Pharmacopsychiatry 2012; 45(03): 83-95
DOI: 10.1055/s-0031-1291346
Review
© Georg Thieme Verlag KG Stuttgart · New York

Renin-Angiotensin-Aldosterone System: The Forgotten Stress Hormone System: Relationship to Depression and Sleep

H. Murck
1   Covance, Princeton, NJ, USA
3   Clinic of Psychiatry and Psychotherapy of the Philipps University, Marburg, Germany
,
P. Schüssler
2   Max-Planck Institute of Psychiatry, Munich, Germany
,
A. Steiger
2   Max-Planck Institute of Psychiatry, Munich, Germany
› Author Affiliations
Further Information

Publication History

received 22 March 2011
revised 18 September 2011

accepted 05 October 2011

Publication Date:
30 January 2012 (online)

Abstract

Introduction:

Neuroendocrine changes in depression have long been recognized, with a focus mainly on hypercortisolism. The other hormone of the hypothalamus-pituitary adrenocortical system, aldosterone, has been widely neglected.

Methods:

Here we summarize the involvement of the renin-angiotensin-aldosterone system (RAAS) and the regulation of aldosterone in health with a particular focus on sleep-related changes and its role in stress-related conditions, like major depression.

Results:

We highlight its role in functional systems which could be relevant in the therapy for refractory depression, like inflammatory mechanisms, the monoaminergic and the glutamatergic systems. Furthermore, anatomic areas which specifically mediate the action of aldosterone have been identified. In particular the nucleus of the solitary tract (NTS) seems to have an important role and appears to be a target for antidepressive manipulations, like vagus nerve stimulation. Clinical data demonstrating the efficacy of aldosterone-reducing strategies for specific depressive syndromes are reviewed.

Discussion:

In particular aspects of differentiation between melancholic vs. atypical depression spectrum disorders are discussed.

 
  • References

  • 1 Almeida OP, Flicker L, Norman P et al. Association of cardiovascular risk factors and disease with depression in later life. Am J Geriatr Psychiatry 2007; 15: 506-513
  • 2 Bruce DG, Casey G, Davis WA et al. Vascular depression in older people with diabetes. Diabetologia 2006; 49: 2828-2836
  • 3 Sneed JR, Rindskopf D, Steffens DC et al. The vascular depression subtype: evidence of internal validity. Biological Psychiatry 2008; 64: 491-497
  • 4 Papakostas GI, Iosifescu DV, Renshaw PF et al. Brain MRI white matter hyperintensities and one-carbon cycle metabolism in non-geriatric outpatients with major depressive disorder (Part II). Psychiatry Res 2005; 140: 301-307
  • 5 Sheline YI, Pieper CF, Barch DM et al. Support for the vascular depression hypothesis in late-life depression: results of a 2-site, prospective, antidepressant treatment trial. Arch Gen Psychiatry 2010; 67: 277-285
  • 6 Beer C, Ebenezer E, Fenner S et al. Contributors to cognitive impairment in congestive heart failure: a pilot case-control study. Intern Med J 2009; 39: 600-605
  • 7 Purandare N, Oude Voshaar RC, Davidson Y et al. Deletion/insertion polymorphism of the angiotensin-converting enzyme gene and white matter hyperintensities in dementia: A pilot study. J Am Geriatr Soc 2006; 54: 1395-1400
  • 8 Schmidt H, Fazekas F, Kostner GM et al. Angiotensinogen gene promoter haplotype and microangiopathy-related cerebral damage: results of the Austrian Stroke Prevention Study. Stroke 2001; 32: 405-412
  • 9 Schmidt R, Fazekas F, Enzinger C et al. Risk factors and progression of small vessel disease-related cerebral abnormalities. J Neural Transm Suppl 2002; 47-52
  • 10 Thase ME, Murck H, Post A. The clinical relevance of disturbances of sleep and vigilance in major depression: a review. Prim Care Companion J Clin Psychiatry 2010; 12: online DOI: 10.4088/PCC.08m00676gry.
  • 11 Kaneita Y, Ohida T, Uchiyama M et al. The relationship between depression and sleep disturbances: a Japanese nationwide general population survey. J Clin Psychiatry 2006; 67: 196-203
  • 12 Meisinger C, Heier M, Lowel H et al. Sleep duration and sleep complaints and risk of myocardial infarction in middle-aged men and women from the general population: the MONICA/KORA Augsburg cohort study. Sleep 2007; 30: 1121-1127
  • 13 Ayas NT, White DP, Manson JE et al. A prospective study of sleep duration and coronary heart disease in women. Arch Intern Med 2003; 163: 205-209
  • 14 Empana JP, Dauvilliers Y, Dartigues JF et al. Excessive daytime sleepiness is an independent risk indicator for cardiovascular mortality in community-dwelling elderly: the three city study. Stroke 2009; 40: 1219-1224
  • 15 Qureshi AI, Giles WH, Croft JB et al. Habitual sleep patterns and risk for stroke and coronary heart disease: a 10-year follow-up from NHANES I. Neurology 1997; 48: 904-911
  • 16 Vgontzas AN, Mastorakos G, Bixler EO et al. Sleep deprivation effects on the activity of the hypothalamic-pituitary-adrenal and growth axes: potential clinical implications. Clin Endocrinol (Oxf) 1999; 51: 205-215
  • 17 Charloux A, Otzenberger H, Gronfier C et al. Oscillations in sympatho-vagal balance oppose variations in delta-wave activity and the associated renin release. J Clin Endocrinol Metabol 1998; 83: 1523-1528
  • 18 Hubain PP, Souery D, Jonck L et al. Relationship between the Newcastle scale and sleep polysomnographic variables in major depression: a controlled study. Eur Neuropsychopharmacol 1995; 5: 129-134
  • 19 Murck H. Magnesium and affective disorders. Nutr Neurosci 2002; 5: 375-389
  • 20 Armbruster H, Vetter W, Beckerhoff R et al. Diurnal variations of plasma aldosterone in supine man: relationship to plasma renin activity and plasma cortisol. Acta Endocrinol (Copenh) 1975; 80: 95-103
  • 21 Hlavacova N, Jezova D. Effect of single treatment with the antihypertensive drug eplerenone on hormone levels and anxiety-like behaviour in rats. Endocrine Regulations 2008; 42: 147-153
  • 22 Vellacott ID, Shroff NE, Pearce MY et al. A double-blind, placebo-controlled evaluation of spironolactone in the premenstrual syndrome. Curr Med Res Opin 1987; 10: 450-456
  • 23 Steiger A, Murck H.. REM sleep in patients with depression. In: Mallick BN, Pandi-Perumal SR, Mc Carley RM, Morrison A. editors Rapid Eye Movement Sleep: Regulation And Function. Cambridge: Cambridge University Press; 2011. . p. 383-394
  • 24 Marquet P, Lac G, Chassain AP et al. Dexamethasone in resting and exercising men. I. Effects on bioenergetics, minerals, and related hormones. J Appl Physiol 1999; 87: 175-182
  • 25 Vinson GP, Coghlan JP. Expanding view of aldosterone action, with an emphasis on rapid action. Clin Exp Pharmacol Physiol 2010; 37: 410-416
  • 26 Fluharty SJ, Epstein AN. Sodium appetite elicited by intracerebroventricular infusion of angiotensin II in the rat: II. Synergistic interaction with systemic mineralocorticoids. Behav Neurosci. 1983. 97. 746-758
  • 27 Geerling JC, Loewy AD. Aldosterone in the brain. Am J Physiol Renal Physiol 2009; 297: F559-F576
  • 28 De Kloet ER, Vreugdenhil E, Oitzl MS et al. Brain corticosteroid receptor balance in health and disease. Endocr Rev 1998; 19: 269-301
  • 29 Mondadori C, Borkowski J, Gentsch C. The memory-facilitating effects of the competitive NMDA-receptor antagonist CGP 37849 are steroid-sensitive, whereas its memory-impairing effects are not. Psychopharmacology 1996; 124: 380-383
  • 30 Mondadori C, Gentsch C, Hengerer B et al. Pretreatment with aldosterone or corticosterone blocks the memory-enhancing effects of nimodipine, captopril, CGP 37,849, and strychnine in mice. Psychopharmacology 1992; 109: 383-389
  • 31 Buckley TM, Mullen BC, Schatzberg AF. The acute effects of a mineralocorticoid receptor (MR) agonist on nocturnal hypothalamic-adrenal-pituitary (HPA) axis activity in healthy controls. Psychoneuroendocrinology 2007; 32: 859-864
  • 32 August JT, Nelson DH, Thorn GW. Response of normal subjects to large amounts of aldosterone. J Clin Invest 1958; 37: 1549-1555
  • 33 Sonino N, Fallo F, Fava GA. Psychological aspects of primary aldosteronism. Psychother Psychosom 2006; 75: 327-330
  • 34 Stewart PM, Whorwood CB. 11 beta-Hydroxysteroid dehydrogenase activity and corticosteroid hormone action. Steroids 1994; 59: 90-95
  • 35 Geerling JC, Kawata M, Loewy AD. Aldosterone-sensitive neurons in the rat central nervous system. J Comp Neurol 2006; 494: 515-527
  • 36 Ulrich-Lai YM, Herman JP. Neural regulation of endocrine and autonomic stress responses. Nature Rev 2009; 10: 397-409
  • 37 Nemeroff CB, Mayberg HS, Krahl SE et al. VNS therapy in treatment-resistant depression: clinical evidence and putative neurobiological mechanisms. Neuropsychopharmacology 2006; 31: 1345-1355
  • 38 Maier SF, Watkins LR. Cytokines for psychologists: implications of bidirectional immune-to-brain communication for understanding behavior, mood, and cognition. Psychological Rev 1998; 105: 83-107
  • 39 Maier SF, Goehler LE, Fleshner M et al. The role of the vagus nerve in cytokine-to-brain communication. Annal N Y Acad Sci 1998; 840: 289-300
  • 40 Gottesmann C. The neurophysiology of sleep and waking: intracerebral connections, functioning and ascending influences of the medulla oblongata. Prog Neurobiol 1999; 59: 1-54
  • 41 Valdes-Cruz A, Magdaleno-Madrigal VM, Martinez-Vargas D et al. Chronic stimulation of the cat vagus nerve: effect on sleep and behavior. Prog Neuro-Psychopharmacol Biological Psychiatry 2002; 26: 113-118
  • 42 Aguilera G, Young WS, Kiss A et al. Direct regulation of hypothalamic corticotropin-releasing-hormone neurons by angiotensin II. Neuroendocrinology 1995; 61: 437-444
  • 43 Jezova D, Ochedalski T, Kiss A et al. Brain angiotensin II modulates sympathoadrenal and hypothalamic pituitary adrenocortical activation during stress. J Neuroendocrinol 1998; 10: 67-72
  • 44 Ganong WF. Blood, pituitary, and brain renin-angiotensin systems and regulation of secretion of anterior pituitary gland. Front Neuroendocrinol 1993; 14: 233-249
  • 45 Gomez-Sanchez CE, Zhou MY, Cozza EN et al. Aldosterone biosynthesis in the rat brain. Endocrinology 1997; 138: 3369-3373
  • 46 Steiger A. Neurochemical regulation of sleep. J Psychiatr Res 2007; 41: 537-552
  • 47 Brandenberger G, Follenius M, Muzet A et al. Ultradian oscillations in plasma renin activity: their relationships to meals and sleep stages. J Clin Endocrinol Metab 1985; 61: 280-284
  • 48 Brandenberger G. Symposium: Normal and abnormal rem sleep regulation: Episodic hormone release in relation to REM sleep. J Sleep Res. 1993. 2. 193-198
  • 49 Charloux A, Gronfier C, Lonsdorfer-Wolf E et al. Aldosterone release during the sleep-wake cycle in humans. Am J Physiol 1999; 276 (1 Pt 1) E43-E49
  • 50 Obàl Jr F, Beranek L, Brandenberger G. Sleep-associated variations in plasma renin activity and blood pressure in the rat. Neurosci Lett 1994; 179: 83-86
  • 51 Luthringer R, Brandenberger G, Schaltenbrand N et al. Slow wave electroencephalic activity parallels renin oscillations during sleep in humans. Electroencephalogr Clin Neurophysiol 1995; 95: 318-322
  • 52 Brandenberger G, Simon C, Follenius M. Night-day differences in the ultradian rhythmicity of plasma renin activity. Life Sci 1987; 40: 2325-2330
  • 53 Brandenberger G, Krauth MO, Ehrhart J et al. Modulation of episodic renin release during sleep in humans. Hypertension 1990; 15: 370-375
  • 54 Viola AU, Simon C, Ehrhart J et al. Sleep processes exert a predominant influence on the 24-h profile of heart rate variability. J Biol Rhythms 2002; 17: 539-547
  • 55 Charloux A, Piquard F, Ehrhart J et al. Time-courses in renin and blood pressure during sleep in humans. J Sleep Res 2002; 11: 73-79
  • 56 Schmidt BM, Montealegre A, Janson CP et al. Short term cardiovascular effects of aldosterone in healthy male volunteers. J Clin Endocrinol Metab 1999; 84: 3528-3533
  • 57 Ovaert P, Elliott J, Bernay F et al. Aldosterone receptor antagonists  −  how cardiovascular actions may explain their beneficial effects in heart failure. J Vet Pharmacol Ther 2010; 33: 109-117
  • 58 Schüssler P, Yassouridis A, Uhr M et al. Sleep and active renin levels – interaction with age, gender, growth hormone and cortisol. Neuropsychobiology 2010; 61: 113-121
  • 59 Charloux A, Gronfier C, Chapotot F et al. Sleep deprivation blunts the night time increase in aldosterone release in humans. J Sleep Res 2001; 10: 27-33
  • 60 Murck H, Uhr M, Ziegenbein M et al. Renin-angiotensin-aldosterone system, HPA-axis and sleep-EEG changes in unmedicated patients with depression after total sleep deprivation. Pharmacopsychiatry 2006; 39: 23-29
  • 61 Armitage R, Hoffmann R, Trivedi M et al. Slow-wave activity in NREM sleep: sex and age effects in depressed outpatients and healthy controls. Psychiatry Res 2000; 95: 201-213
  • 62 Riemann D, Berger M, Voderholzer U. Sleep and depression  −  results from psychobiological studies: an overview. Biol Psychol 2001; 57: 67-103
  • 63 Kupfer DJ, Ulrich RF, Coble PA et al. Application of automated REM and slow wave sleep analysis: I. Normal and depressed subjects. Psychiatry Res 1984; 13: 325-334
  • 64 Kupfer DJ, Ulrich RF, Coble PA et al. Electroencephalographic sleep of younger depressives. Comparison with normals. Arch Gen Psychiatry 1985; 42: 806-810
  • 65 Thase ME, Kupfer DJ, Fasiczka AJ et al. Identifying an abnormal electroencephalographic sleep profile to characterize major depressive disorder. Biological Psychiatry 1997; 41: 964-973
  • 66 Borbely AA, Wirz-Justice A. Sleep, sleep deprivation and depression. A hypothesis derived from a model of sleep regulation. Human Neurobiol 1982; 1: 205-210
  • 67 Lauer C, Riemann D, Wiegand M et al. From early to late adulthood. Changes in EEG sleep of depressed patients and healthy volunteers. Biol Psychiatry 1991; 29: 979-993
  • 68 Armitage R, Hoffmann R, Fitch T et al. Temporal characteristics of delta activity during NREM sleep in depressed outpatients and healthy adults: group and sex effects. Sleep 2000; 23: 607-617
  • 69 Kerkhofs M, Kempenaers C, Linkowski P et al. Multivariate study of sleep EEG in depression. Acta Psychiatrica Scand 1988; 77: 463-468
  • 70 Feinberg M, Carroll BJ, Greden JF et al. Sleep EEG, depression rating scales, and diagnosis. Biological Psychiatry 1982; 17: 1453-1458
  • 71 Angst J, Gamma A, Sellaro R et al. Toward validation of atypical depression in the community: results of the Zurich cohort study. J Affect Disord 2002; 72: 125-138
  • 72 Makatsori A, Duncko R, Moncek F et al. Modulation of neuroendocrine response and non-verbal behavior during psychosocial stress in healthy volunteers by the glutamate release-inhibiting drug lamotrigine. Neuroendocrinology 2004; 79: 34-42
  • 73 Grippo AJ, Francis J, Beltz TG et al. Neuroendocrine and cytokine profile of chronic mild stress-induced anhedonia. Physiol Behav 2005; 84: 697-706
  • 74 Heuser I, Deuschle M, Weber B et al. Increased activity of the hypothalamus-pituitary-adrenal system after treatment with the mineralocorticoid receptor antagonist spironolactone. Psychoneuroendocrinology 2000; 25: 513-518
  • 75 Born J, De Kloet ER, Wenz H et al. Gluco- and antimineralocorticoid effects on human sleep: a role of central corticosteroid receptors. Am J Physiol 1991; 260: E183-E188
  • 76 Steiger A, Rupprecht R, Spengler D et al. Functional properties of deoxycorticosterone and spironolactone: molecular characterization and effects on sleep-endocrine activity. J Psychiatr Res 1993; 27: 275-284
  • 77 Altamura AC, Morganti A. Plasma renin activity in depressed patients treated with increasing doses of lithium carbonate. Psychopharmacologia 1975; 45: 171-175
  • 78 Holsboer F, Müller OA, Doerr HG et al. ACTH and multisteroid responses to corticotropin-releasing factor in depressive illness: relationship to multisteroid responses after ACTH stimulation and dexamethasone suppression. Psychoneuroendocrinology 1984; 9: 147-160
  • 79 Targum SD, White ME, Collins-Rothe H et al. Serum aldosterone following dexamethasone in depressed patients. Psychoneuroendocrinology 1984; 9: 305-309
  • 80 Murck H, Held K, Ziegenbein M et al. The renin-angiotensin-aldosterone system in patients with depression compared to controls  −  a sleep endocrine study. BMC Psychiatry 2003; 3: 15
  • 81 Emanuele E, Geroldi D, Minoretti P et al. Increased plasma aldosterone in patients with clinical depression. Arch Med Res 2005; 36: 544-548
  • 82 Hallberg L, Westrin A, Isaksson A et al. Decreased aldosterone in the plasma of suicide attempters with major depressive disorder. Psychiatry Res 2011; 187: 135-139
  • 83 Baghai TC, Schüle C, Zwanzger P et al. Hypothalamic-pituitary-adrenocortical axis dysregulation in patients with major depression is influenced by the insertion/deletion polymorphism in the angiotensin I-converting enzyme gene. Neurosci Lett 2002; 328: 299-303
  • 84 Baghai TC, Schüle C, Zwanzger P et al. Influence of a functional polymorphism within the angiotensin I-converting enzyme gene on partial sleep deprivation in patients with major depression. Neurosci Lett 2003; 339: 223-226
  • 85 Baghai TC, Schüle C, Zill P et al. The angiotensin I converting enzyme insertion/deletion polymorphism influences therapeutic outcome in major depressed women, but not in men. Neurosci Lett 2004; 363: 38-42
  • 86 Maes M, Scharpe S, Meltzer HY et al. Lower angiotensin I converting enzyme activity in melancholic subjects: a pilot study. Biol Psychiatry 1992; 32: 621-624
  • 87 Carroll BJ. The dexamethasone suppression test for melancholia. Br J Psychiatry 1982; 140: 292-304
  • 88 Saavedra JM, Benicky J. Brain and peripheral angiotensin II play a major role in stress. Stress 2007; 10: 185-193
  • 89 Holsboer F. The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 2000; 23: 477-501
  • 90 Takase B, Akima T, Satomura K et al. Effects of chronic sleep deprivation on autonomic activity by examining heart rate variability, plasma catecholamine, and intracellular magnesium levels. Biomed Pharmacother 2004; 58 (Suppl. 01) S35-S39
  • 91 Brown AD, Barton DA, Lambert GW. Cardiovascular abnormalities in patients with major depressive disorder: autonomic mechanisms and implications for treatment. CNS Drugs 2009; 23: 583-602
  • 92 Balogh S, Fitzpatrick DF, Hendricks SE et al. Increases in heart rate variability with successful treatment in patients with major depressive disorder. Psychopharmacol Bull 1993; 29: 201-206
  • 93 Morris MJ, Na ES, Grippo AJ et al. The effects of deoxycorticosterone-induced sodium appetite on hedonic behaviors in the rat. Behav Neurosci 2006; 120: 571-579
  • 94 Hlavacova N, Jezova D. Chronic treatment with the mineralocorticoid hormone aldosterone results in increased anxiety-like behavior. Horm Behav 2008; 54: 90-97
  • 95 Hlavacova N, Bakos J, Jezova D. Eplerenone, a selective mineralocorticoid receptor blocker, exerts anxiolytic effects accompanied by changes in stress hormone release. J Psychopharmacol 2010; 24: 779-786
  • 96 Hlavacova N, Wes PD, Ondrejcakova M et al. Subchronic treatment with aldosterone induces depression-like behaviours and gene expression changes relevant to major depressive disorder. Int J Neuropsychopharmacol 2011; 1-19 DOI: 10.1017/S1461145711000368.
  • 97 Brady LS, Gold PW, Herkenham M et al. The antidepressants fluoxetine, idazoxan and phenelzine alter corticotropin-releasing hormone and tyrosine hydroxylase mRNA levels in rat brain: therapeutic implications. Brain Res 1992; 572: 117-125
  • 98 Brady LS, Whitfield Jr HJ, Fox RJ et al. Long-term antidepressant administration alters corticotropin-releasing hormone, tyrosine hydroxylase, and mineralocorticoid receptor gene expression in rat brain. Therapeutic implications. J Clin Invest 1991; 87: 831-837
  • 99 Heydendael W, Jacobson L. Differential effects of imipramine and phenelzine on corticosteroid receptor gene expression in mouse brain: potential relevance to antidepressant response. Brain Res 2008; 1238: 93-107
  • 100 Van de Kar LD, Javed A, Zhang Y et al. 5-HT2A receptors stimulate ACTH, corticosterone, oxytocin, renin, and prolactin release and activate hypothalamic CRF and oxytocin-expressing cells. J Neurosci 2001; 21: 3572-3579
  • 101 Brandenberger G, Luthringer R, Muller G et al. 5-HT2 receptors are partially involved in the relationship between renin release and delta relative power. J Endocrinol Invest 1996; 19: 556-562
  • 102 Van de Kar LD. Forebrain pathways mediating stress-induced renin secretion. Clin Exp Pharmacol Physiol 1996; 23: 166-170
  • 103 Franklin M, Bermudez I, Murck H et al. Sub-chronic dietary tryptophan depletion H – An animal model of depression with improved face and good construct validity. J Psychiatr Res in press
  • 104 Zhang Y, Raap DK, Garcia F et al. Long-term fluoxetine produces behavioral anxiolytic effects without inhibiting neuroendocrine responses to conditioned stress in rats. Brain Res 2000; 855: 58-66
  • 105 Morton KD, Johnson MD, Van de Kar LD. Serotonin and stress-induced increases in renin secretion are not blocked by sympathectomy/adrenal medullectomy but are blocked by beta antagonists. Brain Res 1995; 698: 185-192
  • 106 Krauth MO, Saini J, Follenius M et al. Nocturnal oscillations of plasma aldosterone in relation to sleep stages. J Endocrinol Invest 1990; 13: 727-735
  • 107 Artigas F, Romero L, De Montigny C et al. Acceleration of the effect of selected antidepressant drugs in major depression by 5-HT1A antagonists. Trends Neurosci 1996; 19: 378-383
  • 108 Garrett BN, Ram CV, Kaplan NM. Effect of pindolol on potassium homeostasis in patients with essential hypertension. Clin Therapeutics 1984; 6: 524-535
  • 109 Wilcox CS, Lewis PS, Peart WS et al. Renal function, body fluid volumes, renin, aldosterone, and noradrenaline during treatment of hypertension with pindolol. J Cardiovasc Pharmacol 1981; 3: 598-611
  • 110 Portella MJ, de Diego-Adelino J, Ballesteros J et al. Can we really accelerate and enhance the selective serotonin reuptake inhibitor antidepressant effect? a randomized clinical trial and a meta-analysis of pindolol in nonresistant depression. J Clin Psychiatry 2011; 72: 962-969
  • 111 Naqvi TZ, Rafique AM, Andreas V et al. Predictors of depressive symptoms post-acute coronary syndrome. Gend Med 2007; 4: 339-351
  • 112 Schiffer AA, Pelle AJ, Smith OR et al. Somatic versus cognitive symptoms of depression as predictors of all-cause mortality and health status in chronic heart failure. J Clin Psychiatry 2009; 70: 1667-1673
  • 113 Sulser F, Gillespie DD, Mishra R et al. Desensitization by antidepressants of central norepinephrine receptor systems coupled to adenylate cyclase. Ann N Y Acad Sci 1984; 430: 91-101
  • 114 Stewart JW, McGrath PJ, Quitkin FM. Can mildly depressed outpatients with atypical depression benefit from antidepressants?. Am J Psychiatry 1992; 149: 615-619
  • 115 Quitkin FM, Liebowitz MR, Stewart JW et al. l-Deprenyl in atypical depressives. Arch Gen Psychiatry 1984; 41: 777-781
  • 116 Robinson DS, Gilmor ML, Yang Y et al. Treatment effects of selegiline transdermal system on symptoms of major depressive disorder: a meta-analysis of short-term, placebo-controlled, efficacy trials. Psychopharmacol Bull 2007; 40: 15-28
  • 117 Wang M, Hammarback S, Lindhe BA et al. Treatment of premenstrual syndrome by spironolactone: a double-blind, placebo-controlled study. Acta Obstetricia Gynecologica Scand 1995; 74: 803-808
  • 118 Olajide D, Lader M. Psychotropic effects of enalapril maleate in normal volunteers. Psychopharmacology 1985; 86: 374-376
  • 119 Tye SJ, Miller AD, Blaha CD. Differential corticosteroid receptor regulation of mesoaccumbens dopamine efflux during the peak and nadir of the circadian rhythm: a molecular equilibrium in the midbrain?. Synapse 2009; 63: 982-990
  • 120 Roitman MF, Patterson TA, Sakai RR et al. Sodium depletion and aldosterone decrease dopamine transporter activity in nucleus accumbens but not striatum. Am J Physiology 1999; 276: R1339-R1345
  • 121 Roitman MF, Na E, Anderson G et al. Induction of a salt appetite alters dendritic morphology in nucleus accumbens and sensitizes rats to amphetamine. J Neurosci 2002; 22: RC225
  • 122 Grippo AJ, Moffitt JA, Beltz TG et al. Reduced hedonic behavior and altered cardiovascular function induced by mild sodium depletion in rats. Behav Neurosci 2006; 120: 1133-1143
  • 123 Carta M, Fadda F, Stancampiano R. Tryptophan-deficient diet increases the neurochemical and behavioral response to amphetamine. Brain Res 2006; 1094: 86-91
  • 124 Tremblay LK, Naranjo CA, Cardenas L et al. Probing brain reward system function in major depressive disorder: altered response to dextroamphetamine. Arch Gen Psychiatry 2002; 59: 409-416
  • 125 Jenkins TA. Effect of angiotensin-related antihypertensives on brain neurotransmitter levels in rats. Neurosci Lett 2008; 444: 186-189
  • 126 Jenkins TA, Mendelsohn FA, Chai SY. Angiotensin-converting enzyme modulates dopamine turnover in the striatum. J Neurochem 1997; 68: 1304-1311
  • 127 Reardon KA, Mendelsohn FA, Chai SY et al. The angiotensin converting enzyme (ACE) inhibitor, perindopril, modifies the clinical features of Parkinson’s disease. Aust NZ J Med 2000; 30: 48-53
  • 128 Steiger A, Benkert O, Holsboer F. Effects of long-term treatment with the MAO-A inhibitor moclobemide on sleep EEG and nocturnal hormonal secretion in normal men. Neuropsychobiology 1994; 30: 101-105
  • 129 Smit AJ, Lieverse AG, van Veldhuisen D et al. Dopaminergic modulation of physiological and pathological neurohumoral activation in man. Hypertens Res 1995; 18 (Suppl. 01) S107-S111
  • 130 Smit AJ, Meijer S, Wesseling H et al. Effect of metoclopramide on dopamine-induced changes in renal function in healthy controls and in patients with renal disease. Clin Sci (Lond) 1988; 75: 421-428
  • 131 Missale C, Lombardi C, De Cotiis R et al. Dopaminergic receptor mechanisms modulating the renin-angiotensin system and aldosterone secretion: an overview. J Cardiovasc Pharmacol 1989; 14 (Suppl. 08) S29-S39
  • 132 Mannelli M, Lazzeri C, Ianni L et al. Dopamine and sympathoadrenal activity in man. Clin Exp Hypertens 1997; 19: 163-179
  • 133 Coupland NJ, Wilson SJ, Potokar JP et al. A comparison of the effects of phenelzine treatment with moclobemide treatment on cardiovascular reflexes. Int Clin Psychopharmacol 1995; 10: 229-238
  • 134 Coppen A. Mineral metabolism in affective disorders. Br J Psychiatry 1965; 111: 1133-1142
  • 135 Coppen A. Disorders of mineral metabolism in depressive patients. Psychiatria, Neurologia, Neurochirurgia 1969; 72: 189-193
  • 136 Hullin RP. Biochemistry of the affective disorders. J Int Med Res 1977; 5 (1 Suppl) 140-145
  • 137 Morris ME. Brain and CSF magnesium concentrations during magnesium deficit in animals and humans: neurological symptoms. Magnes Res 1992; 5: 303-313
  • 138 Oppelt WW, MacInyre I, Rall DP. Magnesium exchange between blood and cerebrospinal fluid. Am J Physiol 1963; 205: 959-962
  • 139 Chutkow JG. Metabolism of magnesium in central nervous system. Relationship between concentrations of magnesium in cerebrospinal fluid and brain in magnesium deficiency. Neurology 1974; 24: 780-787
  • 140 Charlton JA, Armstrong DG. The effect of an intravenous infusion of aldosterone upon magnesium metabolism in the sheep. Q J Exp Physiol 1989; 74: 329-337
  • 141 Horton R, Biglieri EG. Effect of aldosterone on the metabolism of magnesium. J Clin Endocrinol Metabol 1962; 22: 1187-1192
  • 142 Barr CS, Lang CC, Hanson J et al. Effects of adding spironolactone to an angiotensin-converting enzyme inhibitor in chronic congestive heart failure secondary to coronary artery disease. Am J Cardiol 1995; 76: 1259-1265
  • 143 Ebel H, Wolff JR, Dorn F et al. The effect of hormones on the levels of electrolytes, ATPase and the structure of the endoplasmic reticulum in rat brain. Z klin Chem klin Biochem 1971; 9: 249-256
  • 144 Whyte KF, Addis GJ, Whitesmith R et al. Adrenergic control of plasma magnesium in man. Clin Sci 1987; 72: 135-138
  • 145 Singewald N, Sinner C, Hetzenauer A et al. Magnesium-deficient diet alters depression- and anxiety-related behavior in mice  −  influence of desipramine and Hypericum perforatum extract. Neuropharmacology 2004; 47: 1189-1197
  • 146 Iosifescu DV, Nierenberg AA, Mischoulon D et al. An open study of triiodothyronine augmentation of selective serotonin reuptake inhibitors in treatment-resistant major depressive disorder. J Clin Psychiatry 2005; 66: 1038-1042
  • 147 Nowak L, Bregestovski P, Ascher P et al. Magnesium gates glutamate-activated channels in mouse central neurones. Nature 1984; 307: 462-465
  • 148 Hallak M, Berman RF, Irtenkauf SM et al. Magnesium sulfate treatment decreases N-methyl-D-aspartate receptor binding in the rat brain: an autoradiographic study. J Soc Gynecol Investig 1994; 1: 25-30
  • 149 Poleszak E, Szewczyk B, Kedzierska E et al. Antidepressant- and anxiolytic-like activity of magnesium in mice. Pharmacol Biochem Behav 2004; 78: 7-12
  • 150 Poleszak E, Wlaz P, Kedzierska E et al. NMDA/glutamate mechanism of antidepressant-like action of magnesium in forced swim test in mice. Pharmacol Biochem Behav 2007; 88: 158-164
  • 151 Eby GA, Eby KL. Rapid recovery from major depression using magnesium treatment. Med Hypoth 2006; 67: 362-370
  • 152 Berman RM, Cappiello A, Anand A et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 2000; 47: 351-354
  • 153 Preskorn SH, Baker B, Kolluri S et al. An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP-101,606, in patients with treatment-refractory major depressive disorder. J Clin Psychopharmacol 2008; 28: 631-637
  • 154 Sapna S, Ranjith SK, Shivakumar K. Cardiac fibrogenesis in magnesium deficiency: a role for circulating angiotensin II and aldosterone. Am J Physiol Heart Circ Physiol 2006; 291: H436-H440
  • 155 Laurant P, Dalle M, Berthelot A et al. Time-course of the change in blood pressure level in magnesium-deficient Wistar rats. Br J Nutrit 1999; 82: 243-251
  • 156 Ahokas RA, Warrington KJ, Gerling IC et al. Aldosteronism and peripheral blood mononuclear cell activation: a neuroendocrine-immune interface. Circ Res 2003; 93: e124-e135
  • 157 Gerling IC, Sun Y, Ahokas RA et al. Aldosteronism: an immunostimulatory state precedes proinflammatory/fibrogenic cardiac phenotype. Am J Physiol Heart Circ Physiol 2003; 285: H813-H821
  • 158 Duprez DA. Role of the renin-angiotensin-aldosterone system in vascular remodeling and inflammation: a clinical review. J Hypertens 2006; 24: 983-991
  • 159 Falkenstein E, Christ M, Feuring M et al. Specific nongenomic actions of aldosterone. Kidney Int 2000; 57: 1390-1394
  • 160 Sontia B, Montezano AC, Paravicini T et al. Downregulation of renal TRPM7 and increased inflammation and fibrosis in aldosterone-infused mice: effects of magnesium. Hypertension 2008; 51: 915-921
  • 161 Sanchez-Lemus E, Murakami Y, Larrayoz-Roldan IM et al. Angiotensin II AT1 receptor blockade decreases lipopolysaccharide-induced inflammation in the rat adrenal gland. Endocrinology 2008; 149: 5177-5188
  • 162 Savoia C, Touyz RM, Amiri F et al. Selective mineralocorticoid receptor blocker eplerenone reduces resistance artery stiffness in hypertensive patients. Hypertension 2008; 51: 432-439
  • 163 Saavedra JM, Ando H, Armando I et al. Anti-stress and anti-anxiety effects of centrally acting angiotensin II AT1 receptor antagonists. Regul Pept 2005; 128: 227-238
  • 164 Zorrilla EP, Luborsky L, McKay JR et al. The relationship of depression and stressors to immunological assays: a meta-analytic review. Brain, Behav Immunity 2001; 15: 199-226
  • 165 Eller T, Vasar V, Shlik J et al. Pro-inflammatory cytokines and treatment response to escitalopram in major depressive disorder. Progr Neuro-Psychopharmacol Biol Psychiatry 2008; 32: 445-450
  • 166 O’Brien SM, Scully P, Fitzgerald P et al. Plasma cytokine profiles in depressed patients who fail to respond to selective serotonin reuptake inhibitor therapy. J Psychiatric Res 2007; 41: 326-331
  • 167 Muller N, Schwarz MJ, Dehning S et al. The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry 2006; 11: 680-684
  • 168 Peet M, Horrobin DF. A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs. Arch Gen Psychiatry 2002; 59: 913-919
  • 169 Murck H, Song C, Horrobin DF et al. Ethyl-eicosapentaenoate and dexamethasone resistance in therapy-refractory depression. Int J Neuropsychopharmacol 2004; 7: 341-349
  • 170 Zubenko GS, Nixon RA. Mood-elevating effect of captopril in depressed patients. Am J Psychiatry 1984; 141: 110-111
  • 171 Gard PR, Mandy A, Sutcliffe MA. Evidence of a possible role of altered angiotensin function in the treatment, but not etiology, of depression. Biol Psychiatry 1999; 45: 1030-1034
  • 172 Hertzman M, Adler LW, Arling B et al. Lisinopril may augment antidepressant response. J Clin Psychopharmacol 2005; 25: 618-620
  • 173 Gunduz H, Georges JL, Fleishman S. Quinapril and depression. Am J Psychiatry 1999; 156: 1114-1115
  • 174 Pavlatou MG, Mastorakos G, Lekakis I et al. Chronic administration of an angiotensin II receptor antagonist resets the hypothalamic-pituitary-adrenal (HPA) axis and improves the affect of patients with diabetes mellitus type 2: preliminary results. Stress 2008; 11: 62-72
  • 175 Nasr SJ, Crayton JW, Agarwal B et al. Lower frequency of antidepressant use in patients on renin-angiotensin-aldosterone system modifying medications. Cell Mol Neurobiol 2011; 31: 615-618
  • 176 Holsboer F. The rationale for corticotropin-releasing hormone receptor (CRH-R) antagonists to treat depression and anxiety. J Psychiatric Res 1999; 33: 181-214
  • 177 Otte C, Hinkelmann K, Moritz S et al. Modulation of the mineralocorticoid receptor as add-on treatment in depression: a randomized, double-blind, placebo-controlled proof-of-concept study. J Psychiatric Res 2010; 44: 339-346
  • 178 Rosenfeld R, Livne D, Nevo O et al. Hormonal and volume dysregulation in women with premenstrual syndrome. Hypertension 2008; 51: 1225-1230
  • 179 Yonkers KA, Brown C, Pearlstein TB et al. Efficacy of a new low-dose oral contraceptive with drospirenone in premenstrual dysphoric disorder. Obstetr Gynecol 2005; 106: 492-501
  • 180 Odber J, Cawood EH, Bancroft J. Salivary cortisol in women with and without perimenstrual mood changes. J Psychosom Res 1998; 45: 557-568
  • 181 Murck H. Atypical depression spectrum disorder – neurobiology and treatment. Acta Neuropsychiatrica 2003; 15: 227-241
  • 182 Sonino N, Tomba E, Genesia ML et al. Psychological assessment of primary aldosteronism: a controlled study. J Clin Endocrinol Metab 2011; 96: E878-E883
  • 183 Stewart JW, McGrath PJ, Fava M et al. Do atypical features affect outcome in depressed outpatients treated with citalopram?. Int J Neuropsychopharmacol 2010; 13: 15-30
  • 184 Ahmed AH, Calvird M, Gordon RD et al. Effects of two selective serotonin reuptake inhibitor antidepressants, sertraline and escitalopram, on aldosterone/renin ratio in normotensive depressed male patients. J Clin Endocrinol Metab 2011; 96: 1039-1045
  • 185 Boneva RS, Decker MJ, Maloney EM et al. Higher heart rate and reduced heart rate variability persist during sleep in chronic fatigue syndrome: a population-based study. Auton Neurosci 2007; 137: 94-101
  • 186 Stewart JW, Quitkin FM, McGrath PJ et al. Defining the boundaries of atypical depression: evidence from the HPA axis supports course of illness distinctions. J Affect Disord 2005; 86: 161-167
  • 187 Reiner PB. Correlational analysis of central noradrenergic neuronal activity and sympathetic tone in behaving cats. Brain Res 1986; 378: 86-96
  • 188 Elam M, Svensson TH, Thoren P. Locus coeruleus neurons and sympathetic nerves: activation by cutaneous sensory afferents. Brain Res 1986; 366: 254-261
  • 189 Koob GF. Corticotropin-releasing factor, norepinephrine, and stress. Biol Psychiatry 1999; 46: 1167-1180
  • 190 Davis M, Whalen PJ. The amygdala: vigilance and emotion. Mol Psychiatry 2001; 6: 13-34
  • 191 Schulkin J, Gold PW, McEwen BS. Induction of corticotropin-releasing hormone gene expression by glucocorticoids: implication for understanding the states of fear and anxiety and allostatic load. Psychoneuroendocrinology 1998; 23: 219-243