Serotonin in aging, late-life depression, and Alzheimer's disease: The emerging role of functional imaging

Neuropsychopharmacology

Volumn 18, Issue 6, 1998, Pages 407-430

  Meltzer, Carolyn Cidis ^a   Smith, Gwenn ^a   Dekosky, Steven T ^a   Pollock, Bruce G ^a   Mathis, Chester A ^a   Moore, Robert Y ^a   Kupfer, David J ^a   Reynolds III, Charles F ^a  

^a Advanced Center for Interventions and Services Research for Late Life Mood Disorders   (United States)

Author keywords

Aging; Alzheimer's disease; Depression; Emission computed tomography; Receptors; Serotonin

Indexed keywords

SEROTONIN; SEROTONIN RECEPTOR;

AGING; ALZHEIMER DISEASE; BRAIN METABOLISM; BRAIN PERFUSION; COGNITIVE DEFECT; DEPRESSION; HUMAN; PATHOPHYSIOLOGY; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; REVIEW; SEROTONINERGIC NERVE CELL; SEROTONINERGIC TRANSMISSION;

AGED; AGING; ALZHEIMER DISEASE; DEPRESSION; HUMANS; SEROTONIN; TOMOGRAPHY, EMISSION-COMPUTED;

EID: 0031944188     PISSN: 0893133X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0893-133X(97)00194-2     Document Type: Review

References (250)

1. Agren H, Reibring L PET studies of presynaptic monoamine metabolism in depressed patients and healthy volunteers. Pharmacopsychiatry. 27:1994;2-6.
2. Albert M, Sandor T, Moss M, Jolesz F Measurement of age-related differences in gray matter, white matter, and cerebrospinal fluid. Radiology. 185(P):1992;200.
3. Alder J, Chen C-H, Francis P, Hope T, Heath P, Bowen D Pre and postsynaptic serotonergic markers in a community acquired study of Alzheimer's disease. Soc Neurosci Abstr. 21(Part 3):1995;1977.
4. Alexopoulos GS, Abrams RC Depression in Alzheimer's disease. Psychiatr Clin NA. 14:1991;327-340.
5. Alexopoulos G, Young R, Shindledecker R Brain computed tomography findings in geriatric depression and primary degenerative dementia. Biol Psychiatry. 31:1992;591-599.
6. Alexopoulos G, Meyers B, Young R, Mattis S, Kakuma T The course of geriatric depression with "reversible dementia" A controlled study Am J Psychiatry. 150:1993;1693-1699.
7. Alexopoulos G, Meyers B, Young R, Kakuma T, Feder M, Einhorn A, Rosendahl E Recovery in geriatric depression. Arch Gen Psychiatry. 53:1996;305-312.
8. Altman HJ, Nordy D, Ogren S Role of serotonin in memory. Facilitation by alaproclate and zimeldine Psychopharmacology. 84:1984;496-502.
9. Altman HJ, Normile HJ, Galloway MP, Ramirez A, Azmitia EC Enhanced spatial discrimination learning in rats following 5, 7-DHT-induced serotonergic deafferentation of the hippocampus. Brain Res. 518:1990;61-66.
10. 3H]paroxetine binding to 5-HT uptake sites in Alzheimer's disease. Neurobiol Aging. 12:1991;531-534.
11. 3H]paroxetine binding. Gerontology. 38:1992;127-132.
12. Arai H, Ichimiya Y, Kosaka K, Moroji T, Iizuka R Neurotransmitter changes in early- and late-onset Alzheimer-type dementia. Prog Neuropsychopharmacol Biol Psychiatry. 16:1992;883-890.
13. 2 and β-adrenergic receptor binding sites in the brain of suicide victims. Arch Gen Psychiatry. 47:1990;1038-1047.
14. Arango V, Underwood M, Mann J Alterations in monoamine receptors in the brian of suicide victims. J Clin Psychopharmacol. 12(Suppl.):1992;8S-12S.
15. Arango V, Underwood M, Gubbi A, Mann J Localized alterations in pre- and postsynaptic serotonin binding sites in the ventrolateral prefrontal cortex of suicide victims. Brain Res. 688:1995;121-133.
16. 3H-imipramine binding in the frontal cortex of suicides. Psychiatr Res. 30:1989;125-135.
17. 2 binding sites in the frontal cortex of suicide victims and control subjects Am J Psychiatry. 146:1989;730-736.
18. Arora R, Emery O, Meltzer H Serotonin uptake in the blood platelets of Alzheimer's disease patients. Neurology. 41:1991;1307-1309.
19. Arranz B, Eriksson A, Mellerup E, Plenge P, Marcusson J Effect of aging in human cortical pre- and postsynaptic serotonin binding sites. Brain Res. 620:1993;163-166.
20. 3H]SR 46349B kinetics in rat brain Nucl Med Biol. 23:1996;245-250.
21. Azmitia EC, Whitaker-Azmitia PM Awakening the sleeping giant. Anatomy and plasticity of the brain serotonergic system J Clin Psychiatry. 52:1991;4-16.
22. Baldwin RC, Tomenson B Depression in later life. A comparison of symptoms and risk factors in early and late onset cases. Br J Psychiatry. 167:1995;649-652.
23. 3 receptors mediate inhibition of acetylcholine release in cortical tissue. Nature. 338:1989;762-763.
24. Baxter L, Schwartz J, Phelps M, Mazziotta J, Guze B, Selin C, Gerner R, Sumida R Reduction of prefrontal cortex glucose metabolism common to three types of depression. Arch Gen Psychiatry. 46:1989;243-250.
25. Beats B, Levy R, Forstl H Ventricular enlargement and caudate hyperdensity in elderly depressives. Biol Psychiatry. 30:1991;452-458.
26. Bench C, Friston K, Brown R, Scott L, Frackowiak R, Dolan R The anatomy of melancholia - Focal abnormalities of cerebral blood flow in major depression. Psychol Med. 22:1992;607-615.
27. Bergman I, Brane G, Gottfries CG, Jostell K-G, Karlsson I, Svennerholm L Alaproclate. A pharmacokinetic and biochemical study in patients with dementia of the Alzheimer type Psychopharmacology. 80:1983;279-283.
28. 2 receptors on human blood platelets. Psychopharmacology. 180:1992;210-212.
29. 2 receptors in humans using positron emission tomography. Eur J Nucl Med. 21:1994;937-946.
30. 2 receptors in the living human brain. Neurosci Lett. 204:1996;25-28.
31. 2 receptors. A film and electronic autoradiographic study Nucl Med Biol. 24:1997;357-360.
32. Blazer D, Hughes D, George L The epidemiology of depression in an elderly community population. Gerontologist. 27:1987;281-287.
33. Blier P, de Montigny C, Chaput Y A role for the serotonin system in the mechanism of action of antidepressant treatments. preclinical evidence J Clin Psychiatry. 51:1990;14-20.
34. 2 receptors in Alzheimer's disease. Brain. 116:1993;497-510.
35. Bonne O, Krausz Y, Shapira B, Bocher M, Karger H, Gorfine M, Chisin R, Lerer B Increased cerebral blood flow in depressed patients responding to electroconvulsive therapy. J Nucl Med. 37:1996;1075-1080.
36. Bonte FJ, Ross ED, Chehabi HH, Devous MD SPECT study of regional cerebral blood flow in Alzheimer disease. J Comput Assist Tomogr. 10:1986;579-583.
37. Bonte FJ, Hom J, Tintner R, Weiner MF Single photon tomography in Alzheimer disease and the dementias. Semin Nucl Med. 20:1990;342-352.
38. Borson S, Barnes R, Kukull W, Okimoto J, Veith R, Inui T, Carter W, Raskind M Symptomatic depression in elderly medical outpatients. I. Prevalence, demography, and health service utilization. J Am Geriatr Soc. 34:1986;341-347.
39. Bowen DM, Allen SJ, Benton JS, Goodhardt MJ, Haan EA, Palmer AM, Sims NR, Smith CCT, Spillane JA, Esiri MM, Neary D, Snowdon JS, Wilcock GK, Davison AN Biochemical assessment of serotonergic and cholinergic dysfunction and cerebral atrophy in Alzheimer's disease. J Neurochem. 41:1983;266-272.
40. Bowen DM, Najlerahim A, Procter A, Francis P, Murphy E Circumscribed changes of the cerebral cortex in neuropsychiatric disorders of late life. Proc Natl Acad Sci USA. 86:1989;9504-9508.
41. Briley M, Langer S, Raisman R, Sechter D, Zarifian E Tritiated imipramine binding sites are decreased in platelets of untreated depressed patients. Science. 209:1980;303-305.
42. Burke WJ, Chung HD, Huang JS, Huang SS, Haring JH, Strong R, Marshall GL, Joh TH Evidence for retrograde degeneration of epinephrine neurons in Alzheimer's disease. Ann Neurol. 24:1988;532-536.
43. Burns A, Tyrrell P Association of age with regional cerebral oxygen utilization. A positron emission tomography study Age Aging. 21:1992;316-320.
44. 1A receptor agonist, impairs performance in a passive avoidance task. Eur J Pharmacol. 211:1992;227-234.
45. Casey D Depression in the elderly. South Med J. 87(5):1994;559-563.
46. Chan-Palay V Serotonin axons in the supra- and subependymal plexuses and in the leptomeninges. Their roles in local alterations of cerebrospinal fluid and vasomotor activity Brian Res. 102:1976;103-130.
47. Chawluk J, Alavi A, Hurtig H, Dann R, Rosen M, Kushner MJ, Silver FL, Reivich M Altered patterns of regional cerebral glucose metabolism in aging and dementia. J Cereb Blood Flow Metab. 5(Suppl. 1):1985;S121-S122.
48. 2 receptor binding sites in depressed suicide victims. Brain Res. 443:1988;272-280.
49. Chen C-H, Hope R, Alder J, Eastwood S, Gedling K, McDonald B, Francis P, Esiri M, Bowen D Loss of paroxetine binding in the neocortex is associated with depression in Alzheimer's disease. Iqbal K, Mortimer J, Winblad B, Wisniewski H Research Advances in Alzheimer's Disease and Related Disorders. 1995;467-473 John Wiley & Sons Ltd, New York.
50. Chen C-H, Alder J, Bowen D, Esiri M, McDonald B, Hope T, Jobst K, Francis P Presynaptic serotonergic markers in community-acquired cases of Alzheimer's disease. Correlations with depression and neuroleptic medication J Neurochem. 66:1996;1592-1598.
51. 2 receptor binding in Lewy body dementia, Alzheimer's and Parkinson's diseases. J Neurol Sci. 106:1991;50-55.
52. Coffey CE, Wilkinson WE, Parashos IA, Soady SAR, Sullivan RJ, Patterson LJ, Figiel GS, Webb MC, Spritzer CE, Djang WT Quantitative cerebral anatomy of the aging human brain. A cross-sectional study using magnetic resonance imaging Neurology. 42:1992;527-536.
53. Condon B, Wyper D, Grant R, Patterson J, Hadley D, Teasdale G, Rowan J Use of magnetic resonance imaging to measure intracranial cerebrospinal fluid volume. Lancet. 1:1986;1355-1357.
54. Costall B, Barnes JM, Hamon M, Muller WE, Briley M Biochemical models for cognition enhancers. Pharmacopsychiatry. 23(Suppl. 2):1990;85-88.
55. Cowen P Serotonin receptor subtypes in depression. Evidence from studies in neuroendocrine regulation Clin Neuropharmacol. 16(Suppl. 3):1993;6-18.
56. Craik F, Jennings J Human Memory. Craik F, Salthouse T The Handbook of Aging and Cognition. 1992;51-111 Lawrence Elrbaum Publishers, New York.
57. Cross AJ Serotonin in Alzheimer-type dementia and other dementing illness. Ann NY Acad Sci. 600:1990;405-417.
58. Cross A, Crow T, Ferrier I, Johnson J, Bloom S, Corsellis J Serotonin receptor changes in dementia of Alzheimer type. J Neurochem. 43:1984;1574-1581.
59. Cross P, Gurland B (1986): The Epidemiology of Dementing Disorders (Contract report prepared for the Office of Technology Assessment, U.S. Congress). Washington, DC, U.S. Government Printing Office.
60. Crouzel C, Guillaume M, Barre L, Lemaire C, Pike V Ligands and tracers for PET studies of the 5-HT system - current status [review]. Int J Radiat Appl Instrum Part B, Nucl Med Biol. 19:1992;857-870.
61. Crow T, Cross A, Cooper S, Deakin J, Ferrier I, Johnson J, Joseph M, Owen FMP, Lofthouse R, Corsellis J, Chambers D, Blessed G, Perry E, Perry R, Tomlinson B Neurotransmitter receptors and monoamine metabolites in the brains of patients with Alzheimer-type dementia and depression, and suicides. Neuropharmacology. 23:1984;1561-1569.
62. Curcio C, Kemper T Nucleus raphe dorsalis in dementia of the Alzheimer type. Neurofibrillary changes and neuronal packing density J Neuropathol Exp Neurol. 43:1984;359-368.
63. Cutler NR, Haxby JV, Duara R, Grady CL, Kay AD, Kessler RM, Sundaram M, Rapoport SI Clinical history, brain metabolism, and neuropsychological function in Alzheimer disease. Ann Neurol. 18:1985;298-309.
64. D'Amato R, Zwieg R, Whitehouse P, Wenk G, Singer H, Mayeaux R, Price D, Snyder S Aminergic systems in Alzheimer's disease and Parkinson's disease. Ann Neurol. 22:1987;229-239.
65. Davies P, Maloney AJ Selective loss of central cholinergic neurons in Alzheimer's disease [letter]. Lancet. 2:1976;1403.
66. 3H]imipramine binding sites. Association with serotonergic neurons Brain Res Bull. 11:1983;325-334.
67. DeKosky S, Palmer A Neurochemistry of aging. Albert M, Knoefel J Clinical Neurology of Aging. 1994;79-101 Oxford Press, New York.
68. DeKosky S, Scheff S, Markesberry W Laminar organization of cholinergic circuits in human frontal cortex in Alzheimer's disease and aging. Neurology. 35:1985;1425-1431.
69. DeKosky S, Shih W-J, Schmitt F, Coupal J, Kirkpatrick C Assessing utility of single photon emission computerized tomography (SPECT) scan in Alzheimer's disease. Correlation with cognitive severity Alzheimer's Disease Related Disorders. 4:1990;14-23.
70. de Leon M, Ferris S, George A, Christman D, Fowler J, Gentes C, Reisberg B, Gee B, Emmerich M, Yonekura Y, Brodie J, Kricheff I, Wolf A Positron emission tomographic studies of aging and Alzheimer disease. Am J Neuroradiol. 4:1983;568-571.
71. de Montigny C Electroconvulsive shock treatment enhance responsiveness of forebrain neurons to serotonin. J Pharmacol Exp Ther. 228:1984;230-234.
72. Delgado P, Charney D, Price L, Aghajanian G, Landis H, Heninger G Serotonin function and the mechanism of antidepressant action. Arch Gen Psychiatry. 47:1990;411-418.
73. Denys A, Maunoury C, Cuenod C, Boller F, Jehenson P Amygdala and hippocampal formation MR measurements. diagnostic value in early stage of Alzheimer disease Radiology. 185(P):1992;200.
74. Descarries L, Beaudet A, Watkins K Serotonin nerve terminals in adult rat neocortex. Brain Res. 100:1975;563-588.
75. Devanand D, Sano M, Tang M-X, Taylor S, Gurland B, Wilder D, Stern Y, Mayneux R Depressed mood and the incidence of Alzheimer's disease in the elderly living in the community. Arch Gen Psychiatry. 53:1996;175-182.
76. 2 receptors in dementia of Alzheimer type. A quantitative autoradiographic study of frontal cortex and hippocampus J Neural Transm. 2:1990;129-137.
77. 2 antagonist. Soc Neurosci Abstr. 20:1994;1552.
78. 2 receptors in depression. Psychiatr Res. Neuroimaging 45:1992;227-237.
79. Diksic M, Nagahiro S, Chaly T, Sourkes T, Yamamoto Y, Feindel W Serotonin synthesis rate measured in living dog brain by positron emission tomography. J Neurochem. 56:1991;153-160.
80. Diksic M, Nagahiro S, Grdisa M The regional rate of serotonin synthesis estimated by the δ-methyl-tryptophan method in rat brain from a single time point. J Cereb Blood Flow Metab. 15:1995;806-813.
81. 1A receptor binding in the human brain postmortem. Effects of age and alcohol Brain Res. 554:1991;56-64.
82. Drevets WC, Videen TO, Price JL, Preskorn SH, Carmichael ST, Raichle ME A functional anatomical study of unipolar depression. J Neurosci. 12:1992;3628-3641.
83. Drevets W, Price J, Simpson J, Todd R, Reich T, Raichle M State- and trait-like neuroimaging abnormalities in depression. effects of antidepressant treatment Soc Neurosci Abstr. 22:1996;264.
84. Duara R, Grady C, Haxby J, Ingvar D, Sokoloff L, Margolin R, Manning R, Cutler NR, Rappaport SI Human brain glucose utilization and cognitive function in relation to age. Ann Neurol. 16:1984;702-713.
85. Duara R, Grady C, Haxby J, Sundaram M, Cutler NR, Heston L, Moore A, Schlageter N, Larson S, Rappaport SI Positron emission tomography in Alzheimer's disease. Neurology. 36:1986;879-887.
86. 1b receptors in an animal model of depression. Neuropharmacology. 30:1991;101-105.
87. 3H-imipramine binding during recovery from depression. Acta Psychiatr Scand. 86:1992;108-112.
88. Engleman E, Murphy J, Zhou F, Hingtgen J Response suppression induced with selective 5-HT agonists can be differentially blocked with LY53857 in an animal model of depression. Neurochem Res. 176:1992;483-488.
89. Erkinjuntti T, Lee DH, Gao F, Steenhuis R, Eliasziw M, Fry R, Merskey H, Hachinski VC Temporal lobe atrophy on magnetic resonance imaging in the diagnosis of early Alzheimer's disease. Arch Neurol. 50:1993;305-310.
90. Ernst RL, Hay JW The US economic and social costs of Alzheimer's disease revisited. Am J Public Health. 84:1994;1261-1264.
91. Evans D, Funkenstein H, Albert M, Scherr P, Cook N, Chown M, Herbert L, Hennekens C, Taylor J Prevalence of Alzheimer's disease in a community population of older persons. Higher than previously reported JAMA. 262:1989;2551-2556.
92. Figiel G, Krishnan K, Doraiswamy P, Rao V, Nemeroff C, Boyko O Subcortical hyperintensities on brain magnetic resonance imaging. A comparison between late age onset and early onset elderly depressed subjects Neurobiol Aging. 12:1991;245-247.
93. Fisher P, Simanyi M, Danielczyk W Depression in dementia of the Alzheimer type and in multi-infarct dementia. Am J Psychiatry. 147:1990;1484-1487.
94. Fitz AG, Teri L Depression, cognition, and functional ability in patients with Alzheimer's disease. J Am Geriatr Soc. 42:1994;186-191.
95. Fletcher A, Pike VW, Cliffe IA Visualization and characterization of 5-HT receptors and transporters in vivo and in man. Semin Neurosci. 7:1995;421-431.
96. Foster NL, Chase TN, Mansi L, Brooks R, Fedio P, Patronas NJ, Di Chiro G Cortical abnormalities in Alzheimer's disease. Ann Neurol. 16:1984;649-654.
97. Francis PT, Pangalos MN, Stephens PH, Bartlett JR, Bridges PK, Malizia AL, Neary D, Proctor AW, Thomas DJ, Bowen DM Antemortem measurements of neurotransmission. Possible implications for pharmacotherapy of Alzheimer's disease and depression J Neurol Neurosurg Psychiatry. 56:1993;80-84.
98. Frankfurt M, McKittrick C, Mendelson S, McEwen B Effect of 5, 7-dihydroxy-tryptamine, ovariectomy and gonadal steroids on serotonin receptor binding in rat brain. Neuroendocrinology. 59:1994;245-250.
99. Friedland RP, Budinger TF, Ganz E, Yano Y, Mathis CA, Koss B, Ober BA, Huesman RH, Derenzo SE Regional cerebral metabolic alterations in dementia of the Alzheimer type. Positron emission tomography with 18F-fluorodeoxyglucose J Comput Assist Tomogr. 7:1983;590-598.
100. Frlich L, Eilles C, Ihl R, Maurer K, Lanczik M Stage-dependent reductions of regional cerebral blood flow measured by HMPAO-SPECT in dementia of Alzheimer type. Psychiatry Res. 29:1989;347-350.
101. Frost J Imaging the serotonergic system by positron emission tomography. Ann NY Acad Sci. 600:1990;272-280.
102. Fuxe K, Calza L, Benfenati F, Zini I, Agnatti L Quantitative autoradiographic localization of [3H]imipramine binding sites in the brain of the rat. Relationship to ascending 5-hydroxytryptamine neuron systems. Proc Natl Acad Sci USA. 80:1983;3836-3840.
103. German DC, White CLD, Sparkman DR Alzheimer's disease. Neurofibrillary tangles in nuclei that project to the cerebral cortex Neuroscience. 21:1987;305-312.
104. Gilewski MJ, Farberow NL, Gallagher DE, Thompson LW Interaction of depression and bereavement on mental health in the elderly. Psychol Aging. 6:1991;67-75.
105. Golden RN, Gilmore JH, Corrigan MHN, Ekstrom RD, Knight BT, Garbutt JC Serotonin, suicide, and aggression. clinical studies J Clin Psychiatry. 52:1991;61-69.
106. Gonzales G, Carillo C Blood serotonin levels in postmenopausal women. Effects of age and serum oestradiol levels Maturitas. 17:1993;23-29.
107. Gottfries C Neurochemical aspects on aging and disease with cognitive impairment. J Neurosci Res. 27:1990;541-547.
108. 3H]ketansterin binding in the human brain postmortem. effect of suicide Brain Res. 507:1990;208-215.
109. Hajdu MA, McElmurry RT, Heistad DD, Baumbach GL Effects of aging on cerebral vascular responses to serotonin in rats. Am J Physiol. 264:1993;H2136-2140.
110. Halliday GM, McCann HL, Pamphlett R, Brooks WS, Creasey H, McCusker E, Cotton RGH, Broe GA, Harper CG Brain stem serotonin-synthesizing neurons in Alzheimer's disease. A clinicopathological correlation Acta Neuropathol. 84:1992;638-650.
111. Hayakawa H, Okamoto Y, Shimizu M, Nishida A, Motohashi N, Yamawaki S Single or repeated treatment with electroconvulsive shock increases number of serotonin uptake binding sites in the frontal cortex. Biol Psychiatry. 31:1995;1-5.
112. Holman BL, Nagel JS, Johnson KA, Hill TC Imaging dementia with SPECT. Ann NY Acad Sci. 620:1991;165-174.
113. Hoyer D, Martin G 5-HT receptor classification and nomenclature. Towards a harmonization with the human genome Neuropharmacology. 36:1997;419-428.
114. 3H]imipramine localization and relationship to serotonin transporter J Pharmacol Exp Ther. 252:1990;410-418.
115. 2 sites in cortex and amygdala Brain Res. 614:1993;37-44.
116. Hume SP, Ashworth S, Opacka-Juffry J, Ahier RG, Lammertsma AA, Pike VW, Cliffe IA, Fletcher A, White AC Evaluation of [O-methyl-3H]WAY-100635 as an in vivo radioligand for 5-HT1A receptors in rat brain. Eur J Pharmacol. 271:1994;515-523.
117. Husain M, Knight D, Doraiswamy P, Krishnan K, Nemeroff C Platelet [3H]-imipramine binding and leukoencephalopathy in geriatric depression. Biol Psychiatry. 29:1991;665-670.
118. 14C]5-hydroxytryptamine Neurosci Lett. 163:1993;8-10.
119. 2 receptors in living human brain. Prog Neuro-Psychopharmacol Biol Psychiatry. 17:1993;415-421.
120. Jack CR, Petersen RC, O'Brien PC, Tangalos EG MR-based hippocampal volumetry in the diagnosis of Alzheimer disease. Neurology. 42:1992;183-188.
121. Jacobs B, Azmitia E Structure and function of the brain serotonin system. Physiol Rev. 72:1992;165-229.
122. Jaffe E, De Frias V, Ibarra C Changes in basal and stimulated release of endogenous serotonin from different nuclei of rats subjected to two models of depression. Neurosci Lett. 162:1993;157-160.
123. Jagust WJ, Budinger TF, Reed BR The diagnosis of dementia with single photon emission computed tomography. Arch Neurol. 44:1987;258-262.
124. Jagust WJ, Reed BR, Seab PJ, Budinger TF Alzheimer disease. Age at onset and single-photon emission computed tomographic patterns of regional cerebral blood flow Arch Neurol. 47:1990;628-633.
125. Jamieson DG, Chawluk JB, Alavi A, Hurtig HI, Rosen M, Bais S, Dann R, Kushner M, Reivich M The effect of disease severity on local cerebral glucose metabolism in Alzheimer's disease. J Cereb Blood Flow Metab. 7:1987;S410.
126. Jansen KLR, Faull RLM, Dragunow M, Synek BL Alzheimer's disease. Changes in hippocampal N-methyl-D-aspartate, quisqualate, neurotensen, adenosine, benzodiazepine, serotonin and opioid receptors - An autoradiographic study Neuroscience. 39:1990;613-627.
127. Jernigan TL, Press GA, Hesselink JR Methods for measuring brain morphologic features on magnetic resonance images. Arch Neurol. 47:1990;27-32.
128. Kennedy GJ, Kelman HR, Thomas C Persistence and remission of depressive symptoms in late life. Am J Psychiatry. 148:1991;174-178.
129. Kennett G Mechanisms of serotonergic affect control. Schwarcz R, Young S, Brown R Kynurenine and Serotonin Pathways. 1991;231-243 Plenum Press, New York.
130. Komahashi T, Ohmori K, Nakana T, Fujinuma H, Higashimoto T, Nakaya M, Kuroda J, Asahi H, Yoshikawa J, Mastumura S Epidemiological survey of dementia and depression among the aged living in the community in Japan. Jpn J Psychiatry Neurol. 48:1994;517-526.
131. Koren P, Diver-Haber A, Adunsky A, Rabinowitz M, Hershkowitz M Uptake of serotonin into platelets of senile dementia of the Alzheimer type patients. J Gerontol. 48:1993;B93-B96.
132. 1A receptor agonists in animal models of depression and anxiety. Pharmacol Toxicol. 71:1992;24-30.
133. Kovachich G, Aronson C, Brunswick D Effect of repeated administration of antidepressants on serotonin uptake sites in limbic and neocortical structures of rat brain determined by quantitative autoradiography. Neuropsychopharmacology. 7:1992;317-324.
134. Kral VA, Emery OB Long-term follow-up of depressive pseudodementia of the aged. Can J Psychiatry - Revue Canadienne de Psychiatrie. 34:1989;445-446.
135. Kuhl D, Metter E, Riege W, Phelps M Effects of human aging on patterns of local cerebral glucose utilization determined by the [18F]fluorodeoxyglucose method. J Cereb Blood Flow Metab. 2:1982;163-171.
136. Kumar A, Newberg A, Alavi A, Berlin J, Smith R, Reivich M Regional cerebral glucose metabolism in late-life depression and Alzheimer disease. A preliminary positron emission tomography study Proc Natl Acad Sci USA. 90:1993;7019-7023.
137. Kumar A, Miller D, Samuels S, Burke L, Ewbank D, Gottlieb G MRI volumetrics in late life depression and Alzheimer's disease. Biol Psychiatry. 35:1994;615-747.
138. Lawlor BA, Sunderland T, Mellow AM, Molchan SE, Martinez R, Murphy DL A pilot placebo-controlled study of chronic m-CPP administration in Alzheimer's disease. Biol Psychiatry. 30:1991;140-144.
139. 3H]paroxetine, in antidepressant-free depressed suicides. Brain Res. 526:1990;17-22.
140. Leake A, Fairbairn A, McKeith I, Ferrier I Studies on the serotonin uptake binding site in major depressive disorder and control post-mortem brain. Neurochemical and clinical correlates Psychiatry Res. 39:1991;155-165.
141. Lemaire C, Cantineau R, Guillaume M, Plenevaux A, Christiaens L Fluorine-18altanserin. A radioligand for the study of serotonin receptors with PET: Radiolabeling and in vivo biologic behavior in rats J Nucl Med. 32:1991;2266-2272.
142. 2 receptor studies. Neuropsychopharmacology. 3:1990;361-369.
143. Little J, Broocks A, Martin A, Hill J, Tune L, Mack C, Cantillon M, Molchan S, Murphy D, Sunderland T Serotonergic modulation of anticholinergic effects on cognition and behavior in elderly humans. Psychopharmacology. 120:1995;280-288.
144. Loessner A, Alavi A, Lewandrowski K-U, Mozley D, Souder E, Gur R Regional cerebral function determined by FDG-PET in healthy volunteers. Normal patterns and changes with age J Nucl Med. 36:1995;1141-1149.
145. 2A receptors with positron emission tomography. Life Sci. 58:1996;187-192.
146. 1A receptors. Br J Pharmacol. 108:1993;669-677.
147. Maes M, Meltzer H The serotonin hypothesis of major depression. Bloom F, Kupfer D Psychopharmacology. The Fourth Generation of Progress:1995;933-944 Raven Press, Ltd, New York.
148. Mann DMA, Yates PO, Marcyniuk B Alzheimer's presenile dementia, senile dementia of Alzheimer type and Down's syndrome in middle age form an age-related continuum of pathological changes. Neuropathol Appl Neurobiol. 10:1984;185-207.
149. Mann J, Malone K, Diehl D, Perel J, Cooper T, Mintun M Demonstration in vivo of reduced serotonin responsivity in the brain of untreated depressed patients. Am J Psychiatry. 153:1996;174-182.
150. Marcusson J, Morgan D, Winblad B, Finch C Serotonin-2 binding sites in human frontal cortex and hippocampus. Selective loss of S-2A sites with age. Brain Res. 311:1984;51-56.
151. Marcusson J, Oreland L, Winblad B Effect of age on human brain serotonin (S-1) binding sites. J Neurochem. 43:1984;1699-1705.
152. Marcusson J, Alafuzoff I, Backstrom I, Ericson E, Gottfries C, Winblad B 5-Hydroxytryptamine-sensitive [3H]im-ipramine binding of protein nature in the human brain. II. Effect of normal aging and dementia disorders. Brain Res. 425:1987;137-145.
153. Marcyniuk B, Mann DM, Yates PO The topography of cell loss from locus coeruleus in Alzheimer's disease. J Neurol Sci. 76:1986;335-345.
154. Martin A, Friston K, Colebatch J, Frackowiak R Decreases in regional cerebral blood flow with normal aging. J Cereb Blood Flow Metab. 11:1991;684-689.
155. 1A receptors with positron emission tomography Life Sci. 55:1994;PL403-407.
156. 2A receptors labelled with 11C at two different positions J Labelled Compd Radiopharm. 27:1995;316-318.
157. 2A receptor system Med Chem Res. 6:1996;1-10.
158. 1A binding sites in frontal cortex of suicide victims J Neural Transm. 85:1991;181-194.
159. Mayberg H (1994): Frontal lobe dysfunction in secondary depression. J Neuropsychiatry 428-442.
160. Mayberg H, Brannan S, Liotti M, Mahurin R, Brickman J, Silva J, Tekell C, Jerebek P, Martin C, Fox P The role of the cingulate in mood homeostasis. Soc Neurosci Abstr. 22:1996;267.
161. McBean DE, Sharkey J, Ritchie IM, Kelly PA Evidence for a possible role for serotonergic systems in the control of cerebral blood flow. Brain Res. 537:1990;307-310.
162. 1A receptor activation. Brain Res. 555:1991;159-163.
163. 2 receptor indices to major depressive disorder, personality traits, and suicidal behavior. Biol Psychiatry. 35:1994;295-308.
164. McGuire M, Rabins P Mood disorders. Coffey C, Cummings J The American Psychiatric Press Textbook of Geriatric Neuropsychiatry. 1994;244-260 American Psychiatric Press, Inc, Washington, DC/London.
165. McLoughlin D, Lucey J, Dinan T Central serotonergic hyperresponsivity in late-onset Alzheimer's disease. Am J Psychiatry. 151:1994;1701-1703.
166. Meltzer CC, Leal JP, Mayberg HS, Wagner HJ, Frost JJ Correction of PET data for partial volume effects in human cerebral cortex by MR imaging. J Comp Assist Tomogr. 14:1990;561-570.
167. Meltzer C, Nichols T, Mintun M Effect of resolution on recovery of gray matter activity in FDG PET. J Nucl med. 36:1995;114P.
168. Meltzer C, Zubieta J, Brandt J, Tune L, Mayberg H, Frost J Regional hypometabolism in Alzheimer disease as measured by PET following correction for effects of partial volume averaging. Neurology. 47:1996;454-461.
169. Meltzer H Role of serotonin in depression. Ann NY Acad Sci. 600:1990;486-500.
170. Middlemiss D, Palmer A, Edel N, Bowen D Binding of the novel serotonin agonist 8-hydroxy-2-(di-n-propylamino) tetralin in normal and Alzheimer brain. J Neurochem. 46:1986;993-996.
171. Mueller-Gaertner H, Links J, Prince J, Bryan R, McVeigh E, Leal J, Davatzikos C, Frost J Measurement of radiotracer concentration in brain gray matter using positron emission tomography. MRI-based correction for partial volume effects J Cereb Blood Flow Metab. 12:1992;571-583.
172. Murphy D, DeCarli C, Schapiro M, Rapoport S, Horwitz B Age-related differences in volumes of subcortical nuclei, brain matter, and cerebrospinal fluid in healthy men as measured with magnetic resonance imaging. Arch Neurol. 49:1992;839-845.
173. Myers BL, Badia P Changes in circadian rhythms and sleep quality with aging. Mechanisms and interventions Neurosci Biobehav Rev. 19:1995;553-571.
174. 1A agonist and antidepressants. J Pharmacol Exp Ther. 260:1992;16-20.
175. Nishizawa S, Benkelfat C, Young SN, Leyton M, Mzengeza S, Demontigny C, Blier P, Diksic M Differences between males and females in rates of serotonin synthesis in human brain. Proc Natl Acad Sci USA. 94:1997;5308-5313.
176. Nordberg A Neuroreceptor changes in Alzheimer disease. Cerebrovasc Brain Metab Rev. 4:1992;303-328.
177. Normile H, Altman H Effects of combined acetylcholinesterase inhibition and serotonergic receptor blockade on age-associated memory impairments in rats. Neurobiol Aging. 13:1992;735-740.
178. 11C-deoxyglucose accumulation, CSF monoamine metabolites and neuropsychological test performance in patients and healthy subjects J Neurol Neurosurg Psychiatry. 54:1991;672-678.
179. Nyth A, Gottfries C The clinical efficacy of citalopram in treatment of emotional disturbances in dementia disorders. BR J Psychiatry. 157:1990;894-901.
180. Osman S, Lundkvist C, Pike V, Halldin C, McCarron J, Swahn C-G, Ginovart N, Luthra S, Bench C, Grasby P, Wikström H, Barf T, Cliffe I, Fletcher A, Farde L Characterization of the radioactive metabolites of the 5-HT1A receptor radioligande, [O-methyl-11C]WAY-100635, in monkey and human plasma by HPLC. Comparison of the behaviour of an identified radioactive metabolite with parent radioligand in monkey using PET Nucl Med Biol. 23:1996;627-634.
181. 2 receptors and suicide. Lancet ii:1256.
182. Owen F, Chambers DR, Cooper SJ, Crow TJ, Johnson JA, Lofthouse R, Poulter M Serotonergic mechanisms in brains of suicide victims. Brain Res. 362:1986;185-188.
183. Palacios J, Waeber C, Hoyer D, Mengod G Distribution of serotonin receptors. Ann NY Acad Sci. 600:1990;36-52.
184. Palmer AM, Francis PT, Benton JS, Sims NR, Mann DMA, Neary D, Snowden JS, Bowen DM Presynaptic serotonergic dysfunction in patients with Alzheimer's disease. J Neurochem. 48:1987;8-15.
185. 1A Receptors. 1987;286-299 Ellis Horwood Ltd, Chichester.
186. Palmer AM, Stratmann GC, Proctor AWP, Bowen DM Possible neurotransmitter basis of behavioral changes in Alzheimer's disease. Ann Neurol. 23:1988;616-620.
187. Parmelee P, Katz I, Lawton M Depression among institutionalized aged. Assessment and prevalence estimation J Gerontol. 44:1989;M22-M29.
188. Paul S, Rehavi M, Skolnick P, Ballenger J, Goodwin F Depressed patients have decreased binding of tritiated imipramine to platelet serotonin "transporter." Arch Gen Psychiatry. 38:1981;1315-1317.
189. 1B/D receptor antagonists. Gen Pharmacol. 29:1997;293-303.
190. Peroutka SJ Molecular biology of serotonin (5-HT) receptors. Synapse. 18:1994;241-260.
191. Perry EK, Tomlinson BE, Blessed G, Bergmann K, Gibson PH, Perry RH Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J. 2:1978;1457-1459.
192. Perry E, Marshall E, Blessed G, Tomlinson B, Perry R Decreased imipramine binding in the brains of patients with depressive illness. Br J Psychiatry. 142:1983;188-192.
193. 11C]WAY-100635. Eur J Pharmacol. 301:1996;R5-R7.
194. Polinsky RJ, Noble J, Di Chiro G, Nee LE, Feldman RG, Brown RT Dominantly inherited Alzheimer disease. Cerebral glucose metabolism J Neurol Neurosurg Psychiatry. 50:1987;752-757.
195. 11C]WAY 100635 and PET. Meyers R, Cunningham V, Bailey D, Jones T Quantification of Brain Function Using PET. 1996;257-261 Academic Press, San Diego.
196. Proctor AW, Francis PT, Stratmann GC, Bowen DM Serotonergic pathology is not widespread in Alzheimer patients without prominent aggressive symptoms. Neurochem Res. 17:1992;917-922.
197. Quirion R, Richard J Differential effects of selective lesions of cholinergic and dopaminergic neurons on serotonin-type 1 receptors in rat brain. Synapse. 1:1987;124-130.
198. Quirion R, Richard J, Dam TV Evidence for the existence of serotonin type-2 receptors on cholinergic terminals in rat cortex. Brain Res. 333:1985;345-349.
199. Rapp P, Amaral D Individual differences in the cognitive and neurobiological consequences of normal aging. Trends Neurosci. 15:1992;340-345.
200. Reiman E, Caselli R, Yun L, Chen K, Bandy D, Minoshima S, Thibodeau S, Osborne D Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. N Engl J Med. 334:1996;752-758.
201. Reinikainen KJ, Soininen H, Reikkinen PJ Neurotransmitter changes in Alzheimer's disease. Implications to diagnostics and therapy J Neurosci Res. 27:1990;576-586.
202. Reynolds C, Kupfer D, Hoch C, Stack J, Houck P, Sewitch D Two-year follow-up of elderly patients with mixed depression and dementia. Clinical and electroencephalographic sleep findings. J Am Geriatr Soc. 34:1986;793-799.
203. 2 receptors in severe dementia of the Alzheimer type. Neurosci Lett. 44:1984;47-51.
204. Richter-Levin G, Segal M Age-related cognitive deficits in rats are associated with a combined loss of cholinergic and serotonergic functions. Ann NY Acad Sci. 600:1990;254-257.
205. 1A and nicotinic cholinergic receptors in the regulation of water maze navigation behavior. Brain Res. 649:1994;174-180.
206. 2 receptors in mouse brain. Mol Pharmacol. 43:1993;84-89.
207. 1A partial agonists in depression. A composite analysis of buspirone in the treatment of depression J Clin Psychopharmacol. 10:1990;67S-76S.
208. Robinson SE Effect of specific serotonergic lesions on cholinergic neurons in the hippocampus, cortex and striatum. Life Sci. 32:1983;345-353.
209. Robson L, Gower A, Kendall D, Marsden C Age-related behavioural, neurochemical and radioligand binding changes in the central 5-HT system of Sprague-Dawley rats. Psychopharmacology. 113:1993;274-281.
210. 2 receptor imaging in the human brain using positron emission tomography and a new radioligand, [81F]altanserin. Results in young normal controls J Cereb Blood Flow Metab. 15:1995;787-797.
211. Salmon E, Maquet P, Sadzot B, Degueldre C, Lemaire C, Franck G Decrease of frontal metabolism demonstrated by positron emission tomography in a population of healthy elderly volunteers. Acta Neurol Belg. 91:1991;288-295.
212. Saudou F, Hen R 5-hydroxytryptamine receptor subtypes in vertebrates and invertebrates. Neurochem Int. 25:1994;503-532.
213. Schneider LS, Severson J, Chui H, Pollock V, Sloane R, Fredrickson E Platelet H3-imipramine binding in Alzheimer's disease patients with agitation and delusions. Psychiatry Res. 25:1988;311-322.
214. Schone W, Ludwig M A double-blind study of paroxetine compared with fluoxetine in elderly patients with major depression. J Clin Psychopharmacol. 13(Suppl 2):1993;34S-39S.
215. Seab JP, Jagust WP, Wong STS, Roos MS, Reed BR, Budinger TF Quantitative NMR measurements of hippocampal atrophy in Alzheimer's disease. Magn Reson Med. 8:1988;200-208.
216. Shapira B, Lerer B, Kindler S, Lichtenberg P, Gropp C, Cooper T, Calev A Enhanced serotonergic responsivity following electroconvulsive therapy in patients with major depression. Br J Psychiatry. 160:1992;223-229.
217. 2C receptors Neuropharmacology. 33:1994;467-471.
218. Shefer VF Absolute numbers of neurons and thickness of the cerebral cortex during aging, senile and vascular dementia, and Pick's and Alzheimer's diseases. Neurosci Behav Physiol. 6:1972;319-324.
219. Shih J, Young H The alteration of serotonin binding sites in aged human brained. Life Sci. 23:1978;1441-1448.
220. Shuttleworth EC, Huber SJ, Paulson GW Depression in patients with dementia of the Alzheimer type. J Natl Med Assoc. 79:1987;733-736.
221. Small G, Mazziotta J, Collins M Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease. JAMA. 273:1995;942-947.
222. Sparks D Aging and Alzheimer's disease. Altered cortical serotonergic binding. Arch Neurol. 46:1989;138-140.
223. Sparks D, Markesbery W, Slevin J Alzheimer's disease. Monoamines and spiperone binding reduced in nucleus basalis Ann Neurol. 19:1986;602-604.
224. 2 receptor antagonism and slow-wave sleep in major depression. Acta Psychiatr Scand. 86:1992;133-137.
225. Stanley M, Mann J (1983): Increased serotonin-2 binding sites in the frontal cortex of suicide victims. Lancet i:214-216.
226. Stanley M, Virgilio J, Gershon S Tritiated imipramine binding sites are decreased in the frontal cortex of suicides. Science. 216:1982;1337-1339.
227. Stockmeier C, Dilley G, Shapiro L, Overholser J, Thompson P, Meltzer H Serotonin receptors in suicide victims with major depression. Neuropsychopharmacology. 16:1996;162-173.
228. Strosznajder J, Samochocki M, Duran M Aging diminishes serotonin-stimulated arachidonic acid uptake and cholinergic receptor-activated arachidonic acid release in rat brain cortex membrane. J Neurochem. 62:1994;1048-1054.
229. Suehiro M, Scheffel U, Dannals R, Ravert H, Ricaurte G, Wagner H Jr. A PET radiotracer for studying serotonin uptake sites. Carbon-11-McN-5652Z J Nucl Med. 34:1993;120-127.
230. Suehiro M, Scheffel U, Ravert H, Dannals R, Wagner H Jr. [11C](+)McN5652 as a radiotracer for imaging serotonin uptake sites with PET. Life Sci. 53:1993;883-892.
231. Szabo Z, Kao P, Scheffel U, Suehiro M, Mathews W, Ravert H, Musachio J, Marenco S, Kim S, Ricaurte G, Wong D, Wagner H, Dannals R Positron emission tomography imaging of serotonin transporters in the human brain using [11C](+)McN5652. Synapse. 20:1995;37-43.
232. 11C]McN5652. J Cereb Blood Flow Metab. 15:1995;798-805.
233. Takada H, Nagata K, Hirata Y, Satoh Y, Watahiki Y, Sugawara J, Yokoyama E, Kondoh Y, Shishido F, Inugami A, Fujita H, Ogawa T, Murakami M, Iida H, Kanno I Age-related decline of cerebral oxygen metabolism in normal population detected with positron emission tomography. Neurol Res. 14(Suppl.):1992;128-131.
234. Tejani-Butt S, Yang J, Pawlyk A Altered serotonin transporter sites in Alzheimer's disease raphe and hippocampus. Neuro Report. 6:1995;1207-1210.
235. Teri L, Reifler B Depression and dementia. Carstensen L, Edelstein B Handbook of Clinical Gerontology. 1987;112-119 Pergamon Press, New York.
236. Terry RD, Peck A, DeTeresa R, Schechter R, Horoupian DS Some morphometric aspects of the brain in senile dementia of the Alzheimer type. Ann Neurol. 10:1981;184-192.
237. Tork I Anatomy of the serotonergic system. Ann NY Acad Sci. 600:1990;9-35.
238. Tsuiki K, Mück-Seler C, Diksic M Autoradiographic evaluation of the influence of hypothalamic 5, 7-dihydroxytryptamine lesion on brain serotonin synthesis. Biochem Pharmacol. 49:1995;633-642.
239. Tsuiki K, Yamamoto Y, Diksic M Effect of acute fluoxetine treatment on the brain serotonin synthesis as measured by the δ-methyl-L-tryptophan autoradiographic method. J Neurochem. 65:1995;250-256.
240. Venero J, de la Roza C, Machado A, Cano J Age-related changes on monoamine turnover in hippocampus of rats. Brain Res. 631:1993;89-96.
241. Vizi ES, Harsing LG, Zsilla G Evidence of the modulatory role of serotonin in acetylcholine release from striatal interneurons. Brain Res. 212:1981;89-99.
242. Whitehouse PJ, Struble RG, Hedreen JC, Clark AW, Price DL Alzheimer's disease and related dementias. Selective involvement of specific neuronal systems CRC Crit Rev Clin Neurobiol. 1:1985;319-339.
243. 2 receptors and brain circulation. J Cardiovasc Pharmacol. 16:1990;S20-S24.
244. Wong D, Wagner HJ, Dannals R, Links J, Frost J, Ravert H, Wilson A, Rosenbaum A, Gjedde A, Douglass K, Petronis J, Folstein M, Toung J, Burns H, Kuhar M Effects of age on dopamine and serotonin receptors measured by positron tomography in the living human brain. Science. 226:1984;1393-1396.
245. Yamaguchi T, Yamagata A Serotonergic ligand binding in aging brain of experimental animals. Neurochem Res. 16:1991;469-473.
246. Yoshii F, Barker W, Chang J, Loewenstein D, Apicella A, Smith D, Boothe T, Ginsberg M, Pascal S, Duara R Sensitivity of cerebral glucose metabolism to age, gender, brain volume, brain atrophy, and cerebrovascular risk factors. J Cereb Blood Flow Metab. 8:1988;654-661.
247. 2 receptors in rat hippocampus. Soc Neurosci Abstr. 21:1994;1548.
248. Zola-Morgan S, Squire L, Rempel N, Clower R, Amaral D Enduring memory impairment in monkeys after ischemic damage to the hippocampus. J Neurosci. 12:1992;2582-2596.
249. Zubenko G, Moossy J, Martinez A, Rao G, Classen D, Rosen J, Kopp U Neuropathologic and neurochemical correlates of psychosis in primary dementia. Arch Neurol. 48:1991;619-624.
250. Zweig R, Swiergiel T, Steele C, Price D, Ross C The dorsal raphe and depression in Alzheimer's disease. Soc Neurosci Abstr. 21(Part 3):1995;1977.