The Hypothalamic-Pituitary-Adrenal Axis in Major Depressive Disorder

Abstract

BACKGROUND: One of the most enduring and replicated findings in biological psychiatry is activation of the hypothalamic-pituitary-adrenal (HPA) axis in a subset of patients with major depressive disorder. This review will discuss some of these findings and their pertinence to the assessment and treatment of depressed patients. METHOD: MEDLINE, PsychINFO, and Current Contents databases were searched for pertinent articles on the HPA axis in patients with depression. In addition, hand searches were conducted of references from these sources and abstracts from meetings and books on this topic. Articles that would provide an overview of major or interesting studies in the field were selected for inclusion. RESULTS: The data support that HPA axis activation is common in depressed patients. Frequently reported findings include elevated cortisol and corticotropin-releasing hormone (CRH), nonsuppression on the dexamethasone suppression test, a blunted adrenocorticotropic hormone (ACTH) response to CRH, and hippocampal volume reduction. Evidence of HPA axis activation appears to have prognostic value and is associated with increased risk of depression relapse and even suicide. CONCLUSION: Future research in this area will focus on a better understanding of the etiology and long-term consequences of HPA axis activation in depressed patients. In addition, medications that act on the HPA axis are currently in development and may be part of the psychiatrist's and primary care physician's pharmacopoeia in the near future.

Novel Phospholipid Signature of Depressive Symptoms in Patients With Coronary Artery Disease

“…The resulting neuroinflammation increases oxidative stress, which changes neuronal membrane stability and affects catecholamine neurotransmission, a mechanism involved in traditional depressive pathophysiology 35. Similarly, peripheral SA levels increase brain inflammation through activation of toll‐like receptor 4 in the hypothalamus 36 and may be responsible for dysregulation of the hypothalamus‐pituitary‐adrenal axis, a frequent observation in depressed populations 37. Taken together, we postulate that the association of lignoceric acid, PA, and SA with inflammation may be relevant in the progression of depression in CAD.…”

Characterizing the psychophysiological signature of boredom

“…Furthermore, the effects of chronic boredom could be further examined with respect to depression. One of the most highly replicated findings in biological psychiatry is the association of prolonged hypersecretion of HPA axis hormones, including cortisol, and depression (Nemeroff & Evans, 1984;Sachar et al, 1985;Varghese & states.…”

“…Examining the psychophysiology of boredom in such a manner could also help clarify whether boredom is characterized by an increase or a decrease in physiological arousal. Research has indicated that resting heart rates are elevated in individuals with depression as are cortisol levels (Kamphuis et al, 2007;Nemeroff & Evans, 1984;Sachar et al, 1985;Taylor, 2010;Varghese & Brown, 2001;Whooley et al, 2008). It seems then that both boredom and symptoms of depression may be associated with increased physiological arousal.…”

Estrogen receptor beta in the brain: From form to function

“…Major depressive disorder (MDD) is one of the most common psychiatric illnesses with a lifetime prevalence of greater than 17% in the general population (Osterlund et al, 1998;Varghese and Brown, 2001). Several studies have consistently reported that MDD episodes are twice as common in women as compared to men (Angold and Worthman, 1993;Weissman et al, 1993;Kornstein, 1997;Llewellyn et al, 1997).…”