Abstract
Stress activates the central and peripheral components of the stress system, i.e., the hypothalamic-pituitary-adrenal (HPA) axis and the arousal/sympathetic system. The principal effectors of the stress system are corticotropin-releasing hormone (CRH), arginine vasopressin, the proopiomelanocortin-derived peptides α-melanocyte-stimulating hormone and β-endorphin, the glucocorticoids, and the catecholamines norepinephrine and epinephrine. Appropriate responsiveness of the stress system to stressors is a crucial prerequisite for a sense of well-being, adequate performance of tasks and positive social interactions. By contrast, inappropriate responsiveness of the stress system may impair growth and development, and may account for a number of endocrine, metabolic, autoimmune and psychiatric disorders. The development and severity of these conditions primarily depend on the genetic vulnerability of the individual, the exposure to adverse environmental factors and the timing of the stressful event(s), given that prenatal life, infancy, childhood and adolescence are critical periods characterized by increased vulnerability to stressors. The developing brain undergoes rapid growth and is characterized by high turnover of neuronal connections during the prenatal and early postnatal life. These processes and, hence, brain plasticity, slow down during childhood and puberty, and plateau in young adulthood. Hormonal actions in early life, and to a much lesser extent later, can be organizational, i.e., can have effects that last for long periods of time, often for the entire life of the individual. Hormones of the stress system and sex steroids have such effects, which influence the behavior and certain physiologic functions of individuals for life. Exposure of the developing brain to severe and/or prolonged stress may result in hyperactivity/hyperreactivity of the stress system, with resultant amygdala hyperfunction (fear reaction), decreased activity of the hippocampus (defective glucocorticoid-negative feedback, cognition), and the mesocorticolimbic dopaminergic system (dysthymia, novelty-seeking, addictive behaviors), hyperactivation of the HPA axis (hypercortisolism), suppression of reproductive, growth, thyroid and immune functions, and changes in pain perception. These changes may be accompanied by abnormal childhood, adolescent and adult behaviors, including excessive fear (‘inhibited child syndrome’) and addictive behaviors, dysthymia and/or depression, and gradual development of components of the metabolic syndrome X, including visceral obesity and essential hypertension. Prenatal stress exerted during the period of sexual differentiation may be accompanied by impairment of this process with behavioral and/or somatic sequelae. The vulnerability of individuals to develop varying degrees and/or components of the above life-long syndrome is defined by as yet unidentified genetic factors, which account for up to 60% of the variance. CRH has marked kindling and glucocorticoids have strong consolidating properties, hence both of these hormones are crucial in development and can alone produce the above syndrome. CRH and glucocorticoids may act in synergy, as in acoustic startle, while glucocorticoids may suppress or stimulate CRH, as in the hypothalamus and amygdala, respectively. A CRH type 1 receptor antagonist, antalarmin, inhibits both the development and expression of conditioned fear in rats, and has anxiolytic properties in monkeys. Profound stressors, such as those from sexual abuse, may elicit the syndrome in older children, adolescents and adults. Most frequently, chronic dysthymia and/or depression may develop in association with gastrointestinal complaints and/or the premenstrual tension syndrome. A lesser proportion of individuals may develop the classic posttraumatic stress disorder, which is characterized by hypocortisolism and intrusive and avoidance symptoms; in younger individuals it may present as dissociative personality disorder.
References
1.
Habib KE, Gold PW, Chrousos GP: Neuroendocrinology of stress. Endocrinol Metab Clin North Am 2001;30:695–728.
2.
Chrousos GP, Gold PW: The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA 1992;267:1244–1252.
3.
Chrousos GP: Organization and integration of the endocrine system; in Sperling M (ed): Pediatric Endocrinology. Philadelphia, Saunders, 1996, pp 1–14.
4.
Calogero AE, Gallucci WT, Chrousos GP, Gold PW: Catecholamine effects upon rat hypothalamic corticotropin-releasing hormone secretion in vitro. J Clin Invest 1988;82:839–846.
5.
Valentino RJ, Foote SL, Aston-Jones G: Corticotropin-releasing factor activates noradrenergic neurons of the locus coeruleus. Brain Res 1983;270:363–367.
6.
Kiss A, Aguilera G: Participation of α1-adrenergic receptors in the secretion of hypothalamic corticotropin-releasing hormone during stress. Neuroendocrinology 1992;56:153–160.
7.
Calogero AE, Gallucci WT, Gold PW, Chrousos GP: Multiple feedback regulatory loops upon rat hypothalamic corticotropin-releasing hormone secretion. Potential clinical implications. J Clin Invest 1988;82:767–774.
8.
Silverman AJ, Hou-Yu A, Chen WP: Corticotropin-releasing factor synapses within the paraventricular nucleus of the hypothalamus. Neuroendocrinology 1989;49:291–299.
9.
Aghajanian GK, Van der Maelen CP: α2-Adrenoceptor-mediated hyperpolarization of locus coeruleus neurons: Intracellular studies in vivo. Science 1982;215:1394–1396.
10.
Calogero AE, Bagdy G, Szemeredi K, Tartaglia ME, Gold PW, Chrousos GP: Mechanisms of serotonin receptor agonist-induced activation of the hypothalamic-pituitary-adrenal axis in the rat. Endocrinology 1990;126:1888–1894.
11.
Fuller RW: Serotonin receptors involved in regulation of pituitary-adrenocortical function in rats. Behav Brain Res 1996;73:215–219.
12.
Calogero AE, Gallucci WT, Chrousos GP, Gold PW: Interaction between GABAergic neurotransmission and rat hypothalamic corticotropin-releasing hormone secretion in vitro. Brain Res 1988;463:28–36.
13.
Overton JM, Fisher LA: Modulation of central nervous system actions of corticotropin-releasing factor by dynorphin-related peptides. Brain Res 1989;488:233–240.
14.
Keller-Wood ME, Dallman MF: Corticosteroid inhibition of ACTH secretion. Endocr Rev 1984;5:1–24.
15.
Chrousos GP: Regulation and dysregulation of the hypothalamic-pituitary-adrenal axis: The corticotropin-releasing hormone perspective. Endocrinol Metab Clin North Am 1992;21:833–858.
16.
Tsigos C, Chrousos GP: Physiology of the hypothalamic-pituitary-adrenal axis in health and dysregulation in psychiatric and autoimmune disorders. Endocrinol Metab Clin North Am 1994;23:451–466.
17.
Gillies GE, Linton EA, Lowry PJ: Corticotropin-releasing activity of the new CRF is potentiated several times by vasopressin. Nature 1982;299:355–357.
18.
Abou-Samra AB, Harwood JP, Catt KJ, Aguilera G: Mechanisms of action of CRF and other regulators of ACTH release in pituitary corticotrophs. Ann NY Acad Sci 1987;512:67–84.
19.
Horrocks PM, Jones AF, Ratcliffe WA, Holder G, White A, Holder R, Ratcliffe JG, London DR: Patterns of ACTH and cortisol pulsatility over twenty-four hours in normal males and females. Clin Endocrinol (Oxf) 1990;32:127–134.
20.
Iranmanesh A, Lizarralde G, Short D, Veldhuis JD: Intensive venous sampling paradigms disclose high-frequency adrenocorticotropin release episodes in normal men. J Clin Endocrinol Metab 1990;71:1276–1283.
21.
Veldhuis JD, Iranmanesh A, Johnson ML, Lizarralde G: Amplitude, but not frequency, modulation of adrenocorticotropin secretory bursts gives rise to the nyctohemeral rhythm of the corticotropic axis in man. J Clin Endocrinol Metab 1990;71:452–463.
22.
Calogero AE, Norton JA, Sheppard BC, Listwak SJ, Cromack DT, Wall R, Jensen RT, Chrousos GP: Pulsatile activation of the hypothalamic-pituitary-adrenal axis during major surgery. Metabolism 1992;41:839–845.
23.
Holmes MC, Antoni FA, Aguilera G, Catt KJ: Magnocellular axons in passage through the median eminence release vasopressin. Nature 1986;319:326–329.
24.
Andreis PG, Neri G, Mazzocchi G, Musajo F, Nussdorfer GG: Direct secretagogue effect of corticotropin-releasing factor on the rat adrenal cortex: The involvement of the zona medullaris. Endocrinology 1992;131:69–72.
25.
Ottenweller JE, Meier AH: Adrenal innervation may be an extrapituitary mechanism able to regulate adrenocortical rhythmicity in rats. Endocrinology 1982;111:1334–1338.
26.
Bornstein SR, Chrousos GP: Clinical review 104: Adrenocorticotropin (ACTH)- and non-ACTH-mediated regulation of the adrenal cortex: Neural and immune inputs. J Clin Endocrinol Metab 1999;84:1729–1736.
27.
Munck A, Guyre PM, Holbrook NJ: Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev 1984;5:25–44.
28.
Kino T, Chrousos GP: Glucocorticoid and mineralocorticoid resistance/hypersensitivity syndromes. J Endocrinol 2001;169:437–445.
29.
Chrousos GP: The neuroendocrinology of stress: Its relation to the hormonal milieu, growth and development. Growth Genet Horm 1997;13:1–8.
30.
Roth RH, Tam SY, Ida Y, Yang JX, Deutch AY: Stress and the mesocorticolimbic dopamine systems. Ann NY Acad Sci 1988;537:138–147.
31.
Imperato A, Puglisi-Allegra S, Casolini P, Angelucci L: Changes in brain dopamine and acetylcholine release during and following stress are independent of the pituitary-adrenocortical axis. Brain Res 1991;538:111–117.
32.
Diorio D, Viau V, Meaney MJ: The role of the medial prefrontal cortex (cingulate gyrus) in the regulation of hypothalamic-pituitary-adrenal responses to stress. J Neurosci 1993;13:3839–3847.
33.
Gray TS: Amygdala: Role in autonomic and neuroendocrine responses to stress; in McCubbin JA, Kaufman PG, Nemeroff CB (eds): Stress, Neuropeptides and Systemic Disease. New York, Academic Press, 1989, p 37.
34.
Nikolarakis KE, Almeida OF, Herz A: Stimulation of hypothalamic β-endorphin and dynorphin release by corticotropin-releasing factor (in vitro). Brain Res 1986;399:152–155.
35.
Diamant M, de Wied D: Autonomic and behavioral effects of centrally administered corticotropin-releasing factor in rats. Endocrinology 1991;129:446–454.
36.
Mora F, Lee TF, Myers RD: Involvement of α- and β-adrenoreceptors in the central action of norepinephrine on temperature, metabolism, heart and respiratory rates of the conscious primate. Brain Res Bull 1983;11:613–616.
37.
Liu JP, Clarke IJ, Funder JW, Engler D: Studies of the secretion of corticotropin-releasing factor and arginine vasopressin into the hypophyseal-portal circulation of the conscious sheep. II. The central noradrenergic and neuropeptide Y pathways cause immediate and prolonged hypothalamic-pituitary-adrenal activation. Potential involvement in the pseudo-Cushing’s syndrome of endogenous depression and anorexia nervosa. J Clin Invest 1994;93:1439–1450.
38.
Egawa M, Yoshimatsu H, Bray GA: Neuropeptide Y suppresses sympathetic activity to interscapular brown adipose tissue in rats. Am J Physiol 1991;260:R328–R334.
39.
Rahmouni K, Haynes WG: Leptin signaling pathways in the central nervous system: Interactions between neuropeptide Y and melanocortins. Bioessays 2001;23:1095–1099.
40.
Raposinho PD, Pierroz DD, Broqua P, White RB, Pedrazzini T, Aubert ML: Chronic administration of neuropeptide Y into the lateral ventricle of C57BL/6J male mice produces an obesity syndrome including hyperphagia, hyperleptinemia, insulin resistance and hypogonadism. Mol Cell Endocrinol 2001;185:195–204.
41.
Burguera B, Muruais C, Penalva A, Dieguez C, Casanueva FF: Dual and selective actions of glucocorticoids upon basal and stimulated growth hormone release in man. Neuroendocrinology 1990;51:51–58.
42.
Magiakou MA, Mastorakos G, Gomez MT, Rose SR, Chrousos GP: Suppressed spontaneous and stimulated growth hormone secretion in patients with Cushing’s disease before and after surgical cure. J Clin Endocrinol Metab 1994;78:131–137.
43.
Magiakou MA, Mastorakos G, Chrousos GP: Final stature in patients with endogenous Cushing’s syndrome. J Clin Endocrinol Metab 1994;79:1082–1085.
44.
Bamberger CM, Schulte HM, Chrousos GP: Molecular determinants of glucocorticoid receptor function and tissue sensitivity to glucocorticoids. Endocr Rev 1996;17:245–261.
45.
Raza J, Massoud AF, Hindmarsh PC, Robinson IC, Brook CG: Direct effects of corticotrophin-releasing hormone on stimulated growth hormone secretion. Clin Endocrinol (Oxf) 1998;48:217–222.
46.
Uhde TW, Tancer ME, Rubinow DR, Roscow DB, Boulenger JP, Vittone B, Gurguis G, Geraci M, Black B, Post RM: Evidence for hypothalamo-growth hormone dysfunction in panic disorder: Profile of growth hormone responses to clonidine, yohimbine, caffeine, glucose, GRF and TRH in panic disorder patients versus healthy volunteers. Neuropsychopharmacology 1992;6:101–118.
47.
Abelson JL, Glitz D, Cameron OG, Lee MA, Bronzo M, Curtis GC: Blunted growth hormone response to clonidine in patients with generalized anxiety disorder. Arch Gen Psychiatry 1991;48:157–162.
48.
Rodgers BD, Lau AO, Nicoll CS: Hypophysectomy or adrenalectomy of rats with insulin-dependent diabetes mellitus partially restores their responsiveness to growth hormone. Proc Soc Exp Biol Med 1994;207:220–226.
49.
Skuse D, Albanese A, Stanhope R, Gilmour J, Voss L: A new stress-related syndrome of growth failure and hyperphagia in children, associated with reversibility of growth hormone insufficiency. Lancet 1996;348:353–358.
50.
Albanese A, Hamill G, Jones J, Skuse D, Matthews DR, Stanhope R: Reversibility of physiological growth hormone secretion in children with psychosocial dwarfism. Clin Endocrinol (Oxf) 1994;40:687–692.
51.
Malozowski S, Muzzo S, Burrows R, Leiva L, Loriaux L, Chrousos G, Winterer J, Cassorla F: The hypothalamic-pituitary-adrenal axis in infantile malnutrition. Clin Endocrinol (Oxf) 1990;32:461–465.
52.
Brun TA, Nezam-Mafi S, Moshiri M, Margen S: Growth hormone response to arginine infusion in malnourished children. Diabetes Metab 1978;4:27–33.
53.
Goodfriend MS: Treatment of attachment disorder of infancy in a neonatal intensive care unit. Pediatrics 1993;91:139–142.
54.
Goland RS, Jozak S, Warren WB, Conwell IM, Stark RI, Tropper PJ: Elevated levels of umbilical cord plasma corticotropin-releasing hormone in growth-retarded fetuses. J Clin Endocrinol Metab 1993;77:1174–1179.
55.
Chrousos GP, Gold PW: The inhibited child syndrome; in Schmidt LA, Schulkin J (eds): Origins, Biological Mechanisms and Clinical Outcomes. New York, Oxford University Press 1999, pp 193–200.
56.
Benker G, Raida M, Olbricht T, Wagner R, Reinhardt W, Reinwein D: TSH secretion in Cushing’s syndrome: Relation to glucocorticoid excess, diabetes, goitre and the ‘sick euthyroid syndrome’. Clin Endocrinol (Oxf) 1990;33:777–786.
57.
Rivier C, Rivier J, Vale W: Stress-induced inhibition of reproductive functions: Role of endogenous corticotropin-releasing factor. Science 1986;231:607–609.
58.
Vamvakopoulos NC, Chrousos GP: Hormonal regulation of human corticotropin-releasing hormone gene expression: Implications for the stress response and immune/inflammatory reaction. Endocr Rev 1994;15:409–420.
59.
Chrousos GP, Torpy DJ, Gold PW: Interactions between the hypothalamic-pituitary-adrenal axis and the female reproductive system: Clinical implications. Ann Intern Med 1998;129:229–240.
60.
MacAdams MR, White RH, Chipps BE: Reduction of serum testosterone levels during chronic glucocorticoid therapy. Ann Intern Med 1986;104:648–651.
61.
Pau KY, Spies HG: Neuroendocrine signals in the regulation of gonadotropin-releasing hormone secretion. Chin J Physiol 1997;40:181–196.
62.
Mantzoros CS: Role of leptin in reproduction. Ann N Y Acad Sci 2000;900:174–183.
63.
Luger A, Deuster PA, Kyle SB, Gallucci WT, Montgomery LC, Gold PW, Loriaux DL, Chrousos GP: Acute hypothalamic-pituitary-adrenal responses to the stress of treadmill exercise. Physiologic adaptations to physical training. N Engl J Med 1987;316:1309–1315.
64.
MacConnie SE, Barkan A, Lampman RM, Schork MA, Beitins IZ: Decreased hypothalamic gonadotropin-releasing hormone secretion in male marathon runners. N Engl J Med 1986;315:411–417.
65.
Vamvakopoulos NC, Chrousos GP: Evidence of direct estrogenic regulation of human corticotropin-releasing hormone gene expression. Potential implications for the sexual dimorphism of the stress response and immune/inflammatory reaction. J Clin Invest 1993;92:1896–1902.
66.
Sasaki A, Shinkawa O, Margioris AN, Liotta AS, Sato S, Murakami O, Go M, Shimizu Y, Hanew K, Yoshinaga K: Immunoreactive corticotropin-releasing hormone in human plasma during pregnancy, labor and delivery. J Clin Endocrinol Metab 1987;64:224–229.
67.
Sasaki A, Liotta AS, Luckey MM, Margioris AN, Suda T, Krieger DT: Immunoreactive corticotropin-releasing factor is present in human maternal plasma during the third trimester of pregnancy. J Clin Endocrinol Metab 1984;59:812–814.
68.
Gold PW, Loriaux DL, Roy A, Kling MA, Calabrese JR, Kellner CH, Nieman LK, Post RM, Pickar D, Gallucci W, et al: Responses to corticotropin-releasing hormone in the hypercortisolism of depression and Cushing’s disease. Pathophysiologic and diagnostic implications. N Engl J Med 1986;314:1329–1335.
69.
Pasquali R, Cantobelli S, Casimirri F, Capelli M, Bortoluzzi L, Flamia R, Labate AM, Barbara L: The hypothalamic-pituitary-adrenal axis in obese women with different patterns of body fat distribution. J Clin Endocrinol Metab 1993;77:341–346.
70.
Chrousos GP: The role of stress and the hypothalamic-pituitary-adrenal axis in the pathogenesis of the metabolic syndrome: Neuroendocrine and target tissue-related causes. Int J Obes Relat Metab Disord 2000;24(suppl 2):S50–S55.
71.
Roy MS, Roy A, Gallucci WT, Collier B, Young K, Kamilaris TC, Chrousos GP: The ovine corticotropin-releasing hormone-stimulation test in type 1 diabetic patients and controls: Suggestion of mild chronic hypercortisolism. Metabolism 1993;42:696–700.
72.
Gold PW, Chrousos GP: Organization of the stress system and its dysregulation in melancholic and atypical depression: High vs. low CRH/NE states. Mol Psychiatry 2002;7:254–275.
73.
Tsigos C, Young RJ, White A: Diabetic neuropathy is associated with increased activity of the hypothalamic-pituitary-adrenal axis. J Clin Endocrinol Metab 1993;76:554–558.
74.
Michelson D, Stratakis C, Hill L, Reynolds J, Galliven E, Chrousos G, Gold P: Bone mineral density in women with depression. N Engl J Med 1996;335:1176–1181.
75.
Tache Y, Monnikes H, Bonaz B, Rivier J: Role of CRF in stress-related alterations of gastric and colonic motor function. Ann NY Acad Sci 1993;697:233–243.
76.
Habib KE, Weld KP, Rice KC, Pushkas J, Champoux M, Listwak S, Webster EL, Atkinson AJ, Schulkin J, Contoreggi C, Chrousos GP, McCann SM, Suomi SJ, Higley JD, Gold PW: Oral administration of a corticotropin-releasing hormone receptor antagonist significantly attenuates behavioral, neuroendocrine and autonomic responses to stress in primates. Proc Natl Acad Sci USA 2000;97:6079–6084.
77.
Suto G, Kiraly A, Tache Y: Interleukin-1β inhibits gastric emptying in rats: Mediation through prostaglandin and corticotropin-releasing factor. Gastroenterology 1994;106:1568–1575.
78.
Drossman DA, Leserman J, Nachman G, Li ZM, Gluck H, Toomey TC, Mitchell CM: Sexual and physical abuse in women with functional or organic gastrointestinal disorders. Ann Intern Med 1990;113:828–833.
79.
Chrousos GP: The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N Engl J Med 1995;332:1351–1362.
80.
Boumpas DT, Chrousos GP, Wilder RL, Cupps TR, Balow JE: Glucocorticoid therapy for immune-mediated diseases: Basic and clinical correlates. Ann Intern Med 1993;119:1198–1208.
81.
DeRijk R, Michelson D, Karp B, Petrides J, Galliven E, Deuster P, Paciotti G, Gold PW, Sternberg EM: Exercise and circadian rhythm-induced variations in plasma cortisol differentially regulate IL-1β, IL-6 and TNF-α production in humans: High sensitivity of TNF-α and resistance of IL-6. J Clin Endocrinol Metab 1997;82:2182–2191.
82.
Van Gool J, van Vugt H, Helle M, Aarden LA: The relation among stress, adrenalin, interleukin-6 and acute phase proteins in the rat. Clin Immunol Immunopathol 1990;57:200–210.
83.
Mastorakos G, Weber JS, Magiakou MA, Gunn H, Chrousos GP: Hypothalamic-pituitary-adrenal axis activation and stimulation of systemic vasopressin secretion by recombinant interleukin-6 in humans: Potential implications for the syndrome of inappropriate vasopressin secretion. J Clin Endocrinol Metab 1994;79:934–939.
84.
Mastorakos G, Chrousos GP, Weber JS: Recombinant interleukin-6 activates the hypothalamic-pituitary-adrenal axis in humans. J Clin Endocrinol Metab 1993;77:1690–1694.
85.
Elenkov IJ, Papanicolaou DA, Wilder RL, Chrousos GP: Modulatory effects of glucocorticoids and catecholamines on human interleukin-12 and interleukin-10 production: Clinical implications. Proc Assoc Am Physicians 1996;108:374–381.
86.
Elenkov IJ, Chrousos GP: Stress hormones, Th1/Th2 patterns, pro/anti-inflammatory cytokines and susceptibility to disease. Trends Endocrinol Metab 1999;10:359–368.
87.
Gold PW, Goodwin FK, Chrousos GP: Clinical and biochemical manifestations of depression. Relation to the neurobiology of stress. 1. N Engl J Med 1988;319:348–353.
88.
Gold PW, Goodwin FK, Chrousos GP: Clinical and biochemical manifestations of depression. Relation to the neurobiology of stress. 2. N Engl J Med 1988;319:413–420.
89.
Wong ML, Kling MA, Munson PJ, Listwak S, Licinio J, Prolo P, Karp B, McCutcheon IE, Geracioti TD Jr, DeBellis MD, Rice KC, Goldstein DS, Veldhuis JD, Chrousos GP, Oldfield EH, McCann SM, Gold PW: Pronounced and sustained central hypernoradrenergic function in major depression with melancholic features: Relation to hypercortisolism and corticotropin-releasing hormone. Proc Natl Acad Sci USA 2000;97:325–330.
90.
De Bellis MD, Chrousos GP, Dorn LD, Burke L, Helmers K, Kling MA, Trickett PK, Putnam FW: Hypothalamic-pituitary-adrenal axis dysregulation in sexually abused girls. J Clin Endocrinol Metab 1994;78:249–255.
91.
De Bellis MD, Lefter L, Trickett PA, Putnam FW Jr: Urinary catecholamine excretion in sexually abused girls. J Am Acad Child Adolesc Psychiatry 1994;33:320–327.
92.
Kaye WH, Gwirtsman HE, George DT, Ebert MH, Jimerson DC, Tomai TP, Chrousos GP, Gold PW: Elevated cerebrospinal fluid levels of immunoreactive corticotropin-releasing hormone in anorexia nervosa: Relation to state of nutrition, adrenal function, and intensity of depression. J Clin Endocrinol Metab 1987;64:203–208.
93.
Gold PW, Pigott TA, Kling MA, Kalogeras K, Chrousos GP: Basic and clinical studies with corticotropin-releasing hormone. Implications for a possible role in panic disorder. Psychiatr Clin North Am 1988;11:327–334.
94.
Wand GS, Dobs AS: Alterations in the hypothalamic-pituitary-adrenal axis in actively drinking alcoholics. J Clin Endocrinol Metab 1991;72:1290–1295.
95.
Von Bardeleben U, Heuser I, Holsboer F: Human CRH stimulation response during acute withdrawal and after medium-term abstention from alcohol abuse. Psychoneuroendocrinology 1989;14:441–449.
96.
Jeanrenaud B, Rohner-Jeanrenaud F: CNS-periphery relationships and body weight homeostasis: Influence of the glucocorticoid status. Int J Obes Relat Metab Disord 2000(suppl 2):S74–S76.
97.
Pacak K, McCarty R, Palkovits M, Cizza G, Kopin IJ, Goldstein DS, Chrousos GP: Decreased central and peripheral catecholaminergic activation in obese Zucker rats. Endocrinology 1995;136:4360–4367.
98.
Ehlert U, Gaab J, Heinrichs M: Psychoneuroendocrinological contributions to the etiology of depression, posttraumatic stress disorder, and stress-related bodily disorders: The role of the hypothalamus-pituitary-adrenal axis. Biol Psychol 2001;57:141–152.
99.
Demitrack MA, Crofford LJ: Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome. Ann NY Acad Sci 1998;840:684–697.
100.
Puddey IB, Vandongen R, Beilin LJ, English D: Haemodynamic and neuroendocrine consequences of stopping smoking – A controlled study. Clin Exp Pharmacol Physiol 1984;11:423–426.
101.
Gomez MT, Magiakou MA, Mastorakos G, Chrousos GP: The pituitary corticotroph is not the rate-limiting step in the postoperative recovery of the hypothalamic-pituitary-adrenal axis in patients with Cushing’s syndrome. J Clin Endocrinol Metab 1993;77:173–177.
102.
Sternberg EM, Hill JM, Chrousos GP, Kamilaris T, Listwak SJ, Gold PW, Wilder RL: Inflammatory mediator-induced hypothalamic-pituitary-adrenal axis activation is defective in streptococcal cell wall arthritis-susceptible Lewis rats. Proc Natl Acad Sci USA 1989;86:2374–2378.
103.
Petrich J, Holmes TH: Life change and onset of illness. Med Clin North Am 1977;61:825–838.
104.
Chikanza IC, Petrou P, Kingsley G, Chrousos G, Panayi GS: Defective hypothalamic response to immune and inflammatory stimuli in patients with rheumatoid arthritis. Arthritis Rheum 1992;35:1281–1288.
105.
Magiakou MA, Mastorakos G, Rabin D, Dubbert B, Gold PW, Chrousos GP: Hypothalamic corticotropin-releasing hormone suppression during the postpartum period: Implications for the increase in psychiatric manifestations at this time. J Clin Endocrinol Metab 1996;81:1912–1917.
106.
Elenkov IJ, Wilder RL, Bakalov VK, Link AA, Dimitrov MA, Fisher S, Crane M, Kanik KS, Chrousos GP: IL-12, TNF-α and hormonal changes during late pregnancy and early postpartum: Implications for autoimmune disease activity. J Clin Endocrinol Metab 2001;86:4933–4938.
107.
Plomin R, Owen MJ, McGuffin P: The genetic basis of complex human behaviors. Science 1994;264:1733–1739.
108.
Bouchard TJ Jr: Genes, environment and personality. Science 1994;264:1700–1701.
109.
Suomi SJ: Early stress and adult emotional reactivity in rhesus monkeys. Ciba Found Symp 1991;156:171–188.
110.
Goland RS, Jozak S, Warren WB, Conwell IM, Stark RI, Tropper PJ: Elevated levels of umbilical cord plasma corticotropin-releasing hormone in growth-retarded fetuses. J Clin Endocrinol Metab 1993;77:1174–1179.
111.
Ward IL: Prenatal stress feminizes and demasculinizes the behavior of males. Science 1972;175:82–84.
112.
Ward IL: Sexual behavioral differentiation: Prenatal hormonal and environmental control; in Friedman RC, Richard RM, Van de Wiele RL (eds): Sex Differences in Behavior. New York, Wiley, 1974, pp 3–17.
113.
Pollard I, Dyer SL: Effect of stress administered during pregnancy on the development of fetal testes and their subsequent function in the adult rat. J Endocrinol 1985;107:241–245.
114.
Holson RR, Gough B, Sullivan P, Badger T, Sheehan DM: Prenatal dexamethasone or stress but not ACTH or corticosterone alter sexual behavior in male rats. Neurotoxicol Teratol 1995;17:393–401.
115.
Francis DD, Caldji C, Champagne F, Plotsky PM, Meaney MJ: The role of corticotropin-releasing factor–norepinephrine systems in mediating the effects of early experience on the development of behavioral and endocrine responses to stress. Biol Psychiatry 1999;46:1153–1166.
116.
Meaney MJ: Maternal care, gene expression and the transmission of individual differences in stress reactivity across generations. Annu Rev Neurosci 2001;24:1161–1192.
117.
Liu D, Caldji C, Sharma S, Plotsky PM, Meaney MJ: Influence of neonatal rearing conditions on stress-induced adrenocorticotropin responses and norepinepherine release in the hypothalamic paraventricular nucleus. J Neuroendocrinol 2000;12:5–12.
118.
Caldji C, Francis D, Sharma S, Plotsky PM, Meaney MJ: The effects of early rearing environment on the development of GABAA and central benzodiazepine receptor levels and novelty-induced fearfulness in the rat. Neuropsychopharmacology 2000;22:219–229.
119.
Otagiri A, Wakabayashi I, Shibasaki T: Selective corticotropin-releasing factor type 1 receptor antagonist blocks conditioned fear-induced release of noradrenaline in the hypothalamic paraventricular nucleus of rats. J Neuroendocrinol 2000;12:1022–1026.
120.
Habib KE, Weld KP, Rice KC, Pushkas J, Champoux M, Listwak S, Webster EL, Atkinson AJ, Schulkin J, Contoreggi C, Chrousos GP, McCann SM, Suomi SJ, Higley JD, Gold PW: Oral administration of a corticotropin-releasing hormone receptor antagonist significantly attenuates behavioral, neuroendocrine and autonomic responses to stress in primates. Proc Natl Acad Sci USA 2000;97:6079–6084.
121.
Liu D, Diorio J, Tannenbaum B, Caldji C, Francis D, Freedman A, Sharma S, Pearson D, Plotsky PM, Meaney MJ: Maternal care, hippocampal glucocorticoid receptors and hypothalamic-pituitary-adrenal responses to stress. Science 1997;277:1659–1662.
122.
Caldji C, Diorio J, Meaney MJ: Variations in maternal care in infancy regulate the development of stress reactivity. Biol Psychiatry 2000;48:1164–1174.
123.
McCauley J, Kern DE, Kolodner K, Dill L, Schroeder AF, DeChant HK, Ryden J, Derogatis LR, Bass EB: Clinical characteristics of women with a history of childhood abuse: Unhealed wounds. JAMA 1997;277:1362–1368.
124.
Holmes SJ, Robins LN: The role of parental disciplinary practices in the development of depression and alcoholism. Psychiatry 1988;51:24–36.
125.
Canetti L, Bachar E, Galili-Weisstub E, De-Nour AK, Shalev AY: Parental bonding and mental health in adolescence. Adolescence 1997;32:381–394.
126.
Russak LG, Schwartz GE: Feelings of parental care predict health status in midlife: A 35-year follow-up of the Harvard Mastery of Stress Study. J Behav Med 20:1–11.
127.
Heim C, Newport DJ, Bonsall R, Miller AH, Nemeroff CB: Altered pituitary-adrenal axis responses to provocative challenge tests in adult survivors of childhood abuse. Am J Psychiatry 2001;158:575–581.
128.
Chrousos GP: The future of pediatric and adolescent endocrinology. Ann NY Acad Sci 1997;816:4–8.
© 2003 S. Karger AG, Basel
2003
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.
