1. Three monitors of autonomic and metabolic function were employed to study the periodic frequency and amplitude of non-specific, spontaneous, endogenous oscillations in 18 untreated psychiatric patients at rest. Seventeen drugs were then exhibited individually to the patients and the longitudinal study continued kinetically so that their effects on these oscillations could be observed.
2. Confirmation was obtained for earlier reported findings that frequency analysis of resting spontaneous periodic oscillations of capillary blood-oxygen saturation, capillary corpuscular blood flow and skin tissue cell changes reliably distinguishes between patients with schizophrenia and those belonging to certain other psychiatric diagnostic groups.
3. The effects of drugs on these spontaneous periodicities was found to depend principally on whether or not the drug in question influenced the brain stem ascending reticular activating system. Drugs such as the phenothiazines and reserpines affecting this system brought about a frequency change in the autonomic oscillations; drugs not affecting the system did not do so.
4. Amplitude analysis showed that drugs affected the three monitors in a fashion quite different from their effects on frequency.
5. The known and suggested mechanisms of action of the ataractic drugs are reviewed and arguments suggesting a combined neurophysiological and vascular action for them are presented.
6. It is suggested that these findings offer an objective technique for the rapid clinical screening of psychopharmacologic agents.
References
1.
AltschuleM. D.Effects of factors that modify cerebral blood flow on hallucinations in schizophrenia.J. clin. exper. Psychopathol.12, 123–129, 1951.
2.
BeinH. J.Significance of selected central mechanisms for the analysis of the action of reserpine.Ann. N.Y. Acad. Sci.61, (1) 4–16, 1955.
3.
CazzulloC. L.Biological aspects of pharmacodynamics in psychoses. In, Ed. RinkelM., and, DenberH. C. B.: Chemical Concepts of Psychosis.Toronto, G. J. McLeod Ltd. 1958. pp. 331–340.
4.
CazzulloC. L., and GuareschiA.Influenza di un derivato delia fenotiazine (Largactil) sull' attivata ellettrica dell' encephalo del cane.Riv. Neur.24, 602–632, 1954.
5.
CourvoisierS., FournelJ., DucrotR., KolskyM., and KoetschetP.Propriétés pharmacodynamiques du chlorhydrate de chloro-3 (diméthylamino-3' propyl)-10 phénothiazine (4.560 R.P.).Arch. internat. Pharmacodyn.92, 305–361, 1953.
6.
DavisE., HalpernL., LaszloL., and DanaD.The effect of chlorpromazine and the modifying action of adrenaline on human capillaries.Confin. Neurol.17, 10–15, 1957.
7.
DoustJ. W. Lovett.Spontaneous endogenous oscillating systems in autonomic and metabolic effectors: their relation to mental illness.J. Nerv. Ment. Dis.131, 335–347, 1960.
8.
DoustJ. W. Lovett.The capillary system in patients with psychiatric disorder: The ontogenetic structural determination of the nail fold capillaries as observed by photomicroscopy.J. Nerv. Ment. Dis.121, 516–526, 1955.
9.
DoustJ. W. Lovett.The capillary system in patients, with psychiatric disorder: Increased “capillary blood pressures” in neurosis and psychosis and its relation to some correlates of anoxemia.A.M.A. Arch. Neurol. and Psychiat.74, 137–143, 1955.
10.
DoustJ. W. Lovett.The capillary system in patients with psychiatric disorders: Diminished capillary resistance as shown by the Göthlin positive pressure test.J. Clin. exper. Psychopathol.16, 272–280, 1955.
11.
DoustJ. W. Lovett.Studies on the physiology of awareness: Oximetric evidence of the role of anoxia in certain psychiatric states.Proc. roy. Soc. Med.44, 347–352, 1951.
12.
DoustJ. W. Lovett.Spectroscopic and photoelectric oximetry in schizophrenia and other psychiatric states.J. Ment. Sci.98, 143–160, 1952.
13.
DoustJ. W. Lovett, and SalnaM. E.Studies on the physiology of awareness: Dynamic metabolic disturbances associated with hallucinations.Canad. Med. Ass. J.72, 803–808, 1955.
14.
FazekasJ. F., AlbertS. N., and AlmanR. W.Influence of chlorpromazine and alcohol on cerebral hemodynamics and metabolism.Am. J. Med. Sci.230, 128–132, 1955.
15.
FazekasJ. F., SheaJ. G., and SullivanP. D.Ataractics in medical practice.General Practitioner14, 75–81, 1956.
16.
FeldsteinA., HoaglandH., and FreemanH.On the relationship of serotonin to schizophrenia.Science128, 358, 1958.
17.
FieldE. J., GraysonJ., and RogersA. F.Observations on the blood flow in the spinal cord of the rabbit.J. Physiol.114, 56–70, 1951.
18.
FosterC. A., O'MullaneE. J., GaskellP., and Churchill-DavidsonH. C.Chlorpromazine: a study of its action on the circulation in man.Lancetii, 614–617, 1954.
19.
GranitR.Receptors and sensory perception.New Haven, Yale University Press,1955. pp. 366, esp. pp. 81–112.
20.
HafkenschielJ. H., SellersA. M., KingG. A., and ThornerM. W.Preliminary observations on the effect of parenteral reserpine on cerebral blood flow, oxygen and glucose metabolism and electroencephalograms with essential hypertension, Ann. N.Y. Acad. Sci.61 (1), 78–84, 1955.
21.
IngvarD. H., and SoderbergU.A direct method for the measurement of cerebral blood flow.Nature, Lond.177, 339–340, 1956.
22.
IngvarD. H., and SöderbergU.Effects of chlorpromazine on cerebral circulation and electroencephalogram in cats.A.M.A. Arch. Neurol. & Psychiat.78, 254–258, 1957.
23.
KetyS. S., WoodfordR. B., HarmelM. H., FreyhanF. A., AppelK. E., and SchmidtC. F.Cerebral blood flow and metabolism in schizophrenia: effects of barbiturate semi-narcosis, insulin coma.Am. J. Psychiat.104, 765–770, 1948.
24.
Kinross-WrightV.Chlorpromazine and reserpine in the treatment of psychosis.Am. N.Y. Acad. Sci.61, 174–182, 1955.
25.
KlehJ., and FazekasJ. F.The use of reserpine in the hypertensive arteriosclerotic syndrome.Am. J. Med. Sci.228, 560–567, 1954.
26.
KlineN. S., BarsaJ., and GoslineE.Management of the side effects of reserpine and combined reserpine-chlorpromazine treatment.Dis. Nerv. Syst.17, 352–358, 1956.
27.
LassenN. A.Cerebral blood flow and oxygen consumption in man.Physiol. Rev.39, 183–238, 1959.
28.
LehmannH. E.Therapeutic results with chlorpromazine (Largactil) in psychiatric conditions.Canad. Med. Ass. J.72, 91–99, 1955.
29.
Le VineD., GordonG. S., and AdamsJ. E.Cerebral metabolic activity of the serpasil solvent. Quoted by H. Freeman: The tranquillizing drugs. In, Ed. BellakL.: Schizophrenia, a review of the syndrome.New York, Logos Press, 1958. pp. 473–500.
30.
LewisN. D. C.Nerv. and Ment. Dis. Mongr. No. 35. Washington, 1923.
31.
McQueenE. J., DoyleA. E., and SmirkF. H.The circulatory effects of reserpine.Circulation11, 161–169, 1955.
32.
MonnierM.Topic action of psychotropic drugs on the electrical activity of cortex, rhinencephalon and mesodiencephalon. In, Ed. GarattiniS., and, GhettiV.: Psychotropic drugs.Amsterdam.Elsevier Press, 1957. pp. 217–234.
33.
MonroeR. R., HeathR. G., MickleW. A., and MillerW.A comparison of cortical and subcortical brain waves in normal, barbiturate, reserpine and chlorpromazine sleep.Ann. N.Y. Acad. Sci.61 (1), 56–71, 1955.
34.
MoyerJ. H., MorrisG., PontiusR., and HershbergerR.Effect of chlorpromazine on cerebral oxygen metabolism in man.Circulation14, 380–385, 1956.
35.
RichterD.Biochem. Soc. Symposium, No. 8. 1952. p. 62.
36.
RinaldiR., and HimwichH. E.Drugs affecting psychotic behaviour and the function of the mesodiencephalic activating system.Dis. Nerv. System16, 3–11, 1955.
37.
RudyL. H., HimwichH. E., and RinaldiF.A clinical evaluation of psychopharmacological agents in the management of disturbed mentally defective patients.Amer. J. Ment. Deficiency62, 855–860, 1958.
38.
SamuelsS. S.The vasodilation action of Rauwolfia serpentina.Angiology7, 86–87, 1956.
39.
SanthaK., and CiprianiA.Focal alterations in subcortical circulation resulting from stimulation of the cerebral cortex.Proc. Assn. Res. Nerv. Ment. Dis., 18, 346–364, 1937.
40.
SchlichterW., BristowM. E., SchultzS., and HendersonA. L.Seizures occurring during intensive chlorpromazine therapy.Canad. Med. Assoc. J.74, 364–366, 1956.
41.
SerotaH. M.Temperature changes in the cortex and hypothalamus during sleep.J. Neurophysiol.2, 42–47, 1939.
42.
SloaneB., and DoustJ. W. Lovett.Psychophysiological investigations in experimental psychoses: results of the exhibition of d-lysergic acid diethylamide to psychiatric patients.J. Ment. Sci.100, 129–144, 1954.
43.
SokoloffL., PerlinS., KornetskyC., and KetyS. S.The effects of D-Lysergic acid diethylamide on cerebral circulation and over-all metabolism.Ann. N.Y. Acad. Sci.66, 468–477, 1957.
44.
TrapoldJ. H., PlummerA. J., and YonkmanF. F.Cardiovascular and respiratory effects of serpasil, a new crystalline alkaloid from rauwolfia serpentina benth, in the dog.J. Pharm. & Exper. Therap.110, 205–214, 1954.
45.
UnnaK. R.A review of the neurophysiological effects of psychomimetic drugs.Ann. N.Y. Acad. Sci.66, (3), 777–783, 1957.
46.
Van MeterW. G., OwensH. F., and HimwichH. E.Effects of Tofranil, an anti-depressant drug, on electrical potentials of rabbit brain.Canad. Psychiat. Ass. J. Supp.4, S113–S119, 1959.
47.
WertheimerM., and WertheimerN.Capillary structure: its relation to psychiatric diagnosis and morphology.J. Nerv. Ment. Dis.122, 14–27, 1955.
48.
WiklerA.The relation of psychiatry to pharmacology.Baltimore, Williams and Wilkins Company. 1957. p. 322.
49.
WoolleyD. W.Participation of serotonin in mental processes. In, Ed. RinkelM., and DenberH. C. B.Chemical concepts of psychosis.Toronto: G. J. McLeod Ltd.1958. p. 176–189.
50.
YablonskiM. D., StockmanA. M., CalivaF. S., and LyonsR. H.Some cardiovascular effects of reserpine.Am. J. Med. Sci.235, 639–643, 1958.
