen G, Swaab DF . The stress system in depression and neurodegeneration: focus on the human hypothalamus. Brain Res Rev 2008; 57: 531–553.

    Article  CAS  PubMed  Google Scholar 

  2. Nemeroff CB . The corticotropin-releasing factor (CRF) hypothesis of depression: new findings and new directions. Mol Psychiatry 1996; 1: 336–342.

    CAS  PubMed  Google Scholar 

  3. Holsboer F . The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 2000; 23: 477–501.

    Article  CAS  PubMed  Google Scholar 

  4. Raadsheer FC, Hoogendijk WJ, Stam FC, Tilders FJ, Swaab DF . Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients. Neuroendocrinology 1994; 60: 436–444.

    Article  CAS  PubMed  Google Scholar 

  5. Raadsheer FC, van Heerikhuize JJ, Lucassen PJ, Hoogendijk WJ, Tilders FJ, Swaab DF . Corticotropin-releasing hormone mRNA levels in the paraventricular nucleus of patients with Alzheimer's disease and depression. Am J Psychiatry 1995; 152: 1372–1376.

    Article  CAS  PubMed  Google Scholar 

  6. Holsboer F . Stress, hypercortisolism and corticosteroid receptors in depression: implications for therapy. J Affect Disord 2001; 62: 77–91.

    Article  CAS  PubMed  Google Scholar 

  7. Liu Z, Zhu F, Wang G, Xiao Z, Wang H, Tang J et al. Association of corticotropin-releasing hormone receptor1 gene SNP and haplotype with major depression. Neurosci Lett 2006; 404: 358–362.

    Article  CAS  PubMed  Google Scholar 

  8. Wasserman D, Sokolowski M, Rozanov V, Wasserman J . The CRHR1 gene: a marker for suicidality in depressed males exposed to low stress. Genes Brain Behav 2008; 7: 14–19.

    CAS  PubMed  Google Scholar 

  9. Heuser I, Bissette G, Dettling M, Schweiger U, Gotthardt U, Schmider J et al. Cerebrospinal fluid concentrations of corticotropin-releasing hormone, vasopressin, and somatostatin in depressed patients and healthy controls: response to amitriptyline treatment. Depress Anxiety 1998; 8: 71–79.

    Article  CAS  PubMed  Google Scholar 

  10. Stenzel-Poore MP, Heinrichs SC, Rivest S, Koob GF, Vale WW . Overproduction of corticotropin-releasing factor in transgenic mice: a genetic model of anxiogenic behavior. J Neurosci 1994; 14 (5 Part 1): 2579–2584.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Grammatopoulos DK, Chrousos GP . Functional characteristics of CRH receptors and potential clinical applications of CRH-receptor antagonists. Trends Endocrinol Metab 2002; 13: 436–444.

    Article  CAS  PubMed  Google Scholar 

  12. Keck ME, Holsboer F . Hyperactivity of CRH neuronal circuits as a target for therapeutic interventions in affective disorders. Peptides 2001; 22: 835–844.

    Article  CAS  PubMed  Google Scholar 

  13. Ruhe HG, Mason NS, Schene AH . Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies. Mol Psychiatry 2007; 12: 331–359.

    Article  CAS  PubMed  Google Scholar 

  14. Swaab DF, Fliers E, Hoogendijk WJ, Veltman DJ, Zhou JN . Interaction of prefrontal cortical and hypothalamic systems in the pathogenesis of depression. Prog Brain Res 2000; 126: 369–396.

    Article  CAS  PubMed  Google Scholar 

  15. Reyes BA, Valentino RJ, Xu G, Van Bockstaele EJ . Hypothalamic projections to locus coeruleus neurons in rat brain. Eur J Neurosci 2005; 22: 93–106.

    Article  PubMed  Google Scholar 

  16. de Kloet ER, Derijk RH, Meijer OC . Therapy insight: is there an imbalanced response of mineralocorticoid and glucocorticoid receptors in depression? Nat Clin Pract Endocrinol Metab 2007; 3: 168–179.

    Article  CAS  PubMed  Google Scholar 

  17. Young EA, Lopez JF, Murphy-Weinberg V, Watson SJ, Akil H . Mineralocorticoid receptor function in major depression. Arch Gen Psychiatry 2003; 60: 24–28.

    Article  CAS  PubMed  Google Scholar 

  18. Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM . Neurobiology of depression. Neuron 2002; 34: 13–25.

    Article  CAS  PubMed  Google Scholar 

  19. Miller DB, O’Callaghan JP . Aging, stress and the hippocampus. Ageing Res Rev 2005; 4: 123–140.

    Article  CAS  PubMed  Google Scholar 

  20. Trapp T, Rupprecht R, Castren M, Reul JM, Holsboer F . Heterodimerization between mineralocorticoid and glucocorticoid receptor: a new principle of glucocorticoid action in the CNS. Neuron 1994; 13: 1457–1462.

    Article  CAS  PubMed  Google Scholar 

  21. Muller MB, Wurst W . Getting closer to affective disorders: the role of CRH receptor systems. Trends Mol Med 2004; 10: 409–415.

    Article  PubMed  CAS  Google Scholar 

  22. Imaki T, Katsumata H, Miyata M, Naruse M, Imaki J, Minami S . Expression of corticotropin-releasing hormone type 1 receptor in paraventricular nucleus after acute stress. Neuroendocrinology 2001; 73: 293–301.

    Article  CAS  PubMed  Google Scholar 

  23. Valdez GR, Zorrilla EP, GF K . Homeostasis within the corticotropin-releasing factor system via CRF2 receptor activation: a novel approach for the treatment of anxiety. Drug Dev Res 2005; 65: 205–215.

    Article  CAS  Google Scholar 

  24. Meynen G, Unmehopa UA, van Heerikhuize JJ, Hofman MA, Swaab DF, Hoogendijk WJ . Increased arginine vasopressin mRNA expression in the human hypothalamus in depression: a preliminary report. Biol Psychiatry 2006; 60: 892–895.

    Article  CAS  PubMed  Google Scholar 

  25. Wigger A, Sanchez MM, Mathys KC, Ebner K, Frank E, Liu D et al. Alterations in central neuropeptide expression, release, and receptor binding in rats bred for high anxiety: critical role of vasopressin. Neuropsychopharmacology 2004; 29: 1–14.

    Article  CAS  PubMed  Google Scholar 

  26. Meynen G, Unmehopa UA, Hofman MA, Swaab DF, Hoogendijk WJ . Hypothalamic oxytocin mRNA expression and melancholic depression. Mol Psychiatry 2007; 12: 118–119.

    Article  CAS  PubMed  Google Scholar 

  27. Legradi G, Holzer D, Kapcala LP, Lechan RM . Glucocorticoids inhibit stress-induced phosphorylation of CREB in corticotropin-releasing hormone neurons of the hypothalamic paraventricular nucleus. Neuroendocrinology 1997; 66: 86–97.

    Article  CAS  PubMed  Google Scholar 

  28. Bao AM, Hestiantoro A, Van Someren EJ, Swaab DF, Zhou JN . Colocalization of corticotropin-releasing hormone and oestrogen receptor-alpha in the paraventricular nucleus of the hypothalamus in mood disorders. Brain 2005; 128 (Part 6): 1301–1313.

    Article  PubMed  Google Scholar 

  29. Bao AM, Fischer DF, Wu YH, Hol EM, Balesar R, Unmehopa UA et al. A direct androgenic involvement in the expression of human corticotropin-releasing hormone. Mol Psychiatry 2006; 11: 567–576.

    Article  CAS  PubMed  Google Scholar 

  30. Huitinga I, van der Cammen M, Salm L, Erkut Z, van Dam A, Tilders F et al. IL-1beta immunoreactive neurons in the human hypothalamus: reduced numbers in multiple sclerosis. J Neuroimmunol 2000; 107: 8–20.

    Article  CAS  PubMed  Google Scholar 

  31. Himmerich H, Binder EB, Kunzel HE, Schuld A, Lucae S, Uhr M et al. Successful antidepressant therapy restores the disturbed interplay between TNF-alpha system and HPA axis. Biol Psychiatry 2006; 60: 882–888.

    Article  CAS  PubMed  Google Scholar 

  32. Kuno R, Yoshida Y, Nitta A, Nabeshima T, Wang J, Sonobe Y et al. The role of TNF-alpha and its receptors in the production of NGF and GDNF by astrocytes. Brain Res 2006; 1116: 12–18.

    Article  CAS  PubMed  Google Scholar 

  33. Tissing WJ, Meijerink JP, den Boer ML, Brinkhof B, Pieters R . mRNA expression levels of (co)chaperone molecules of the glucocorticoid receptor are not involved in glucocorticoid resistance in pediatric ALL. Leukemia 2005; 19: 727–733.

    Article  CAS  PubMed  Google Scholar 

  34. Braak H, Braak E . Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol (Berl) 1991; 82: 239–259.

    Article  CAS  Google Scholar 

  35. van de Nes JA, Kamphorst W, Ravid R, Swaab DF . Comparison of beta-protein/A4 deposits and Alz-50-stained cytoskeletal changes in the hypothalamus and adjoining areas of Alzheimer's disease patients: amorphic plaques and cytoskeletal changes occur independently. Acta Neuropathol (Berl) 1998; 96: 129–138.

    Article  CAS  Google Scholar 

  36. Koning N, Bo L, Hoek RM, Huitinga I . Downregulation of macrophage inhibitory molecules in multiple sclerosis lesions. Ann Neurol 2007; 62: 504–514.

    Article  CAS  PubMed  Google Scholar 

  37. Kamphuis W, Schneemann A, van Beek LM, Smit AB, Hoyng PF, Koya E . Prostanoid receptor gene expression profile in human trabecular meshwork: a quantitative real-time PCR approach. Invest Ophthalmol Vis Sci 2001; 42: 3209–3215.

    CAS  PubMed  Google Scholar 

  38. 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: RESEARCH0034.1-0034.11.

    Article  Google Scholar 

  39. Dheda K, Huggett JF, Bustin SA, Johnson MA, Rook G, Zumla A . Validation of housekeeping genes for normalizing RNA expression in real-time PCR. Biotechniques 2004; 37: 112–114, 116, 118–119.

    Article  CAS  PubMed  Google Scholar 

  40. Huggett J, Dheda K, Bustin S, Zumla A . Real-time RT-PCR normalisation; strategies and considerations. Genes Immun 2005; 6: 279–284.

    Article  CAS  PubMed  Google Scholar 

  41. Bustin SA, Benes V, Nolan T, Pfaffl MW . Quantitative real-time RT-PCR—a perspective. J Mol Endocrinol 2005; 34: 597–601.

    Article  CAS  PubMed  Google Scholar 

  42. Tricarico C, Pinzani P, Bianchi S, Paglierani M, Distante V, Pazzagli M et al. Quantitative real-time reverse transcription polymerase chain reaction: normalization to rRNA or single housekeeping genes is inappropriate for human tissue biopsies. Anal Biochem 2002; 309: 293–300.

    Article  CAS  PubMed  Google Scholar 

  43. Elberg G, Elberg D, Logan CJ, Chen L, Turman MA . Limitations of commonly used internal controls for real-time RT-PCR analysis of renal epithelial-mesenchymal cell transition. Nephron Exp Nephrol 2006; 102: e113–e122.

    Article  CAS  PubMed  Google Scholar 

  44. Batschelet . Circular Statistics in Biology. Academic Press: New York, 1981.

    Google Scholar 

  45. Merali Z, Kent P, Du L, Hrdina P, Palkovits M, Faludi G et al. Corticotropin-releasing hormone, arginine vasopressin, gastrin-releasing peptide, and neuromedin B alterations in stress-relevant brain regions of suicides and control subjects. Biol Psychiatry 2006; 59: 594–602.

    Article  CAS  PubMed  Google Scholar 

  46. Mansi JA, Rivest S, Drolet G . Regulation of corticotropin-releasing factor type 1 (CRF1) receptor messenger ribonucleic acid in the paraventricular nucleus of rat hypothalamus by exogenous CRF. Endocrinology 1996; 137: 4619–4629.

    Article  CAS  PubMed  Google Scholar 

  47. Imaki T, Naruse M, Harada S, Chikada N, Imaki J, Onodera H et al. Corticotropin-releasing factor up-regulates its own receptor mRNA in the paraventricular nucleus of the hypothalamus. Brain Res Mol Brain Res 1996; 38: 166–170.

    Article  CAS  PubMed  Google Scholar 

  48. Silverman AJ, Hou-Yu A, Chen WP . Corticotropin-releasing factor synapses within the paraventricular nucleus of the hypothalamus. Neuroendocrinology 1989; 49: 291–299.

    Article  CAS  PubMed  Google Scholar 

  49. Papiol S, Arias B, Gasto C, Gutierrez B, Catalan R, Fananas L . Genetic variability at HPA axis in major depression and clinical response to antidepressant treatment. J Affect Disord 2007; 104: 83–97.

    Article  CAS  PubMed  Google Scholar 

  50. Kishimoto T, Radulovic J, Radulovic M, Lin CR, Schrick C, Hooshmand F et al. Deletion of crhr2 reveals an anxiolytic role for corticotropin-releasing hormone receptor-2. Nat Genet 2000; 24: 415–419.

    Article  CAS  PubMed  Google Scholar 

  51. Kunzel HE, Zobel AW, Nickel T, Ackl N, Uhr M, Sonntag A et al. Treatment of depression with the CRH-1-receptor antagonist R121919: endocrine changes and side effects. J Psychiatr Res 2003; 37: 525–533.

    Article  PubMed  Google Scholar 

  52. Zubenko GS, Maher B, Hughes III HB, Zubenko WN, Stiffler JS, Kaplan BB et al. Genome-wide linkage survey for genetic loci that influence the development of depressive disorders in families with recurrent, early-onset, major depression. Am J Med Genet B Neuropsychiatr Genet 2003; 123: 1–18.

    Article  Google Scholar 

  53. Nicholson RC, King BR, Smith R . Complex regulatory interactions control CRH gene expression. Front Biosci 2004; 9: 32–39.

    Article  CAS  PubMed  Google Scholar 

  54. Wolfl S, Martinez C, Majzoub JA . Inducible binding of cyclic adenosine 3′,5′-monophosphate (cAMP)-responsive element binding protein (CREB) to a cAMP-responsive promoter in vivo. Mol Endocrinol 1999; 13: 659–669.

    CAS  PubMed  Google Scholar 

  55. DeRijk RH, Schaaf M, Stam FJ, de Jong IE, Swaab DF, Ravid R et al. Very low levels of the glucocorticoid receptor beta isoform in the human hippocampus as shown by Taqman RT-PCR and immunocytochemistry. Brain Res Mol Brain Res 2003; 116: 17–26.

    Article  CAS  PubMed  Google Scholar 

  56. de Kloet ER . Hormones, brain and stress. Endocr Regul 2003; 37: 51–68.

    CAS  PubMed  Google Scholar 

  57. Cole RL, Sawchenko PE . Neurotransmitter regulation of cellular activation and neuropeptide gene expression in the paraventricular nucleus of the hypothalamus. J Neurosci 2002; 22: 959–969.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Han F, Ozawa H, Matsuda K, Nishi M, Kawata M . Colocalization of mineralocorticoid receptor and glucocorticoid receptor in the hippocampus and hypothalamus. Neurosci Res 2005; 51: 371–381.

    Article  CAS  PubMed  Google Scholar 

  59. Han F, Ozawa H, Matsuda KI, Lu H, De Kloet ER, Kawata M . Changes in the expression of corticotrophin-releasing hormone, mineralocorticoid receptor and glucocorticoid receptor mRNAs in the hypothalamic paraventricular nucleus induced by fornix transection and adrenalectomy. J Neuroendocrinol 2007; 19: 229–238.

    Article  CAS  PubMed  Google Scholar 

  60. Webster MJ, Knable MB, O'Grady J, Orthmann J, Weickert CS . Regional specificity of brain glucocorticoid receptor mRNA alterations in subjects with schizophrenia and mood disorders. Mol Psychiatry 2002; 7: 985–994, 924.

    Article  CAS  PubMed  Google Scholar 

  61. Xing GQ, Russell S, Webster MJ, Post RM . Decreased expression of mineralocorticoid receptor mRNA in the prefrontal cortex in schizophrenia and bipolar disorder. Int J Neuropsychopharmacol 2004; 7: 143–153.

    Article  CAS  PubMed  Google Scholar 

  62. Shen WW, Liu HC, Yang YY, Lin CY, Chen KP, Yeh TS et al. Anti-heat shock protein 90 is increased in acute mania. Aust N Z J Psychiatry 2006; 40: 712–716.

    Article  PubMed  Google Scholar 

  63. Shimizu S, Nomura K, Ujihara M, Sakamoto K, Shibata H, Suzuki T et al. An allele-specific abnormal transcript of the heat shock protein 70 gene in patients with major depression. Biochem Biophys Res Commun 1996; 219: 745–752.

    Article  CAS  PubMed  Google Scholar 

  64. Geng Y-G, Su Q-R, Su L-Y, Chen Q, Ren G-Y, Shen S-Q et al. Comparison of the polymorphisms of androgen receptor gene and estrogen alpha and beta gene between adolescent females with first-onset major depressive disorder and controls. Int J Neurosci 2007; 117: 539–547.

    Article  CAS  PubMed  Google Scholar 

  65. Vamvakopoulos NC, Chrousos GP . Evidence of direct estrogenic regulation of human corticotropin-releasing hormone gene expression. Potential implications for the sexual dimophism of the stress response and immune/inflammatory reaction. J Clin Invest 1993; 92: 1896–1902.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Paech K, Webb P, Kuiper GG, Nilsson S, Gustafsson J, Kushner PJ et al. Differential ligand activation of estrogen receptors ERalpha and ERbeta at AP1 sites. Science 1997; 277: 1508–1510.

    Article  CAS  PubMed  Google Scholar 

  67. Osterlund MK, Gustafsson JA, Keller E, Hurd YL . Estrogen receptor beta (ERbeta) messenger ribonucleic acid (mRNA) expression within the human forebrain: distinct distribution pattern to ERalpha mRNA. J Clin Endocrinol Metab 2000; 85: 3840–3846.

    CAS  PubMed  Google Scholar 

  68. Lund TD, Munson DJ, Haldy ME, Handa RJ . Androgen inhibits, while oestrogen enhances, restraint-induced activation of neuropeptide neurones in the paraventricular nucleus of the hypothalamus. J Neuroendocrinol 2004; 16: 272–278.

    Article  CAS  PubMed  Google Scholar 

  69. Bodo C, Rissman EF . New roles for estrogen receptor beta in behavior and neuroendocrinology. Front Neuroendocrinol 2006; 27: 217–232.

    Article  CAS  PubMed  Google Scholar 

  70. Besedovsky HO, del Rey A . Immune-neuro-endocrine interactions: facts and hypotheses. Endocr Rev 1996; 17: 64–102.

    Article  CAS  PubMed  Google Scholar 

  71. Hayley S, Poulter MO, Merali Z, Anisman H . The pathogenesis of clinical depression: stressor- and cytokine-induced alterations of neuroplasticity. Neuroscience 2005; 135: 659–678.

    Article  CAS  PubMed  Google Scholar 

  72. Berkenbosch F, van Oers J, del Rey A, Tilders F, Besedovsky H . Corticotropin-releasing factor-producing neurons in the rat activated by interleukin-1. Science 1987; 238: 524–526.

    Article  CAS  PubMed  Google Scholar 

  73. Melik Parsadaniantz S, Levin N, Lenoir V, Roberts JL, Kerdelhue B . Human interleukin 1 beta: corticotropin releasing factor and ACTH release and gene expression in the male rat: in vivo and in vitro studies. J Neurosci Res 1994; 37: 675–682.

    Article  CAS  PubMed  Google Scholar 

  74. O'Brien SM, Scott LV, Dinan TG . Cytokines: abnormalities in major depression and implications for pharmacological treatment. Hum Psychopharmacol 2004; 19: 397–403.

    Article  CAS  PubMed  Google Scholar 

  75. Hurbin A, Boissin-Agasse L, Orcel H, Rabie A, Joux N, Desarmenien MG et al. The V1a and V1b, but not V2, vasopressin receptor genes are expressed in the supraoptic nucleus of the rat hypothalamus, and the transcripts are essentially colocalized in the vasopressinergic magnocellular neurons. Endocrinology 1998; 139: 4701–4707.

    Article  CAS  PubMed  Google Scholar 

  76. Hurbin A, Orcel H, Alonso G, Moos F, Rabie A . The vasopressin receptors colocalize with vasopressin in the magnocellular neurons of the rat supraoptic nucleus and are modulated by water balance. Endocrinology 2002; 143: 456–466.

    Article  CAS  PubMed  Google Scholar 

  77. Pietranera L, Saravia F, Roig P, Lima A, De Nicola AF . Mineralocorticoid treatment upregulates the hypothalamic vasopressinergic system of spontaneously hypertensive rats. Neuroendocrinology 2004; 80: 100–110.

    Article  CAS  PubMed  Google Scholar 

  78. Videbech P, Ravnkilde B . Hippocampal volume and depression: a meta-analysis of MRI studies. Am J Psychiatry 2004; 161: 1957–1966.

    Article  PubMed  Google Scholar 

  79. Zhou JN, Riemersma RF, Unmehopa UA, Hoogendijk WJ, van Heerikhuize JJ, Hofman MA et al. Alterations in arginine vasopressin neurons in the suprachiasmatic nucleus in depression. Arch Gen Psychiatry 2001; 58: 655–662.

    Article  CAS  PubMed  Google Scholar 

  80. Fischer P, Simanyi M, Danielczyk W . Depression in dementia of the Alzheimer type and in multi-infarct dementia. Am J Psychiatry 1990; 147: 1484–1487.

    Article  CAS  PubMed  Google Scholar 

  81. Vingerhoets AJ, Ratliff-Crain J, Jabaaij L, Tilders FJ, Moleman P, Menges LJ . Self-reported stressors, symptom complaints and psychobiological functioning-II: psychoneuroendocrine variables. J Psychosom Res 1996; 40: 191–203.

    Article  CAS  PubMed  Google Scholar 

  82. Nemeroff CB . Dosing the antipsychotic medication olanzapine. J Clin Psychiatry 1997; 58 (Suppl 10): 45–49.

    CAS  PubMed  Google Scholar 

  83. Oldehinkel AJ, van den Berg MD, Flentge F, Bouhuys AL, ter Horst GJ, Ormel J . Urinary free cortisol excretion in elderly persons with minor and major depression. Psychiatry Res 2001; 104: 39–47.

    Article  CAS  PubMed  Google Scholar 

  84. Marar IE, Amico JA . Vasopressin, oxytocin, corticotrophin-releasing factor, and sodium responses during fluoxetine administration in the rat. Endocrine 1998; 8: 13–18.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We are indebted to the Netherlands Brain Bank at the Netherlands Institute for Neuroscience for providing us with the brain material and patient information. We thank Dr Michel A Hofman and Dr Aimin Bao for their statistical assistance, Dr Gerben Meynen for the psychiatric evaluations, Dimitra Kontostavlaki for providing us with the primers and Dr Elly Hol, Nathalie Koning, Dr Yinhui Wu, Tian Zhou, Bart Fisser, Rawien A Balesar, Arja A Sluiter, Unga A Unmehopa, Joop Van Heerikhuize and Paula van Hulten van Run for their technical advice. This investigation was supported by the projects of the Royal Netherlands Academy of Arts and Sciences (06CDP026) and the Natural Science Foundation of China (30530310).

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  1. Netherlands Institute for Neuroscience, Amsterdam, The Netherlands

    S-S Wang, W Kamphuis, I Huitinga & D F Swaab

  2. Hefei National Laboratory for Physical Sciences at Microscale and Department of Neurobiology and Biophysics, Life Science School, University of Science and Technology of China, Hefei, Anhui, PR China

    S-S Wang & J-N Zhou

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Correspondence to J-N Zhou.

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Wang, SS., Kamphuis, W., Huitinga, I. et al. Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances. Mol Psychiatry 13, 786–799 (2008). https://doi.org/10.1038/mp.2008.38

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