INDUCTION OF DEPRESSION BY EXPOSURE TO DAMP ...

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As support for the monoamine hypothesis waned, other hypothesized mechanisms for the development of depression emerged. Three of the more studied hypotheses involved 1) dysregulation of the HPA axis, 2) elevated peripheral and neurogenic inflammation levels, and 3) decreased neurogenesis and neuroplasticity in various areas of the brain (Gold and Chrousos, 2002; Nemeroff, 1996; Dantzer et al., 2008;Pittenger and Duman, 2008). A fourth and newer hypothesis includes dysregulation between the sympathetic and parasympathetic nervous systems. However, the effects of dysregulation are thought to include over-activation of the HPA axis and a lessening of anti- inflammatory effects of acetylcholine release from afferent vagal nerve fibers (Pavlov et al., 2008). Thus, for the purposes of this paper, dysregulation of autonomic nervous system will be discussed in context of the other three hypotheses. While these three hypotheses may be seen as separate, they are not mutually exclusive and there are vast areas of overlap in mechanisms. The mechanisms explained by all three may be physiologically relevant and explain various manifestations of depression and related disorders. In addition, the dysregulation of neurotransmitters is likely still an important aspect of these disorders, depending on the manifestation, and may be explained by aspects of the newer hypotheses. While the purpose of this paper is not to elaborate in detail on these hypotheses, it is important to discuss the basic evidence and ideas and to relate how they may be induced by exposure to damp buildings. Hypothalamus-Pituitary-Adrenal Axis Dysregulation Hypothesis The HPA axis controls many endocrine hormones, including glucocorticoids, mineralcorticoids, catecholamines (epinephrine and norepinephrine), endorphins, and melanocyte-stimulating hormone (MSH), to name a few. This axis has significant 4
influence on homeostasis, mood, memory, and learning. One mechanism of the HPA axis directly relating to this discussion is the release of glucocorticoids, specifically cortisol from the adrenal glands (Fox, 1996). The mechanism for controlling cortisol release begins with corticotropin-releasing hormone (CRH). First, CRH is released by the paraventricular nucleus of the hypothalamus due to nervous control. Next, CRH is transported to the anterior pituitary through a portal system. Corticotropes in the anterior pituitary are then stimulated by CRH to secrete adrenocorticotropic hormone (ACTH), which travels through the blood to the adrenal glands. The adrenal cortex is stimulated by ACTH to release glucocorticoids. Glucocorticoids prepare the body for stress by facilitating gluconeogenesis and decreasing inflammation and immune cell activity to conserve energy. Glucocorticoids provide a negative feedback loop by binding to glucocorticoid receptors (GR) and mineralcorticoids receptors (MR) in the hypothalamus, lowering the release of CRH (de Kloet, 1991). Many studies have shown abnormalities in the function of the HPA axis in people with psychiatric disorders and those that experience psychological events. Both hypercortisolemia and hypocortisolemia may occur depending on the disorder. Major depression appears to be related to hypercortisolemia due to impaired HPA negative feedback (Gold and Chrousos, 2002; Nemeroff, 1996). Hypercorticosolism has been documented in depressed patients using samples of urine, cerebrospinal fluid and plasma (Zobel et al., 2001; Carroll et al., 1976; Linkowski et al., 1985). Enlargement of both the pituitary and adrenal glands have also been documented (Nemeroff, 1996; Nemeroff et al., 1992; Rubin et al., 1995). Enhanced HPA negative feedback leading to hypocortisolism is associated with atypical depression and other 5
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Page 4 and 5: TABLE OF CONTENTS Introduction ....
Page 6 and 7: generalized and chronic inflammatio
Page 10 and 11: psychological/physiological syndrom
Page 12 and 13: The similarities between symptoms o
Page 14 and 15: noradrenaline availability. Noradre
Page 16 and 17: While neurogenesis is most active i
Page 18 and 19: al., 2008). However, increasing NMD
Page 20 and 21: A polymorphism in a chaperone prote
Page 22 and 23: of prostaglandins, thromboxanes, an
Page 24 and 25: the result of exposure to chemicals
Page 26 and 27: 202 unexposed individuals, the pati
Page 28 and 29: inflammatory reaction in allergic m
Page 30 and 31: may be a factor in chronic inflamma
Page 32 and 33: to 10-100 times greater than that f
Page 34 and 35: While some studies have provided ad
Page 36 and 37: few exceptions, many of the genera
Page 38 and 39: Penicillium notatum, Aspergillus ni
Page 40 and 41: Motile bacteria Flagellin TLR-5 Gra
Page 42 and 43: al., 2007). One study exposed mice
Page 44 and 45: complement present in the plasma as
Page 46 and 47: Fungal and Bacterial Hemolysins and
Page 48 and 49: Donohue and colleagues found that 1
Page 50 and 51: mycotoxins in relation to health ha
Page 52 and 53: References Afrah, A., Gustafsson, H
Page 54 and 55: Cameron, H., McEwen, B., & Gould, E
Page 56 and 57: Fang, L., Clausen, G., & Fanger, P.
Page 58 and 59:
A: kinetics and potentiation by bac
Page 60 and 61:
Miotto, D., hollenberg, M., Bunnett
Page 62 and 63:
Park, J., & Ikeda, K. (2006) Variat
Page 64 and 65:
Shoemaker, R., & House, D. (2006) S
Page 66:
Wichers, M., Koek, G., Robaeys, G.,
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