Recently certain hypotheses with a biochemical flavour have been proposed to explain the etiology of psychosis. These hypotheses suggest that a disturbance in the metabolism of some important substance such as serotonin (5-hydroxytryptamine), nor-adrenaline or adrenaline results in a chemical imbalance in the brain, or leads to the formation of an abnormal product which is toxic to the brain, although not completely interfering with its metabolic activities; and, further, that this disturbance is causative in psychoses.
In this paper the various hypotheses are described and evaluated. For example, the metabolic disturbance has been attributed to (1) excessive accumulation of serotonin in the brain, (2) a deficiency of it in that organ, or (3) excessive conversion to bufotenine, its dimethyl derivative. “Adrenaline theories” postulate the conversion of (1) nor-adrenaline to a mescaline-like substance, or (2) adrenaline to adrenolutine, adrenochrome or “adrenoxine”, the conversion product playing the role of the toxic, psychosis-producing agent.
The limited and contradictory evidence available to these hypotheses is pointed out, as well as the frankly speculative nature of some of the views. A brief indication is made of the considerable biochemical research on the function of serotonin and catecholamines in the brain, research which is going on in many laboratories quite apart from the described hypotheses. The importance of such research for neuropsychiatry is emphasized.
References
1.
AgnewN., and HofferA.: Nicotinic acid modified LSD psychosis, J. Ment. Sci.101, 12–27 (1955).
2.
AminA. H., CrawfordT. B. B., and GaddumJ. H.: The distribution of substance P and 5-hydroxytryptamine in the central nervous system of the dog, J. Physiol. (London)126, 596–618 (1954).
3.
BenitezH. H., MurrayM. R., and WoolleyD. W.: Effects of serotonin and certain of its antagonists upon oligodendroglial cells in vitro, IInd International Congress of Neuropathology, London, Sept. 12-17, 1955, Abstracted in Excerpta Medica8, VIII, 877 (1955).
4.
BlaschkoH.: Adrenaline and sympathin. In: The hormones: physiology, chemistry and applications. Vol. II, 601. Academic Press, Inc., New York, 1950.
5.
BlaschkoH.: Amine oxidase and amine metabolism,Pharmacol. Rev.4, 415–458 (1952).
6.
BumpusF. M., and PageI. H.: Serotonin and its methylated derivatives in human urine,J. Biol. Chem.212, 111–116 (1955).
7.
ClarkC. T., WeissbachH., and UdenfriendS.: 5-Hydroxytryptophan decarboxylase: preparation and properties.J. Biol. Chem.210, 139–148 (1954).
8.
ElliottK. A. C., PageI. H., and QuastelJ. H., Eds.: Neurochemistry: The chemical dynamics of brain and nerve.Blackwell, Oxford, 368 pp., 1955.
9.
ErspamerV.: II sistema cellulare enterrocromaffine e l'enteramina, Rendiconti Scientifici Farmitalia1, 1–193 (1954).
10.
ErspamerV.: Pharmacology of indolealkylamines,Pharmacol. Rev.6, 425–487 (1954).
11.
ErspamerV.: Observations on the fate of indolealkylamines in the organism, J. Physiol. (London)127, 118–133 (1955).
12.
EvartsE.: quoted by Erspamer (10).
13.
FeldbergW., and SherwoodS. L.: Injections of drugs into the lateral ventrical of the cat, J. Physiol. (London)123, 148–167 (1954).
14.
FischerR.: Schizophrenie, ein regressiver Adaptationsprozess,Monatschr. Psychiat. u. Neurol.126, 315–333 (1953).
HofferA., OsmondH., and SmythiesJ.: Schizophrenia, a new approach. II. Results of a year's research,J. Ment. Sci.100, 29–45 (1954).
17.
KoelleG. B., editor: Symposium on neurohumoral transmission,Pharmacol. Rev.6, 1–131 (1954).
18.
LangemannH.: Oxytryptamin (Serotonin) als neues Hormon,Schweiz. Med. Wochschr.85, 957–972 (1955).
19.
MacLaganN. F., and WilkinsonJ. H.: The biological action of substances related to thyroxine. 7. The metabolism of butyl 4-hydroxy-3:5-diiodobenzoate, Biochem. J. (London)56, 211–215 (1954).
20.
MarrazziA.: Some indications of cerebral humoral mechanisms, Science118, 367–370 (1953).
21.
MarrazziA. S., and HartE. R.: Relationship of hallucinogens to adrenergic cerebral neurohumors, Science, 121, 365–367 (1955).
22.
OsmondH., and SmythiesJ.: Schizophrenia, a new approach,J. Ment. Sci.98, 309–315 (1952).
Proceedings of the Conference on Psychopharmacological Agents, McGill University, March, 26, 1955.
25.
QuastelJ. H., and WooldridgeW. R.: Some properties of the dehydrogenting enzymes of bacteria.Biochem. J. (London)22, 689–702 (1928).
26.
RinkelM., HydeR. W., and SolomonH. C.: Experimental psychiatry, III. A chemical concept of psychosis, Dis. Nerv. System15, 259–264 (1954).
27.
RinkelM., HydeR. W., and SolomonH. C.: Experimental psychiatry. IV. Hallucinogens, tools in experimental psychiatry, Dis. Nerv. System16, 229–232 (1955).
28.
SherlockS., SumerskillW. H. J., WhiteL. P., and PhearE. A.: Portal-systemic encephalopathy, neurological complications of liver disease, Lancetii.453–457 (1954).
29.
ShoreP. A., SilverS. L., and BrodieB. B.: Interaction of reserpine, serotonin, and lysergic acid diethylamide in brain, Science122, 284–285 (1955).
30.
SjoerdsmaA., SmithT. E., StevensonT.D., and UdenfriendsS.: Metabolism of 5-hydroxytryptamine (serotonin) by monoamine oxidase.Proc. Soc. Exptl. Biol Med.89, 36–38 (1955).
31.
SourkesT. L.: Transmethylases, Chap. 33 in Sumner and Myrbäck, The enzymes, 1, Pt., 2, 1068–1078, Academic Press, Inc., New York, 1951.
32.
SourkesT. L.: Inhibition of dihydroxyphenylalanine decarboxylase by derivatives of phenylalanine,Arch. Biochem. Biophys.51, 444–456 (1954).
33.
SourkesT. L.: Substrate specificity of hydroxy-L-phenylalanine decarboxylases and related enzymes,Rev. Can. de Biol.14, 49–63 (1955).
34.
SourkesT. L., and TownsendE.: Effects of a-methyl-DL-tryptophan on the oxidation of tryptophan,Can. J. Biochem. Physiol.33, 735–740 (1955).
35.
SourkesT. L., TownsendE., and HansenG. N.: The oxidation of tryptamine by rat liver and other tissue suspensions,Can. J. Biochem. Physiol.33, 725–735 (1955).
36.
SpiesT. D., and StoneR. E.: Effect of serotonin on blood pressure and lack of effect of antimetabolite.J. Amer. Med. Assoc.150, 1599–1600 (1952).
37.
TwarogB. M., and PageI. H.: Serotonin content of some mammalian tissues and urine and a method for its determination,Am. J. Physiol.175, 157–161 (1953).
38.
UdenfriendS., ClarkC. T., and TitusE.: Hydroxylation of the 5-position of tryptophan as first step in its metabolic conversion to 5-hydroxytryptamine (serotonin),Fed. Proc.12, 282 (1953).
39.
VogtM.: The concentration of sympathin in different parts of the central nervous system under normal conditions and after the administration of drugs, J. Physiol. (London)123, 451–481 (1954).
40.
WaelschH., editor: Biochemistry of the developing nervous system.Academic Press, 537pp., 1955, New York.
41.
Weil-MalherbeH.: The concentration of adrenaline in human plasma and its relation to mental activity.J. Ment. Sci.101, 733–755 (1955).
42.
WittP. N.: d-Lysergsäure-diäthylamid (LSD 25) in Spinnentest, Experientia7, 310–311 (1951).
43.
WittP. N.: Ein einfaches Prinzip zur Deutung einiger Proportionen im Spinnenetz, Behaviour4, 172–189 (1952).
44.
WoolleyD. W.: Studies on the basis of selectivity of action of antimetabolites, in “Antimetabolites”,Ann. N.Y. Acad, Sciences52, Art. 8, 1235–1248 (1950). See also, A study of antimetabolites, 269 pp. Wiley, 1952, New York.
45.
WoolleyD. W., and ShawE.: Some neurophysiological aspects of serotonin,Brit. Med. J.ii, 122–126 (1954).
46.
ZetlerG., and SchlosserL.: Ueber das Vorkommen von 5-Hydroxytryptamin im Gehirn von Säugetieren, Arch. exp. Path. Pharmakol.222, 345–351 (1954).
