Effects of Isometric Exercise on Serum Creatine Phosphokinase David J.

Goode, MD, Herbert




\s=b\ The

effect of isometric exercise on serum creatinine phosin 14 psychotic patients in remission and ten normal controls was studied. The increases in serum CPK activity at 18 and 42 hours after exercise were not significantly different in patients and controls. The postexercise serum CPK activities in the patients were significantly less than the peak serum CPK levels when they were psychotic. There were no significant correlations between postexercise serum CPK activity and preexercise or peak serum CPK activity in the patient group. It is unlikely that increased isometric muscle tension is a major causative factor in the increased serum CPK levels frequently found in psychotic patients. (Arch Gen Psychiatry 33:1207-1211, 1976)

phokinase (CPK) activity

in serum have been


Increases activity reported acutely psychotic patients

phosphokinase (CPK)

in 50% to 70% of studied during the initial seven days of a psychotic episode.1 The increase in serum CPK activity during an acute psychotic episode is generally two to three times the upper limit of normal, but may range up to 50 times normal. Following the increases in serum CPK activity during the first days of a psychotic episode, the levels usually return to normal.-""'-" Serum CPK activity may increase later during hospitalization, generally in association with an exacerbation of clinical symptoms."' The CPK is separable into at least three isoenzymes: skeletal muscle, cardiac muscle, and brain.17 The CPK isoenzyme present in increased amounts in serum during the acute psychotic episode is the skeletal muscle type.218 Skeletal muscle, therefore, is the most likely source of the increased serum CPK activity observed in acutely psychotic patients. Moreover, morphological muscle abnor¬ malities in patients with functional psychoses have been to




Accepted for publication June 12, 1975. From the Department of Psychiatry, Pritzker School of Medicine, University of Chicago. Reprint requests to 950 E 59th St, Chicago, IL 60637 (Dr Goode).

demonstrated with both



and electron


A number of variables known to affect serum CPK have been evaluated as possible causes of the serum CPK activity elevations observed during the acute psychotic episode. Intramuscularly administered medica¬ tions may cause increases in serum CPK activity,-1 but psychotic patients who have received such injections have been excluded from our reports.-'-'•I·8·11·12 Stress does not generally increase serum CPK activity in man. There are no increases in serum CPK activity in hospitalized nonpsychotic, acutely anxious or neurotically depressed psychiat¬ ric patients,-"' nor are there increases in serum CPK activity prior to major surgery.-1 Other variables, such as weight loss, corticosteroid secretion, and oral neuroleptic medication have been shown to be unrelated to serum CPK activity increases during acute psychosis.'-' Several recent studies have not found serum CPK activity increases in newly admitted psychiatric patients and have attributed the elevated values observed in the previously cited investigations to, among other things, the effect of physical activity.-"'-'1 It is well established that physical activity can increase serum CPK activity in man."'2" The increases vary in magnitude with the strenand inversely with the degree uousness of the exercise-*of muscle training.-' Serum CPK activity correlated signif¬ icantly with independent ratings of increased motor activity in psychotic patients in two studies.4-1" Kupfer and Foster1' reported that in some, but not all, psychotic patients there was a small but significant correlation between serum CPK levels and motor activity monitored by a motion detector worn on the wrist of the nondominant hand and broadcast via an FM transmitter to a receiver attached to a mechanical printout. However, only a small portion of the variance in serum CPK levels was accounted for by motor activity measured in this fashion. Meltzer and


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Table 1.—Serum CPK Activity Prior to Exercise, at 18 and 42 Hours After Exercise, and Peak 18 or 42 Hours


Medication at Time of Exercise,


Percentage Change at

Maximum Plasma CPK

Activity During Hospitalization, mU/Liter

Age. yr/ Sex/Race



Chronic paranoid





schizophrenia Acute schizophrenia





Trifluoperazine hydrochloride, 20 Chlorpromazine, 200 Lithium carbonate, 1,800 Chlorpromazine, 600




4/18/M/B 5/33/M/W 6/33/F/B 7/19/M/W

Acute undifferentiated

schizophrenia Acute paranoid schizophrenia Acute paranoid schizophrenia Acute paranoid schizophrenia


Chronic undifferentiated


schizophrenia Acute paranoid schizophrenia


Psychotic depression


Acute paranoid

12/42/F/W 13/20/F/W 14/22/M/W

schizophrenia Chronic schizophrenia Chronic schizophrenia Acute paranoid schizophrenia


1,137 57


Chlorpromazine, 400 Thioridazine, 200 Chlorpromazine, 800





Lithium carbonate, 1,800 Dantrolene sodium, 600 Trifluoperazine hydrochloride, 20 Imipramine hydrochloride, 150 Thioridazine, 400 Thioridazine, 200 Chlorpromazine, 200 Thyroid Thioridazine, 600 Trifluoperazine hydrochloride, 20 Means

Moline"1 studied the effects of exhausting isotonic exercise (stationary bicycle riding) on serum CPK levels in psychiatric patients. Increases in serum CPK activity 20 hours after exercise were significantly smaller than those observed during the acute phase of the psychosis. However, patients who had developed large increases in serum CPK activity during the acute phase had significantly greater increases in serum CPK levels following exercise. Isotonic muscle activity was the subject of the studies of

Meltzer and Moline1" and Kupfer and Foster.1"' However, the possible effect of isometric muscle activity on serum CPK activity in psychotic patients has not been evaluated. Increased isometric muscle activity might be present in psychiatric patients independent of the amount of isotonic muscle activity and could conceivably attribute to increased serum CPK activity in these individuals. Increased levels of electromyographic activity reported in psychiatric patients may be in part due to increased covert isometric motor activity."-14 We now wish to report the results of a study of the effects of a series of isometric exercises on serum CPK activity in ten normal controls and in 14 patients recovering from psychotic episodes.

METHODS The patients in this study were hospitalized on a research unit at the Illinois State Psychiatric Institute. The patients were exer¬ cised following remission of psychotic symptoms, usually two to four weeks after admission. Serum CPK activity in morning



16 61






107 306 109

25 19

48 32.0 ±3.9

specimens was determined from Monday through Friday through¬ hospitalization in these patients. Ten normal controls without personal or family history of psychiatric or muscle disease were also studied. The mean ages of the patients (26.0 ± 1.8 SE) and controls (28.3 ± 2.2 SE) were not significantly different. None of the patients or controls were engaged in any regular athletic activity. There were six women and eight men in the patient out

group, and four women and six men in the control group. The controls consisted of nine whites and one Oriental, whereas the patient group had ten whites and four blacks. The isometric exercise procedure, which lasted approximately 60 minutes, util¬ ized stationary wall bars. Subjects were instructed to push against a bar with maximum force for 10-second periods at intervals of approximately 20 seconds. By varying the limbs used as well as the angle of attack, the series of exercises required maximal use of all major muscle groups. In addition, isometric push-ups, sit-ups, and neck exercises were performed. The series was repeated three times during the 60-minute exercise period, which generally took place in the afternoon. The subjects described the exercises as extremely fatiguing and believed that the procedure was at or near the limit of their endurance. Eleven of the 14 patients were receiving phenothiazines, lithium carbonate, or imipramine. Three were not receiving any active medication. Blood for serum CPK determination was drawn the morning before and 18 and 42 hours after exercise. Plasma or serum CPK activity was assayed by the method of Rosalki'' within 48 hours after collection, using a spectrophotometer. The coefficient of variation of the assay was 5% with 20 duplicate samples. The 95% upper limits for serum or plasma CPK activity in ambulatory normal controls in our laboratory are 110

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12 Plasma CPK

Plasma CPK


Peak % Change in Plasma CPK




42 hr

Postexercise, mU/Liter

Postexercise, mU/Liter



Postexercise -274






M 83











+ 25







29 20 26





+ 19






21 28

+ 12 + 11 -15


+ 81.8



9.5 9


6.5 6


46.1 ±8.5


4.5 4

3.5 3 2.5


mU/ml for black males, 70 mU/ml for white men, 70 mU/ml for black women, and 50 mU/ml for white women.'"


RESULTS Serum CPK activity prior to exercise, at 18 and 42 hours after exercise, and the peak percentage change at 18 or 42 hours are given in Table 1. Serum CPK levels increased in 13 of the 14 patients at either 18 or 42 hours after exercise. In five patients, serum CPK activity was lower 18 hours after exercise, but in four of these patients serum CPK activity rose to greater than preexercise levels at 42 hours. In five patients (subjects 1 through 5), the increase in serum CPK levels was two to three times greater than preexercise serum CPK activity (median percentage increase 183%, range 133% to 274%); however, because preexercise serum CPK activity in these five patients was well below normal limits, their highest postexercise serum CPK activity was only 20% to 60% above the upper limit of normal for the appropriate race-sex group in four of these patients and below the upper limit of normal in the other. Altogether, postexercise serum CPK levels did not exceed the upper limit of normal in ten of the 14 patients. The maximum percentage increase in serum CPK activity following exercise was not significantly different in the male and female patients (Mann-Whitney U-test U 17.0, =



It is of interest to compare the maximum serum CPK activity increases produced by isometric exercise with the






HOSPITALIZATION CPK activity occurring during hospitalization to maximum serum CPK activity following exercise in


compared 14 patients recovering

from acute


magnitude of serum CPK activity increases during the period of psychosis. This relationship is summarized in the Figure. Maximum CPK activities during the acute psychotic episode exceeded the upper limit of normal for the appropriate race-sex group in 11 of the 14 patients by

1,040% (median 110%). However, maximum CPK activity increases following exercise exceeded race-sex norms in only four of the 14 patients by 23% to 60% (median 44%). The maximum CPK activity following isometric exercise exceeded the maximum CPK activity during

6% to

hospitalization in only two of the 14 patients studied (subjects 1 and 2). Both of these patients had had only slightly elevated serum CPK activity when they had

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manifest psychotic symptoms. The peak serum CPK activity 18 or 42 hours following exercise was not significantly correlated with preexercise serum CPK activity (Pearson r .0418, > .5) or peak serum CPK levels during hospitalization (Pearson r =





There was no significant relationship between medica¬ tion and increase in serum CPK activity following iso¬ metric exercise. Of the five patients with large postexer¬ cise increases (> 100%), two were not receiving medica¬ tion, two were receiving phenothiazines, and one was receiving both lithium carbonate and a phenothiazine. Of the nine patients who had smaller or no increases in serum CPK activity, one was receiving thyroid extract, five were receiving phenothiazines, one was receiving lithium carbonate, one was receiving tricyclics and phenothiazines, and one was receiving both dantrolene sodium, a muscle relaxant, and phenothiazines. The preexercise and postexercise plasma CPK levels and the largest percentage change in plasma CPK activity at either 18 or 42 hours after exercise in control subjects are given in Table 2. The peak percentage increases in serum CPK activity levels that occurred in the controls were not significantly different than those in the patients by a Mann-Whitney U-test (U 48, > .05). =


The isometric exercises utilized in this study were quite Subjects who have performed both this series of isometric exercises and the isotonic exercises previously utilized by Meltzer and Moline"' (ten miles on a bicycle exerciser with tension equivalent to a low-grade hill) subjectively experienced both forms of exercises to be equally strenuous. Most patients and controls experienced muscle soreness after isometric exercises. We did not quantify the amount of isometric exercise performed by any of the subjects. It was our subjective impression that all subjects heeded the instructions to develop as much tension as possible during the exercise. However, the considerable variation in changes in serum CPK activity following exercise could reflect differences in intensity with which subjects performed the exercise. It does not appear from these studies that the tendency strenuous.

develop increases in serum CPK activity following brief intense isometric exercise is significantly different in normal controls and psychotic patients. The relatively small size of the increases following isometric exercise is indicative that isometric tension of a brief, but intense nature does not cause increases in serum CPK activity of the magnitude frequently found in the acute psychotic state. While it might be argued that isometric tension in the acute psychotic state might be developed for a much longer time, the amount of tension developed during this exercise protocol was at or close to the limit of these subjects' endurance. It is unlikely that patients could exceed this amount of isometric activity on a sustained basis, because they would not have the stamina and would find it painful. No effect of medication on the increase in serum CPK activity was noted when evaluating the postex¬ ercise serum CPK increases within the patient group or in comparing the increases in the patients and controls, which were not significantly different. There is some evidence that lithium carbonate can diminish serum CPK activity," but there is no evidence that it can diminish increases due to


physical activity.

The lack of relationship between increased serum CPK activity and isometric muscle tension in psychotic patients is paralleled by findings of no increase in serum CPK levels in patients with stiff-man syndrome,38 tetanus following the development of spasms,1"' and parkinsonism with muscle rigidity (Stahl and Meltzer, unpublished data). In addition, competitive amateur wrestling, which involves a mixture of isotonic exercise, isometric exercise, and some muscle trauma, does not increase serum CPK activity.40 In conclusion, strenuous isometric motor activity does not produce increases in serum CPK activity comparable in

magnitude to those present during the acute psychotic episode. A previous study by Meltzer and Moline1" demon¬ strated that isotonic exercise also did not produce increases in serum CPK activity in remitted psychotic patients that were as large as those present during a period of acute psychosis. Physical activity, either isotonic or isometric, of less intensity but of longer duration is not likely to have a greater and more sustained effect on serum CPK activity because of the lack of an increase in serum CPK activity in stiff-man syndrome. The relationship between physical

Table 2.—Study Two: Plasma CPK Activity of Ten Normal Subjects Immediately Before and 18 and 42 Hours After Isometric Exercise* Subject

No./Age, yr/Sex/Race


1/38/F/W 2/30/ M/W


3/35/M/O 4/21/F/W 5/22/F/W

6/33/M/W 7/20/M/W 8/19/M/W 9/33/M/W 10/32/ F/W Mean ± SE t test for

Peak % Change

Plasma CPK Activity, mU/ml


79 30 41 46


63 46 31 59.1 ±11.1


24 hr

Postexercise 153 358 179 55 65 67 68 90 63 29 112.7±30.9

paired values comparing preexercise values with 24-hr postexercise values

48 hr Postexercise



+ 151 + 140

49 63 54 27

40 86.0 ±25.5 =



Effects of isometric exercise on serum creatine phosphokinase activity.

Effects of Isometric Exercise on Serum Creatine Phosphokinase David J. Goode, MD, Herbert Y. Meltzer, MD \s=b\ The effect of isometric exercise...
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