Journal of Psychosomatic Rrsearch. Vol. 23, pp. 263 to 266. Pergamon Press Ltd. 1979. Printed in Great Britain.
URINARY CATECHOLAMINES HABITUATION IN MAXIMUM HOSPITAL PATIENTS* D.
D.
AND TEST SECURITY
WGGDMAN
(Received 12 March 1979)
Abstract-The effect of anticipation of a complex stress test on maximum security hospital detainees elicits atypical biochemical responses in approximately 25 o? of such subjects. This paper describes the effects of repeating the same test procedure on two consecutive days. Subjects whose initial reactions were normal showed a statistically significant habituation response relating to urinary adrenaline. Subjects whose initial reaction was atypical showed either an exaggerated habituation response or no habituation response relating to urinary adrenaline. The maintenance of an atypical catecholamine response on the second day of testing appeared highly correlated with violent personal crimes resulting in fatality. AVERILL et al.[l] and Hare et al. [2] have reported
decreasing cardiac responses and reducing skin conductance change responses elicited by repeated viewing of slides of murder or industrial accident victims, while Mangelsdoff and Zuckerman [3] using slides of massacre scenes taken in Vietnam have shown similar cardiac and skin conductance response habituation together with decreasing levels of self-reported agitation by volunteer subjects. Biochemical responses to stressors have also been shown to depend on the familiarity of a situation, in that novel events elicit increased adrenaline production and cortisol secretion [4,5]. As the subject becomes used to the stimulus and is no longer faced with an event which is unfamiliar, the endocrine response is attenuated. We have recently reported studies describing the reactions of criminally deviant subjects to stress, which appear to suggest that there is a group of men whose biochemical and physiological reactions to stressful stimuli are abnormal [6-81, and that as a group these men had been convicted of more serious crimes than had the remainder of the special hospital population. This paper describes the effects of the anticipation of the same stress test administered on two consecutive days to this group of special hospital subjects. MATERIALS
AND METHODS
The subjects studied were new admissions to a special hospital during the period 197551977 inclusive and have been described previously [8]. The subdivision of these patients into the physiologically hyporesponsive and responsive categories on the basis of catecholamines and psychophysiological criteria previously described [8] was used again, giving a total of 56 responsive and 13 hyporesponsive subjects in the study. The ‘stress test’ used has been reported in detail elsewhere [9] and included a variety of stimuli, intended to simulate types of stress encountered in everyday life, including criticism, praise, simple numerical and alphabetical tasks within an imposed time limit, viewing black and white slides of human suffering (concentration camp victims), 100 dB white noise and a cold pressor test. The test was administered on two consecutive days between 9 and 11 a.m. Subjects were briefed on the general contents of the test session several days prior to the experiment, and participation was voluntary. Urinary free adrenaline and noradrenaline were determined on urine collected between emptying of the bladder on rising (approximately 7.00 a.m.) and the beginning of the formal test session at 9.00 a.m. following an overnight fast, on each of the two days. Urinary catecholamines were determined using a modification of the method of Euler and Lishajko [lo], a method which in our hands had a coefficient of variation of 3.8 ‘A for total catecholamines and 7.9 % for adrenaline alone. The values of adrenaline and noradrenaline were expressed in terms of the amount excreted in micrograms per gram of creatinine. RESULTS Table 1 shows the mean value and standard deviation for urinary catecholamines for each of the two special hospital groups during the period of anticipation preceding each of the two stress test sessions. The statistical significance of the difference between the two days values (using Student’s *From the Research Division, Beecham Pharmaceuticals, Essex. 263
Medicinal Research Centre, Harlow,
264
D. D. WOODMAN
TABLE I.-COMPARISON
OF URINE CATECHOLAMINE VALUES OBTAINED ON TWO
CONSFCIJTIW
DAYS OF
“STRESS TEST" ANTICIPATION
Adrenaline (nmol/g creatinine)
Noradrenaline (nmol/g creatinine)
NAiA
Ratio
n
Mean
S.D.
Mean
S.D.
Mean
56 56
106.6 96.7
44.6 46.1 p < 0.5
246.1 238.6
101.0 92.0 NS
2.6 3.1
I.2 1.9 p < 0.5
Physiologically hyporesponsive Day I 13 Day 2 13 Statistical significance
39.9 58.2
9.7 29.5 4 < 0.05
370.8 288.1
60.7 99.0 z, < 0.02
10.0 6.7
3.3 3.7 a < 0.05
Group Physiologically responsive Day 1 Day 2 Statistical significance
S.D.
t-test) is also given. It can be seen that in the case of the large group of physiologically responsive patients, the mean adrenaline excretion on day 2 was slightly lower than on day I. However, this difference was significant only at the 5% level of probability. The decrease in noradrenaline from day 1 to day 2 was not statistically significant. The resulting increase in the noradrcnaline to adrenaline ratio was significant at the 5% level of probability. The smaller group of hyporesponsive subjects showed a rather different pattern. Urine adrenaline excretion during the period of anticipation preceding the first day’s testing was abnormally low, and the statistical distribution much narrower than in the responsive group. However, on day 2 the mean adrenaline value had risen, and despite the much wider spread of values was significantly higher (p < 0.05) than on day I. Urine noradrenaline decreased markedly on day 2 compared with day 1, the decrease being statistically significant (p < 0.02). These changes resulted in a significant decrease (p < 0.05) in noradrenaline to adrenaline ratio. However, the changes in mean adrenaline and noradrenaline on day 2 in this group, although statistically significant were not representative of the group as a whole, and were in fact due to the weighting given to the group by the results of four individuals. Table 2 gives the individual results of these four subjects, and the mean catecholamine values for the remaining nine members of this group are given in Table 2. The results from Table 2 indicate that while the decrease in noradrenaline is still apparent its statistical significance is much tcss (p < O.l), while the day to day adrenaline, and noradrenaline to adrenaline ratio values are no longer significant. We have previously drawn attention
TABLE
2.-INDIVIDUAL
DATA FOR THE FOUR “HYPORESP~NSIVE" CATECHOLAMINE EXCRETIONCHANGEON
Adrenaline n mol/g creatinine Subject
Day
1
Noradrenaline n mol/g creatinine
Day 2
Day
1
Day 2
SUBJECTS SI%OWING DAY 2
NA/A Day
Ratio
1
Day 2
1 2
44 47
99 114
353 494
460 182
7.9 10.6
4.7 1.6
3
31
100
431
124
14.6
1.2
4
24
77
344
89
14.5
1.2
TABLE 3.-GROUP
DATAFORTHFNINF“HYPORESI'ONSIVE"SUBJ~CTSSHOWINC~ HABITUATION
Adrenaline Day Day SigniIica&z Student’s
1 2
; 9 by t-test
Mean 41.4 40.7
S.D. 9.4 13.8 NS
SD. 53.7 33.6 p co.1
Conviction Arson Child stealing, common assau It Sexual assaults on children. Attempted rape Murder, rape
NOADRENAL~NF
Noradrenaline Mean 355.3 321.1
EXAGGERATED
RESPO~SF
NA/A Mean 9.2 x.7
ratio S.D. 3.2 2.5
NS
Urinary catecholamines
and test habituation
in maximum security hospital patients
265
to the case record data differences between the responsive and hyporesponsive groups [7] indicating the much greater proportion of convictions for violent crimes resulting in fatality in the latter group. Four out of I3 of this latter group in this study show a markedly different catecholamine excretion when faced with the repeated test programme from their results on the first day, having urine catecholamine values of the order of those seen in the responsive group. The crimes of which these men were convicted include only 1 fatality. Of the remaining nine subjects, five had been convicted of manslaughter, three of murder and one, malicious wounding and grievous bodily harm, i.e. only one out of nine convictions were not for a crime resulting in a fatality. DISCUSSION To avoid the emotional overload which would occur from repeated exposure to stressful stimuli, the biological response to any particular stimulus is attenuated with each repeated exposure. In this way an individual can become relatively unaffected by a stimulus which at first was highly disturbing, the process being known as habituation. Physiologically, the major response to novel unpleasant or threatening situations is an increase in electrodermal and cardiovascular activity [l-3] and biochemically an increased secretion of adrenaline [4]. During recent studies on patients committed to a maximum security hospital, we reported finding a proportion of patients whose physiological responses to stressors were much less than those of both controls and the remainder of the special hospital population. The biochemical responses of these subjects to a threatening uncertain situation (a taped programme of mild stressors) was not the expected increase in adrenaline but a decrease in adrenaline and an increase in noradrenaline. The results of this study have indicated that the subjects who were originally categorised as being normoresponsive physiologically and biochemically show a small but statistically significant decrease in adrenaline and in the balance of adrenaline relative to noradrenaline on the second day of testing. The subjects originally categorised as having atypical responses showed the opposite pattern, i.e. increased adrenaline and decreased noradrenaline on the second day of testing, However, although these changes are in the opposite direction to those in the normoresponsive subjects, the initial change was in the opposite direction, and the results from both groups on day two therefore showed a tendency to return towards normal basal levels. Of the group of atypical subjects 4 out of 13 showed a complete contrast in the second day results to those seen on the first day, and in fact the results from these four subjects entirely accounted for the statistically significant changes in adrenaline and noradrenaline to adrenaline ratio, and were the major contributory factor to the high level of significance of the noradrenaline change. This is clearly illustrated when the results of the remaining nine subjects in this group are compared between sessions. In these subjects there was no significant change in adrenaline values, and although there was still a decrease in noradrenaline, its statistical significance was much weaker. Faced with this data an immediate question arises; is this radically changed response in these four individuals significant orjust a coincidence? The difference between the day 1 and 2 values in each of the four subjects are much greater than could be accounted for by analytical variation, so it seems likely that these changes are a genuine reflection of catecholamine status. On such small numbers, any conclusions drawn from case histories would be highly premature; but it is of interest that of the four subjects showing what may well be an habituation response, only one had a conviction for a killing, or indeed serious violent attack. Of the nine subjects whose initial response was abnormal, and who did not show any noticeable change in adrenaline excretion to the second day’s testing, 8 had convictions for killing, and the other for a serious wounding. Since it has recently been shown that the abnormal response to stress seen on day 1 is reproducable in these subjects retested after periods varying between 4 months and two years after the initial test [I I], it argues very strongly for a much fuller long term appraisal of the significance of these findings. Should the very striking correlation between consistent abnormal catecholamine response to stress and extreme violence be more than coincidence, a powerful tool for the diagnosis, treatment and understanding of psychopathy and dangerous criminal deviance might well emerge. REFERENCES AVERILLJ. R., MALhfsraoM E. J., KORIATA. and LAZARUSR. S. Habituation to complex emotional stimuli. J. Ahnorm. Psycho/. 80, 20-28 (1972). HARE R. D., WOOD K., BRITAINS. and SHADMANJ. Autonomic responses to affective visual stimulation. Psychophysiology 7, 408417 (1970). MANCELSDOFF A. D. and ZUCKERMANM. Habituation to scenes of violence. Psychophysiology 12, 124129 (1975). MASONJ. W., MANGENG. F. JR., BRADYJ. V., CONRADD. and RIOCH D. McK. Concurrent plasma epinephrine, norepinephrine and 17-hydroxy corticosteroid levels during conditioned emotional disturbances in monkeys. Psychosom. Med. 23, 344353 (1961).
266
D. D. WOODMAN
5. YUWILER A. In Handbook of Neurochemistry, Vol. 6 (Edited by LAJTHA A.). Plenum Press, New York (1971). 6. W~~DMAN D. D., HINTONJ. W. and O’NEILL M. T. Plasma catecholamines, stress and aggression in maximum security uatients. Biol. Psvchol. 6. 147-154 (1977). 7. W~~DMAN D. D., &I&ON J. W. and ~‘NEILL’ M. T. Coitisoi secretion and stress in maximum security hospital patients. J. Psychosom. Res. 22, 133-136 (1978). 8. WOODMAN D. D. and HINTON J. W. Catecholamine balance during stress anticipation. J. Psychosom. Res. (In press). mechanisms and abnormal behaviour. In Handbook of Bio9. HINTON J. W. Aggression-brain logical Psychiatry, Vol. 3 (Edited by VAN PRAGG H. M., LADER M. H., RAFAELSEN0. J. and SADUR E. J.) Marcel1 Dekker, New York (in press). 10. EULERU. S. VON and LISHAJROF. Improved technique for the fluorimetric estimation of catecholamines. Actu Physiol. stand. 51,348-355 (1961). 11. WOODMAND. D. Evidence of a permanent imbalance in catecholamine secretion in violent social deviants. J. Psychosom. Res. (in press).
URINARY CATECHOLAMINES HABITUATION IN MAXIMUM HOSPITAL PATIENTS* D.
D.
AND TEST SECURITY
WGGDMAN
(Received 12 March 1979)
Abstract-The effect of anticipation of a complex stress test on maximum security hospital detainees elicits atypical biochemical responses in approximately 25 o? of such subjects. This paper describes the effects of repeating the same test procedure on two consecutive days. Subjects whose initial reactions were normal showed a statistically significant habituation response relating to urinary adrenaline. Subjects whose initial reaction was atypical showed either an exaggerated habituation response or no habituation response relating to urinary adrenaline. The maintenance of an atypical catecholamine response on the second day of testing appeared highly correlated with violent personal crimes resulting in fatality. AVERILL et al.[l] and Hare et al. [2] have reported
decreasing cardiac responses and reducing skin conductance change responses elicited by repeated viewing of slides of murder or industrial accident victims, while Mangelsdoff and Zuckerman [3] using slides of massacre scenes taken in Vietnam have shown similar cardiac and skin conductance response habituation together with decreasing levels of self-reported agitation by volunteer subjects. Biochemical responses to stressors have also been shown to depend on the familiarity of a situation, in that novel events elicit increased adrenaline production and cortisol secretion [4,5]. As the subject becomes used to the stimulus and is no longer faced with an event which is unfamiliar, the endocrine response is attenuated. We have recently reported studies describing the reactions of criminally deviant subjects to stress, which appear to suggest that there is a group of men whose biochemical and physiological reactions to stressful stimuli are abnormal [6-81, and that as a group these men had been convicted of more serious crimes than had the remainder of the special hospital population. This paper describes the effects of the anticipation of the same stress test administered on two consecutive days to this group of special hospital subjects. MATERIALS
AND METHODS
The subjects studied were new admissions to a special hospital during the period 197551977 inclusive and have been described previously [8]. The subdivision of these patients into the physiologically hyporesponsive and responsive categories on the basis of catecholamines and psychophysiological criteria previously described [8] was used again, giving a total of 56 responsive and 13 hyporesponsive subjects in the study. The ‘stress test’ used has been reported in detail elsewhere [9] and included a variety of stimuli, intended to simulate types of stress encountered in everyday life, including criticism, praise, simple numerical and alphabetical tasks within an imposed time limit, viewing black and white slides of human suffering (concentration camp victims), 100 dB white noise and a cold pressor test. The test was administered on two consecutive days between 9 and 11 a.m. Subjects were briefed on the general contents of the test session several days prior to the experiment, and participation was voluntary. Urinary free adrenaline and noradrenaline were determined on urine collected between emptying of the bladder on rising (approximately 7.00 a.m.) and the beginning of the formal test session at 9.00 a.m. following an overnight fast, on each of the two days. Urinary catecholamines were determined using a modification of the method of Euler and Lishajko [lo], a method which in our hands had a coefficient of variation of 3.8 ‘A for total catecholamines and 7.9 % for adrenaline alone. The values of adrenaline and noradrenaline were expressed in terms of the amount excreted in micrograms per gram of creatinine. RESULTS Table 1 shows the mean value and standard deviation for urinary catecholamines for each of the two special hospital groups during the period of anticipation preceding each of the two stress test sessions. The statistical significance of the difference between the two days values (using Student’s *From the Research Division, Beecham Pharmaceuticals, Essex. 263
Medicinal Research Centre, Harlow,
264
D. D. WOODMAN
TABLE I.-COMPARISON
OF URINE CATECHOLAMINE VALUES OBTAINED ON TWO
CONSFCIJTIW
DAYS OF
“STRESS TEST" ANTICIPATION
Adrenaline (nmol/g creatinine)
Noradrenaline (nmol/g creatinine)
NAiA
Ratio
n
Mean
S.D.
Mean
S.D.
Mean
56 56
106.6 96.7
44.6 46.1 p < 0.5
246.1 238.6
101.0 92.0 NS
2.6 3.1
I.2 1.9 p < 0.5
Physiologically hyporesponsive Day I 13 Day 2 13 Statistical significance
39.9 58.2
9.7 29.5 4 < 0.05
370.8 288.1
60.7 99.0 z, < 0.02
10.0 6.7
3.3 3.7 a < 0.05
Group Physiologically responsive Day 1 Day 2 Statistical significance
S.D.
t-test) is also given. It can be seen that in the case of the large group of physiologically responsive patients, the mean adrenaline excretion on day 2 was slightly lower than on day I. However, this difference was significant only at the 5% level of probability. The decrease in noradrenaline from day 1 to day 2 was not statistically significant. The resulting increase in the noradrcnaline to adrenaline ratio was significant at the 5% level of probability. The smaller group of hyporesponsive subjects showed a rather different pattern. Urine adrenaline excretion during the period of anticipation preceding the first day’s testing was abnormally low, and the statistical distribution much narrower than in the responsive group. However, on day 2 the mean adrenaline value had risen, and despite the much wider spread of values was significantly higher (p < 0.05) than on day I. Urine noradrenaline decreased markedly on day 2 compared with day 1, the decrease being statistically significant (p < 0.02). These changes resulted in a significant decrease (p < 0.05) in noradrenaline to adrenaline ratio. However, the changes in mean adrenaline and noradrenaline on day 2 in this group, although statistically significant were not representative of the group as a whole, and were in fact due to the weighting given to the group by the results of four individuals. Table 2 gives the individual results of these four subjects, and the mean catecholamine values for the remaining nine members of this group are given in Table 2. The results from Table 2 indicate that while the decrease in noradrenaline is still apparent its statistical significance is much tcss (p < O.l), while the day to day adrenaline, and noradrenaline to adrenaline ratio values are no longer significant. We have previously drawn attention
TABLE
2.-INDIVIDUAL
DATA FOR THE FOUR “HYPORESP~NSIVE" CATECHOLAMINE EXCRETIONCHANGEON
Adrenaline n mol/g creatinine Subject
Day
1
Noradrenaline n mol/g creatinine
Day 2
Day
1
Day 2
SUBJECTS SI%OWING DAY 2
NA/A Day
Ratio
1
Day 2
1 2
44 47
99 114
353 494
460 182
7.9 10.6
4.7 1.6
3
31
100
431
124
14.6
1.2
4
24
77
344
89
14.5
1.2
TABLE 3.-GROUP
DATAFORTHFNINF“HYPORESI'ONSIVE"SUBJ~CTSSHOWINC~ HABITUATION
Adrenaline Day Day SigniIica&z Student’s
1 2
; 9 by t-test
Mean 41.4 40.7
S.D. 9.4 13.8 NS
SD. 53.7 33.6 p co.1
Conviction Arson Child stealing, common assau It Sexual assaults on children. Attempted rape Murder, rape
NOADRENAL~NF
Noradrenaline Mean 355.3 321.1
EXAGGERATED
RESPO~SF
NA/A Mean 9.2 x.7
ratio S.D. 3.2 2.5
NS
Urinary catecholamines
and test habituation
in maximum security hospital patients
265
to the case record data differences between the responsive and hyporesponsive groups [7] indicating the much greater proportion of convictions for violent crimes resulting in fatality in the latter group. Four out of I3 of this latter group in this study show a markedly different catecholamine excretion when faced with the repeated test programme from their results on the first day, having urine catecholamine values of the order of those seen in the responsive group. The crimes of which these men were convicted include only 1 fatality. Of the remaining nine subjects, five had been convicted of manslaughter, three of murder and one, malicious wounding and grievous bodily harm, i.e. only one out of nine convictions were not for a crime resulting in a fatality. DISCUSSION To avoid the emotional overload which would occur from repeated exposure to stressful stimuli, the biological response to any particular stimulus is attenuated with each repeated exposure. In this way an individual can become relatively unaffected by a stimulus which at first was highly disturbing, the process being known as habituation. Physiologically, the major response to novel unpleasant or threatening situations is an increase in electrodermal and cardiovascular activity [l-3] and biochemically an increased secretion of adrenaline [4]. During recent studies on patients committed to a maximum security hospital, we reported finding a proportion of patients whose physiological responses to stressors were much less than those of both controls and the remainder of the special hospital population. The biochemical responses of these subjects to a threatening uncertain situation (a taped programme of mild stressors) was not the expected increase in adrenaline but a decrease in adrenaline and an increase in noradrenaline. The results of this study have indicated that the subjects who were originally categorised as being normoresponsive physiologically and biochemically show a small but statistically significant decrease in adrenaline and in the balance of adrenaline relative to noradrenaline on the second day of testing. The subjects originally categorised as having atypical responses showed the opposite pattern, i.e. increased adrenaline and decreased noradrenaline on the second day of testing, However, although these changes are in the opposite direction to those in the normoresponsive subjects, the initial change was in the opposite direction, and the results from both groups on day two therefore showed a tendency to return towards normal basal levels. Of the group of atypical subjects 4 out of 13 showed a complete contrast in the second day results to those seen on the first day, and in fact the results from these four subjects entirely accounted for the statistically significant changes in adrenaline and noradrenaline to adrenaline ratio, and were the major contributory factor to the high level of significance of the noradrenaline change. This is clearly illustrated when the results of the remaining nine subjects in this group are compared between sessions. In these subjects there was no significant change in adrenaline values, and although there was still a decrease in noradrenaline, its statistical significance was much weaker. Faced with this data an immediate question arises; is this radically changed response in these four individuals significant orjust a coincidence? The difference between the day 1 and 2 values in each of the four subjects are much greater than could be accounted for by analytical variation, so it seems likely that these changes are a genuine reflection of catecholamine status. On such small numbers, any conclusions drawn from case histories would be highly premature; but it is of interest that of the four subjects showing what may well be an habituation response, only one had a conviction for a killing, or indeed serious violent attack. Of the nine subjects whose initial response was abnormal, and who did not show any noticeable change in adrenaline excretion to the second day’s testing, 8 had convictions for killing, and the other for a serious wounding. Since it has recently been shown that the abnormal response to stress seen on day 1 is reproducable in these subjects retested after periods varying between 4 months and two years after the initial test [I I], it argues very strongly for a much fuller long term appraisal of the significance of these findings. Should the very striking correlation between consistent abnormal catecholamine response to stress and extreme violence be more than coincidence, a powerful tool for the diagnosis, treatment and understanding of psychopathy and dangerous criminal deviance might well emerge. REFERENCES AVERILLJ. R., MALhfsraoM E. J., KORIATA. and LAZARUSR. S. Habituation to complex emotional stimuli. J. Ahnorm. Psycho/. 80, 20-28 (1972). HARE R. D., WOOD K., BRITAINS. and SHADMANJ. Autonomic responses to affective visual stimulation. Psychophysiology 7, 408417 (1970). MANCELSDOFF A. D. and ZUCKERMANM. Habituation to scenes of violence. Psychophysiology 12, 124129 (1975). MASONJ. W., MANGENG. F. JR., BRADYJ. V., CONRADD. and RIOCH D. McK. Concurrent plasma epinephrine, norepinephrine and 17-hydroxy corticosteroid levels during conditioned emotional disturbances in monkeys. Psychosom. Med. 23, 344353 (1961).
266
D. D. WOODMAN
5. YUWILER A. In Handbook of Neurochemistry, Vol. 6 (Edited by LAJTHA A.). Plenum Press, New York (1971). 6. W~~DMAN D. D., HINTONJ. W. and O’NEILL M. T. Plasma catecholamines, stress and aggression in maximum security uatients. Biol. Psvchol. 6. 147-154 (1977). 7. W~~DMAN D. D., &I&ON J. W. and ~‘NEILL’ M. T. Coitisoi secretion and stress in maximum security hospital patients. J. Psychosom. Res. 22, 133-136 (1978). 8. WOODMAN D. D. and HINTON J. W. Catecholamine balance during stress anticipation. J. Psychosom. Res. (In press). mechanisms and abnormal behaviour. In Handbook of Bio9. HINTON J. W. Aggression-brain logical Psychiatry, Vol. 3 (Edited by VAN PRAGG H. M., LADER M. H., RAFAELSEN0. J. and SADUR E. J.) Marcel1 Dekker, New York (in press). 10. EULERU. S. VON and LISHAJROF. Improved technique for the fluorimetric estimation of catecholamines. Actu Physiol. stand. 51,348-355 (1961). 11. WOODMAND. D. Evidence of a permanent imbalance in catecholamine secretion in violent social deviants. J. Psychosom. Res. (in press).
