Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states

Abstract

Stress precipitates depression and alters its natural history. Major depression and the stress response share similar phenomena, mediators and circuitries. Thus, many of the features of major depression potentially reflect dysregulations of the stress response. The stress response itself consists of alterations in levels of anxiety, a loss of cognitive and affective flexibility, activation of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system, and inhibition of vegetative processes that are likely to impede survival during a life-threatening situation (eg sleep, sexual activity, and endocrine programs for growth and reproduction). Because depression is a heterogeneous illness, we studied two diagnostic subtypes, melancholic and atypical depression. In melancholia, the stress response seems hyperactive, and patients are anxious, dread the future, lose responsiveness to the environment, have insomnia, lose their appetite, and a diurnal variation with depression at its worst in the morning. They also have an activated CRH system and may have diminished activities of the growth hormone and reproductive axes. Patients with atypical depression present with a syndrome that seems the antithesis of melancholia. They are lethargic, fatigued, hyperphagic, hypersomnic, reactive to the environment, and show diurnal variation of depression that is at its best in the morning. In contrast to melancholia, we have advanced several lines of evidence of a down-regulated hypothalamic-pituitary adrenal axis and CRH deficiency in atypical depression, and our data show us that these are of central origin. Given the diversity of effects exerted by CRH and cortisol, the differences in melancholic and atypical depression suggest that studies of depression should examine each subtype separately. In the present paper, we shall first review the mediators and circuitries of the stress system to lay the groundwork for placing in context physiologic and structural alterations in depression that may occur as part of stress system dysfunction. Molecular Psychiatry (2002) 7, 254-275. DOI: 10.1038/sj/mp/4001032 Keywords: atypical depression; corticotropin releasing hormone (CRH); melancholic depression; norepinephrine (NE); stress Stress precipitates major depression and influences its incidence, severity and course. 1,2 The stress response and major depression share many features because of similar brain circuitries and mediators (reviewed in 3-5 ). Each is associated with a diminution of cognitive and affective flexibility, alterations in arousal, and perturbations in neuroendocrine and autonomic function (reviewed in 5 ). Because major depression is a heterogeneous disorder, we focus here on two subtypes, melancholic and atypical depression. Our data and those of others indicate that the principal arousal producing mediators of the stress response, such as the corticotropin releasing hormone (CRH) system, are hyperactive in melancholic depression. 6 Not surprisingly, melan- cholia is associated with anxiety, dread of the ...

Emotional eating and food intake after sadness and joy

“…This is remarkable, because the typical and predominant response of people is to eat less when being in a sad mood (Gold & Chrousos, 2002, Stone & Brownell, 1994. However, on close inspection and when comparing the food intake of the low emotional eaters in the present study with those of a different study with a distress manipulation (Van Strien et al, 2012b, study 2, p282) the low emotional eaters ate comparable amounts in the distress condition.…”

“…Inspired by the results of Nolan et al (2010), we hypothesized that people with high scores on the DEBQ-E would show higher food intake after the sad than after the joy mood induction. In contrast, low emotional eaters were expected to show the typical and predominant response to distress (Gold & Chrousos, 2002, Stone & Brownell, 1994 and eat less after the sad than after the joy mood induction. To enhance the chance of finding any interaction effect, which are easily missed in studies with a small number of subjects (Whisman & McClelland, 2005), we only used participants with scores from the extreme ends of the DEBQ emotional eating subscale.…”

Circadian affective, cardiopulmonary, and cortisol variability in depressed and nondepressed individuals at risk for cardiovascular disease

“…Maes and colleagues (1994) suggested that increased activation of the HPA-axis is more prominent in severe than moderate depression. Further, hypercortisolism in depression has been most consistently found in subjects with "severe forms of depression", for instance those with psychotic features (Keller et al, 2006), which none of our subjects had, or with melancholia (Gold & Chrousos, 2002;Stewart, Quitkin, McGrath, & Klein, 2005). Nonpsychotic subjects with more moderate levels of depression may not show hypercortisolemia (Keller et al, 2006).…”

The role of the posterior medial bed nucleus of the stria terminalis in modulating hypothalamic–pituitary–adrenocortical axis responsiveness to acute and chronic stress

“…However, despite the presence of an enhanced glucocorticoid feedback signals, HPA responses to new stressors are either maintained or augmented following chronic stress a process known as stress facilitation (Armario et al, 1985;Bhatnagar and Dallman, 1998;Bhatnagar and Vining, 2003;Dallman et al, 1992;Hauger et al, 1990;Kiss and Aguilera, 1993;Ostrander et al, 2006). Additionally, chronic stress is implicated in the dysregulation of glucocorticoid secretion that is associated with many disease states such as depression, post-traumatic stress disorder (PTSD) and other anxiety disorders (see (Gold and Chrousos, 2002)). …”