Platelet monoamine oxidase activity in mentally disordered violent offenders Belfrage H, Lidberg L, Oreland L. Platelet monoamine oxidase activity in mentally disordered violent offenders. Acta Psychiatr Scand 1992: 85: 218-221. The activity of monoamine oxidase (MAO) in blood platelets among criminals undergoing forensic psychiatric examinations was studied. As compulsiveness, disturbed perceptions of reality, etc. are states not known to be related to M A 0 and yet possibly cause aggressiveness and violence among psychotic patients, we divided the patients into 2 groups, psychotic and nonpsychotic offenders. There was lower M A 0 activity among violent offenders than among nonviolent offenders. The difference between the violent and nonviolent offenders became greater when the subjects with a history of psychosis were removed. Furthermore, in the group of psychotic offenders, there was no statistical difference between violent and nonviolent individuals in this regard.
The activity of monoamine oxidase (MAO; E.C. 1.4.3.4) in blood platelets is mainly genetically determined and appears to be relatively stable over time (1). Experimental and clinical findings suggest that the platelet M A 0 activity is a marker for the size or capacity of the serotonergic system in the central nervous system (CNS) (2). Thus, a positive correlation has been found between levels of 5hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) and platelet M A 0 in volunteers and in chronic pain patients (3-4). Low levels of CSF 5HIAA are likely to reflect low central serotonergic turnover ( 5 ) and have been associated with traits such as impulsiveness, sensation-seeking and psychopathy (6) and with poor control of aggression (7). The hypothesis that low serotonergic turnover is of importance for the control of violent acts is supported by the findings of low levels of CSF 5-HIAA in men who had killed a sexual partner (8) and in impulsive violent behavior (9). Furthermore, there is a strong connection between low platelet M A 0 activity and personality variables such as aggressive behavior, sensation-seeking and impulsiveness, which are supposed to be linked to low serotonergic activity (10). Recently, also neuropsychological variables likely to reflect low serotonergic activity, such as many failed inhibitions, have been found to be associated with low platelet M A 0 activity (6, 11). In psychiatric patients, a correlation has been established between low platelet M A 0 activity and some diagnoses such as psychopathy, suicidal behavior and alcoholism (12-16). In all those cases, however, there are reasons to believe that the low 218
H. Belfrage’, L. Lidberg’, L. Oreland2
’
Department of Social and Forensic Psychiatry, Stockholm, * Department of Medical Pharmacology, Uppsala University, Sweden
Key words: monoamine oxidase; violence; offenders Dr. Henrik Belfrage, Department of Social and Forensic Psychiatry, Karolinska Institute, Box 4044, S-141 04 Huddinge, Sweden Accepted for publication October 12, 1991
platelet M A 0 activity is not connected with the disorder per se, but with personality traits making the individual more vulnerable to the respective disorder (2,171. With regard to violence in connection with crime, Davis et al. (8) reported about low platelet M A 0 activities in violent offenders. However, in another report on the same series of patients, no difference was found between violent and nonviolent offenders (19). In a recent study, Palmstierna & Wistedt (20) observed violent behavior prior to admission in 40 % of a consecutive sample of acutely admitted and involuntarily treated patients at a psychiatric clinic. In a preliminary investigation on that series of patients, there was no correlation between violent behavior and platelet M A 0 activity (21). However, in their series, about 80% of the patients were in a psychotic state, and it may be speculated that aggressive behavior in psychotics could be connected with other biological phenomena than in the case among healthy individuals or patients with other mental disorders. In the present investigation, we have studied whether there is any connection between violent crimes and low platelet M A 0 activity among criminals undergoing forensic psychiatric examinations. As compulsiveness, disturbed perceptions of reality, etc. are states not known to be correlated with M A 0 and yet possibly cause aggressiveness and violence among psychotic patients, we divided the patients into 2 groups, psychotic and nonpsychotic offenders.
MA0 activity in violent offenders Table 2. Division of the subjects according to violent and nonviolent crimes (psychotics within parentheses)
Material and methods The series
The series includes 59 males who underwent forensic psychiatric examinations at the Stockholm Forensic Psychiatric Clinic in 1988-1989, and voluntarily submitted to blood tests. Only 6 of these were under medication (neuroleptics). The mean age was 33 years (range 19-61). Table 1 shows the distribution of principle diagnoses (the most serious diagnosis for each patient according to ICD-9). When the subjects were divided according to crimes involving violence vs nonviolence, 37 were classified into the former group and 22 into the latter (Table 2). Included in the category of violent crimes are murder, manslaughter, assault, illegal threats, sexual crimes, and robbery that were, at least in part, violent. The robbers and sexual offenders who were referred to the category of nonviolent crimes had been sentenced for aggravated robbery or sexual acts with children, whereas the robbers and sexual offenders in the category of violent crimes had been sentenced for robbery of people (involving violence) and aggravated rape. The number of psychotic offenders in each group is shown within parentheses. The division of the material into violent crimes and nonviolent crimes, however, is somewhat crude. The offenders sentenced for violent crimes may never before have shown aggressiveness and vice versa. Based on the sparse material in the forensic psychiatric reports, we therefore also tried to classify the offenders with regard to their aggressiveness. As aggressive were coded those who previously showed signs of aggressiveness, or in the forensic psychiatric assessment had been stated to be aggressive, or in the current crime had displayed clear aggressiveness. In this way, 35 subjects were assessed as aggressive and 24 subjects as nonaggressive. Seven of the subjects sentenced for violent crimes were coded as nonaggressive. Four of these were sentenced for attempted murder. They had committed seemingly unprovoked crimes under the influence of psychosis
Table 1. The distribution of diagnoses and MA0 activity (expressed as nmol of phenylethylamineoxidized/min/ 10” platelets)
p-
Number
Platelet MA0 activity
Psychopathy Psychosis Psychosexual disturbance Brain damage Alcohol-linked dementia
33 20
12.49k3.91 12.46f5.55
Total
59
Diagnosis
12.22 13.77 9.11
3 2 1 Mean
12.45-1-4.55
Violent crimes Murder, manslaughter, assault, illegal threat Robbery Sexual crimes Property crimes Arson Drug crimes Total
Nonviolent crimes
32 (12) 1(1) 4 (2)
-
-
-
37 115)
(in 2 cases against their parents). Two were sentenced for assault; one had suddenly hit a woman unknown (to him) with his fist and the other had, at one occasion, repeatedly hit his wife with his fist. The seventh offender was sentenced for repeated illegal threats, but did not carry them through. On the other hand, 5 of the nonviolent offenders in the material were judged to be aggressive according to the criteria mentioned above. The 5 were sentenced for property crimes. Finally, the subjects were divided into alcoholics and nonalcoholics, based on the forensic psychiatric reports. As alcoholics were classified those who were diagnosed as alcohol abusers according to ICD-9. Based on these criteria, 33 subjects were classified as alcoholics. Platelet MA0 activity
Samples of blood ( 5 ml) were drawn into Vacutainer tubes containing sodium citrate, and the red cells were allowed to self-sediment for approximately 4 h. After about 1 ml of platelet-rich plasma was removed by careful suction, the platelet concentration was counted by the Coulter Counter (Dunstable, UK) and the plasma was frozen at - 70 O C. After thawing, the samples were sonicated for 1 min and estimation of the enzyme activity performed as described previously by incubation at 37°C for 4 min with 14C-tryptamine, final concentration 50 uM, or 14 C-2-phenylethyl amine, final concentration 50 uM (New England Nuclear, Boston, MA) as substrate (22). The 2 substrates were used in parallel to increase the reliability of the estimation and the estimations carried out in duplicate. Similar results were obtained with either of the two substrates (Y = 0.85) and, for this reason, only the results with 2phenylethyl amine are shown in the tables. As a further control of the reliability of the estimation, a standard platelet M A 0 preparation was estimated 20 times with each substrate at regular intervals during the estimation. The mean activity of this standard was 16.20 f 2.14 nmol of 2-phenylethylamine 219
Belfrage et al. oxidized/min/ 10” platelets. Thus, the coefficient of variation for the estimations was 13.2% during the period of estimation.
Table 4. Platelet MA0 activity in psychotic and nonpsychotic subjects MA0 activity? SD Category of offenders
Results
The mean platelet M A 0 activities in the various diagnostic groups are shown in Table 1. Statistical treatment could be performed only with regard to the groups of psychopathy and psychosis (NS). The 6 medicated people did not differ from the nonmedicated ones. A comparison of platelet M A 0 activities in the material divided according to violent and nonviolent, aggressive and nonaggressive as well as alcoholic and nonalcoholic offenders is shown in Table 3. There was lower M A 0 activity among violent offenders than among nonviolent offenders ( t = 2.05, P< 0.05), and among aggressive offenders than nonaggressive offenders (t = 2.01, P< 0.05). The difference between violent and nonviolent offenders was still present, even if robbers and sexual offenders were excluded. With regard to alcohol abuse, there was a tendency towards lower platelet M A 0 activity among the alcoholics than the nonalcoholics ( t = 1.89, P
The activity of monoamine oxidase (MAO; E.C. 1.4.3.4) in blood platelets is mainly genetically determined and appears to be relatively stable over time (1). Experimental and clinical findings suggest that the platelet M A 0 activity is a marker for the size or capacity of the serotonergic system in the central nervous system (CNS) (2). Thus, a positive correlation has been found between levels of 5hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) and platelet M A 0 in volunteers and in chronic pain patients (3-4). Low levels of CSF 5HIAA are likely to reflect low central serotonergic turnover ( 5 ) and have been associated with traits such as impulsiveness, sensation-seeking and psychopathy (6) and with poor control of aggression (7). The hypothesis that low serotonergic turnover is of importance for the control of violent acts is supported by the findings of low levels of CSF 5-HIAA in men who had killed a sexual partner (8) and in impulsive violent behavior (9). Furthermore, there is a strong connection between low platelet M A 0 activity and personality variables such as aggressive behavior, sensation-seeking and impulsiveness, which are supposed to be linked to low serotonergic activity (10). Recently, also neuropsychological variables likely to reflect low serotonergic activity, such as many failed inhibitions, have been found to be associated with low platelet M A 0 activity (6, 11). In psychiatric patients, a correlation has been established between low platelet M A 0 activity and some diagnoses such as psychopathy, suicidal behavior and alcoholism (12-16). In all those cases, however, there are reasons to believe that the low 218
H. Belfrage’, L. Lidberg’, L. Oreland2
’
Department of Social and Forensic Psychiatry, Stockholm, * Department of Medical Pharmacology, Uppsala University, Sweden
Key words: monoamine oxidase; violence; offenders Dr. Henrik Belfrage, Department of Social and Forensic Psychiatry, Karolinska Institute, Box 4044, S-141 04 Huddinge, Sweden Accepted for publication October 12, 1991
platelet M A 0 activity is not connected with the disorder per se, but with personality traits making the individual more vulnerable to the respective disorder (2,171. With regard to violence in connection with crime, Davis et al. (8) reported about low platelet M A 0 activities in violent offenders. However, in another report on the same series of patients, no difference was found between violent and nonviolent offenders (19). In a recent study, Palmstierna & Wistedt (20) observed violent behavior prior to admission in 40 % of a consecutive sample of acutely admitted and involuntarily treated patients at a psychiatric clinic. In a preliminary investigation on that series of patients, there was no correlation between violent behavior and platelet M A 0 activity (21). However, in their series, about 80% of the patients were in a psychotic state, and it may be speculated that aggressive behavior in psychotics could be connected with other biological phenomena than in the case among healthy individuals or patients with other mental disorders. In the present investigation, we have studied whether there is any connection between violent crimes and low platelet M A 0 activity among criminals undergoing forensic psychiatric examinations. As compulsiveness, disturbed perceptions of reality, etc. are states not known to be correlated with M A 0 and yet possibly cause aggressiveness and violence among psychotic patients, we divided the patients into 2 groups, psychotic and nonpsychotic offenders.
MA0 activity in violent offenders Table 2. Division of the subjects according to violent and nonviolent crimes (psychotics within parentheses)
Material and methods The series
The series includes 59 males who underwent forensic psychiatric examinations at the Stockholm Forensic Psychiatric Clinic in 1988-1989, and voluntarily submitted to blood tests. Only 6 of these were under medication (neuroleptics). The mean age was 33 years (range 19-61). Table 1 shows the distribution of principle diagnoses (the most serious diagnosis for each patient according to ICD-9). When the subjects were divided according to crimes involving violence vs nonviolence, 37 were classified into the former group and 22 into the latter (Table 2). Included in the category of violent crimes are murder, manslaughter, assault, illegal threats, sexual crimes, and robbery that were, at least in part, violent. The robbers and sexual offenders who were referred to the category of nonviolent crimes had been sentenced for aggravated robbery or sexual acts with children, whereas the robbers and sexual offenders in the category of violent crimes had been sentenced for robbery of people (involving violence) and aggravated rape. The number of psychotic offenders in each group is shown within parentheses. The division of the material into violent crimes and nonviolent crimes, however, is somewhat crude. The offenders sentenced for violent crimes may never before have shown aggressiveness and vice versa. Based on the sparse material in the forensic psychiatric reports, we therefore also tried to classify the offenders with regard to their aggressiveness. As aggressive were coded those who previously showed signs of aggressiveness, or in the forensic psychiatric assessment had been stated to be aggressive, or in the current crime had displayed clear aggressiveness. In this way, 35 subjects were assessed as aggressive and 24 subjects as nonaggressive. Seven of the subjects sentenced for violent crimes were coded as nonaggressive. Four of these were sentenced for attempted murder. They had committed seemingly unprovoked crimes under the influence of psychosis
Table 1. The distribution of diagnoses and MA0 activity (expressed as nmol of phenylethylamineoxidized/min/ 10” platelets)
p-
Number
Platelet MA0 activity
Psychopathy Psychosis Psychosexual disturbance Brain damage Alcohol-linked dementia
33 20
12.49k3.91 12.46f5.55
Total
59
Diagnosis
12.22 13.77 9.11
3 2 1 Mean
12.45-1-4.55
Violent crimes Murder, manslaughter, assault, illegal threat Robbery Sexual crimes Property crimes Arson Drug crimes Total
Nonviolent crimes
32 (12) 1(1) 4 (2)
-
-
-
37 115)
(in 2 cases against their parents). Two were sentenced for assault; one had suddenly hit a woman unknown (to him) with his fist and the other had, at one occasion, repeatedly hit his wife with his fist. The seventh offender was sentenced for repeated illegal threats, but did not carry them through. On the other hand, 5 of the nonviolent offenders in the material were judged to be aggressive according to the criteria mentioned above. The 5 were sentenced for property crimes. Finally, the subjects were divided into alcoholics and nonalcoholics, based on the forensic psychiatric reports. As alcoholics were classified those who were diagnosed as alcohol abusers according to ICD-9. Based on these criteria, 33 subjects were classified as alcoholics. Platelet MA0 activity
Samples of blood ( 5 ml) were drawn into Vacutainer tubes containing sodium citrate, and the red cells were allowed to self-sediment for approximately 4 h. After about 1 ml of platelet-rich plasma was removed by careful suction, the platelet concentration was counted by the Coulter Counter (Dunstable, UK) and the plasma was frozen at - 70 O C. After thawing, the samples were sonicated for 1 min and estimation of the enzyme activity performed as described previously by incubation at 37°C for 4 min with 14C-tryptamine, final concentration 50 uM, or 14 C-2-phenylethyl amine, final concentration 50 uM (New England Nuclear, Boston, MA) as substrate (22). The 2 substrates were used in parallel to increase the reliability of the estimation and the estimations carried out in duplicate. Similar results were obtained with either of the two substrates (Y = 0.85) and, for this reason, only the results with 2phenylethyl amine are shown in the tables. As a further control of the reliability of the estimation, a standard platelet M A 0 preparation was estimated 20 times with each substrate at regular intervals during the estimation. The mean activity of this standard was 16.20 f 2.14 nmol of 2-phenylethylamine 219
Belfrage et al. oxidized/min/ 10” platelets. Thus, the coefficient of variation for the estimations was 13.2% during the period of estimation.
Table 4. Platelet MA0 activity in psychotic and nonpsychotic subjects MA0 activity? SD Category of offenders
Results
The mean platelet M A 0 activities in the various diagnostic groups are shown in Table 1. Statistical treatment could be performed only with regard to the groups of psychopathy and psychosis (NS). The 6 medicated people did not differ from the nonmedicated ones. A comparison of platelet M A 0 activities in the material divided according to violent and nonviolent, aggressive and nonaggressive as well as alcoholic and nonalcoholic offenders is shown in Table 3. There was lower M A 0 activity among violent offenders than among nonviolent offenders ( t = 2.05, P< 0.05), and among aggressive offenders than nonaggressive offenders (t = 2.01, P< 0.05). The difference between violent and nonviolent offenders was still present, even if robbers and sexual offenders were excluded. With regard to alcohol abuse, there was a tendency towards lower platelet M A 0 activity among the alcoholics than the nonalcoholics ( t = 1.89, P
