Serotonergic function is reduced in dementia of Alzheimer type (DAT) and abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are also common. There is considerable interaction between the two systems. Effects of lowering brain serotonin on salivary and plasma cortisol were assessed in patients with DAT and in control subjects. A double-blind, cross-over design involving administration of two nutritionally balanced amino acid mixtures with or without tryptophan was used. Salivary and plasma cortisol were measured at intervals before and after the drink. DAT patients had higher salivary cortisol than controls. Despite a reduction of approximately 70% in plasma free tryptophan after 4 h in both groups, there was no effect on salivary or plasma cortisol. We conclude that, in subjects with DAT and healthy elderly subjects, acute tryptophan depletion had no effect on cortisol secretion.
Benton A L, Hamsher K (1976) Multilingual aphasia examination. University of Iowa, Iowa City
2.
Biggio G, Fadda F, Fanni P, Tagliamonte A, Gessa G L (1974) Rapid depletion of serum tryptophan, brain tryptophan, serotonin and 5-hydroxyindoleacetic acid by a tryptophan-free diet. Life Sci14: 1321–1329
3.
Calogero A E, Bernardini R, Margioris A N, Bagdy G, Gallucci W T, Munson P J, Tamarkin L, Tomai T P, Brady L, Gold P W (1989) Effects of serotonergic agonists and antagonists on corticotropin-releasing hormone secretion by explanted rat hypothalami. Peptides10: 189–200
4.
Cegalis J, Bowlin J (1991) Vigil: software for the assessment of attention. Forthought, Nashua, NH
5.
Cross A J (1990) Serotonin in Alzheimer-type dementia and other dementing illnesses. Ann NY Acad Sci600: 405–417
6.
Cross A J, Crow T J, Ferrier I N, Johnson J A (1986) The selectivity of the reduction of serotonin S2 receptors in Alzheimer-type dementia. Neurobiol Aging7: 3–7
7.
Deuschle M, Gotthardt U, Schweiger U, Weber B, Korner A, Schmider J, Standhardt H, Lammers C H, Heuser I (1997) With aging in humans the activity of the hypothalamus-pituitary-adrenal system increases and its diurnal amplitude flattens. Life Sci61: 2239–2246
8.
Dinan T G (1996) Serotonin and the regulation of hypothalamic-pituitary-adrenal axis function. Life Sci58: 1683–1694
9.
Dodt C, Dittmann J, Hruby J, Spath-Schwalbe E, Born J, Schuttler R, Fehm H L (1991) Different regulation of adrenocorticotropin and cortisol secretion in young, mentally healthy elderly and patients with senile dementia of Alzheimer's type. J Clin Endocrinol Metabol72: 272–276
10.
Folstein M, Folstein S, McHugh P (1975) ‘Mini mental state’ a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res12: 189–198
11.
Franklin M, Chi J (1999) Effect of tryptophan depletion on 5-HT2A receptors in the rat. J Psychopharmacol13: A32-A32
12.
Franklin M, Craven R D, Dowling B, Campling G, Elliott J M, Cowen P J (1999) Effect of a long-term low tryptophan diet on the 5-HT1A and 5-HT2C agonists, 8-OH-DPAT and mCPP in the male rat. J Psychopharmacol13: 58–63
13.
Fuller R W (1992) The involvement of serotonin in regulation of pituitary-adrenocortical function. Front Neuroendocrinol13: 250–270
14.
Gartside S E, Cowen P J, Sharp T (1992) Effect of 5-hydroxy-L-tryptophan on the release of 5-HT in rat hypothalamus in vivo as measured by microdialysis. Neuropharmacology31: 9–14
15.
Hesselmann B, Neumeister A, Praschak-Rieder N, Vitouch O, Kasper S (1997) Cortisol concentration during tryptophan depletion in depressed and remitted patients with seasonal affective disorder (SAD), Sixth World Congress of Biological Psychiatry. Nice, pp. 39–123
16.
Heuser I J, Gotthardt U, Schweiger U, Schmider J, Lammers CH, Dettling M, Holsboer F (1994) Age-associated changes of pituitary-adrenocortical hormone regulation in humans: importance of gender. Neurobiol Aging15: 227–231
17.
Joseph M H, Kennett G A (1983) Corticosteroid response to stress depends upon increased tryptophan availability. Psychopharmacology79: 79–81
18.
Katz F H, Shannon I L (1969) Parotid fluid cortisol and cortisone. J Clin Invest48: 848–855
19.
Kennett G A, Joseph M H (1981) The functional importance of increased brain tryptophan in the serotonergic response to restraint stress. Neuropharmacology20: 39–43
20.
Kirschbaum C, Pirke K M, Hellhammer D H (1993) The ‘Trier Social Stress Test’ – a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology28: 76–81
21.
Lawlor B A, Sunderland T, Mellow A M, Hill J L, Molchan S E, Murphy D L (1989) Hyperresponsivity to the serotonin agonist m-chlorophenylpiperazine in Alzheimer's disease. A controlled study. Arch Gen Psychiatry46: 542–549
22.
Lesch K P, Sohnle K, Poten B, Schoellnhammer G, Rupprecht R, Schulte H M (1990) Corticotropin and cortisol secretion after central 5-hydroxytryptamine-1A (5-HT1A) receptor activation: effects of 5-HT receptor and beta-adrenoceptor antagonists. J Clin Endocrinol Metabol70: 670–674
23.
Liposits Z, Phelix C, Paull W K (1987) Synaptic interaction of serotonergic axons and corticotropin releasing factor (CRF) synthesizing neurons in the hypothalamic paraventricular nucleus of the rat. A light and electron microscopic immunocytochemical study. Histochemistry86: 541–549
24.
Lupien S, Lecours A R, Lussier I, Schwartz G, Nair N P, Meaney M J (1994) Basal cortisol levels and cognitive deficits in human aging. J Neurosci14: 2893–2903
25.
Lupien S J, Gaudreau S, Tchiteya B M, Maheu F, Sharma S, Nair N P, Hauger R L, McEwen B S, Meaney M J (1997) Stress-induced declarative memory impairment in healthy elderly subjects: relationship to cortisol reactivity. J Clin Endocrinol Metabol82: 2070–2075
26.
Marchi M, Paudice P, Bella M, Raiteri M (1986) Dicyclomine-and pirenzepine-sensitive muscarinic receptors mediate inhibition of [3H]serotonin release in different rat brain areas. Eur J Pharmacol129: 353–357
27.
Marshall E F, Kennedy W N, Eccleston D (1987) Whole blood serotonin and plasma tryptophan using high-pressure liquid chromatography with electrochemical detection. Biochem Med Metabol Biol37: 81–86
28.
McEntee W J, Crook T H (1991) Serotonin, memory, and the aging brain. Psychopharmacology103: 143–149
29.
McKeith I G (1984) Clinical use of the DST in a psychogeriatric population. Br J Psychiatry145: 389–393
30.
Meltzer H Y, Maes M (1994) Effects of buspirone on plasma prolactin and cortisol levels in major depressed and normal subjects. Biol Psychiatry35: 316–323
31.
Montgomery S A, Asberg M (1979) A New Depression Scale Designed to be Sensitive to Change. Br J Psychiatry134: 382–389
32.
Nasman B, Olsson T, Fagerlund M, Eriksson S, Viitanen M, Carlstrom K (1996) Blunted adrenocorticotropin and increased adrenal steroid response to human corticotropin-releasing hormone in Alzheimer's disease [see comments]. Biol Psychiatry39: 311–318
33.
Nishizawa S, Benkelfat C, Young S N, Leyton M, Mzengeza S, de Montigny C, Blier P, Diksic M (1997) Differences between males and females in rates of serotonin synthesis in human brain [see comments]. Proc Natl Acad Sci USA94: 5308–5313
34.
O'Brien J, Schweitzer I, Ames D, Tuckwell V, Mastwyk M (1994) Cortisol suppression by dexamethasone in the healthy elderly: effects of age, dexamethasone levels, and cognitive function. Biol Psychiatry36: 389–394
35.
O'Brien J T, Ames D, Schweitzer I, Colman P, Desmond P, Tress B (1996) Clinical and magnetic resonance imaging correlates of hypothalamic-pituitary-adrenal axis function in depression and Alzheimer's disease. Br J Psychiatry168: 679–687
36.
Pardridge W M (1986) Blood-brain barrier transport of nutrients. Nutr Rev44: 15–25
37.
Park S B, Coull J T, McShane R H, Young A H, Sahakian B J, Robbins T W, Cowen P J (1994) Tryptophan depletion in normal volunteers produces selective impairments in learning and memory. Neuropharmacology33: 575–588
38.
Porter R J, Walker L L M, Leitch M M, Alderson E, Ballard C, Gray J, O'Brien J T (1998) Tryptophan depletion causes cognitive changes in patients with Alzheimer's disease and in healthy elderly subjects, CINP 21st Congress. Glasgow, UK
39.
Porter R J, Lunn B S, Walker L L, Gray J M, Ballard C G, O'Brien J T (2000) Cognitive deficit induced by acute tryptophan depletion in patients with Alzheimer's disease. Am J Psychiatry157: 638–640
40.
Price L H, Malison R T, McDougle C J, McCance-Katz E F, Owen K R, Heninger G R (1997) Neurobiology of tryptophan depletion in depression: effects of m-chlorophenylpiperazine (mCPP). Neuropsychopharmacology17: 342–350
41.
Price L H, Malison R T, McDougle C J, Pelton G H, Heninger G R (1998) The neurobiology of tryptophan depletion in depression: effects of intravenous tryptophan infusion. Biol Psychiatry43: 339–347
42.
Raskind M, Peskind E, Rivard M F, Veith R, Barnes R (1982) Dexamethasone suppression test and cortisol circadian rhythm in primary degenerative dementia. Am J Psychiatry139: 1468–1471
43.
Rey A (1964) L'examen clinique en psychologie. Press Universitaire de France, Paris
44.
Robbins T W, James M, Owen A M, Sahakian B J, McInnes L, Rabbitt P (1994) Cambridge Neuropsychological Test Automated Battery (CANTAB): a factor analytic study of a large sample of normal elderly volunteers. Dementia5: 266–281
45.
Sahakian B J, Owen A M (1992) Computerized assessment in neuropsychiatry using CANTAB: discussion paper. J Roy Soc Med85: 399–402
46.
Seckl J R, Olsson T (1995) Glucocorticoid hypersecretion and the age-impaired hippocampus: cause or effect?J Endocrinol145: 201–211
47.
Steckler T, Sahgal A (1995) The role of serotonergic–cholinergic interactions in the mediation of cognitive behaviour. Behav Brain Res67: 165–199
48.
Teng E L, Chui H C (1987) The Modified Mini-Mental State (3MS) examination. J Clin Psychiatry48: 314–318
49.
Walker R F, Riad-Fahmy D, Read G F (1978) Adrenal status assessed by direct radioimmunoassay of cortisol in whole saliva or parotid saliva. Clin Chem24: 1460–1463
50.
Wechsler D (1981) Wechsler Adult Intelligence Scale – Revised. The Psychological Corporation, New York
51.
Weiner M F, Vobach S, Svetlik D, Risser R C (1993) Cortisol secretion and Alzheimer's disease progression: a preliminary report. Biol Psychiatry34: 158–161
52.
Weiner M F, Vobach S, Olsson K, Svetlik D, Risser R C (1997) Cortisol secretion and Alzheimer's disease progression. Biol Psychiatry42: 1030–1038
53.
Young S N, Ervin F R, Pihl R O, Finn P (1989) Biochemical aspects of tryptophan depletion in primates. Psychopharmacology98: 508–511
