Abstract
The purpose of the present study was to explore 5HT1A-mediated cortisol release in major depressive disorder (MDD) patients in order to determine whether the degree of 5HT1A-receptor sensitivity can predict response to treatment with selective serotonin reuptake inhibitors (SSRIs). We examined whether the sensitivity of the 5HT1A receptor, as measured by the difference in salivary cortisol levels immediately before and 90 min following the administration of a single dose of the 5HT1A-selective agonist buspirone, predicted treatment outcome following an 8-week, fixed-dose, open trial of the SSRI escitalopram in 17 outpatients with MDD. Change in cortisol levels before and 90 min after the administration of buspirone were not found to predict treatment outcome, whether defined as clinical response (50% or greater reduction in symptom severity), or remission of symptoms. In conclusion, in the present study, we did not find that the change in salivary cortisol levels following the administration of a 5HT1A-selective agonist predicted treatment outcome following an 8-week, fixed-dose, open-label trial of the SSRI escitalopram among outpatients with MDD. Although the 5HT1A-desensetization hypothesis is still a valid one, the results of the present study could not provide any evidence in support.
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Amsterdam JD, Winokur A, Bryant S, Larkin J, Rickels K (1983) The dexamethasone suppression test as a predictor of treatment response. Psychopharmacology (Berl) 80:43–45
Atkinson JH Jr, Kremer EF, Risch SC, Dana R, Janowsky DS (1986) Neuroendocrine responses in psychiatric and pain patients with major depression. Biol Psychiatry 21(7):612–620
Baghai TC, Schüle C, Zwanzger P, Minov C, Holme C, Padberg F, Bidlingmaier M, Strasburger CJ, Rupprecht R (2002) Evaluation of a salivary based combined dexamethasone/CRH test in patients with major depression. Psychoneuroendocrinology 27(3):385–399
Banki CM, Bissette G, Arato M, O’Connor L, Nemeroff CB (1987) CSF corticotropin-releasing factor-like immunoreactivity in depression and schizophrenia. Am J Psychiatry 144:873–877
Baumgartner A, Graf KJ, Kurten I (1986) Serial dexamethasone suppression tests in psychiatric illness: PartII. A study in major depressive disorder. Psychiatry Res 18(1):25–43
Berlin I, Warot D, Legout V, Guillemant S, Schollnhammer G, Puech A (1998) Blunted 5-HT-1A receptor agonist-induced corticotropin and cortisol responses after long-term ipsapirone and fluoxetine administration to healthy subjects. Clin Pharmacol Ther 63(4):428–436
Blier P (2001) Pharmacology of rapid-onset antidepressant treatment strategies. J Clin Psychiatry 62:12–17
Catalan R, Gallard JM, Castellanos JM, Galard R (1998) Plasma corticotropin-releasing factor in depressive disorders. Biol Psychiatry 44:15–20
Cowen PJ (2000) Psychopharmacology of 5-HT(1A) receptors. Nucl Med Biol 27(5):437–439
Cryan JF, Leonard BE (2000) 5-HT1A and beyond: the role of serotonin and its receptors in depression and the antidepressant response. Hum Psychopharmacol 15(2):113–135
Dahl RE, Ryan ND, Puig-Antich J, Nguyen NA, al-Shabbout M, Meyer VA, Perel J (1991) 24-hour cortisol measures in adolescents with major depression: a controlled study. Biol Psychiatry 30(1):25–36
Dinan TG (1996) Serotonin and the regulation of hypothalamic–pituitary–adrenal axis function. Life Sci 58(20):1683–1694
Drevets WC, Thase ME, Moses-Kolko EL, Price J, Frank E, Kupfer DJ, Mathis C (2007) Serotonin-1A receptor imaging in recurrent depression: replication and literature review. Nucl Med Biol 34(7):865–877
Evans DL, Nemeroff CB, Haggerty JJ Jr, Pedersen CA (1987) Use of the dexamethazone suppression test with DSM-III criteria in psychiatrically hospitalized adolescents. Psychoneuroendocrinology 12(3):203–209
First BM, Spitzer RL, Gibbon M, Williams JBW (1995) Structured clinical interview for DSM-IV axis I disorders—patient edition (SCID I/P). Biometrics Research Department, State Psychiatric Institute, New York
Galard R, Gallart JM, Catalan R, Schwartz S, Arguello JM, Castellanos JM (1991) Salivary cortisol levels and their correlation with plasma ACTH levels in depressed patients before and after the DST. Am J Psychiatry 148(4):505–508
Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62
Ising M, Horstmann S, Kloiber S, Lucae S, Binder EB, Kern N, Künzel HE, Pfennig A, Uhr M, Holsboer F (2007) Combined dexamethasone/corticotropin releasing hormone test predicts treatment response in major depression—a potential biomarker? Biol Psychiatry 62(1):47–54
Ising M, Künzel HE, Binder EB, Nickel T, Modell S, Holsboer F (2005) The combined dexamethasone/CRH test as a potential surrogate marker in depression. Prog Neuropsychopharmacol Biol Psychiatry 29(6):1085–1093
Janicak PG, Pandey GN, Sharma R, Boshes R, Bresnahan D, Davis JM (1987) Pretreatment dexamethasone suppression test as a predictor of response to phenelzine. J Clin Psychiatry 48(12):480–482
Kin NM, Nair NP, Schwartz G, Ahmed SK, Holm P, Katona C, Kragh-Sorensen P, Klitgaard N, Song WY, West TE, Stage K (1997) The dexamethazone suppression test and treatment outcome in elderly depressed patients participating in a placebo-controlled multicenter trial involving moclobemide and nortriptyline. Biol Psychiatry 42(10):925–931
Leonard BE (2005) The HPA and immune axes in stress: the involvement of the serotonergic system. Eur Psychiatry 20(3):S302–S306
Lerer B, Gelfin Y, Gorfine M, Allolio B, Lesch KP, Newman ME (1999) 5-HT1A receptor function in normal subjects on clinical doses of fluoxetine: blunted temperature and hormone responses to ipsapirone challenge. Neuropsychopharmacology 20(6):628–639
Linkowski P, Mandlewicz J, Kerkhofs M, Leclercq R, Goldstein J, Brasseur M, Copinschi G, Van Cauter E (1987) 24-hour profiles of adrenocorticotropin, cortisol, and growth hormone in major depressive illness: effect of antidepressant treatment. J Clin Endocrinol Metab 65(1):141–152
Michael A, Jenaway A, Paykel ES, Herbert J (2000) Altered salivary dehydroepiandrosterone levels in major depression. Biol Psychiatry 48(10):989–995
Moffoot AP, O’Carroll RE, Bennie J, Carroll S, Dick H, Ebmeier KP, Goodwin GM (1994) Diurnal variation of mood and neuropsychological function in major depression with melancholia. J Affect Disord 32(4):257–269
Navinés R, Martín-Santos R, Gómez-Gil E, Martínez de Osaba MJ, Imaz ML, Gastó C (2007) Effects of citalopram treatment on hypothermic and hormonal responses to the 5-HT1A receptor agonist buspirone in patients with major depression and therapeutic response. Psychoneuroendocrinology 32(4):411–416
O’Toole SM, Sekula LK, Rubin RT (1997) Pituitary–adrenal cortical axis measures as predictors of sustained remission in major depression. Biol Psychiatry 42(2):85–89
Plotsky PM, Owens MH, Nemeroff CB (1998) Psychoneuroendocrinology of depression Hypothalamic–pituitary–adrenal axis. Psychiatr Clin North Am 21(2):293–307
Posener JA, deBattista C, Williams GH, Chmura Kraemer H, Kalezhan BM, Schatzberg AF (2000) 24-hour monitoring of cortisol and corticotropin secretion in psychotic and nonpsychotic major depression. Arch Gen Psychiatry 57(8):755–760
Raadscheer FC, Hoogendijk WJG, Stam FC, Tilders FJH, Swaab DF (1994) Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients. Neuroendocrinology 60:436–443
Rausch JL, Stahl SM, Hauger RL (1990) Cortisol and growth hormone responses to the 5-HT1A agonist gepirone in depressed patients. Biol Psychiatry 28(1):73–78
Schüle C, Baghai TC, Eser D, Häfner S, Born C, Herrmann S, Rupprecht R (2009) The combined dexamethasone/CRH test (DEX/CRH test) and prediction of acute treatment response in major depression. PLoS ONE 4(1):e4324
Stahl SM (1992) Neuroendocrine markers of serotonin responsivity in depression. Prog Neuropsychopharmacol Biol Psychiatry 16(5):655–659
Stahl S (1994) 5HT1A receptors and pharmacotherapy: Is serotonin receptor down-regulation linked to the mechanism of action of antidepressant drugs? Psychopharmacol Bull 30(1):39–43
Stahl SM (1998) Mechanism of action of selective serotonin reuptake inhibitors: Serotonin receptors and pathways mediate therapeutic effects and side effects. J Affect Disord 51(3):215–235
Thase ME, Dube S, Bowler K, Howland RH, Myers JE (1996) Hypothalamic–pituitary–adrenocortical activity and response to cognitive behavior therapy in unmedicated, hospitalized depressed patients. Am J Psychiatry 153(7):886–891
Weber B, Lewicka S, Deuschle M, Colla M, Vecsei P, Heuser I (2000) Increased diurnal plasma concentrations of cortisone in depressed patients. J Clin Endocrinol Metab 85(3):1133–1136
Wong ML, Kling MA, Munson PJ, Listwak S, Licino J, Prolo P, Karp B, McCutcheon IE, Geracioti TJ Jr, DeBellis MD, Rice KC, Goldstein DS, Veldhuis JD, Chrousos GP, Oldfield EH, McCann SM, Gold PW (2000) Pronounced and sustained central hypernoradrenergic function in major depression with melancholic features: relation to hypercortisolism and corticotropin-releasing hormone. Proc Natl Acad Sci USA 97(1):325–330
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Supported by the Harvard Medical School/Kaplen Fellowship and Livingston Award in Depression Research (GIP).
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Papakostas, G.I., Chuzi, S.E., Sousa, J.L. et al. 5HT1A-mediated stimulation of cortisol release in major depression: use of non-invasive cortisol measurements to predict clinical response. Eur Arch Psychiatry Clin Neurosci 260, 175–180 (2010). https://doi.org/10.1007/s00406-009-0035-z
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DOI: https://doi.org/10.1007/s00406-009-0035-z