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Letter to the Editor   |    
Antidepressant Effects of Hydrocortisone
STUART WATSON, M.D., M.R.C.PSYCH.; ALLAN H. YOUNG, M.D., PH.D., M.R.C.PSYCH.
Am J Psychiatry 2001;158:1536-a-1537. doi:10.1176/appi.ajp.158.9.1536-a

To the Editor: We read with great interest the report by Charles DeBattista, D.M.H., M.D., and co-authors (1) of their double-blind, placebo-controlled trial with depressed patients in which the patients who received 15 mg of intravenous hydrocortisone demonstrated a significantly greater reduction in Hamilton Depression Rating Scale scores over a 24-hour period than those who received placebo or ovine corticotropin-releasing hormone. This mood-elevating effect of hydrocortisone has previously been noted by Goodwin et al. (2). The authors considered a number of explanations for the finding of the antidepressant-like effects of hydrocortisone injections. They hypothesized that the hydrocortisone may have enhanced negative feedback and thereby reduced hypothalamic-pituitary-adrenal axis activity overall, enhanced dopamine activity, corrected a state of hypocortisolemia, or increased β endorphin levels. We suggest an alternative explanation—namely, that the antidepressant effect of hydrocortisone may have been mediated by means of the serotonin (5-HT) system.

The antidepressant effects of tricyclic antidepressants, serotonin-specific reuptake inhibitors, lithium, and ECT are possibly mediated by an attenuation of inhibitory somatodendritic 5-HT1A receptor function, with a subsequent facilitation of 5-HT transmission (3). Elevated plasma cortisol levels, induced by acute stress or administration of hydrocortisone, attenuate somatodendritic 5-HT1A receptor function in both mice and humans, thereby facilitating 5-HT1A neurotransmission in an antidepressant-like manner (46). This is in marked contrast to the effects of long-term elevation of corticosteroids, which reduce postsynaptic 5-HT1A receptor numbers, an effect that may promote depression (7). We propose that this attenuation of somatodendritic 5-HT1A receptor function is the basis of the mood-elevating effects produced by hydrocortisone in the study by Dr. DeBattista et al. and illustrates a potential neurobiological basis of resilience in the face of psychosocial stress. Failure of this response, due, for example, to deficient glucocorticoid receptor function, may be central to the development of depressive illness (8).

DeBattista C, Posener JA, Kalehzan BM, Schatzberg AF: Acute antidepressant effects of intravenous hydrocortisone and CRH in depressed patients: a double-blind, placebo-controlled study. Am J Psychiatry 2000; 157:1334-  1337
 
Goodwin G, Muir W, Seckl J, Bennie J, Carroll S, Dick H, Fink G: The effects of cortisol infusion upon hormone secretion from the anterior pituitary and subjective mood in depressive illness and in controls. J Affect Disord  1992; 26:73-83
[PubMed]
[CrossRef]
 
Goodwin G: The effects of antidepressant treatments and lithium upon 5-HT1A receptor function. Prog Neuropsychopharmacol Biol Psychiatry  1989; 13:445-451
[PubMed]
[CrossRef]
 
Young AH, Sharpley AL, Campling GM, Hockney RA, Cowen PJ: Effects of hydrocortisone on brain 5-HT function and sleep. J Affect Disord  1994; 32:139-146
[PubMed]
[CrossRef]
 
Young AH, Goodwin GM, Dick H, Fink G: Effects of glucocorticoids on 5-HT1A presynaptic function in the mouse. Psychopharmacology  1994; 114:360-364
[PubMed]
[CrossRef]
 
Laaris N, Le Poul E, Laporte A, Hamon M, Lanfumey L: Differential effects of stress on presynaptic and postsynaptic 5-hydroxytryptamine-1A receptors in the rat brain: an in vitro electrophysiological study. Neuroscience  1999; 91:947-958
[PubMed]
[CrossRef]
 
McAllister-Williams RH, Young AH: The pathology of depression: a synthesis of the role of serotonin and corticosteroids, in Advances in Biological Psychiatry, vol 19. Edited by Ebert D, Ebmeier K. Basel, Switzerland, Karger, 1998, pp 170-198
 
Steckler T, Holsboer F, Reul JM: Glucocorticoids and depression. Baillieres Best Pract Res Clin Endocrinol Metab  1999; 13:597-614
[PubMed]
[CrossRef]
 
+

References

DeBattista C, Posener JA, Kalehzan BM, Schatzberg AF: Acute antidepressant effects of intravenous hydrocortisone and CRH in depressed patients: a double-blind, placebo-controlled study. Am J Psychiatry 2000; 157:1334-  1337
 
Goodwin G, Muir W, Seckl J, Bennie J, Carroll S, Dick H, Fink G: The effects of cortisol infusion upon hormone secretion from the anterior pituitary and subjective mood in depressive illness and in controls. J Affect Disord  1992; 26:73-83
[PubMed]
[CrossRef]
 
Goodwin G: The effects of antidepressant treatments and lithium upon 5-HT1A receptor function. Prog Neuropsychopharmacol Biol Psychiatry  1989; 13:445-451
[PubMed]
[CrossRef]
 
Young AH, Sharpley AL, Campling GM, Hockney RA, Cowen PJ: Effects of hydrocortisone on brain 5-HT function and sleep. J Affect Disord  1994; 32:139-146
[PubMed]
[CrossRef]
 
Young AH, Goodwin GM, Dick H, Fink G: Effects of glucocorticoids on 5-HT1A presynaptic function in the mouse. Psychopharmacology  1994; 114:360-364
[PubMed]
[CrossRef]
 
Laaris N, Le Poul E, Laporte A, Hamon M, Lanfumey L: Differential effects of stress on presynaptic and postsynaptic 5-hydroxytryptamine-1A receptors in the rat brain: an in vitro electrophysiological study. Neuroscience  1999; 91:947-958
[PubMed]
[CrossRef]
 
McAllister-Williams RH, Young AH: The pathology of depression: a synthesis of the role of serotonin and corticosteroids, in Advances in Biological Psychiatry, vol 19. Edited by Ebert D, Ebmeier K. Basel, Switzerland, Karger, 1998, pp 170-198
 
Steckler T, Holsboer F, Reul JM: Glucocorticoids and depression. Baillieres Best Pract Res Clin Endocrinol Metab  1999; 13:597-614
[PubMed]
[CrossRef]
 
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