人体下丘脑室旁核多基因平衡紊乱与抑郁症
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摘要
下丘脑室旁核(PVN)中的促肾上腺皮质激素释放激素(CRH)神经元活性上调是抑郁症的主要神经生物学特征。因此,CRH在抑郁症的发病机制中到重要的作用。PVN中CRH神经元受以下诸多因素激动或抑制性调节:(ⅰ)糖激素受体GR和盐皮质激素受体MR及其伴侣分子热休克蛋白(HSP)70和HSP90;(ⅱ)雌激素受体ESR和雄激素受体AR;(ⅲ)CRH受体CRHR1和CRHR2;(ⅳ)细胞因子白介素1β(IL1B)和肿瘤坏死因子α(TNFA):(ⅴ)血管加压素(AVP)及其受体AVPR1A、催产素(OXT);(ⅵ)转录因子CREB。
我们假设抑郁症患者下丘脑促进下丘脑-垂体-肾上腺(HPA)轴的基因转录水平上调,而对HPA轴起到抑制作用的基因转录水平下调。我们首次利用激光显微分离技术结合实时定量PCR,在抑郁症(N=7)和正常对照(N=7)人尸检的下丘脑,定量分析这些与CRH活性调控有关的基因转录水平的改变。分析结果发现,抑郁症组下丘脑PVN中CRH转录水平显著增高,伴随着多受体基因转录的改变。其中,这些促进CRH基因表达或者可激活CRH神经元活性的基因,如CRHR1,ESR1,MR,AVPR1A的转录水平比正常组高,而抑制CRH基因表达的AR低于正常组。根据我们的研究结果,提出抑郁症中下丘脑室旁核多受体平衡紊乱假说,可能与抑郁症中HPA轴活性上调有关,对抑郁症发病机制研究提出了新的研究思路,并且为临床治疗提供了新的治疗靶点。
Hyperactivity of corticotropin-releasing hormone(CRH)neurons in the paraventricular nucleus(PVN)of the hypothalamus is a prominent feature in depression and may play a central role in the etiology of this disease.The activity of the CRH neurons in the stress response is modulated by a number of factors that stimulate or inhibit CRH expression,including:(ⅰ)corticosteroid receptors and their chaperones,heat shock proteins(HSP)70 and 90,(ⅱ)sex hormone receptors,(ⅲ) CRH receptorsl(CRHR1)and 2(CRHR2),(ⅳ)cytokines interleukin 1beta(IL1B) and tumor necrosis factor alpha(TNFA),(ⅴ)neuropeptides and receptors,vasopressin (AVP),vasopressin receptor 1 a(AVPR1A)and oxytocin(OXT)and,(ⅵ)transcription factor CREB.
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 micro-dissection and real time PCR in the PVN and as a control in the supraoptic nucleus(SON).Snap frozen postmortem hypothalami of 7 depressed and 7 matched controls were used.We found significantly increased CRH mRNA levels in the PVN of the depressed patients.This was accompanied by a significantly increased expression of 4 genes that are involved in the activation of CRH neurons,i.e.CR.HR1-,estrogen receptor alpha(ESR1), AVPR1A and mineralocorticoid receptor(MR),while the expression of the androgen receptor(AR)mRNA involved in the inhibition of CRH 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.This study indicates new research targets for future work,and may also offer new therapeutic strategies for depressed patients.
我们假设抑郁症患者下丘脑促进下丘脑-垂体-肾上腺(HPA)轴的基因转录水平上调,而对HPA轴起到抑制作用的基因转录水平下调。我们首次利用激光显微分离技术结合实时定量PCR,在抑郁症(N=7)和正常对照(N=7)人尸检的下丘脑,定量分析这些与CRH活性调控有关的基因转录水平的改变。分析结果发现,抑郁症组下丘脑PVN中CRH转录水平显著增高,伴随着多受体基因转录的改变。其中,这些促进CRH基因表达或者可激活CRH神经元活性的基因,如CRHR1,ESR1,MR,AVPR1A的转录水平比正常组高,而抑制CRH基因表达的AR低于正常组。根据我们的研究结果,提出抑郁症中下丘脑室旁核多受体平衡紊乱假说,可能与抑郁症中HPA轴活性上调有关,对抑郁症发病机制研究提出了新的研究思路,并且为临床治疗提供了新的治疗靶点。
Hyperactivity of corticotropin-releasing hormone(CRH)neurons in the paraventricular nucleus(PVN)of the hypothalamus is a prominent feature in depression and may play a central role in the etiology of this disease.The activity of the CRH neurons in the stress response is modulated by a number of factors that stimulate or inhibit CRH expression,including:(ⅰ)corticosteroid receptors and their chaperones,heat shock proteins(HSP)70 and 90,(ⅱ)sex hormone receptors,(ⅲ) CRH receptorsl(CRHR1)and 2(CRHR2),(ⅳ)cytokines interleukin 1beta(IL1B) and tumor necrosis factor alpha(TNFA),(ⅴ)neuropeptides and receptors,vasopressin (AVP),vasopressin receptor 1 a(AVPR1A)and oxytocin(OXT)and,(ⅵ)transcription factor CREB.
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 micro-dissection and real time PCR in the PVN and as a control in the supraoptic nucleus(SON).Snap frozen postmortem hypothalami of 7 depressed and 7 matched controls were used.We found significantly increased CRH mRNA levels in the PVN of the depressed patients.This was accompanied by a significantly increased expression of 4 genes that are involved in the activation of CRH neurons,i.e.CR.HR1-,estrogen receptor alpha(ESR1), AVPR1A and mineralocorticoid receptor(MR),while the expression of the androgen receptor(AR)mRNA involved in the inhibition of CRH 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.This study indicates new research targets for future work,and may also offer new therapeutic strategies for depressed patients.
引文
[1] Antoni, F. A. (1993). "Vasopressinergic control of pituitary adrenocorticotropin secretion comes of age." Front Neuroendocrinol 14(2): 76-122.
[2] Antonijevic, I. A. (2006). "Depressive disorders -- is it time to endorse different pathophysiologies?" Psychoneuroendocrinology 31(1): 1-15.
[3] Bamberger, C. M., A. M. Bamberger, et al. (1995). "Glucocorticoid receptor beta, a potential endogenous inhibitor of glucocorticoid action in humans." J Clin Invest 95(6):2435-41.
[4] Ban, E., G. Milon, et al. (1991). "Receptors for interleukin-1 (alpha and beta) in mouse brain: mapping and neuronal localization in hippocampus." Neuroscience 43(1): 21-30.
[5] Bao, A. M, D. F. Fischer, et al. (2006). "A direct androgenic involvement in the expression of human corticotropin-releasing hormone." Mol Psychiatry 11(6): 567-76.
[6] Bao, A. M., A. Hestiantoro, et al. (2005). "Colocalization of corticotropin-releasing hormone and oestrogen receptor-alpha in the paraventricular nucleus of the hypothalamus in mood disorders." Brain 128(Pt 6): 1301-13.
[7] Bao, A. M, Y. F. Ji, et al. (2004). "Diurnal rhythms of free estradiol and cortisol during the normal menstrual cycle in women with major depression." Horm Behav 45(2):93-102.
[8] Barden, N. (1996). "Modulation of glucocorticoid receptor gene expression by antidepressant drugs." Pharmacopsychiatry 29(1): 12-22.
[9] Belanoff, J. K., A. J. Rothschild, et al. (2002). "An open label trial of C-1073 (mifepristone) for psychotic major depression." Biol Psychiatry 52(5): 386-92.
[10] Benjamin J. Sadock, V. A. S. (2000). "Kaplan & Sadock's Comprehensive Textbook of Psychiatry (2 Volume Set)."
[11] Berkenbosch, F., J. van Oers, et al. (1987). "Corticotropin-releasing factor-producing neurons in the rat activated by interleukin-1." Science 238(4826): 524-6.
[12] Besedovsky, H. O. and A. del Rey (1996). "Immune-neuro-endocrine interactions: facts and hypotheses." Endocr Rev 17(1): 64-102.
[13] Blum, I., M. Lerman, et al. (2004). "Lack of plasma norepinephrine cyclicity, increased estradiol during the follicular phase, and of progesterone and gonadotrophins at ovulation in women with premenstrual syndrome." Neuropsychobiology 50(1): 10-5.
[14] Campagne, D. M. (2004). "The obstetrician and depression during pregnancy." Eur J Obstet Gynecol Reprod Biol 116(2): 125-30.
[15] Capuron, L, P. Hauser, et al. (2002). "Treatment of cytokine-induced depression." Brain Behav Immun 16(5): 575-80.
[16] Carroll, B. J., F. Cassidy, et al. (2007). "Pathophysiology of hypercortisolism in depression." Acta Psychiatr Scand Suppl(433): 90-103.
[17] Checkley, S. (1996). "The neuroendocrinology of depression and chronic stress." Br Med Bull 52(3): 597-617.
[18] Chesnokova, V. and S. Melmed (2002). "Minireview: Neuro-immuno-endocrine modulation of the hypothalamic-pituitary-adrenal (HPA) axis by gpl30 signaling molecules." Endocrinology 143(5): 1571-4.
[19] Chrousos, G. P. (1998). "Stressors, stress, and neuroendocrine integration of the adaptive response. The 1997 Hans Selye Memorial Lecture." Ann N Y Acad Sci 851: 311-35.
[20] Chrousos, G. P., D. J. Torpy, et al. (1998). "Interactions between the hypothalamic-pituitary-adrenal axis and the female reproductive system: clinical implications." Ann Intern Med 129(3): 229-40.
[21] Davydov, D. M., D. Shapiro, et al. (2004). "Moods in everyday situations: effects of menstrual cycle, work, and personality." J Psychosom Res 56(1): 27-33.
[22] de Kloet, E. R. (2000). "Stress in the brain." Eur J Pharmacol 405(1-3): 187-98.
[23] de Kloet, E. R. (2003). "Hormones, brain and stress." Endocr Regul 37(2): 51-68.
[24] de Kloet, E. R., R. H. Derijk, et al. (2007). "Therapy Insight: is there an imbalanced response of mineralocorticoid and glucocorticoid receptors in depression?" Nat Clin Pract Endocrinol Metab 3(2): 168-79.
[25] Deyerle, K. L., J. E. Sims, et al. (1992). "Pattern of IL-1 receptor gene expression suggests role in noninflammatory processes." J Immunol 149(5): 1657-65.
[26] Dorn, L. D., E. S. Burgess, et al. (1997). "The longitudinal course of psychopathology in Cushing's syndrome after correction of hypercortisolism." J Clin Endocrinol Metab 82(3):912-9.
[27] Dudas, B. and I. Merchenthaler (2003). "Topography and associations of leu-enkephalin and luteinizing hormone-releasing hormone neuronal systems in the human diencephalon." J Clin.Endocrinol Metab 88(4): 1842-8.
[28] Erkut, Z. A., C. Pool, et al. (1998). "Glucocorticoids suppress corticotropin-releasing hormone and vasopressin expression in human hypothalamic neurons." J Clin Endocrinol Metab 83(6): 2066-73.
[29] Esch, F., N. Ling, et al. (1984). "Isolation and characterization of the bovine hypothalamic corticotropin-releasing factor." Biochem Biophys Res Commun 122(3):899-905.
[30] Feuerstein, G, S. A. Adelberg, et al. (1982). "Hypothalamic sites for cardiovascular and sympathetic modulation by prostaglandin E2." Brain Res 231(2): 335-42.
[31] Gold, P. W., W. C. Drevets, et al. (2002). "New insights into the role of cortisol and the glucocorticoid receptor in severe depression." Biol Psychiatry 52(5): 381-5.
[32] Gold, P. W., K. E. Gabry, et al. (2002). "Divergent endocrine abnormalities in melancholic and atypical depression: clinical and pathophysiologic implications." Endocrinol Metab Clin North Am 31(1): 37-62, vi.
[33] Gold, P. W., J. Licinio, et al. (1995). "Corticotropin releasing hormone in the pathophysiology of melancholic and atypical depression and in the mechanism of action of antidepressant drugs." Ann N Y Acad Sci 771:716-29.
[34] Gormley, G J., M. T. Lowy, et al. (1985). "Glucocorticoid receptors in depression:relationship to the dexamethasone suppression test." Am J Psychiatry 142(11): 1278-84.
[35] Goudsmit, E., M. A. Hofman, et al. (1990). "The supraoptic and paraventricular nuclei of the human hypothalamus in relation to sex, age and Alzheimer's disease." Neurobiol Aging 11(5): 529-36.
[36] Graff, L. A., D. G Dyck, et al. (1991). "Predicting postpartum depressive symptoms: a structural modelling analysis." Percept Mot Skills 73(3 Pt 2): 1137-8.
[37] Grammatopoulos, D. K. and G P. Chrousos (2002). "Functional characteristics of CRH receptors and potential clinical applications of CRH-receptor antagonists." Trends Endocrinol Metab 13(10): 436-44.
[38] Gregoire, A. J., R. Kumar, et al. (1996). "Transdermal oestrogen for treatment of severe postnatal depression." Lancet 347(9006): 930-3.
[39] Hayley, S., M. O. Poulter, et al. (2005). "The pathogenesis of clinical depression: stressor- and cytokine-induced alterations of neuroplasticity." Neuroscience 135(3):659-78.
[40] Hayward, C, J. D. Killen, et al. (1997). "Psychiatric risk associated with early puberty in adolescent girls." J Am Acad Child Adolesc Psychiatry 36(2): 255-62.
[41] Henderson, B. J. and C. Whissell (1997). "Changes in women's emotions as a function of emotion valence, self-determined category of premenstrual distress, and day in the menstrual cycle." Psychol Rep 80(3 Pt 2): 1272-4.
[42] Heuser, I. (2002). "Depression, endocrinologically a syndrome of premature aging?" Maturitas 41 Suppl 1: S19-23.
[43] Heuser, I., G. Bissette, et al. (1998). "Cerebrospinal fluid concentrations of corticotropin-releasing hormone, vasopressin, and somatostatin in depressed patients and healthy controls: response to amitriptyline treatment." Depress Anxiety 8(2): 71-9.
[44] Holsboer, F. (2000). "The corticosteroid receptor hypothesis of depression." Neuropsychopharmacology 23(5): 477-501.
[45] Holsboer, F. (2001). "Stress, hypercortisolism and corticosteroid receptors in depression:implications for therapy." J Affect Disord 62(1-2): 77-91.
[46] Holsboer, F. and N. Barden (1996). "Antidepressants and hypothalamic-pituitary-adrenocortical regulation." Endocr Rev 17(2): 187-205.
Huitinga, I., M. van der Cammen, et al. (2000). "IL-lbeta immunoreactive neurons in the human hypothalamus: reduced numbers in multiple sclerosis." J Neuroimmunol 107(1): 8-20.
[47] Imaki, T., H. Katsumata, et al. (2001). "Expression of corticotropin-releasing hormone type 1 receptor in paraventricular nucleus after acute stress." Neuroendocrinology 73(5):293-301.
[48] Imaki, T., M. Naruse, et al. (1996). "Corticotropin-releasing factor up-regulates its own receptor mRNA in the paraventricular nucleus of the hypothalamus." Brain Res Mol Brain Res 38(1): 166-70.
[49] Joels, M. and E. R. de Kloet (1992). "Control of neuronal excitability by corticosteroid hormones." Trends Neurosci 15(1): 25-30.
[50] Keck, M. E. and F. Holsboer (2001). "Hyperactivity of CRH neuronal circuits as a target for therapeutic interventions in affective disorders." Peptides 22(5): 835-44.
[51] Keck, M. E., T. Welt, et al. (2003). "Reduction of hypothalamic vasopressinergic hyperdrive contributes to clinically relevant behavioral and neuroendocrine effects of chronic paroxetine treatment in a psychopathological rat model."Neuropsychopharmacology 28(2): 235-43.
[52] Kirschbaum, C, K. M. Pirke, et al. (1993). "The 'Trier Social Stress Test'--a tool for investigating psychobiological stress responses in a laboratory setting." Neuropsychobiology 28(1-2): 76-81.
[53] Kudielka, B. M. and C. Kirschbaum (2005). "Sex differences in HPA axis responses to stress: a review." Biol Psychol 69(1): 113-32.
[54] Kurki, T, V. Hiilesmaa, et al. (2000). "Depression and anxiety in early pregnancy and risk for preeclampsia." Obstet Gynecol 95(4): 487-90.
[55] Landgraf, R. (2006). "The involvement of the vasopressin system in stress-related disorders." CNS Neurol Disord Drug Targets 5(2): 167-79.
[56] Legradi, G, D. Holzer, et al. (1997). "Glucocorticoids inhibit stress-induced phosphorylation of CREB in corticotropin-releasing hormone neurons of the hypothalamic paraventricular nucleus." Neuroendocrinology 66(2): 86-97.
[57] Legros, J. J. (2001). "Inhibitory effect of oxytocin on corticotrope function in humans:are vasopressin and oxytocin ying-yang neurohormones?" Psychoneuroendocrinology 26(7): 649-55.
[58] Lehnert, H., C. Schulz, et al. (1998). "Physiological and neurochemical aspects of corticotropin-releasing factor actions in the brain: the role of the locus coeruleus."Neurochem Res 23(8): 1039-52.
[59] Liu, W., J. Wang, et al. (1995). "Steroid receptor heterodimerization demonstrated in vitro and in vivo." Proc Natl Acad Sci U S A 92(26): 12480-4.
[60] Liu, Z., F. Zhu, et al. (2006). "Association of corticotropin-releasing hormone receptorl gene SNP and haplotype with major depression." Neurosci Lett 404(3): 358-62.
[61] Livesey, J. H., A. Carne, et al. (1991). "Structure of equine corticotropin releasing factor." Peptides 12(6): 1437-40.
[62] Malkoski, S. P. and R. I. Dorin (1999). "Composite glucocorticoid regulation at a functionally defined negative glucocorticoid response element of the human corticotropin-releasing hormone gene." Mol Endocrinol 13(10): 1629-44.
[63] Matsubara, T., H. Funato, et al. (2006). "Reduced Glucocorticoid Receptor alpha Expression in Mood Disorder Patients and First-Degree Relatives." Biol Psychiatry 59(8):689-95.
[64] Meynen, G, U. A. Unmehopa, et al. (2007). "Hypothalamic oxytocin mRNA expression and melancholic depression." Mol Psychiatry 12(2): 118-9.
[65] Meynen, G, U. A. Unmehopa, et al. (2006). "Increased arginine vasopressin mRNA expression in the human hypothalamus in depression: A preliminary report." Biol Psychiatry 60(8): 892-5.
[66] Miller, D. B. and J. P. O'Callaghan (2005). "Depression, cytokines, and glial function."Metabolism 54(5 Suppl 1): 33-8.
[67] Morton, A. (1969). "A quantitative analysis of the normal neuron population of the hypothalamic magnocellular nuclei in man and of their projections to the neurohypophysis." J Comp Neurol 136(2): 143-57.
[68] Muller, M. B. and W. Wurst (2004). "Getting closer to affective disorders: the role of CRH receptor systems." Trends Mol Med 10(8): 409-15.
[69] Murphy, B. E. (1997). "Antiglucocorticoid therapies in major depression: a review."Psychoneuroendocrinology 22 Suppl 1: S125-32.
[70] Nakase, S., I. Kitayama, et al. (1998). "Increased expression of magnocellular arginine vasopressin mRNA in paraventricular nucleus of stress-induced depression-model rats."Life Sci 63(1): 23-31.
[71] Nemeroff, C. B. (1996). "The corticotropin-releasing factor (CRF) hypothesis of depression: new findings and new directions." Mol Psychiatry 1(4): 336-42.
[72] Nemeroff, C. B. and M. J. Owens (2004). "Pharmacologic differences among the SSRIs:focus on monoamine transporters and the HPA axis." CNS Spectr 9(6 Suppl 4): 23-31.
[73] Nemeroff, C. B., E. Widerlov, et al. (1984). "Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients." Science 226(4680): 1342-4.
[74] O'Brien, S. M., L. V. Scott, et al. (2004). "Cytokines: abnormalities in major depression and implications for pharmacological treatment." Hum Psychopharmacol 19(6):397-403.
[75] Oren, D. A., K. L. Wisner, et al. (2002). "An open trial of morning light therapy for treatment of antepartum depression." Am J Psychiatry 159(4): 666-9.
[76] Owens, M. J. (2004). "Selectivity of antidepressants: from the monoamine hypothesis of depression to the SSRI revolution and beyond." J Clin Psychiatry 65 Suppl 4: 5-10.
[77] Papiol, S., B. Arias, et al. (2007). "Genetic variability at HPA axis in major depression and clinical response to antidepressant treatment." J Affect Disord 104(1-3): 83-97.
[78] Pardes, H. (1994). "The significance of health care reform for research, innovations, and academic medicine." Ann N Y Acad Sci 729:132-8; discussion 139-42.
[79] Parry, B. L. and R. P. Newton (2001). "Chronobiological basis of female-specific mood disorders." Neuropsychopharmacology 25(5 Suppl): S102-8.
[80] Piccinelli, M. and G Wilkinson (2000). "Gender differences in depression. Critical review." Br J Psychiatry 177:486-92.
[81] Pope, H. G., Jr., E. M. Kouri, et al. (2000). "Effects of supraphysiologic doses of testosterone on mood and aggression in normal men: a randomized controlled trial." Arch Gen Psychiatry 57(2): 133-40; discussion 155-6.
[82] Purba, J. S., W. J. Hoogendijk, et al. (1996). "Increased number of vasopressin- and oxytocin-expressing neurons in the paraventricular nucleus of the hypothalamus in depression." Arch Gen Psychiatry 53(2): 137-43.
[83] Raadsheer, F. C, W. J. Hoogendijk, et al. (1994). "Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients." Neuroendocrinology 60(4): 436-44.
[84] Raadsheer, F. C, A. A. Sluiter, et al. (1993). "Localization of corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the human hypothalamus;age-dependent colocalization with vasopressin." Brain Res 615(1): 50-62.
[85] Raadsheer, F. C, J. J. van Heerikhuize, et al. (1995). "Corticotropin-releasing hormone mRNA levels in the paraventricular nucleus of patients with Alzheimer's disease and depression." Am J Psychiatry 152(9): 1372-6.
[86] Rabin, B. S., R. Ganguli, et al. (1990). "Interaction between the brain and the immune system." Immunol Ser 52:125-54.
[87] Rivier, J., J. Spiess, et al. (1983). "Characterization of rat hypothalamic corticotropin-releasing factor." Proc Natl Acad Sci U S A 80(15): 4851-5.
[88] Roca, C. A., P. J. Schmidt, et al. (2005). "Sex-related differences in stimulated hypothalamic-pituitary-adrenal axis during induced gonadal suppression." J Clin Endocrinol Metab 90(7): 4224-31.
[89] Rubin, R. T., R. E. Poland, et al. (1987). "Neuroendocrine aspects of primary endogenous depression. I. Cortisol secretory dynamics in patients and matched controls."Arch Gen Psychiatry 44(4): 328-36.
[90] Sallee, F. R., L. Nesbitt, et al. (1995). "Lymphocyte glucocorticoid receptor: predictor of sertraline response in adolescent major depressive disorder (MDD)." Psychopharmacol Bull 31(2): 339-45.
[91] Scheinman, R. I., P. C. Cogswell, et al. (1995). "Role of transcriptional activation of I kappa B alpha in mediation of immunosuppression by glucocorticoids." Science 270(5234): 283-6.
[92] Seeman, M. V. (1997). "Psychopathology in women and men: focus on female hormones." Am J Psychiatry 154(12): 1641-7.
[93] Seidman, S. N. (2001). "Testosterone deficiency and depression in aging men: pathogenic and therapeutic implications." J Gend Specif Med 4(2): 44-8.
[94] Seidman, S. N., A. B. Araujo, et al. (2002). "Low testosterone levels in elderly men with dysthymic disorder." Am J Psychiatry 159(3): 456-9.
[95] Shanks, N. and S. L. Lightman (2001). "The maternal-neonatal neuro-immune interface:are there long-term implications for inflammatory or stress-related disease?" J Clin Invest 108(11): 1567-73.
[96] Shibahara, S., Y. Morimoto, et al. (1983). "Isolation and sequence analysis of the human corticotropin-releasing factor precursor gene." EMBO J 2(5): 775-9.
[97] Silverman, A. I, A. Hou-Yu, et al. (1989). "Corticotropin-releasing factor synapses within the paraventricular nucleus of the hypothalamus." Neuroendocrinology 49(3):291-9.
[98] Skobeloff, E. M., W. H. Spivey, et al. (1996). "The effect of the menstrual cycle on asthma presentations in the emergency department." Arch Intern Med 156(16): 1837-40.
[99] Sossin, W. S., J. M. Fisher, et al. (1989). "Cellular and molecular biology of neuropeptide processing and packaging." Neuron 2(5): 1407-17.
[100] Sousa, A. R., S. J. Lane, et al. (2000). "Glucocorticoid resistance in asthma is associated with elevated in vivo expression of the glucocorticoid receptor beta-isoform." J Allergy Clin Immunol 105(5): 943-50.
[101] Stenzel-Poore, M. P., S. C. Heinrichs, et al. (1994). "Overproduction of corticotropin-releasing factor in transgenic mice: a genetic model of anxiogenic behavior." J Neurosci 14(5 Pt 1): 2579-84.
[102] Swaab, D. F. (2003). "The human hypothalamus. Basic and cllinical aspects.."
[103] Tago, K., F. Tsukahara, et al. (2004). "Regulation of nuclear retention of glucocorticoid receptor by nuclear Hsp90." Mol Cell Endocrinol 213(2): 131-8.
[104] Trapp, T., R. Rupprecht, et al. (1994). "Heterodimerization between mineralocorticoid and glucocorticoid receptor: a new principle of glucocorticoid action in the CNS." Neuron 13(6): 1457-62.
[105] Turnbull, A. V. and C. L. Rivier (1999). "Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: actions and mechanisms of action."Physiol Rev 79(1): 1-71.
[106] Valdez GR, Zorrilla EP, et al. (2005). "Homeostasis within the corticotropin-releasing factor system via CRF2 receptor activation: a novel approach for the treatment of anxiety." Drug Dev Res 65: 205-215.
[107] Vale, W., J. Spiess, et al. (1981). "Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin." Science 213(4514): 1394-7.
[108] Vamvakopoulos, N. C. and G P. Chrousos (1993). "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 92(4): 1896-902.
[109] van West, D., F. Van Den Eede, et al. (2006). "Glucocorticoid receptor gene-based SNP analysis in patients with recurrent major depression." Neuropsychopharmacology 31(3):620-7.
[110] Veith, R. C, N. Lewis, et al. (1993). "Effect of desipramine on cerebrospinal fluid concentrations of corticotropin-releasing factor in human subjects." Psychiatry Res 46(1):1-8.
[111] Wasserman, D., M. Sokolowski, et al. (2007). The CRHR1 gene: a marker for suicidality in depressed males exposed to low stress. Genes Brain Behav.
[112] Webster, J. C, R. H. Oakley, et al. (2001). "Proinflammatory cytokines regulate human glucocorticoid receptor gene expression and lead to the accumulation of the dominant negative beta isoform: a mechanism for the generation of glucocorticoid resistance." Proc Natl Acad Sci U S A 98(12): 6865-70.
[113] Whalley, L. I, N. Borthwick, et al. (1986). "Glucocorticoid receptors and depression." Br Med J (Clin Res Ed) 292(6524): 859-61.
[114] Wichers, M. C, G Kenis, et al. (2007). "Interferon-alpha-induced depressive symptoms are related to changes in the cytokine network but not to cortisol." J Psychosom Res 62(2): 207-14.
[115] Wolkowitz, O. M., V. I. Reus, et al. (1999). "Antiglucocorticoid treatment of depression: double-blind ketoconazole." Biol Psychiatry 45(8): 1070-4.
[116] Yehuda, R., D. Boisoneau, et al. (1993). "Glucocorticoid receptor number and cortisol excretion in mood, anxiety, and psychotic disorders." Biol Psychiatry 34(1-2): 18-25.
[117] Young, E. A., J. F. Lopez, et al. (2003). "Mineralocorticoid receptor function in major depression." Arch Gen Psychiatry 60(1): 24-8.
[1] Bale, T. L, A. Contarino, et al. (2000). "Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress." Nat Genet 24(4):410-4.
[2] Bamberger, C. M., H. M. Schulte, et al. (1996). "Molecular determinants of glucocorticoid receptor function and tissue sensitivity to glucocorticoids." Endocr Rev 17(3): 245-61.
[3] Bao, A. M., D. F. Fischer, et al. (2006). "A direct androgenic involvement in the expression of human corticotropin-releasing hormone." Mol Psychiatry 11(6): 567-76.
[4] Bao, A. M., A. Hestiantoro, et al. (2005). "Colocalization of corticotropin-releasing hormone and oestrogen receptor-alpha in the paraventricular nucleus of the hypothalamus in mood disorders." Brain 128(Pt 6): 1301-13.
[5] Bao, A. M., G. Meynen, et al. (2007). "The stress system in depression and neurodegeneration: Focus on the human hypothalamus." Brain Res Rev.
[6] Barden, N. (1996). "Modulation of glucocorticoid receptor gene expression by antidepressant drugs." Pharmacopsychiatry 29(1): 12-22.
[7] Batschelet (1981). "Circular statistics in biology." New York: Academic Press.
[8] Besedovsky, H. O. and A. del Rey (1996). "Immune-neuro-endocrine interactions: facts and hypotheses." Endocr Rev 17(1): 64-102.
[9] Braak, H. and E. Braak (1991). "Neuropathological stageing of Alzheimer-related changes."Acta Neuropathol (Berl) 82(4): 239-59.
[10] Checkley, S. (1996). "The neuroendocrinology of depression and chronic stress." Br Med Bull 52(3): 597-617.
[11] de Kloet, E. R., R. H. Derijk, et al. (2007). "Therapy Insight: is there an imbalanced response of mineralocorticoid and glucocorticoid receptors in depression?" Nat Clin Pract Endocrinol Metab 3(2): 168-79.
[12] DeRijk, R. H., M. Schaaf, et al. (2003). "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 116(1-2): 17-26.
[13] Geng, Y.-G., Q.-R. Su, et al. (2007). "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." International Journal of Neuroscience 117(4): 539 -547.
[14] Grammatopoulos, D. K. and G. P. Chrousos (2002). "Functional characteristics of CRH receptors and potential clinical applications of CRH-receptor antagonists." Trends Endocrinol Metab 13(10): 436-44.
[15] Hayley, S., M. 0. Poulter, et al. (2005). "The pathogenesis of clinical depression: stressor- and cytokine-induced alterations of neuroplasticity." Neuroscience 135(3): 659-78.
[16] Heuser, I., G. Bissette, et al. (1998). "Cerebrospinal fluid concentrations of corticotropin-releasing hormone, vasopressin, and somatostatin in depressed patients and healthy controls: response to amitriptyline treatment." Depress Anxiety 8(2): 71-9.
[17] Himmerich, H., E. B. Binder, et al. (2006). "Successful antidepressant therapy restores the disturbed interplay between TNF-alpha system and HPA axis." Biol Psychiatry 60(8): 882-8.
[18] Holsboer, F. (2001). "Stress, hypercortisolism and corticosteroid receptors in depression:implications for therapy." J Affect Disord 62(1-2): 77-91.
[19] Holsboer, F., N. Barden (1996). "Antidepressants and hypothalamic-pituitary-adrenocortical regulation." Endocr Rev 17(2): 187-205.
[20] Huitinga, I., M. van der Cammen, et al. (2000). "IL-1beta immunoreactive neurons in the human hypothalamus: reduced numbers in multiple sclerosis." J Neuroimmunol 107(1):8-20.
[21] Hurbin, A., L. Boissin-Agasse, et al. (1998). "The Via 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 139(11): 4701-7.
[22] Hurbin, A., H. Orcel, et al. (2002). "The vasopressin receptors colocalize with vasopressin in the magnocellular neurons of the rat supraoptic nucleus and are modulated by water balance." Endocrinology 143(2): 456-66.
[23] Imaki, T., H. Katsumata, et al. (2001). "Expression of corticotropin-releasing hormone type 1 receptor in paraventricular nucleus after acute stress." Neuroendocrinology 73(5): 293-301.
[24] Imaki, T., M. Naruse, et al. (1996). "Corticotropin-releasing factor up-regulates its own receptor mRNA in the paraventricular nucleus of the hypothalamus." Brain Res Mol Brain Res 38(1): 166-70.
[25] Kamphuis, W., A. Schneemann, et al. (2001). "Prostanoid receptor gene expression profile in human trabecular meshwork: a quantitative real-time PCR approach." Invest Ophthalmol Vis Sci 42(13): 3209-15.
[26] Keck, M. E. and F. Holsboer (2001). "Hyperactivity of CRH neuronal circuits as a target for therapeutic interventions in affective disorders." Peptides 22(5): 835-44.
[27] Keck, M. E., T. Welt, et al. (2003). "Reduction of hypothalamic vasopressinergic hyperdrive contributes to clinically relevant behavioral and neuroendocrine effects of chronic paroxetine treatment in a psychopathological rat model." Neuropsychopharmacology 28(2): 235-43.
[28] Kishimoto, T., J. Radulovic, et al. (2000). "Deletion of crhr2 reveals an anxiolytic role for corticotropin-releasing hormone receptor-2." Nat Genet 24(4): 415-9.
[29] Koning, N., L. Bo, et al. (2007). "Downregulation of macrophage inhibitory molecules in multiple sclerosis lesions." Ann Neurol 62(5): 504-14.
[30] Kuno, R., Y. Yoshida, et al. (2006). "The role of TNF-alpha and its receptors in the production of NGF and GDNF by astrocytes." Brain Res 1116(1): 12-8.
[31] Kunzel, H. E., A. W. Zobel, et al. (2003). "Treatment of depression with the CRH-1-receptor antagonist R121919: endocrine changes and side effects." J Psychiatr Res 37(6): 525-33.
[32] Legradi, G., D. Holzer, et al. (1997). "Glucocorticoids inhibit stress-induced phosphorylation of CREB in corticotropin-releasing hormone neurons of the hypothalamic paraventricular nucleus." Neuroendocrinology 66(2): 86-97.
[33] Liu, Z., F. Zhu, et al. (2006). "Association of corticotropin-releasing hormone receptorl gene SNP and haplotype with major depression." Neurosci Lett 404(3): 358-62.
[34] Lund, T. D., D. J. Munson, et al. (2004). "Androgen inhibits, while oestrogen enhances,restraint-induced activation of neuropeptide neurones in the paraventricular nucleus of the hypothalamus." J Neuroendocrinol 16(3): 272-8.
[35] Mansi, J. A., S. Rivest, et al. (1996). "Regulation of corticotropin-releasing factor type 1 (CRF1) receptor messenger ribonucleic acid in the paraventricular nucleus of rat hypothalamus by exogenous CRF." Endocrinology 137(11): 4619-29.
[36] Merali, Z., P. Kent, et al. (2006). "Corticotropin-releasing hormone, arginine vasopressin,gastrin-releasing peptide, and neuromedin B alterations in stress-relevant brain regions of suicides and control subjects." Biol Psychiatry 59(7): 594-602.
[37] Meynen, G, U. A. Unmehopa, et al. (2007). "Hypothalamic oxytocin mRNA expression and melancholic depression." Mol Psychiatry 12(2): 118-9.
[38] Meynen, G, U. A. Unmehopa, et al. (2006). "Increased arginine vasopressin mRNA expression in the human hypothalamus in depression: A preliminary report." Biol Psychiatry 60(8): 892-5.
[39] Miller, D. B. and J. P. O'Callaghan (2005). "Aging, stress and the hippocampus." Ageing Res Rev 4(2): 123-40.
[40] Muller, M. B. and W. Wurst (2004). "Getting closer to affective disorders: the role of CRH receptor systems." Trends Mol Med 10(8): 409-15.
[41] Nakase, S., I. Kitayama, et al. (1998). "Increased expression of magnocellular arginine vasopressin mRNA in paraventricular nucleus of stress-induced depression-model rats." Life Sci 63(1): 23-31.
[42] Nemeroff, C. B. (1996). "The corticotropin-releasing factor (CRF) hypothesis of depression: new findings and new directions." Mol Psychiatry 1(4): 336-42.
[43] Nestler, E. I, M. Barrot, et al. (2002). "Neurobiology of depression." Neuron 34(1): 13-25.
[44] Nicholson, R. C, B. R. King, et al. (2004). "Complex regulatory interactions control CRH gene expression." Front Biosci 9: 32-9.
[45] O'Brien, S. M., L. V. Scott, et al. (2004). "Cytokines: abnormalities in major depression and implications for pharmacological treatment." Hum Psychopharmacol 19(6): 397-403.
[46] Osterlund, M. K., J. A. Gustafsson, et al. (2000). "Estrogen receptor beta (ERbeta) messenger ribonucleic acid (mRNA) expression within the human forebrain: distinct distribution pattern to ERalpha mRNA." J Clin Endocrinol Metab 85(10): 3840-6.
[47] Paech, K., P. Webb, et al. (1997). "Differential ligand activation of estrogen receptors ERalpha and ERbeta at AP1 sites." Science 277(5331): 1508-10.
[48] Papiol, S., B. Arias, et al. (2007). "Genetic variability at HPA axis in major depression and clinical response to antidepressant treatment." J Affect Disord.
[49] Purba, J. S., W. J. Hoogendijk, et al. (1996). "Increased number of vasopressin- and oxytocin-expressing neurons in the paraventricular nucleus of the hypothalamus in depression." Arch Gen Psychiatry 53(2): 137-43.
[50] Raadsheer, F.C., W. J. Hoogendijk, et al. (1994). "Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients." Neuroendocrinology 60(4): 436-44.
[51] Raadsheer, F. C, J. J. van Heerikhuize, et al. (1995). "Corticotropin-releasing hormone mRNA levels in the paraventricular nucleus of patients with Alzheimer's disease and depression." Am J Psychiatry 152(9): 1372-6.
[52] Shen, W. W., H. C. Liu, et al. (2006). "Anti-heat shock protein 90 is increased in acute mania." Aust N Z J Psychiatry 40(8): 712-6.
[53] Shimizu, S., K. Nomura, et al. (1996). "An allel-specific abnormal transcript of the heat shock protein 70 gene in patients with major depression." Biochem Biophys Res Commun 219(3): 745-52.
[54] Silverman, A. J., A. Hou-Yu, et al. (1989). "Corticotropin-releasing factor synapses within the paraventricular nucleus of the hypothalamus." Neuroendocrinology 49(3): 291-9.
[55] Stenzel-Poore, M. P., S. C. Heinrichs, et al. (1994). "Overproduction of corticotropin-releasing factor in transgenic mice: a genetic model of anxiogenic behavior." J Neurosci 14(5 Pt 1): 2579-84.
[56] Swaab, D. F. (2003). "The human hypothalamus. Basic and cllinical aspects.."
[57] Tissing, W. J., J. P. Meijerink, et al. (2005). "mRNA expression levels of (co)chaperone molecules of the glucocorticoid receptor are not involved in glucocorticoid resistance in pediatric ALL." Leukemia 19(5): 727-33.
[58] Trapp, T. and F. Holsboer (1996). "Heterodimerization between mineralocorticoid and glucocorticoid receptors increases the functional diversity of corticosteroid action." Trends Pharmacol Sci 17(4): 145-9.
[59] Trapp, T., R. Rupprecht, et al. (1994). "Heterodimerization between mineralocorticoid and glucocorticoid receptor: a new principle of glucocorticoid action in the CNS." Neuron 13(6):1457-62.
[60] Valdez GR, Zorrilla EP, et al. (2005)." Homeostasis within the corticotropin-releasing factor system via CRF2 receptor activation: a novel approach for the treatment of anxiety." Drug Dev Res 65: 205-215.
[61] Vamvakopoulos, N. C. and G. P. Chrousos (1993). "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 92(4): 1896-902.
[62] Vandesompele, J., K. De Preter, et al. (2002). "Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes." Genome Biol 3(7): RESEARCH0034.
[63] Veith, R. C, N. Lewis, et al. (1993). "Effect of desipramine on cerebrospinal fluid concentrations of corticotropin-releasing factor in human subjects." Psychiatry Res 46(1):1-8.
[64] Wigger, A., M. M. Sanchez, et al. (2004). "Alterations in central neuropeptide expression,release, and receptor binding in rats bred for high anxiety: critical role of vasopressin."Neuropsychopharmacology 29(1): 1-14.
[65] Wolfl, S., C. Martinez, et al. (1999). "Inducible binding of cyclic adenosine 3',5'-monophosphate (cAMP)-responsive element binding protein (CREB) to a cAMP-responsive promoter in vivo." Mol Endocrinol 13(5): 659-69.
[66] Young, E. A., J. F. Lopez, et al. (2003). "Mineralocorticoid receptor function in major depression." Arch Gen Psychiatry 60(1): 24-8.
[67] Zubenko, G S., B. Maher, et al. (2003). "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 123(1): 1-18.
[1] Bao, A. M., D. F. Fischer, et al. (2006). "A direct androgenic involvement in the expression of human corticotropin-releasing hormone." Mol Psychiatry 11(6): 567-76.
[2] Bao, A. M., A. Hestiantoro, et al. (2005). "Colocalization of corticotropin-releasing hormone and oestrogen receptor-alpha in the paraventricular nucleus of the hypothalamus in mood disorders." Brain 128(Pt6): 1301-13.
[3] Bao, A. M. and D. F. Swaab (2007). "Gender difference in age-related number of corticotropin-releasing hormone-expressing neurons in the human hypothalamic paraventricular nucleus and the role of sex hormones." Neuroendocrinology 85(1): 27-36.
[4] de Kloet, E. R. (2003). "Hormones, brain and stress." Endocr Regul 37(2): 51-68.
[5] de Kloet, E. R., R. H. Derijk, et al. (2007). "Therapy Insight: is there an imbalanced response of mineralocorticoid and glucocorticoid receptors in depression?" Nat Clin Pract Endocrinol Metab 3(2): 168-79.
[6] Griebel, G., G Perrault, et al. (1998). "Characterization of the behavioral profile of the non-peptide CRF receptor antagonist CP-154,526 in anxiety models in rodents. Comparison with diazepam and buspirone." Psychopharmacology (Berl) 138(1): 55-66.
[7] Groenink, L., T. Pattij, et al. (2003). "5-HT1A receptor knockout mice and mice overexpressing corticotropin-releasing hormone in models of anxiety." Eur J Pharmacol 463(1-3): 185-97.
[8] Imaki, T., H. Katsumata, et al. (2001). "Expression of corticotropin-releasing hormone type 1 receptor in paraventricular nucleus after acute stress." Neuroendocrinology 73(5): 293-301.
[9] Imaki, T., M. Naruse, et al. (1996). "Corticotropin-releasing factor up-regulates its own receptor mRNA in the paraventricular nucleus of the hypothalamus." Brain Res Mol Brain Res 38(1): 166-70.
[10] Joels, M., H. Karst, et al. (2007). "The coming out of the brain mineralocorticoid receptor."Trends Neurosci.
[11] Keck, M. E., T. Welt, et al. (2003). "Reduction of hypothalamic vasopressinergic hyperdrive contributes to clinically relevant behavioral and neuroendocrine effects of chronic paroxetine treatment in a psychopathological rat model." Neuropsychopharmacology 28(2): 235-43.
[12] Keck, M. E., A. Wigger, et al. (2002). "Vasopressin mediates the response of the combined dexamethasone/CRH test in hyper-anxious rats: implications for pathogenesis of affective disorders." Neuropsychopharmacology 26(1): 94-105.
[13] Kuroda, Y., Y. Watanabe, et al. (1994). "Effects of adrenalectomy and type I or type II glucocorticoid receptor activation on 5-HT1A and 5-HT2 receptor binding and 5-HT transporter mRNA expression in rat brain." Brain Res 648(1): 157-61.
[14] Landgraf, R. (2006). "The involvement of the vasopressin system in stress-related disorders."CNS Neurol Disord Drug Targets 5(2): 167-79.
[15] Landgraf, R., R. Gerstberger, et al. (1995). "VI vasopressin receptor antisense oligodeoxynucleotide into septum reduces vasopressin binding, social discrimination abilities,and anxiety-related behavior in rats." J Neurosci 15(6): 4250-8.
[16] Lopez, J. F., D. M. Vazquez, et al. (1997). "Regulation of 5-HT receptors and the hypothalamic-pituitary-adrenal axis. Implications for the neurobiology of suicide." Ann N Y Acad Sci 836:106-34.
[17] Lund, T. D., D. J. Munson, et al. (2004). "Androgen inhibits, while oestrogen enhances,restraint-induced activation of neuropeptide neurones in the paraventricular nucleus of the hypothalamus." J Neuroendocrinol 16(3): 272-8.
[18] Makino, S., K. Hashimoto, et al. (2002). "Multiple feedback mechanisms activating corticotropin-releasing hormone system in the brain during stress." Pharmacol Biochem Behav 73(1): 147-58.
[19] Mansbach, R. S., E. N. Brooks, et al. (1997). "Antidepressant-like effects of CP-154,526, a selective CRF1 receptor antagonist." Eur J Pharmacol 323(1): 21-6.
[20] Mansi, J. A., S. Rivest, et al. (1996). "Regulation of corticotropin-releasing factor type 1 (CRF1) receptor messenger ribonucleic acid in the paraventricular nucleus of rat hypothalamus by exogenous CRF." Endocrinology 137(11): 4619-29.
[21] Meynen, G, U. A. Unmehopa, et al. (2006). "Increased arginine vasopressin mRNA expression in the human hypothalamus in depression: A preliminary report." Biol Psychiatry 60(8): 892-5.
[22] Nakase, S., I. Kitayama, et al. (1998). "Increased expression of magnocellular arginine vasopressin mRNA in paraventricular nucleus of stress-induced depression-model rats." Life Sci 63(1): 23-31.
[23] Olijslagers, J. E. e. a. (2006). "Rapid enhancement of hippocampal glutamate transmission by corticosterone is mediated via the MEK/ERK pathway." FENS Forum Meeting: 152.17.
[24] Ou, X. M., J. M. Stoning, et al. (2001). "Heterodimerization of mineralocorticoid and glucocorticoid receptors at a novel negative response element of the 5-HT1A receptor gene."J BiolChem 276(17): 14299-307.
[25] Purba, J. S., W. J. Hoogendijk, et al. (1996). "Increased number of vasopressin- and oxytocin-expressing neurons in the paraventricular nucleus of the hypothalamus in depression." Arch Gen Psychiatry 53(2): 137-43.
[26] Raadsheer, F. C, W. J. Hoogendijk, et al. (1994). "Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients." Neuroendocrinology 60(4): 436-44.
[27] Raadsheer, F. C, J. J. van Heerikhuize, et al. (1995). "Corticotropin-releasing hormone mRNA levels in the paraventricular nucleus of patients with Alzheimer's disease and depression." Am J Psychiatry 152(9): 1372-6.
[28] Scott, L. V. and T. G. Dinan (2002). "Vasopressin as a target for antidepressant development: an assessment of the available evidence." J Affect Disord 72(2): 113-24.
[29] Silverman, A. J., A. Hou-Yu, et al. (1989). "Corticotropin-releasing factor synapses within the paraventricular nucleus of the hypothalamus." Neuroendocrinology 49(3): 291-9.
[30] Trapp, T. and F. Holsboer (1996). "Heterodimerization between mineralocorticoid and glucocorticoid receptors increases the functional diversity of corticosteroid action." Trends Pharmacol Sci 17(4): 145-9.
[31] Valdez GR, Zorrilla EP, et al. (2005). "Homeostasis within the corticotropin-releasing factor system via CRF2 receptor activation: a novel approach for the treatment of anxiety." Drug Dev Res 65: 205-215.
[32] Vamvakopoulos, N. C. and G. P. Chrousos (1993). "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 92(4): 1896-902.
[33] Wehling, M. and R. Losel (2006). "Non-genomic steroid hormone effects: membrane or intracellular receptors?" J Steroid Biochem Mol Biol 102(1-5): 180-3.
[34] Young, E. A., J. F. Lopez, et al. (2003). "Mineralocorticoid receptor function in major depression." Arch Gen Psychiatry 60(1): 24-8.
[35] Zobel, A. W., T. Nickel, et al. (2000). "Effects of the high-affinity corticotropin-releasing hormone receptor 1 antagonist R121919 in major depression: the first 20 patients treated." J Psychiatr Res 34(3): 171-81.
[2] Antonijevic, I. A. (2006). "Depressive disorders -- is it time to endorse different pathophysiologies?" Psychoneuroendocrinology 31(1): 1-15.
[3] Bamberger, C. M., A. M. Bamberger, et al. (1995). "Glucocorticoid receptor beta, a potential endogenous inhibitor of glucocorticoid action in humans." J Clin Invest 95(6):2435-41.
[4] Ban, E., G. Milon, et al. (1991). "Receptors for interleukin-1 (alpha and beta) in mouse brain: mapping and neuronal localization in hippocampus." Neuroscience 43(1): 21-30.
[5] Bao, A. M, D. F. Fischer, et al. (2006). "A direct androgenic involvement in the expression of human corticotropin-releasing hormone." Mol Psychiatry 11(6): 567-76.
[6] Bao, A. M., A. Hestiantoro, et al. (2005). "Colocalization of corticotropin-releasing hormone and oestrogen receptor-alpha in the paraventricular nucleus of the hypothalamus in mood disorders." Brain 128(Pt 6): 1301-13.
[7] Bao, A. M, Y. F. Ji, et al. (2004). "Diurnal rhythms of free estradiol and cortisol during the normal menstrual cycle in women with major depression." Horm Behav 45(2):93-102.
[8] Barden, N. (1996). "Modulation of glucocorticoid receptor gene expression by antidepressant drugs." Pharmacopsychiatry 29(1): 12-22.
[9] Belanoff, J. K., A. J. Rothschild, et al. (2002). "An open label trial of C-1073 (mifepristone) for psychotic major depression." Biol Psychiatry 52(5): 386-92.
[10] Benjamin J. Sadock, V. A. S. (2000). "Kaplan & Sadock's Comprehensive Textbook of Psychiatry (2 Volume Set)."
[11] Berkenbosch, F., J. van Oers, et al. (1987). "Corticotropin-releasing factor-producing neurons in the rat activated by interleukin-1." Science 238(4826): 524-6.
[12] Besedovsky, H. O. and A. del Rey (1996). "Immune-neuro-endocrine interactions: facts and hypotheses." Endocr Rev 17(1): 64-102.
[13] Blum, I., M. Lerman, et al. (2004). "Lack of plasma norepinephrine cyclicity, increased estradiol during the follicular phase, and of progesterone and gonadotrophins at ovulation in women with premenstrual syndrome." Neuropsychobiology 50(1): 10-5.
[14] Campagne, D. M. (2004). "The obstetrician and depression during pregnancy." Eur J Obstet Gynecol Reprod Biol 116(2): 125-30.
[15] Capuron, L, P. Hauser, et al. (2002). "Treatment of cytokine-induced depression." Brain Behav Immun 16(5): 575-80.
[16] Carroll, B. J., F. Cassidy, et al. (2007). "Pathophysiology of hypercortisolism in depression." Acta Psychiatr Scand Suppl(433): 90-103.
[17] Checkley, S. (1996). "The neuroendocrinology of depression and chronic stress." Br Med Bull 52(3): 597-617.
[18] Chesnokova, V. and S. Melmed (2002). "Minireview: Neuro-immuno-endocrine modulation of the hypothalamic-pituitary-adrenal (HPA) axis by gpl30 signaling molecules." Endocrinology 143(5): 1571-4.
[19] Chrousos, G. P. (1998). "Stressors, stress, and neuroendocrine integration of the adaptive response. The 1997 Hans Selye Memorial Lecture." Ann N Y Acad Sci 851: 311-35.
[20] Chrousos, G. P., D. J. Torpy, et al. (1998). "Interactions between the hypothalamic-pituitary-adrenal axis and the female reproductive system: clinical implications." Ann Intern Med 129(3): 229-40.
[21] Davydov, D. M., D. Shapiro, et al. (2004). "Moods in everyday situations: effects of menstrual cycle, work, and personality." J Psychosom Res 56(1): 27-33.
[22] de Kloet, E. R. (2000). "Stress in the brain." Eur J Pharmacol 405(1-3): 187-98.
[23] de Kloet, E. R. (2003). "Hormones, brain and stress." Endocr Regul 37(2): 51-68.
[24] de Kloet, E. R., R. H. Derijk, et al. (2007). "Therapy Insight: is there an imbalanced response of mineralocorticoid and glucocorticoid receptors in depression?" Nat Clin Pract Endocrinol Metab 3(2): 168-79.
[25] Deyerle, K. L., J. E. Sims, et al. (1992). "Pattern of IL-1 receptor gene expression suggests role in noninflammatory processes." J Immunol 149(5): 1657-65.
[26] Dorn, L. D., E. S. Burgess, et al. (1997). "The longitudinal course of psychopathology in Cushing's syndrome after correction of hypercortisolism." J Clin Endocrinol Metab 82(3):912-9.
[27] Dudas, B. and I. Merchenthaler (2003). "Topography and associations of leu-enkephalin and luteinizing hormone-releasing hormone neuronal systems in the human diencephalon." J Clin.Endocrinol Metab 88(4): 1842-8.
[28] Erkut, Z. A., C. Pool, et al. (1998). "Glucocorticoids suppress corticotropin-releasing hormone and vasopressin expression in human hypothalamic neurons." J Clin Endocrinol Metab 83(6): 2066-73.
[29] Esch, F., N. Ling, et al. (1984). "Isolation and characterization of the bovine hypothalamic corticotropin-releasing factor." Biochem Biophys Res Commun 122(3):899-905.
[30] Feuerstein, G, S. A. Adelberg, et al. (1982). "Hypothalamic sites for cardiovascular and sympathetic modulation by prostaglandin E2." Brain Res 231(2): 335-42.
[31] Gold, P. W., W. C. Drevets, et al. (2002). "New insights into the role of cortisol and the glucocorticoid receptor in severe depression." Biol Psychiatry 52(5): 381-5.
[32] Gold, P. W., K. E. Gabry, et al. (2002). "Divergent endocrine abnormalities in melancholic and atypical depression: clinical and pathophysiologic implications." Endocrinol Metab Clin North Am 31(1): 37-62, vi.
[33] Gold, P. W., J. Licinio, et al. (1995). "Corticotropin releasing hormone in the pathophysiology of melancholic and atypical depression and in the mechanism of action of antidepressant drugs." Ann N Y Acad Sci 771:716-29.
[34] Gormley, G J., M. T. Lowy, et al. (1985). "Glucocorticoid receptors in depression:relationship to the dexamethasone suppression test." Am J Psychiatry 142(11): 1278-84.
[35] Goudsmit, E., M. A. Hofman, et al. (1990). "The supraoptic and paraventricular nuclei of the human hypothalamus in relation to sex, age and Alzheimer's disease." Neurobiol Aging 11(5): 529-36.
[36] Graff, L. A., D. G Dyck, et al. (1991). "Predicting postpartum depressive symptoms: a structural modelling analysis." Percept Mot Skills 73(3 Pt 2): 1137-8.
[37] Grammatopoulos, D. K. and G P. Chrousos (2002). "Functional characteristics of CRH receptors and potential clinical applications of CRH-receptor antagonists." Trends Endocrinol Metab 13(10): 436-44.
[38] Gregoire, A. J., R. Kumar, et al. (1996). "Transdermal oestrogen for treatment of severe postnatal depression." Lancet 347(9006): 930-3.
[39] Hayley, S., M. O. Poulter, et al. (2005). "The pathogenesis of clinical depression: stressor- and cytokine-induced alterations of neuroplasticity." Neuroscience 135(3):659-78.
[40] Hayward, C, J. D. Killen, et al. (1997). "Psychiatric risk associated with early puberty in adolescent girls." J Am Acad Child Adolesc Psychiatry 36(2): 255-62.
[41] Henderson, B. J. and C. Whissell (1997). "Changes in women's emotions as a function of emotion valence, self-determined category of premenstrual distress, and day in the menstrual cycle." Psychol Rep 80(3 Pt 2): 1272-4.
[42] Heuser, I. (2002). "Depression, endocrinologically a syndrome of premature aging?" Maturitas 41 Suppl 1: S19-23.
[43] Heuser, I., G. Bissette, et al. (1998). "Cerebrospinal fluid concentrations of corticotropin-releasing hormone, vasopressin, and somatostatin in depressed patients and healthy controls: response to amitriptyline treatment." Depress Anxiety 8(2): 71-9.
[44] Holsboer, F. (2000). "The corticosteroid receptor hypothesis of depression." Neuropsychopharmacology 23(5): 477-501.
[45] Holsboer, F. (2001). "Stress, hypercortisolism and corticosteroid receptors in depression:implications for therapy." J Affect Disord 62(1-2): 77-91.
[46] Holsboer, F. and N. Barden (1996). "Antidepressants and hypothalamic-pituitary-adrenocortical regulation." Endocr Rev 17(2): 187-205.
Huitinga, I., M. van der Cammen, et al. (2000). "IL-lbeta immunoreactive neurons in the human hypothalamus: reduced numbers in multiple sclerosis." J Neuroimmunol 107(1): 8-20.
[47] Imaki, T., H. Katsumata, et al. (2001). "Expression of corticotropin-releasing hormone type 1 receptor in paraventricular nucleus after acute stress." Neuroendocrinology 73(5):293-301.
[48] Imaki, T., M. Naruse, et al. (1996). "Corticotropin-releasing factor up-regulates its own receptor mRNA in the paraventricular nucleus of the hypothalamus." Brain Res Mol Brain Res 38(1): 166-70.
[49] Joels, M. and E. R. de Kloet (1992). "Control of neuronal excitability by corticosteroid hormones." Trends Neurosci 15(1): 25-30.
[50] Keck, M. E. and F. Holsboer (2001). "Hyperactivity of CRH neuronal circuits as a target for therapeutic interventions in affective disorders." Peptides 22(5): 835-44.
[51] Keck, M. E., T. Welt, et al. (2003). "Reduction of hypothalamic vasopressinergic hyperdrive contributes to clinically relevant behavioral and neuroendocrine effects of chronic paroxetine treatment in a psychopathological rat model."Neuropsychopharmacology 28(2): 235-43.
[52] Kirschbaum, C, K. M. Pirke, et al. (1993). "The 'Trier Social Stress Test'--a tool for investigating psychobiological stress responses in a laboratory setting." Neuropsychobiology 28(1-2): 76-81.
[53] Kudielka, B. M. and C. Kirschbaum (2005). "Sex differences in HPA axis responses to stress: a review." Biol Psychol 69(1): 113-32.
[54] Kurki, T, V. Hiilesmaa, et al. (2000). "Depression and anxiety in early pregnancy and risk for preeclampsia." Obstet Gynecol 95(4): 487-90.
[55] Landgraf, R. (2006). "The involvement of the vasopressin system in stress-related disorders." CNS Neurol Disord Drug Targets 5(2): 167-79.
[56] Legradi, G, D. Holzer, et al. (1997). "Glucocorticoids inhibit stress-induced phosphorylation of CREB in corticotropin-releasing hormone neurons of the hypothalamic paraventricular nucleus." Neuroendocrinology 66(2): 86-97.
[57] Legros, J. J. (2001). "Inhibitory effect of oxytocin on corticotrope function in humans:are vasopressin and oxytocin ying-yang neurohormones?" Psychoneuroendocrinology 26(7): 649-55.
[58] Lehnert, H., C. Schulz, et al. (1998). "Physiological and neurochemical aspects of corticotropin-releasing factor actions in the brain: the role of the locus coeruleus."Neurochem Res 23(8): 1039-52.
[59] Liu, W., J. Wang, et al. (1995). "Steroid receptor heterodimerization demonstrated in vitro and in vivo." Proc Natl Acad Sci U S A 92(26): 12480-4.
[60] Liu, Z., F. Zhu, et al. (2006). "Association of corticotropin-releasing hormone receptorl gene SNP and haplotype with major depression." Neurosci Lett 404(3): 358-62.
[61] Livesey, J. H., A. Carne, et al. (1991). "Structure of equine corticotropin releasing factor." Peptides 12(6): 1437-40.
[62] Malkoski, S. P. and R. I. Dorin (1999). "Composite glucocorticoid regulation at a functionally defined negative glucocorticoid response element of the human corticotropin-releasing hormone gene." Mol Endocrinol 13(10): 1629-44.
[63] Matsubara, T., H. Funato, et al. (2006). "Reduced Glucocorticoid Receptor alpha Expression in Mood Disorder Patients and First-Degree Relatives." Biol Psychiatry 59(8):689-95.
[64] Meynen, G, U. A. Unmehopa, et al. (2007). "Hypothalamic oxytocin mRNA expression and melancholic depression." Mol Psychiatry 12(2): 118-9.
[65] Meynen, G, U. A. Unmehopa, et al. (2006). "Increased arginine vasopressin mRNA expression in the human hypothalamus in depression: A preliminary report." Biol Psychiatry 60(8): 892-5.
[66] Miller, D. B. and J. P. O'Callaghan (2005). "Depression, cytokines, and glial function."Metabolism 54(5 Suppl 1): 33-8.
[67] Morton, A. (1969). "A quantitative analysis of the normal neuron population of the hypothalamic magnocellular nuclei in man and of their projections to the neurohypophysis." J Comp Neurol 136(2): 143-57.
[68] Muller, M. B. and W. Wurst (2004). "Getting closer to affective disorders: the role of CRH receptor systems." Trends Mol Med 10(8): 409-15.
[69] Murphy, B. E. (1997). "Antiglucocorticoid therapies in major depression: a review."Psychoneuroendocrinology 22 Suppl 1: S125-32.
[70] Nakase, S., I. Kitayama, et al. (1998). "Increased expression of magnocellular arginine vasopressin mRNA in paraventricular nucleus of stress-induced depression-model rats."Life Sci 63(1): 23-31.
[71] Nemeroff, C. B. (1996). "The corticotropin-releasing factor (CRF) hypothesis of depression: new findings and new directions." Mol Psychiatry 1(4): 336-42.
[72] Nemeroff, C. B. and M. J. Owens (2004). "Pharmacologic differences among the SSRIs:focus on monoamine transporters and the HPA axis." CNS Spectr 9(6 Suppl 4): 23-31.
[73] Nemeroff, C. B., E. Widerlov, et al. (1984). "Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients." Science 226(4680): 1342-4.
[74] O'Brien, S. M., L. V. Scott, et al. (2004). "Cytokines: abnormalities in major depression and implications for pharmacological treatment." Hum Psychopharmacol 19(6):397-403.
[75] Oren, D. A., K. L. Wisner, et al. (2002). "An open trial of morning light therapy for treatment of antepartum depression." Am J Psychiatry 159(4): 666-9.
[76] Owens, M. J. (2004). "Selectivity of antidepressants: from the monoamine hypothesis of depression to the SSRI revolution and beyond." J Clin Psychiatry 65 Suppl 4: 5-10.
[77] Papiol, S., B. Arias, et al. (2007). "Genetic variability at HPA axis in major depression and clinical response to antidepressant treatment." J Affect Disord 104(1-3): 83-97.
[78] Pardes, H. (1994). "The significance of health care reform for research, innovations, and academic medicine." Ann N Y Acad Sci 729:132-8; discussion 139-42.
[79] Parry, B. L. and R. P. Newton (2001). "Chronobiological basis of female-specific mood disorders." Neuropsychopharmacology 25(5 Suppl): S102-8.
[80] Piccinelli, M. and G Wilkinson (2000). "Gender differences in depression. Critical review." Br J Psychiatry 177:486-92.
[81] Pope, H. G., Jr., E. M. Kouri, et al. (2000). "Effects of supraphysiologic doses of testosterone on mood and aggression in normal men: a randomized controlled trial." Arch Gen Psychiatry 57(2): 133-40; discussion 155-6.
[82] Purba, J. S., W. J. Hoogendijk, et al. (1996). "Increased number of vasopressin- and oxytocin-expressing neurons in the paraventricular nucleus of the hypothalamus in depression." Arch Gen Psychiatry 53(2): 137-43.
[83] Raadsheer, F. C, W. J. Hoogendijk, et al. (1994). "Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients." Neuroendocrinology 60(4): 436-44.
[84] Raadsheer, F. C, A. A. Sluiter, et al. (1993). "Localization of corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the human hypothalamus;age-dependent colocalization with vasopressin." Brain Res 615(1): 50-62.
[85] Raadsheer, F. C, J. J. van Heerikhuize, et al. (1995). "Corticotropin-releasing hormone mRNA levels in the paraventricular nucleus of patients with Alzheimer's disease and depression." Am J Psychiatry 152(9): 1372-6.
[86] Rabin, B. S., R. Ganguli, et al. (1990). "Interaction between the brain and the immune system." Immunol Ser 52:125-54.
[87] Rivier, J., J. Spiess, et al. (1983). "Characterization of rat hypothalamic corticotropin-releasing factor." Proc Natl Acad Sci U S A 80(15): 4851-5.
[88] Roca, C. A., P. J. Schmidt, et al. (2005). "Sex-related differences in stimulated hypothalamic-pituitary-adrenal axis during induced gonadal suppression." J Clin Endocrinol Metab 90(7): 4224-31.
[89] Rubin, R. T., R. E. Poland, et al. (1987). "Neuroendocrine aspects of primary endogenous depression. I. Cortisol secretory dynamics in patients and matched controls."Arch Gen Psychiatry 44(4): 328-36.
[90] Sallee, F. R., L. Nesbitt, et al. (1995). "Lymphocyte glucocorticoid receptor: predictor of sertraline response in adolescent major depressive disorder (MDD)." Psychopharmacol Bull 31(2): 339-45.
[91] Scheinman, R. I., P. C. Cogswell, et al. (1995). "Role of transcriptional activation of I kappa B alpha in mediation of immunosuppression by glucocorticoids." Science 270(5234): 283-6.
[92] Seeman, M. V. (1997). "Psychopathology in women and men: focus on female hormones." Am J Psychiatry 154(12): 1641-7.
[93] Seidman, S. N. (2001). "Testosterone deficiency and depression in aging men: pathogenic and therapeutic implications." J Gend Specif Med 4(2): 44-8.
[94] Seidman, S. N., A. B. Araujo, et al. (2002). "Low testosterone levels in elderly men with dysthymic disorder." Am J Psychiatry 159(3): 456-9.
[95] Shanks, N. and S. L. Lightman (2001). "The maternal-neonatal neuro-immune interface:are there long-term implications for inflammatory or stress-related disease?" J Clin Invest 108(11): 1567-73.
[96] Shibahara, S., Y. Morimoto, et al. (1983). "Isolation and sequence analysis of the human corticotropin-releasing factor precursor gene." EMBO J 2(5): 775-9.
[97] Silverman, A. I, A. Hou-Yu, et al. (1989). "Corticotropin-releasing factor synapses within the paraventricular nucleus of the hypothalamus." Neuroendocrinology 49(3):291-9.
[98] Skobeloff, E. M., W. H. Spivey, et al. (1996). "The effect of the menstrual cycle on asthma presentations in the emergency department." Arch Intern Med 156(16): 1837-40.
[99] Sossin, W. S., J. M. Fisher, et al. (1989). "Cellular and molecular biology of neuropeptide processing and packaging." Neuron 2(5): 1407-17.
[100] Sousa, A. R., S. J. Lane, et al. (2000). "Glucocorticoid resistance in asthma is associated with elevated in vivo expression of the glucocorticoid receptor beta-isoform." J Allergy Clin Immunol 105(5): 943-50.
[101] Stenzel-Poore, M. P., S. C. Heinrichs, et al. (1994). "Overproduction of corticotropin-releasing factor in transgenic mice: a genetic model of anxiogenic behavior." J Neurosci 14(5 Pt 1): 2579-84.
[102] Swaab, D. F. (2003). "The human hypothalamus. Basic and cllinical aspects.."
[103] Tago, K., F. Tsukahara, et al. (2004). "Regulation of nuclear retention of glucocorticoid receptor by nuclear Hsp90." Mol Cell Endocrinol 213(2): 131-8.
[104] Trapp, T., R. Rupprecht, et al. (1994). "Heterodimerization between mineralocorticoid and glucocorticoid receptor: a new principle of glucocorticoid action in the CNS." Neuron 13(6): 1457-62.
[105] Turnbull, A. V. and C. L. Rivier (1999). "Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: actions and mechanisms of action."Physiol Rev 79(1): 1-71.
[106] Valdez GR, Zorrilla EP, et al. (2005). "Homeostasis within the corticotropin-releasing factor system via CRF2 receptor activation: a novel approach for the treatment of anxiety." Drug Dev Res 65: 205-215.
[107] Vale, W., J. Spiess, et al. (1981). "Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin." Science 213(4514): 1394-7.
[108] Vamvakopoulos, N. C. and G P. Chrousos (1993). "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 92(4): 1896-902.
[109] van West, D., F. Van Den Eede, et al. (2006). "Glucocorticoid receptor gene-based SNP analysis in patients with recurrent major depression." Neuropsychopharmacology 31(3):620-7.
[110] Veith, R. C, N. Lewis, et al. (1993). "Effect of desipramine on cerebrospinal fluid concentrations of corticotropin-releasing factor in human subjects." Psychiatry Res 46(1):1-8.
[111] Wasserman, D., M. Sokolowski, et al. (2007). The CRHR1 gene: a marker for suicidality in depressed males exposed to low stress. Genes Brain Behav.
[112] Webster, J. C, R. H. Oakley, et al. (2001). "Proinflammatory cytokines regulate human glucocorticoid receptor gene expression and lead to the accumulation of the dominant negative beta isoform: a mechanism for the generation of glucocorticoid resistance." Proc Natl Acad Sci U S A 98(12): 6865-70.
[113] Whalley, L. I, N. Borthwick, et al. (1986). "Glucocorticoid receptors and depression." Br Med J (Clin Res Ed) 292(6524): 859-61.
[114] Wichers, M. C, G Kenis, et al. (2007). "Interferon-alpha-induced depressive symptoms are related to changes in the cytokine network but not to cortisol." J Psychosom Res 62(2): 207-14.
[115] Wolkowitz, O. M., V. I. Reus, et al. (1999). "Antiglucocorticoid treatment of depression: double-blind ketoconazole." Biol Psychiatry 45(8): 1070-4.
[116] Yehuda, R., D. Boisoneau, et al. (1993). "Glucocorticoid receptor number and cortisol excretion in mood, anxiety, and psychotic disorders." Biol Psychiatry 34(1-2): 18-25.
[117] Young, E. A., J. F. Lopez, et al. (2003). "Mineralocorticoid receptor function in major depression." Arch Gen Psychiatry 60(1): 24-8.
[1] Bale, T. L, A. Contarino, et al. (2000). "Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress." Nat Genet 24(4):410-4.
[2] Bamberger, C. M., H. M. Schulte, et al. (1996). "Molecular determinants of glucocorticoid receptor function and tissue sensitivity to glucocorticoids." Endocr Rev 17(3): 245-61.
[3] Bao, A. M., D. F. Fischer, et al. (2006). "A direct androgenic involvement in the expression of human corticotropin-releasing hormone." Mol Psychiatry 11(6): 567-76.
[4] Bao, A. M., A. Hestiantoro, et al. (2005). "Colocalization of corticotropin-releasing hormone and oestrogen receptor-alpha in the paraventricular nucleus of the hypothalamus in mood disorders." Brain 128(Pt 6): 1301-13.
[5] Bao, A. M., G. Meynen, et al. (2007). "The stress system in depression and neurodegeneration: Focus on the human hypothalamus." Brain Res Rev.
[6] Barden, N. (1996). "Modulation of glucocorticoid receptor gene expression by antidepressant drugs." Pharmacopsychiatry 29(1): 12-22.
[7] Batschelet (1981). "Circular statistics in biology." New York: Academic Press.
[8] Besedovsky, H. O. and A. del Rey (1996). "Immune-neuro-endocrine interactions: facts and hypotheses." Endocr Rev 17(1): 64-102.
[9] Braak, H. and E. Braak (1991). "Neuropathological stageing of Alzheimer-related changes."Acta Neuropathol (Berl) 82(4): 239-59.
[10] Checkley, S. (1996). "The neuroendocrinology of depression and chronic stress." Br Med Bull 52(3): 597-617.
[11] de Kloet, E. R., R. H. Derijk, et al. (2007). "Therapy Insight: is there an imbalanced response of mineralocorticoid and glucocorticoid receptors in depression?" Nat Clin Pract Endocrinol Metab 3(2): 168-79.
[12] DeRijk, R. H., M. Schaaf, et al. (2003). "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 116(1-2): 17-26.
[13] Geng, Y.-G., Q.-R. Su, et al. (2007). "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." International Journal of Neuroscience 117(4): 539 -547.
[14] Grammatopoulos, D. K. and G. P. Chrousos (2002). "Functional characteristics of CRH receptors and potential clinical applications of CRH-receptor antagonists." Trends Endocrinol Metab 13(10): 436-44.
[15] Hayley, S., M. 0. Poulter, et al. (2005). "The pathogenesis of clinical depression: stressor- and cytokine-induced alterations of neuroplasticity." Neuroscience 135(3): 659-78.
[16] Heuser, I., G. Bissette, et al. (1998). "Cerebrospinal fluid concentrations of corticotropin-releasing hormone, vasopressin, and somatostatin in depressed patients and healthy controls: response to amitriptyline treatment." Depress Anxiety 8(2): 71-9.
[17] Himmerich, H., E. B. Binder, et al. (2006). "Successful antidepressant therapy restores the disturbed interplay between TNF-alpha system and HPA axis." Biol Psychiatry 60(8): 882-8.
[18] Holsboer, F. (2001). "Stress, hypercortisolism and corticosteroid receptors in depression:implications for therapy." J Affect Disord 62(1-2): 77-91.
[19] Holsboer, F., N. Barden (1996). "Antidepressants and hypothalamic-pituitary-adrenocortical regulation." Endocr Rev 17(2): 187-205.
[20] Huitinga, I., M. van der Cammen, et al. (2000). "IL-1beta immunoreactive neurons in the human hypothalamus: reduced numbers in multiple sclerosis." J Neuroimmunol 107(1):8-20.
[21] Hurbin, A., L. Boissin-Agasse, et al. (1998). "The Via 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 139(11): 4701-7.
[22] Hurbin, A., H. Orcel, et al. (2002). "The vasopressin receptors colocalize with vasopressin in the magnocellular neurons of the rat supraoptic nucleus and are modulated by water balance." Endocrinology 143(2): 456-66.
[23] Imaki, T., H. Katsumata, et al. (2001). "Expression of corticotropin-releasing hormone type 1 receptor in paraventricular nucleus after acute stress." Neuroendocrinology 73(5): 293-301.
[24] Imaki, T., M. Naruse, et al. (1996). "Corticotropin-releasing factor up-regulates its own receptor mRNA in the paraventricular nucleus of the hypothalamus." Brain Res Mol Brain Res 38(1): 166-70.
[25] Kamphuis, W., A. Schneemann, et al. (2001). "Prostanoid receptor gene expression profile in human trabecular meshwork: a quantitative real-time PCR approach." Invest Ophthalmol Vis Sci 42(13): 3209-15.
[26] Keck, M. E. and F. Holsboer (2001). "Hyperactivity of CRH neuronal circuits as a target for therapeutic interventions in affective disorders." Peptides 22(5): 835-44.
[27] Keck, M. E., T. Welt, et al. (2003). "Reduction of hypothalamic vasopressinergic hyperdrive contributes to clinically relevant behavioral and neuroendocrine effects of chronic paroxetine treatment in a psychopathological rat model." Neuropsychopharmacology 28(2): 235-43.
[28] Kishimoto, T., J. Radulovic, et al. (2000). "Deletion of crhr2 reveals an anxiolytic role for corticotropin-releasing hormone receptor-2." Nat Genet 24(4): 415-9.
[29] Koning, N., L. Bo, et al. (2007). "Downregulation of macrophage inhibitory molecules in multiple sclerosis lesions." Ann Neurol 62(5): 504-14.
[30] Kuno, R., Y. Yoshida, et al. (2006). "The role of TNF-alpha and its receptors in the production of NGF and GDNF by astrocytes." Brain Res 1116(1): 12-8.
[31] Kunzel, H. E., A. W. Zobel, et al. (2003). "Treatment of depression with the CRH-1-receptor antagonist R121919: endocrine changes and side effects." J Psychiatr Res 37(6): 525-33.
[32] Legradi, G., D. Holzer, et al. (1997). "Glucocorticoids inhibit stress-induced phosphorylation of CREB in corticotropin-releasing hormone neurons of the hypothalamic paraventricular nucleus." Neuroendocrinology 66(2): 86-97.
[33] Liu, Z., F. Zhu, et al. (2006). "Association of corticotropin-releasing hormone receptorl gene SNP and haplotype with major depression." Neurosci Lett 404(3): 358-62.
[34] Lund, T. D., D. J. Munson, et al. (2004). "Androgen inhibits, while oestrogen enhances,restraint-induced activation of neuropeptide neurones in the paraventricular nucleus of the hypothalamus." J Neuroendocrinol 16(3): 272-8.
[35] Mansi, J. A., S. Rivest, et al. (1996). "Regulation of corticotropin-releasing factor type 1 (CRF1) receptor messenger ribonucleic acid in the paraventricular nucleus of rat hypothalamus by exogenous CRF." Endocrinology 137(11): 4619-29.
[36] Merali, Z., P. Kent, et al. (2006). "Corticotropin-releasing hormone, arginine vasopressin,gastrin-releasing peptide, and neuromedin B alterations in stress-relevant brain regions of suicides and control subjects." Biol Psychiatry 59(7): 594-602.
[37] Meynen, G, U. A. Unmehopa, et al. (2007). "Hypothalamic oxytocin mRNA expression and melancholic depression." Mol Psychiatry 12(2): 118-9.
[38] Meynen, G, U. A. Unmehopa, et al. (2006). "Increased arginine vasopressin mRNA expression in the human hypothalamus in depression: A preliminary report." Biol Psychiatry 60(8): 892-5.
[39] Miller, D. B. and J. P. O'Callaghan (2005). "Aging, stress and the hippocampus." Ageing Res Rev 4(2): 123-40.
[40] Muller, M. B. and W. Wurst (2004). "Getting closer to affective disorders: the role of CRH receptor systems." Trends Mol Med 10(8): 409-15.
[41] Nakase, S., I. Kitayama, et al. (1998). "Increased expression of magnocellular arginine vasopressin mRNA in paraventricular nucleus of stress-induced depression-model rats." Life Sci 63(1): 23-31.
[42] Nemeroff, C. B. (1996). "The corticotropin-releasing factor (CRF) hypothesis of depression: new findings and new directions." Mol Psychiatry 1(4): 336-42.
[43] Nestler, E. I, M. Barrot, et al. (2002). "Neurobiology of depression." Neuron 34(1): 13-25.
[44] Nicholson, R. C, B. R. King, et al. (2004). "Complex regulatory interactions control CRH gene expression." Front Biosci 9: 32-9.
[45] O'Brien, S. M., L. V. Scott, et al. (2004). "Cytokines: abnormalities in major depression and implications for pharmacological treatment." Hum Psychopharmacol 19(6): 397-403.
[46] Osterlund, M. K., J. A. Gustafsson, et al. (2000). "Estrogen receptor beta (ERbeta) messenger ribonucleic acid (mRNA) expression within the human forebrain: distinct distribution pattern to ERalpha mRNA." J Clin Endocrinol Metab 85(10): 3840-6.
[47] Paech, K., P. Webb, et al. (1997). "Differential ligand activation of estrogen receptors ERalpha and ERbeta at AP1 sites." Science 277(5331): 1508-10.
[48] Papiol, S., B. Arias, et al. (2007). "Genetic variability at HPA axis in major depression and clinical response to antidepressant treatment." J Affect Disord.
[49] Purba, J. S., W. J. Hoogendijk, et al. (1996). "Increased number of vasopressin- and oxytocin-expressing neurons in the paraventricular nucleus of the hypothalamus in depression." Arch Gen Psychiatry 53(2): 137-43.
[50] Raadsheer, F.C., W. J. Hoogendijk, et al. (1994). "Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients." Neuroendocrinology 60(4): 436-44.
[51] Raadsheer, F. C, J. J. van Heerikhuize, et al. (1995). "Corticotropin-releasing hormone mRNA levels in the paraventricular nucleus of patients with Alzheimer's disease and depression." Am J Psychiatry 152(9): 1372-6.
[52] Shen, W. W., H. C. Liu, et al. (2006). "Anti-heat shock protein 90 is increased in acute mania." Aust N Z J Psychiatry 40(8): 712-6.
[53] Shimizu, S., K. Nomura, et al. (1996). "An allel-specific abnormal transcript of the heat shock protein 70 gene in patients with major depression." Biochem Biophys Res Commun 219(3): 745-52.
[54] Silverman, A. J., A. Hou-Yu, et al. (1989). "Corticotropin-releasing factor synapses within the paraventricular nucleus of the hypothalamus." Neuroendocrinology 49(3): 291-9.
[55] Stenzel-Poore, M. P., S. C. Heinrichs, et al. (1994). "Overproduction of corticotropin-releasing factor in transgenic mice: a genetic model of anxiogenic behavior." J Neurosci 14(5 Pt 1): 2579-84.
[56] Swaab, D. F. (2003). "The human hypothalamus. Basic and cllinical aspects.."
[57] Tissing, W. J., J. P. Meijerink, et al. (2005). "mRNA expression levels of (co)chaperone molecules of the glucocorticoid receptor are not involved in glucocorticoid resistance in pediatric ALL." Leukemia 19(5): 727-33.
[58] Trapp, T. and F. Holsboer (1996). "Heterodimerization between mineralocorticoid and glucocorticoid receptors increases the functional diversity of corticosteroid action." Trends Pharmacol Sci 17(4): 145-9.
[59] Trapp, T., R. Rupprecht, et al. (1994). "Heterodimerization between mineralocorticoid and glucocorticoid receptor: a new principle of glucocorticoid action in the CNS." Neuron 13(6):1457-62.
[60] Valdez GR, Zorrilla EP, et al. (2005)." Homeostasis within the corticotropin-releasing factor system via CRF2 receptor activation: a novel approach for the treatment of anxiety." Drug Dev Res 65: 205-215.
[61] Vamvakopoulos, N. C. and G. P. Chrousos (1993). "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 92(4): 1896-902.
[62] Vandesompele, J., K. De Preter, et al. (2002). "Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes." Genome Biol 3(7): RESEARCH0034.
[63] Veith, R. C, N. Lewis, et al. (1993). "Effect of desipramine on cerebrospinal fluid concentrations of corticotropin-releasing factor in human subjects." Psychiatry Res 46(1):1-8.
[64] Wigger, A., M. M. Sanchez, et al. (2004). "Alterations in central neuropeptide expression,release, and receptor binding in rats bred for high anxiety: critical role of vasopressin."Neuropsychopharmacology 29(1): 1-14.
[65] Wolfl, S., C. Martinez, et al. (1999). "Inducible binding of cyclic adenosine 3',5'-monophosphate (cAMP)-responsive element binding protein (CREB) to a cAMP-responsive promoter in vivo." Mol Endocrinol 13(5): 659-69.
[66] Young, E. A., J. F. Lopez, et al. (2003). "Mineralocorticoid receptor function in major depression." Arch Gen Psychiatry 60(1): 24-8.
[67] Zubenko, G S., B. Maher, et al. (2003). "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 123(1): 1-18.
[1] Bao, A. M., D. F. Fischer, et al. (2006). "A direct androgenic involvement in the expression of human corticotropin-releasing hormone." Mol Psychiatry 11(6): 567-76.
[2] Bao, A. M., A. Hestiantoro, et al. (2005). "Colocalization of corticotropin-releasing hormone and oestrogen receptor-alpha in the paraventricular nucleus of the hypothalamus in mood disorders." Brain 128(Pt6): 1301-13.
[3] Bao, A. M. and D. F. Swaab (2007). "Gender difference in age-related number of corticotropin-releasing hormone-expressing neurons in the human hypothalamic paraventricular nucleus and the role of sex hormones." Neuroendocrinology 85(1): 27-36.
[4] de Kloet, E. R. (2003). "Hormones, brain and stress." Endocr Regul 37(2): 51-68.
[5] de Kloet, E. R., R. H. Derijk, et al. (2007). "Therapy Insight: is there an imbalanced response of mineralocorticoid and glucocorticoid receptors in depression?" Nat Clin Pract Endocrinol Metab 3(2): 168-79.
[6] Griebel, G., G Perrault, et al. (1998). "Characterization of the behavioral profile of the non-peptide CRF receptor antagonist CP-154,526 in anxiety models in rodents. Comparison with diazepam and buspirone." Psychopharmacology (Berl) 138(1): 55-66.
[7] Groenink, L., T. Pattij, et al. (2003). "5-HT1A receptor knockout mice and mice overexpressing corticotropin-releasing hormone in models of anxiety." Eur J Pharmacol 463(1-3): 185-97.
[8] Imaki, T., H. Katsumata, et al. (2001). "Expression of corticotropin-releasing hormone type 1 receptor in paraventricular nucleus after acute stress." Neuroendocrinology 73(5): 293-301.
[9] Imaki, T., M. Naruse, et al. (1996). "Corticotropin-releasing factor up-regulates its own receptor mRNA in the paraventricular nucleus of the hypothalamus." Brain Res Mol Brain Res 38(1): 166-70.
[10] Joels, M., H. Karst, et al. (2007). "The coming out of the brain mineralocorticoid receptor."Trends Neurosci.
[11] Keck, M. E., T. Welt, et al. (2003). "Reduction of hypothalamic vasopressinergic hyperdrive contributes to clinically relevant behavioral and neuroendocrine effects of chronic paroxetine treatment in a psychopathological rat model." Neuropsychopharmacology 28(2): 235-43.
[12] Keck, M. E., A. Wigger, et al. (2002). "Vasopressin mediates the response of the combined dexamethasone/CRH test in hyper-anxious rats: implications for pathogenesis of affective disorders." Neuropsychopharmacology 26(1): 94-105.
[13] Kuroda, Y., Y. Watanabe, et al. (1994). "Effects of adrenalectomy and type I or type II glucocorticoid receptor activation on 5-HT1A and 5-HT2 receptor binding and 5-HT transporter mRNA expression in rat brain." Brain Res 648(1): 157-61.
[14] Landgraf, R. (2006). "The involvement of the vasopressin system in stress-related disorders."CNS Neurol Disord Drug Targets 5(2): 167-79.
[15] Landgraf, R., R. Gerstberger, et al. (1995). "VI vasopressin receptor antisense oligodeoxynucleotide into septum reduces vasopressin binding, social discrimination abilities,and anxiety-related behavior in rats." J Neurosci 15(6): 4250-8.
[16] Lopez, J. F., D. M. Vazquez, et al. (1997). "Regulation of 5-HT receptors and the hypothalamic-pituitary-adrenal axis. Implications for the neurobiology of suicide." Ann N Y Acad Sci 836:106-34.
[17] Lund, T. D., D. J. Munson, et al. (2004). "Androgen inhibits, while oestrogen enhances,restraint-induced activation of neuropeptide neurones in the paraventricular nucleus of the hypothalamus." J Neuroendocrinol 16(3): 272-8.
[18] Makino, S., K. Hashimoto, et al. (2002). "Multiple feedback mechanisms activating corticotropin-releasing hormone system in the brain during stress." Pharmacol Biochem Behav 73(1): 147-58.
[19] Mansbach, R. S., E. N. Brooks, et al. (1997). "Antidepressant-like effects of CP-154,526, a selective CRF1 receptor antagonist." Eur J Pharmacol 323(1): 21-6.
[20] Mansi, J. A., S. Rivest, et al. (1996). "Regulation of corticotropin-releasing factor type 1 (CRF1) receptor messenger ribonucleic acid in the paraventricular nucleus of rat hypothalamus by exogenous CRF." Endocrinology 137(11): 4619-29.
[21] Meynen, G, U. A. Unmehopa, et al. (2006). "Increased arginine vasopressin mRNA expression in the human hypothalamus in depression: A preliminary report." Biol Psychiatry 60(8): 892-5.
[22] Nakase, S., I. Kitayama, et al. (1998). "Increased expression of magnocellular arginine vasopressin mRNA in paraventricular nucleus of stress-induced depression-model rats." Life Sci 63(1): 23-31.
[23] Olijslagers, J. E. e. a. (2006). "Rapid enhancement of hippocampal glutamate transmission by corticosterone is mediated via the MEK/ERK pathway." FENS Forum Meeting: 152.17.
[24] Ou, X. M., J. M. Stoning, et al. (2001). "Heterodimerization of mineralocorticoid and glucocorticoid receptors at a novel negative response element of the 5-HT1A receptor gene."J BiolChem 276(17): 14299-307.
[25] Purba, J. S., W. J. Hoogendijk, et al. (1996). "Increased number of vasopressin- and oxytocin-expressing neurons in the paraventricular nucleus of the hypothalamus in depression." Arch Gen Psychiatry 53(2): 137-43.
[26] Raadsheer, F. C, W. J. Hoogendijk, et al. (1994). "Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients." Neuroendocrinology 60(4): 436-44.
[27] Raadsheer, F. C, J. J. van Heerikhuize, et al. (1995). "Corticotropin-releasing hormone mRNA levels in the paraventricular nucleus of patients with Alzheimer's disease and depression." Am J Psychiatry 152(9): 1372-6.
[28] Scott, L. V. and T. G. Dinan (2002). "Vasopressin as a target for antidepressant development: an assessment of the available evidence." J Affect Disord 72(2): 113-24.
[29] Silverman, A. J., A. Hou-Yu, et al. (1989). "Corticotropin-releasing factor synapses within the paraventricular nucleus of the hypothalamus." Neuroendocrinology 49(3): 291-9.
[30] Trapp, T. and F. Holsboer (1996). "Heterodimerization between mineralocorticoid and glucocorticoid receptors increases the functional diversity of corticosteroid action." Trends Pharmacol Sci 17(4): 145-9.
[31] Valdez GR, Zorrilla EP, et al. (2005). "Homeostasis within the corticotropin-releasing factor system via CRF2 receptor activation: a novel approach for the treatment of anxiety." Drug Dev Res 65: 205-215.
[32] Vamvakopoulos, N. C. and G. P. Chrousos (1993). "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 92(4): 1896-902.
[33] Wehling, M. and R. Losel (2006). "Non-genomic steroid hormone effects: membrane or intracellular receptors?" J Steroid Biochem Mol Biol 102(1-5): 180-3.
[34] Young, E. A., J. F. Lopez, et al. (2003). "Mineralocorticoid receptor function in major depression." Arch Gen Psychiatry 60(1): 24-8.
[35] Zobel, A. W., T. Nickel, et al. (2000). "Effects of the high-affinity corticotropin-releasing hormone receptor 1 antagonist R121919 in major depression: the first 20 patients treated." J Psychiatr Res 34(3): 171-81.