Dexamethasone Suppression Tests in Antidepressant Treatment of Melancholia

Greden, John F.; Gardner, Robert; King, Doug; Grunhaus, Leon; Carroll, Bernard J.; Kronfol, Ziad

doi:10.1001/archpsyc.1983.01790050019002

Cited by 342 publications

(34 citation statements)

References 19 publications

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“…Given that the ability of antidepressants to regulate the HPA axis is tightly coupled to their clinical efficacy (Holsboer and Barden, 1996;Greden et al, 1983;Ribeiro et al, 1993;Zobel et al, 2001), these data suggest that upregulation of the endocannabinoid system is involved in the normalization of hypercortisolemia that accompanies remission of depression. These data also support the suggestion that the endocannabinoid system could serve as a suitable target for the development of novel antidepressants (Hill and Gorzalka, 2005a;Jiang et al, 2005;Gobbi et al, 2005), especially for melancholic depression , which exhibits a preferential response to tricyclic antidepressants and reliably exhibits hyperactivity of the HPA axis (Rush and Weissenburger, 1994;Bielski and Friedel, 1976;Gold and Chrousos, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the ability of glucocorticoid hormones to exert negative feedback on HPA axis activity appears to be deficient in depression, resulting in a feed-forward hyperactivation of this system (Parker et al, 2003;Holsboer, 2000). This enhanced output of the HPA axis appears functionally relevant to depression, as long-term antidepressant treatment attenuates this phenomenon in humans (De Bellis et al, 1993;Pariante et al, 2004;Greden et al, 1983;Michelson et al, 1997), and suppresses stress-induced activation of the HPA axis in other species (Reul et al, 1993;Connor et al, 2000;Holsboer and Barden, 1996;de Medeiros et al, 2005;Butterweck et al, 2001;Stout et al, 2002). The ability of antidepressants to suppress HPA axis hyperactivity has been shown to be coupled to their clinical efficacy (Appelhof et al, 2006;Young et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…The ability of antidepressants to suppress HPA axis hyperactivity has been shown to be coupled to their clinical efficacy (Appelhof et al, 2006;Young et al, 2004). Specifically, normalization of glucocorticoid feedback and hypersecretion is associated with clinical remission, and patients who do not exhibit normalization of this system exhibit a significantly higher tendency to experience depressive relapse and have a poorer long-term prognosis (Ribeiro et al, 1993;Greden et al, 1983;Zobel et al, 2001). These data demonstrate that the ability of antidepressants to regulate the HPA axis could be integral to the remission of depressive symptoms; however, the mechanism by which antidepressants exert this effect is currently not well understood.…”

Section: Introductionmentioning

confidence: 99%

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Involvement of the Endocannabinoid System in the Ability of Long-Term Tricyclic Antidepressant Treatment to Suppress Stress-Induced Activation of the Hypothalamic–Pituitary–Adrenal Axis

Hill

Sinopoli

et al. 2006

Neuropsychopharmacol

110

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The efficacy of antidepressants has been linked in part to their ability to reduce activity of the hypothalamic-pituitary-adrenal (HPA) axis; however, the mechanism by which antidepressants regulate the HPA axis is largely unknown. Given that recent research has demonstrated that endocannabinoids can regulate the HPA axis and exhibit antidepressant potential, we examined the hypothesis that the endocannabinoid system is regulated by long-term antidepressant treatment. Three-week administration of the tricyclic antidepressant desipramine (10 mg/kg/day) resulted in a significant increase in the density of the cannabinoid CB 1 receptor in the hippocampus and hypothalamus, without significantly altering endocannabinoid content in any brain structure examined. Furthermore, chronic desipramine treatment resulted in a reduction in both secretion of corticosterone and the induction of the immediate early gene c-fos in the medial dorsal parvocellular region of the paraventricular nucleus of the hypothalamus (PVN) following a 5 min exposure to swim stress. Acute treatment with the CB 1 receptor antagonist, AM251 (1 mg/kg), before exposure to swim stress, completely occluded the ability of desipramine to reduce both corticosterone secretion and induction of c-fos expression in the PVN. Collectively, these data demonstrate that CB 1 receptor density in the hippocampus and hypothalamus is increased by chronic tricyclic antidepressant treatment, and suggest that this upregulation could contribute to the ability of tricyclic antidepressants to suppress stress-induced activation of the HPA axis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Involvement of the Endocannabinoid System in the Ability of Long-Term Tricyclic Antidepressant Treatment to Suppress Stress-Induced Activation of the Hypothalamic–Pituitary–Adrenal Axis

Hill

Sinopoli

et al. 2006

Neuropsychopharmacol

110

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“…Serial DSTs during a variety of antidepressant drug treatment revealed that whenever cortisol suppression was inappropriate, i.e., above a certain threshold, normalization of the neuroendocrine dysregulation was necessary for clinical remission to become manifest. In addition, if post-dexamethasone plasma cortisol levels increased over time or remained elevated the likelihood for an unfavorable clinical course or nonresponse to treatment was high (Holsboer et al 1982;Greden et al 1983).…”

Section: Functional Impairment Of Central Corticosteroid Receptors CLmentioning

confidence: 99%

The Corticosteroid Receptor Hypothesis of Depression

Holsboer

2000

Neuropsychopharmacology

1,995

1,228

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Clinical EvidenceUntil now, the serendipitous discovery of antidepressants in the 1950s has profoundly inspired hypotheses of the pathogenesis of depression. The well-known pharmacological effects of antidepressants on presynaptic uptake transporters and degradating enzymes (i.e., MAO) of serotonin and norepinephrine has focused research on causality and treatment of depression on the metabolism of functional biogenic amines and the capacity of their respective receptors to alter intracellular signaling pathways that ultimately induce changes in gene activity. Elevated circulating levels of stress hormones among depressives were recognized even before antidepressants were discovered, but these changes were seen as epiphenomena, reflecting the stressful experience of depression, although M. Bleuler (1919) already demonstrated that hormones have diverse psychotropic effects and suggested hormone treatments as potential antidepressants. A vast amount of evidence has accumulated, that reject the view that altered stress hormone secretions in depression are epiphenomenal. During the past decade, several research groups formulated a hypothesis relating aberrant stress hormone dysregulation to causality of depression and submitted that antidepressants may act through normalisation of these HPA changes (

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“…In depressed patients, tricyclic antidepressants and monoamine oxidase inhibitors normalize cortisol levels and restore the suppressibility of cortisol by dexamethasone [26, 27]. Similarly, the endocrine changes seen in the transgenic mouse are normalized by antidepressants such as desipramine [28].…”

Section: Introductionmentioning

confidence: 99%

Central 5-Hydroxytryptamine-2A Receptor Expression in Transgenic Mice Bearing a Glucocorticoid Receptor Antisense

Cyr

Charbonneau²,

Morissette³

et al. 2001

Neuroendocrinology

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Transgenic mice bearing a transgene coding for a glucocorticoid receptor antisense mRNA that partially blocks glucocorticoid receptor expression were used to investigate the long-term effect of hypothalamic-pituitary-adrenal dysfunction on brain 5-hydroxytryptamine-2A (5-HT_2A) receptor expression. The brain 5-HT_2A receptor mRNA levels in transgenic mice were measured by in situ hybridization and compared to those in control mice. We also studied the effect of a 3-week treatment with fluoxetine on brain 5-HT_2A receptor expression in the transgenic mice. No difference in 5-HT_2A mRNA levels was observed between transgenic and control mice in cortical or striatal regions, and fluoxetine treatment was without effect. No difference in hypothalamic 5-HT_2A mRNA levels was observed between transgenic and control mice, while fluoxetine treatment increased these levels in both transgenic as well as in the hypothalamic ventromedial and paraventricular nuclei of control mice. 5-HT_2A receptor mRNA levels were similar in hippocampal CA1 and CA2 subregions of control and transgenic, but were lower in the CA3 and CA4 subregions of transgenic mice. Fluoxetine had no effect on 5-HT_2A mRNA levels of transgenic mice but reduced control mouse 5-HT_2A receptor mRNA levels in the CA3 subregion. These results suggest that impaired glucocorticoid receptor function can affect hippocampal 5-HT_2A receptor expression in transgenic mice and that this is not corrected by fluoxetine treatment.

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Dexamethasone Suppression Tests in Antidepressant Treatment of Melancholia

Cited by 342 publications

References 19 publications

Involvement of the Endocannabinoid System in the Ability of Long-Term Tricyclic Antidepressant Treatment to Suppress Stress-Induced Activation of the Hypothalamic–Pituitary–Adrenal Axis

Involvement of the Endocannabinoid System in the Ability of Long-Term Tricyclic Antidepressant Treatment to Suppress Stress-Induced Activation of the Hypothalamic–Pituitary–Adrenal Axis

The Corticosteroid Receptor Hypothesis of Depression

Central 5-Hydroxytryptamine-2A Receptor Expression in Transgenic Mice Bearing a Glucocorticoid Receptor Antisense

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