Neuroendocrine predictors of the evolution of depression

Abstract

Depression is both clinically and biologically a heterogeneous entity. Despite advances in psychopharmacology, a significant proportion of depressed patients either continue to have residual symptoms or do not respond to antidepressants. It has therefore become essential to determine parameters (or predictors) that would rationalize the therapeutic choice, taking into account not only the clinical features, but also the "biological state," which is a major determinant in the antidepressant response. Such predictors can derive from bioclinical correlates and, in this context, the neuroendocrine strategy appears particularly suited. Numerous studies have investigated neuroendocrine parameters--derived mainly from dynamic challenge tests--in order to (i) determine the predictive profiles of good clinical responders to given antidepressants; (ii) monitor the progression of markers in parallel with the clinical outcome; and (iii) evaluate "in vivo" in humans the mechanisms of action of antidepressant compounds (before, during, and after treatment). This article does not attempt to be exhaustive, but rather uses selected examples to illustrate the usefulness of the investigation of the adrenal and thyroid axes and the assessment of central serotonergic, noradrenergic, and dopaminergic systems by means of neuroendocrine tests. Given methodological constraints, most of these investigations--except for baseline hormone values and the dexamethasone suppression test--cannot be used routinely in psychiatry. Despite these limitations, the neuroendocrine strategy still offers new insights in biology and the treatment of depression. Its possible expansion depends mainly on the development of specific agonists or antagonists for better investigation of the receptors supposedly involved in the pathophysiology of depression. These investigations will help define more homogeneous subgroups from a bioclinical and therapeutic viewpoint.

Cortisol and the Dexamethasone Suppression Test as a Biomarker for Melancholic Depression: A Narrative Review

“…As clinical pictures of mental disorders are unspecific and do not allow for the unequivocal identification of their etiology, any additional information strengthening the diagnosis is helpful. Originally developed for diagnostic purposes (diagnostic BM), it can also be applied to predict the response to somatic treatments such as ECT and medication with TCAs (predictive BM), as DST nonresponders have a higher probability of a successful treatment [ 101 ]. Patients with a still-positive DST (i.e., nonsuppression) after a remission have a much higher risk of relapse than patients with a normalized DST.…”

Molecular Pathways of the Therapeutic Effects of Ayahuasca, a Botanical Psychedelic and Potential Rapid-Acting Antidepressant

“…The etiology of depression has been related to neuroendocrine changes for many decades. Stress-related changes in HPA axis function which result in increased hypothalamic corticotropin-releasing hormone (CRH) and consequently cortisol secretion have consistently been associated with the emergence of depressive symptoms, although it is not yet understood if this contributes as a cause to depressive symptoms or is an epiphenomenon [ 212 , 213 ]. Preclinical evidence has indicated that antidepressant medications facilitate the negative feedback by endogenous glucocorticoids, which in turn reduces HPA axis activity [ 214 ].…”

Surrogate outcomes in neurology, psychiatry, and psychopharmacology

“…Stress-related dysfunctional neuroendocrine regulation implicating the corticotropin-releasing hormone (CRH) system has been consistently demonstrated in major depression, 28 , 29 and it has been proposed that neurodocrine dynamic challenge tests such as the combined dex/CRH test, serve as a screening tool to demonstrate the antidepressive effects of new compounds in clinical drug trials. 30 , 31 …”