Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 7 April 1967:
Vol. 156. no. 3771, pp. 21 - 30
DOI: 10.1126/science.156.3771.21
Prev | Table of Contents | Next

Articles

Biogenic Amines and Emotion

Joseph J. Schildkraut 1 and Seymour S. Kety 2

1 Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland
2 Laboratory of Clinical Science, National Institute of Mental Health

The studies discussed here have shown a fairly consistent relationship between the effects of drugs on biogenic amines, particularly norepinephrine, and affective or behavioral states. Those drugs which cause depletion and inactivation of norepinephrine centrally produce sedation or depression, while drugs which increase or potentiate brain norepinephrine are associated with behavioral stimulation or excitement and generally have an antidepressant effect in man (Table 1). From these findings, a number of investigators have formulated the concept, designated the catecholamine hypothesis of affective disorders (6), that some, if not all, depressions may be associated with a relative deficiency of norepinephrine at functionally important adrenergic receptor sites in the brain, whereas elations may be associated with an excess of such amines.

It is not possible either to confirm or to reject this hypothesis on the basis of currently available clinical data. Although there does appear to be a fairly consistent relationship between the effects of pharmacological agents on norepinephrine metabolism and on affective state, a rigorous extrapolation from pharmacological studies to pathophysiology cannot be made. Confirmation of this hypothesis must ultimately depend upon direct demonstration of the biochemical abnormality in the naturally occurring illness.

It should be emphasized, however, that the demonstration of such a biochemical abnormality would not necessarily imply a genetic or constitutional, rather than an environmental or psychological, etiology of depression.Whereas specific genetic factors may be of importance in the etiology of some, and possibly all, depressions, it is equally conceivable that early experiences of the infant or child may cause enduring biochemical changes and that these may predispose some individuals to depressions in adulthood.

It is not likely that changes in the metabolism of the biogenic amines alone will account for the complex phenomena of normal or pathological affect.Whereas the effects of these amines at particular sites in the brain may be of crucial importance in the regulation of affect, any comprehensive formulation of the physiology of affective state will have to include many other concomitant biochemical, physiological, and psychological factors. Although in this review of the relationship of biogenic amines to affective state relatively little has been said concerning the intricate set of environmental and psychological determinants of emotion, the importance of these factors must be stressed.

The normally occurring alterations in affective state induced by environmental events is well known to all, from personal experience. The interactions between such environmental determinants of affect, various physiological factors, and the complexity of psychological determinants, including cognitive factors derived from the individual's remote and immediate past experiences, have received only limited study under adequately controlled conditions. It may be anticipated, however, that this will prove to be a particularly fruitful area for future research, for only within such a multifactorial framework may one expect to understand fully the relationship of the biogenic amines to emotional state.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression..
J. H. Meyer, N. Ginovart, A. Boovariwala, S. Sagrati, D. Hussey, A. Garcia, T. Young, N. Praschak-Rieder, A. A. Wilson, and S. Houle (2006)
Arch Gen Psychiatry 63, 1209-1216
   Abstract »    Full Text »    PDF »
Neuromodulatory Basis of Emotion.
J.-M. Fellous (1999)
Neuroscientist 5, 283-294
   Abstract »    PDF »
The effects of environmental illumination on melatonin, bodily rhythms and mood states: a review.
P.T. Stone (1999)
Lighting Research and Technology 31, 71-79
   Abstract »    PDF »
Urinary Catecholamine Levels in Children with and without Dental Caries.
A.P. Vanderas, C. Manetas, and L. Papagiannoulis (1995)
Journal of Dental Research 74, 1671-1678
   Abstract »    PDF »
Antidepressant treatments, including electroconvulsive shock and the putative antidepressant sibutramine hydrochloride, do not alter [3H]-prazosin binding to rat cortical membranes.
K.F. Martin, I. Phillips, D.J. Heal, and W.R. Buckett (1989)
J Psychopharmacol 3, 70-75
   Abstract »    PDF »
The brain nucleus locus coeruleus: restricted afferent control of a broad efferent network.
G Aston-Jones, M Ennis, V. Pieribone, W. Nickell, and M. Shipley (1986)
Science 234, 734-737
   Abstract »    PDF »
Cerebrospinal Fluid Amine Metabolites: Relations`phips With Behavioral Measurements in Depressed, Manic, and Healthy Control Subjects.
D. E. Redmond Jr, M. M. Katz, J. W. Maas, A. Swann, R. Casper, and J. M. Davis (1986)
Arch Gen Psychiatry 43, 938-947
   Abstract »    PDF »
{alpha}2-Adrenergic Receptor Function in Depression: The Cortisol Response to Yohimbine.
L. H. Price, D. S. Charney, A. L. Rubin, and G. R. Heninger (1986)
Arch Gen Psychiatry 43, 849-858
   Abstract »    PDF »
Endogenous inhibitors of monoamine oxidase present in human cerebrospinal fluid.
R. Becker, C Giambalvo, R. Fox, and M Macho (1983)
Science 221, 476-478
   Abstract »    PDF »
Increased Plasma MHPG in Dexamethasone-Resistant Depressed Patients.
D. C. Jimerson, T. R. Insel, V. I. Reus, and I. J. Kopin (1983)
Arch Gen Psychiatry 40, 173-176
   Abstract »    PDF »
Histochemical Protein Markers of Monoamine Cell Bodies in Man.
M. T. Panayotacopoulou and M. R. Issidorides (1982)
Arch Neurol 39, 635-639
   Abstract »    PDF »
High-affinity [3H]imipramine binding in rat hypothalamus: association with uptake of serotonin but not of norepinephrine.
S. Langer, C Moret, R Raisman, M. Dubocovich, and M Briley (1980)
Science 210, 1133-1135
   Abstract »    PDF »
Nocturnal Masseter Muscle Activity and Urinary Catecholamine Levels in Bruxers.
G.T. Clark, J.D. Rugh, and S.L. Handelman (1980)
Journal of Dental Research 59, 1571-1576
   Abstract »    PDF »
Tritiated imipramine binding sites are decreased in platelets of untreated depressed patients.
M. Briley, S. Langer, R Raisman, D Sechter, and E Zarifian (1980)
Science 209, 303-305
   Abstract »    PDF »
Urinary 3-Methoxy-4-Hydroxyphenylglycol Circadian Rhythm: Early Timing (Phase-Advance) in Manic-Depressives Compared With Normal Subjects.
T. A. Wehr, G. Muscettola, and F. K. Goodwin (1980)
Arch Gen Psychiatry 37, 257-263
   Abstract »    PDF »
Cerebral norepinephrine: influence on cortical oxidative metabolism in situ.
S. Harik, J. LaManna, A. Light, and M Rosenthal (1979)
Science 206, 69-71
   Abstract »    PDF »
Novel Antidepressants and the Biogenic Amine Hypothesis of Depression: The Case for Iprindole and Mianserin.
A. P. Zis and F. K. Goodwin (1979)
Arch Gen Psychiatry 36, 1097-1107
   Abstract »    PDF »
State Anxiety, Physical Activity, and Urinary 3-Methoxy-4-Hydroxyphenethylene Glycol Excretion.
D. R. Sweeney, J. W. Maas, and G. R. Heninger (1978)
Arch Gen Psychiatry 35, 1418-1423
   Abstract »    PDF »
Primary Affective Disorder, Clinical State Change, and MHPG Excretion: A Longitudinal Study.
D. Pickar, D. R. Sweeney, J. W. Maas, and G. R. Heninger (1978)
Arch Gen Psychiatry 35, 1378-1383
   Abstract »    PDF »
Presynaptic alpha-receptor subsensitivity after long-term antidepressant treatment.
F. Crews and C. Smith (1978)
Science 202, 322-324
   Abstract »    PDF »
Clinical and Biochemical Heterogeneity of Depressive Disorders.
J. W. MAAS (1978)
Ann Intern Med 88, 556-563
   Abstract »    PDF »
Aggravation of Diabetic Hyperglycemia by Chlordiazepoxide.
B. Zumoff and L. Hellman (1977)
JAMA 237, 1960-1961
   Abstract »    PDF »
Norepinephrine-dopamine interactions and behavior.
S. Antelman and A. Caggiula (1977)
Science 195, 646-653
   Abstract »    PDF »
Monoamine Metabolism in Human Brain.
D. S. Robinson, T. L. Sourkes, A. Nies, L. S. Harris, S. Spector, D. L. Bartlett, and I. S. Kaye (1977)
Arch Gen Psychiatry 34, 89-92
   Abstract »    PDF »
Combining Tricyclic and Monoamine Oxidase Inhibitor Antidepressants.
D. G. Spiker and D. D. Pugh (1976)
Arch Gen Psychiatry 33, 828-830
   Abstract »    PDF »
Self-inhibition by dopaminergic neurons.
P. Groves, C. Wilson, S. Young, and G. Rebec (1975)
Science 190, 522-528
   PDF »
Biogenic Amines and Depression: Biochemical and Pharmacological Separation of Two Types of Depression.
J. W. Maas and J. W. Maas (1975)
Arch Gen Psychiatry 32, 1357-1361
   Abstract »    PDF »
Strain differences during intraventricular infusion of norepinephrine: possible role of receptor sensitivity.
D. Segal, M. Geyer, and B. Weiner (1975)
Science 189, 301-303
   Abstract »    PDF »
Norepinephrine-Sensitive Adenylate Cyclases in Rat Brain: Relation to Behavior and Tyrosine Hydroxylase.
P. Skolnick and J. W. Daly (1974)
Science 184, 175-177
   Abstract »    PDF »
Neurochemical, Endocrine, Pharmacological, and Genetic Studies.
(1974)
Arch Neurol 30, 8-23
   Abstract »    PDF »
L-Tryptophan in Mania: Contribution to a Permissive Hypothesis of Affective Disorders.
A. J. Prange Jr., I. C. Wilson, C. W. Lynn, L. B. Alltop, and R. A. Stikeleather (1974)
Arch Gen Psychiatry 30, 56-62
   Abstract »    PDF »
Drug Spotlight Program: Uses of Psychotherapeutic Drugs.
L. E. HOLLISTER (1973)
Ann Intern Med 79, 88-98
   Abstract »    PDF »
Catecholamine Uptake in Cerebral Cortex: Adaptive Change Induced by Fighting.
E. D. Henley, B. Moisset, and B. L. Welch (1973)
Science 180, 1050-1052
   Abstract »    PDF »
Genetic Control of Platelet and Plasma Monoamine Oxidase Activity.
A. Nies, D. S. Robinson, K. R. Lamborn, and R. P. Lampert (1973)
Arch Gen Psychiatry 28, 834-838
   Abstract »    PDF »
Central Norepinephrine Metabolism in Affective Illness: MHPG in the Cerebrospinal Fluid.
R. M. Post, E. K. Gordon, F. K. Goodwin, and W. E. Bunney Jr. (1973)
Science 179, 1002-1003
   Abstract »    PDF »
Rat Fighting Behavior: Serum Dopamine-beta-Hydroxylase and Hypothalamic Tyrosine Hydroxylase.
F. Lamprecht, B. Eichelman, N. B. Thoa, R. B. Williams, and I. J. Kopin (1972)
Science 177, 1214-1215
   Abstract »    PDF »
Catecholamines in the Brain as Mediators of Amphetamine Psychosis.
S. H. Snyder (1972)
Arch Gen Psychiatry 27, 169-179
   Abstract »    PDF »
Thyroid Function and the Response to Liothyronine in Depression.
P. C. Whybrow, A. Coppen, A. J. Prange Jr., R. Noguera, and J. E. Bailey (1972)
Arch Gen Psychiatry 26, 242-245
   Abstract »    PDF »
Catecholamine Metabolism, Depressive Illness, and Drug Response.
J. W. Maas, J. A. Fawcett, and H. Dekirmenjian (1972)
Arch Gen Psychiatry 26, 252-262
   Abstract »    PDF »
Growth Hormone Responses in Depressive Illness: I. Response to Insulin Tolerance Test.
E. J. Sachar, J. Finkelstein, and L. Hellman (1971)
Arch Gen Psychiatry 25, 263-269
   Abstract »    PDF »
Effects of Long-Term Reserpine Treatment on Brain Tyrosine Hydroxylase and Behavioral Activity.
D. S. Segal, J. L. Sullivan III, R. T. Kuczenski, and A. J. Mandell (1971)
Science 173, 847-849
   Abstract »    PDF »
Noradrenaline: Fate and Control of Its Biosynthesis.
J. Axelrod (1971)
Science 173, 598-606
   PDF »
Tricyclic Antidepressants and Monoamine Oxidase Inhibitors: Combination Therapy in the Treatment of Depression.
M. Schuckit, E. Robins, and J. Feighner (1971)
Arch Gen Psychiatry 24, 509-514
   Abstract »    PDF »
Norepinephrine Pools in Rat Brain: Differences in Turnover Rates and Pathways of Metabolism.
J. J. Schildkraut, P. R. Draskoczy, and P. S. Lo (1971)
Science 172, 587-589
   Abstract »    PDF »
Norepinephrine Biosynthesis Inhibition: Effects on Memory in Mice.
C. T. Randt, D. Quartermain, M. Goldstein, and B. Anagnoste (1971)
Science 172, 498-499
   Abstract »    PDF »
Perinatal Undernutrition: Accumulation of Catecholamines in Rat Brain.
W. J. Shoemaker and R. J. Wurtman (1971)
Science 171, 1017-1019
   Abstract »    PDF »
Hydrocortisone-Mediated Increase of Norepinephrine Uptake by Brain Slices.
J. W. Maas and M. Mednieks (1971)
Science 171, 178-179
   Abstract »    PDF »
Psychosis and Other Psychiatric Manifestations of Levodopa Therapy.
G. G. Celesia and A. N. Barr (1970)
Arch Neurol 23, 193-200
   Abstract »    PDF »
Conceptual Developments in Psychosomatic Medicine: 1939-1969.
C. P. KIMBALL (1970)
Ann Intern Med 73, 307-316
   Abstract »    PDF »
Norepinephrine Turnover and Metabolism in Rat Brain after Long-Term Administration of Imipramine.
J. J. Schildkraut, A. Winokur, and C. W. Applegate (1970)
Science 168, 867-869
   Abstract »    PDF »
Catecholamine Metabolism in Affective Disorders: II. Norepinephrine, Normetanephrine, Epinephrine, Metanephrine, and VMA Excretion in Hypomanic Patients.
K. Greenspan, J. J. Schildkraut, E. K. Gordon, B. Levy, and J. Durell (1969)
Arch Gen Psychiatry 21, 710-716
   Abstract »    PDF »
Antiparkinsonian Drugs: Inhibition of Dopamine Uptake in the Corpus Striatum as a Possible Mechanism of Action.
J. T. Coyle and S. H. Snyder (1969)
Science 166, 899-901
   Abstract »    PDF »
Ontogeny of Adrenergic Arousal and Cholinergic Inhibitory Mechanisms in the Rat.
B. A. Campbell, L. D. Lytle, and H. C. Fibiger (1969)
Science 166, 635-637
   Abstract »    PDF »
Dextroamphetamine, Catecholamines, and Behavior: The Effect of Dextroamphetamine in Retarded Children.
A. H. Anton and M. Greer (1969)
Arch Neurol 21, 248-252
   Abstract »    PDF »
Deep Temporal Stimulation in Man: Long Latency, Long Lasting Psychological Changes.
J. R. Stevens, V. H. Mark, F. Erwin, P. Pacheco, and K. Suematsu (1969)
Arch Neurol 21, 157-169
   Abstract »    PDF »
Animal Model of Depression: I. Review of Evidence: Implications for Research.
W. T. McKinney Jr. and W. E. Bunney Jr. (1969)
Arch Gen Psychiatry 21, 240-248
   Abstract »    PDF »
Screening for Aminoacidurias in Psychiatric Inpatients.
E. S. Gershon and R. I. Shader (1969)
Arch Gen Psychiatry 21, 82-88
   Abstract »    PDF »
Hormonal Influences in Female Sexual Response.
F. J. Kane Jr., M. A. Lipton, and J. A. Ewing (1969)
Arch Gen Psychiatry 20, 202-209
   Abstract »    PDF »
Mental Changes Accompanying Thyroid Gland Dysfunction: A Reappraisal Using Objective Psychological Measurement.
P.C. Whybrow, A.J. Prange Jr., and C.R. Treadway (1969)
Arch Gen Psychiatry 20, 48-63
   Abstract »    PDF »
Psychochemical Research Studies in Man.
A. J. Mandell and C. E. Spooner (1968)
Science 162, 1442-1453
   PDF »
Sleep and Depression: Further Considerations.
J. Mendels and D. R. Hawkins (1968)
Arch Gen Psychiatry 19, 445-452
   Abstract »    PDF »
Longitudinal Studies of Sleep and Dream Patterns in Manic-Depressive Patients.
E. Hartmann (1968)
Arch Gen Psychiatry 19, 312-329
   Abstract »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)