The Significance, Limitations and Possibilities of Psycho-Biochemistry Findings
The Psychological Clinic Copyright, 1930, by Lightner Witmer, Editor Vol. XVIII, No. 8 January, 1930
- Author:
Max Trumper, Ph.D.
In charge of Psycho-biochemistry Laboratory, Psychological Clinic, University of Pennsylvania
The importance of making biochemical studies of cases that come to the Psychological Clinic has been shown in a previous paper. The results obtained have been made possible by the perfecting of rapid but accurate chemical methods requiring but a few cubic centimeters of blood. In 1919 I had to obtain from one to two ounces of blood and work intermittently for several hours to determine the amount of uric acid in a case of gout. Today the same test is done more accurately, requiring only a few drops and in an emergency can be rushed through in one-quarter of an hour. At that time in order to obtain the necessary large amount of blood, we had to leave the needle sticking in the patient’s vein for a period of from five to ten minutes. This was quite an ordeal and the only patients who responded kindly to this procedure were those suffering from high blood pressure to whom bleeding in itself often gives relief. Obviously this procedure with its attendant mental strain precluded any blood studies being made that might have been of value to the Psychological Clinic. Czezowska and Goertz in Compt. rend. soc. biol. 98, 147, 1928; report that the wide differences in sugar content of successive samples of blood drawn fifteen minutes apart are attributed to the excitation of the vegetative nervous system and to psychic influences. These authorities report also that subcutaneous injection of one mg. of neutral atropine sulphate immediately before taking the sample by finger puncture annuls the variations of sugar content from the above mentioned causes. In 1919 the biochemical methods had not been perfected; there was not a single book published on blood chemistry and only two pamphlets were available. Now all biochemical works contain data on blood chemistry and the information so gained is being utilized and extended by the Psychiatrist, Neurologist and Psychologist. In many cases we can obtain the necessary chemical data by analysis of the saliva, of the alveolar air, of the oxygen consumption, or by rebreathing tests and cardio-respiratory tests. These tests are well adapted to use in a Psychological Clinic because they do not cause physical discomfort or mental strain to the patient.
Previous to the World War, clinical laboratories confined themselves chiefly to the study of secretions and excretions in diseased conditions. The biochemical methods were too cumbersome and inexact to be used regularly in the Psychological Clinic and the Medical Clinic. The recent advances have so fundamentally extended our knowledge of the normal metabolic activities that even functional derangement may be detected before the irreversible pathologic conditions have developed. This particularly applies to the study of the glandular dystrophies which have so profound psychologic and physiologic effects. Furthermore, clinical laboratory studies are being made to determine the chemical changes that accompany emotions and to discover the psychic factors present in specific toxicities. All these advances do not detract from the value of the data obtained from the study of secretions and excretions. Likewise the advances made in Psychological Tests have neither displaced the necessity nor lessened the value of the ordinary clinical examination. In any case the Psycho-biochemistry laboratory should be used as an adjunct to the general clinical examination, being in itself an aid to diagnosis rather than a sole means to that end.
We all know the tendency of the specialist to place undue emphasis on the value of his own subject. This applies to the medical as well as to the psychological specialists. For example, there is the failure of the Gastro-enterologist to diagnose persistent vomiting as due to increased intra-cranial pressure. There is also the all too frequent removal of appendices when the discomfort is caused by inter-costal neuralgia. For this reason the Psycho-biochemist must be on his guard, especially in the Psychological Clinic, against the assumption that his laboratory findings make unnecessary a case history, obtained by thorough psychological and physical examinations. It would be a waste of time to ask each psychologist to be his own chemist but it is essential that the Psycho-biochemist know the significance as well as the limitations of his tests, especially in their application to the cases that come before the Clinic. On the other hand, the Clinical Psychologist should not neglect the findings of the Psycho-biochemist since such laboratory tests supply information which forms an important supplement to clinical evidence.
Significance of Psycho-biochemical Findings First: Give information clarifying a doubtful case. Many of the cases that come to the Clinic present a picture of undernourishment, malnutrition or anemia. Blood sugar and blood count studies will differentiate the proneness to fatigue due to a sub-normal concentration of sugar in the blood from that due to a lack of hemoglobin and red blood cells. The primary anemias are not common in children and present facts of neurological rather than psychological interest. But the secondary anemias, common in all periods of life do present themselves to the Psychological Clinic. The ready fatiguability and lack of energy in these cases can easily be mistaken for laziness and indifference. The failure to advance in school as well as the inability to perform the normal daily occupations of childhood is therefore often due not to an inherent or congenital defect but to a lack of proper cell nutrition. Some of these cases also show mild but typical symptoms of anoxemia readily confirmed in the laboratory by determining the oxygen-carrying capacity of the blood and the arterial and venous saturation.
Second: Confirm or deny a tentative diagnosis. Without the aid of the laboratory it is extremely difficult to distinguish between sub-thyroid activity and a chronic deep seated infection. In the Clinic the recent case of Jane R. is illustrative. This child was brought to the Speech Clinic because of mental dullness and backwardness in speech. The child’s skin was pasty and cold and gave the impression of sub-thyroid activity. Treatment with thyroid extract, however, led to no improvement. Subsequent laboratory tests revealed specific evidence of either a severe bladder or kidney infection. Preliminary treatment of this infection resulted in striking clinical improvement which should render her teachable. The child became interested in her surroundings and was playful for the first time. Her appetite improved and her general appearance was better. The infection has not been eradicated as yet as it will require more prolonged and perhaps more intensive treatment. It occurs to me that a good plan would be to give cases of this type mental tests before and after treatment to determine the degree of restitution of the mental faculties.
Third: Make more certain treatment and prognosis. What is generally called irritability of muscles, nerves and glands seems to be influenced basically by the balance between sodium and potassium as opposed to calcium and magnesium. This relationship is by no means a simple chemical one but is greatly complicated, among other factors, by the existence of diffusible and non-diffusible fractions of these ions, each having its specific effect. Thus the maintenance of the normal calcium concentration and ionic partition in the blood and tissues is dependent upon several factors: the parathyroid hormone, vitamin D, the hydrogen-ion concentration, the amount and nature of serum proteins and the concentration of phosphate and carbonate ions. Vitamin D is closely related to the action of ultraviolet light and perhaps also to the parathyroid hormone and all of these have the power of affecting the level of the blood serum calcium. Due to the comparatively recent discoveries in the relationship of calcium and parathyroid glands, our knowledge of the influence of calcium has become of practical value. Blood serum calcium and especially its ionized fraction is a neuro-muscular depressant. It is indirectly an accelerator of heart action by its depressant effect on Vagus tone. When a calcium deficiency exists many symptoms appear which are difficult to distinguish from other conditions unless the serum calcium is determined. Thus the unstable, hyper-excitable individual often belongs to the hypocalcemic type who can be improved, if not stablized, by calcium therapy with or without parathyroid hormone. The spasmodic jerky movements usually attributed to mere nervousness may also be due to calcium deficiency. Thus we see the need of laboratory data in the treatment and prognosis of these cases.
Fourth: Decide between alternative views. In cases of unstable personalities with no gross pathology the hyper-excitability closes approximates the hyper-activity seen in Hyperthyroidism. The only way to differentiate these cases is to do frequent Basal Metabolic Determinations. It is useless to do a single metabolic test since this invariably will be higher than subsequent tests. In these cases more accurate laboratory data are obtained from two short tests of eight minutes each rather than a single test extending for sixteen minutes. Instead of placing the patient in bed I have obtained better results by placing the subject in a canvas semiPSYCHO-BIOCHEMISTRY 233 reclining chair at an angle of about 45 degrees. This position was not only restful but made it possible for the subject to read some non-exciting literature and served to direct his attention away from the metabolic test.
An additional diagnostic aid in these cases is the determination of the vital capacity because as Rabinowitch of Montreal (Vital Capacity in Hyperthyroidism, Arch. Int. Med. 1923, 31, 910.) has shown in cases of hyperthyroidism the decrease in vital capacity is in direct ratio to the increase in the metabolic rate. This observation is in itself very satisfactory clinically but in our Clinic the picture is further complicated by the fact that so many of the cases have a low vital capacity not because of thyroid disease but rather because of poor breathing habits. Fortunately if the subject is young and free from pathology and the anatomic breathing mechanism is not fixed we have found improvement in the vital capacity following extended breathing exercises. Here the laboratory is of aid by helping to decide between alternative views and assists in following the cases.
Fifth: In a limited number of cases?make the diagnosis: Mental retardation due to continued and persistent absorption of exogenous or endogenous toxins, can often be suspected but is conclusively proven by biochemical methods. Specific conditions like chronic lead poisoning, chronic carbon monoxide gas poisoning present many psychic features whose unraveling is by way of the laboratory. Finally, Encephalitis with its problem and behaviour syndromes often presents a typical history but at times is dependent for its diagnosis primarily on the sugar content of the spinal fluid.
Limitations of Psycho-biochemical Findings First: In some tests the so-called normal range is very wide. Thus the basal metabolic rate of the same case may have increased say from a minus 10% to a plus 15% over a period of time. This is a change of appreciable magnitude and of clinical significance and yet each finding would have been considered normal if only a single basal metabolic rate had been determined. (The normal range being from a minus 15% to a plus 15%). Here is an instance of the limitation of the performance of but a single test and the advantage of repeated tests. The same considerations are also apparent when we recall how easily the basal metabolic rate may be increased by mental stress. The average of 18 metabolic tests made on a woman student while qualifying for her Ph.D. was 40.12 Cal234 THE PSYCHOLOGICAL CLINIC ories per sq. meter of body surface per hour. Eight additional tests made after all her scholastic work had been finished showed a drop of 10.5% from her previous level. ‘’The mental let-down is the only apparent cause for this decrease in the metabolic rate.”1 Second: The absence of positive findings from the laboratory is no proof of the absence of organic dysfunction or of disease. An organ may seem to function normally so far as our present tests can indicate although that organ is the seat of much disease. In this connection it is well to remember the large margin of safety in all our organs, making it possible for individuals to get along with one kidney, or one lung, or with half their stomach removed. With the advances made in this country and abroad in Encephalography it is amazing to see how much of the brain may be destroyed by disease and yet permit an individual to function normally both mentally and physically as a member of society, even to the extent of self support. Third: The degree of sensitiveness of the test used is most important for its interpretation. From time to time improvements are made in a given test and it is therefore essential to know which particular test gave the results obtained. The new Belote’s fluorescein test which is a modification of Fresenius’ test for the detection of bromine is so sensitive that one part of bromine can be detected in 50,000 parts of urine. Thus we are now able to diagnose very early cases of bromism which previously were reported as negative. Formerly we had to wait until the mental and physical symptoms became marked before this diagnosis could be made.
Fourth: Many chemical changes that occur in mental disease are not pathognomonic and may also be present under normal conditions. For example, there are many mental conditions which are associated with acidosis in varying degrees. The chemical change taking place here with the presence of acetone is the result of the absence of sufficient carbohydrate in the diet. This may also be found normally when the diet lacks carbohydrates.
Psycho-biochemical Possibilities
Psychology needs biochemical assistance since the processes of thinking as well as the transmission of impulses through the nerves are associated with chemical changes. The cases seen in the Clinic as a rule have not reached the degree of irreversibility that characterizes the pathologic cases that come before the psychiatrist and the alienist. When the underlying physico-chemical mechanisms as1F. A. Hitchcock, Columbus, Ohio. Variations in the Basal Metabolic Rate apparently caused by the mental state of the subject. Xlllth International Congress of Physiologists, Boston, August 19, 1929. PSYCHO-BIOCHEMISTRY 235 sociated with behaviour are discovered the so-called instances of spontaneous cure will be greatly reduced.
Years ago observant clinicians noted some curious facts about immunity and spontaneous cure. One of the most recent examples has been that infectious diseases, particularly those accompanied by high fever, sometimes caused the remission of symptoms in some forms of cerebro-spinal syphilis. Many years passed before anyone applied the mechanism present in high fever. It is now applied in the malarial treatment of paresis. This represents a disease mechanism which is antagnostic in effect to another disease and in this case is applied as a therapeutic procedure in late syphilis. More recently Loevenhart has demonstrated and Leake has confirmed the stimulating cffect created by brief periods of inhalation of a mixture of 30% carbon dioxide with oxygen inducing mental clarity and intelligent responses in certain cases of dementia prtecox catatonia. These favorable effects are only of ten to fifteen minutes duration.)
Another group of phenomena involving intrinsic bodj7 mechanisms centres at the present time in the problem of epilepsy. The cause of idiopathic epilepsy is unknown. Many theories have been presented but found unsatisfactory. The most promising trend at the present time is a physico-chemical approach involving such factors as water balance, distribution of ions, carbon-dioxide, oxygen tension and acid-base equilibrium. The last factor has been used as a basis of a form of treatment from which satisfactory results have been obtained. It rests on the observation and assumption that the development of a condition of relative acidosis reduces the frequency of these attacks. This state is brought about principally by the use of a ketogenic diet and restricted water intake. In this diet carbohydrates are reduced to a minimum and fats increased with the view of increasing the hydrogen-ion concentration of the body tissues and presumably of the sensitive brain tissue, the irritation of which occasions the attack.
The utilization of a mechanism antagonistic to another specific condition offers a fertile field of inquiry to the Psycho-biocliemical laboratory. It seems to me in this regard that a study of possibly great value would be an investigation of the infrequent co-existence of diabetes and epilepsy. In diabetes we have an existing ketosis with dehydration while in epilepsy we strive to produce a similar ketosis with dehydration. Such an investigation would in my opinion reveal that the diabetes has a therapeutic effect on the epilepsy.
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