Jowrrai o/ Ncio.uchcifii\t~l, 1975. Val. 25. pp. 667-673
Pcrgamon Press. Printcd m Great Brltain.
LOWERED MONOAMINE OXIDASE ACTIVITY IN BRAINS FROM ALCOHOLIC SUICIDES C. G. GOTTFRIES,L. ORELAND, A. WIBERGand B. WINBLAD
Department of Psychiatry (C.G.G.),Department of Pharmacology (L.O. & A. W.) and Department of Pathology (B.W.), University of Umeb, S-901 87 Umea, Sweden (Receiued 4 April 1975. Accepted 23 April 1975)
Abstract-Monoamine oxidase (MAO) activity in the brains of 15 suicides. of whom 8 were alcoholics, was compared to a control material of 20 individuals without known mental disorder. A t autopsy 13 dilferent parts of the brain were macroscopically dissected out and the M A 0 activity in the samples estimated with 8-phenylethylamine and tryptamine as substrates. The M A 0 activity in all parts of the brain investigated was found to be significantly lower in the alcoholic suicides as compared to the controls, while there was no significant difference between the non-alcoholic suicides and controls. Different variables which might have influenced the M A 0 activity werc investigatcd. There was no significant correlation between age and tryptamine-oxidizing activity, but a positive correlation between age and P-phenylethylamine-oxidi7ingactivity was found. There was also a significant difference between the series in the time lapse between death and autopsy and in the time during which the dead body was kept at room temperature. However, neither of these variables could cxplain the differences between the series. The results thus demonstrate a connection betwecn low M A 0 activity in the brain and suicidal behaviour among alcoholics.
ALTERATIONS in activity of the monoaminergic pathways in the CNS are believed to be involved in the aetiology of diseases such as Parkinsonism (EHRINGER & HORNYKI~WICS, 1960), affective psychoses (SHAW et al., 1967) and dementia states (GOTTFRIES et al., 1969). Monoamine oxidase (MAO) (monoamine: 0, oxidoreductase, EC 1.4.3.4) plays an important role in regulating the content of biogenic amines (see SCHILDKRAUT & KETY,1967). M A 0 is present in virtually all tissues, but is especially abundant in the liver and in the nervous system (PLETSCHER et al., 1960). Two types of M A 0 can be clearly dis.tinguished: soluble M A 0 in plasma, which probably has pyridoxal phosphate as a prosthetic group (MCEVEN, 1972), and FAD-containing M A 0 bound to mitochondria (TIPTON,1973). The high levels of plasma M A 0 found in older persons have been discussed in connection with the higher prevalence of depressive states in the elderly (ROBINSON et al., 1972), although the physiological function of plasma M A 0 is not yet known (see MCEVEN,1972). We were unable to verify such a connection between depressive states and altered levels of plasma M A O ; this study has been published elsewhere (MATTSSON et al., 1975). Mitochondria1 MAO, on the other hand, is of clearly established significance for the content of biogenic amines in various organs (for refs. see SCHILDKKAUT & KETY,1967). It has been directly shown that the content of norepinephrine and serotonin in the human brain increases after inhibition of the enzyme with M A 0 inhibitors, even at the therapeutic doses of such inhibitors that are used in antidepressive therapy (GANROTet al., 1963). A question of lively current 661
interest is whether mitochondria1 M A 0 occurs in multiple forms. Many reports suggest that such is probably the case (for reviews see SANDLER& YouDIM, 1972; YOUDIM,1973). The existence of multiple forms has not, however, been proved, and recent work has shown that the characteristics of the enzyme are highly dependent on the presence of phospholipids and other membrane components (ORELAND& & TIPTON,1973; TIPTONet EKSrEDT, 1972; HOUSLAY al., 1973). The occurrence of M A 0 in the human brain has been studied by WEINER(1960) among others, who found especially high activity in the regions of the thalamus and hypothalamus. He found no differences in substrate specificity between the enzyme from different regions of the brain, and thus no evidence for multiple forms of MAO. O n the other hand, such differences were observed by COLLINSet al. (1970~). For example, the latter found a six-fold difference in the ratio of M A 0 activities toward tryptamine and dopamine between the hypothalamus and the cerebral cortex, regions of the brain and substrates also investigated by WEINER(1960). Such discrepancies in the literature prompted us to use two substrates in analysing the M A 0 activity in different parts of the brain. As substrates we chose j-phenylethylamine and tryptamine, which are claimed, at least partly, to be deaminated by different forms of M A 0 (see NEFF et al., 1973). It has previously been shown both in certain animals (KUAYA& NAGATSU, 1969) and in man (ROBINSON et al., 1972) that M A 0 activity in the brain increases with advancing age. This increase has been
C. G. G O ~ R I E SL., OKELAND, A. WIBERGand B. WINRLAD
668
related to changes in the contents of biogenic mines cal or liver disease. The cases were also chosen to give and their metabolites associated with ageing. This a uniform spread with respect to age. Cause of death, age, finding has also been assumed to explain the in- sex and brain weight are given in Table 1. At autopsy creased frequency of depressive states in the elderly the degree of arteriosclerosis in the basal cerebral vessels (ROBINSONet al., 1972). The primary purpose of this was graded according to a three-step scale (United States Public Health Service, 1959) and the presence of encephastudy was to compare the M A 0 activity in the brains lomalacia was also noted (Table 1). Since the time elapsed of patients suffering from depressive states with that between death and autopsy could also be of importance in a control material to see whether differences could for M A 0 activity, this is also included in Table 1. The be detected. To this end, M A 0 activity was deter- time during which the dead body was kept in room temmined post mortem in the brains of persons who had perature was also rated as accurate as possible (Table 1). committed suicide. During the course of the investiga- The suicide material consisted of brains from 15 cases tion it became evident that the suicide group had to examined at the Department of Forensic Medicine, U m d be divided into two groups, one with and one without University Hospital. There was no doubt that death was due to suicide according to coroner’s inquest. Additional alcoholic abuse in their anarnnesis. MATERIALS AND METHODS Human brain. The control material consisted of brains from 20 persons with no history of psychiatric, neurologi-
Age
Sex
information was obtained from the autopsy findings including a statement concerning the chemical findings. Health insurance records and hospital records were collected if possible. If the information was considered insufficient an additional family interview was made.
TABLE 1. DIFFERENT DATA
ON PATIENTS IN CONTROL AND SUICIDE SEKlES
Cause of death
Time dead body in room temp. (h)
Control series (n = 20) 61 M Hcart Infarct 55 F Heart Infarct 65 F Heart infarct 60 M Pulmonary embolism 55 M Heart infarct 67 M Heart infarct 44 M Heart infarct 47 M Heart infarct 34 F Pulmonary embolism 22 M Ruptured aortic aneurysm 61 M Heart infarct 27 M Accident 41 M Heart infarct 46 M Heart infarct 87 M Heart infarct 74 M Heart infarct 25 M Accident 38 M Ruptured aortic aneurysm 61 M Heart infarct 55 M Heart infarct Suicide series (n = 15) 61 M Cut throat 47 M Hanging 59 M Drowning 47 M Carbon monoxide* 25 M Carbon monoxide 36 F Intoxication (neuroleptic) 25 M Intoxication* (barbiturate ethanol) 55 M Hanging* 27 M Intoxication (tri-cyclic antidepressant + ethanol) 53 M Hanging* 4 4 M Hanging* 69 F Stabbed chest 47 M Carbon monoxide* 45 M Carbon monoxide* 40 M Carbon monoxide*
* Indicates alcoholic abuse.
4 4 4 4 6 4 4 11
5 46 56 63 44 41 89 148 45 35 76 94 17 88 61 111 59
Brain weight
4
44 73
1.360 1.230 1.w 1390 1.620 1.480 1.620 1.550 1.200 1.940 1.540 1.490 1,450 1440 1,530 1.340 1.530 I.550 1.620 I ,480
11 6 9 5 17 42 17
65 82 80 71 28 82 54
1-480 1.620 1.590 1,340 1.640 1.400 1.350
19 16
93 106
1.610
10 6 16 4 11 14
98 82 110 23 34 103
1.430 1.430 1.540
9 4 8 14 9 5 8 4 24 16
4
+
Time deathautopsy (h)
x9
1,350
1-500
1.480 1.540
Arteriosclerosis cerebri
++
Ence~halomalacias
0
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0
0 0
0 0 0 0
0 0 0 0 0
0 0
0 0
0
0 0 0 0 0 0
+ + 0 0
+
+ 0 0 0
+ 0 + ++ ++
+ 0 0
+ +
0
+ + 0 0
Low brain M A 0 in alcoholic suicides
TABLE2. MEANSAND
STANDARD DEVIATION OF
669
iMAO* (,~-PHENYLETHYLAMINE-OXIDIZING) IN DIFFERENT
PARTS OF HE
HUMAN BRAIN IN CONTROLS AND SUICIDES
Part or hraint Hypothalamust Caudatus Putamen Pallidus Thalamus Mesencephalons Pons Medulla oblongata Hippocampus Cortcx lobus frontalis Cortcx lobus occipitalis Cortex gyrus cinguli Cortex gyrus hippocampus
Control series n=20 mean S.D.
Suicide series
Alcoholic suicide n=8 mean S.D.
Suicides not alcoholics n=7 mean S.D.
4396 i 1054 3601 f 1012 3288 f 444 3252 I 177 2447 11x2 2029 f 495 2959 f 1219 1921 f 856 1 6 0 7 i 684 3115 f 880 2141 783 1811 f 616 2589 ?- 810 1948 f 942 1588 i 526 2808 f 868 1 9 5 0 i 755 1716 f 654 2 2 9 4 i 699 1577 f 568 1366f 449 2701 i 637 1930 f 527 1755 f 538 2416 f 759 1705 k 664 1427 f 582 1569 592 1218 f 525 999 i 289 1315 f 450 884 i 443 692 i 283 1971 f 606 1514 f 709 1204 f 520 1943 f 593 1400 550 1177 i 396
3871 f 1368 292s 1370 2 2 8 0 i 1002 2519 f 881 2360 f 1234 2217 f 876 1819 f 667 2130 f 519 2023 f 697 I469 i 675 1104 541 I780 f 828 1655 f 656
n=lS
mean
+
S.D.
+
+
+
Group difcrences (Students I analyses) Controls! Controls Alcoliolic Controls/ alcoholic iron-8lcoholic ~~O~I-~~~COI~O~~ suicides suicides suicides suicides P i P< P< P< 0.05 0.05 001
0.005 0.05 0.005 0005 0.001 0-01 ns. 0.01 ns.
001
0.005 0001 0.0 I 0001 0.005 0-05 0.005
0005 0.005 0005 0.005 0.02 0.005
n.s. n s.
n.s.
ns. n.s. n s. n s. n.s. 0.05 ns. n.s. n.s.
n.s. n.s. n.s.
n.s. n.s.
IlS.
LS.
ns. n.s. n.s. n.s. ns. n.s. n s.
* Activity expressed in d.p.m. 1 d.p.m. corresponds to 19 x 10-6 nmol/mg wet wt. t The preparation of brain nuclei or brain parts were carried out macroscopically on
the basis of gross anatomical landmarks. To ensure that adjacent parts were not included in the sample, central parts, but as large as possible, of brain nuclei were dissected. $ After removal of the chiasma opticum, the infundibulum and hypophysis cerebri a block of tissue containing the hypothalamic nuclei was dissected out as follows: a transverse section behind the corpora mamillaria exposing the 3rd ventricle, thereafter sections just laterally of the corpora mamillaria on both sides, dorsally along the sulcus hypothalamicus and frontally behind the commisura anterior. $After removal of the pedunculi cerebellaris a transverse section at the level of the upper border of the corpora quadrigemina superior (es) was made followed by a longitudinal transverse section including the aquaeductus cerebri, the tegmentum and the substantia nigra but excluding the crura cerebri and pons. A transverse section distal to the pars superior fossa rhomboidea including locus caeruleus constituted the lower limit. The immediate cause of death and other data as for the controls are given in Table 1. Studying data from the suicide group it was obvious that 6 suicides before death had a heavy abuse of alcohol and could be considered chronic alcoholics. In two cases there had been abuse or alcohol to a certain extent. In these two cases the abuse was secondary to psychic factors. The suicide material could subsequently be divided into one group with alcohol abuse (n = 8) and one group with no alcohol abuse (n = 7). As shown in Table 1 there were three cases with death due to intoxication (barbiturates, neuroleptics and tricyclic antidepressant) of whom two wcre alcoholics. At autopsy 13 different parts of the brain were macroscopically dissected out (Tables 2 and 3). The material was frozen in air-tight packages and was stored for not more than 1
TABLE 3. MEANS AND STANDARD DEVIATION
OF
MAO*
week at -20°C until estimation of M A 0 activity. At the time of analysis, a representative part of each excised structure-usually the central third-was carefully removed, weighed and homogenized in 0.154 M-pOtaSSiUm phosphate (pH 7.4) in a Potter-Elvehjem homogenizer (Teflon pestle), three strokes at 1000 r.p.m. to a final concentration of 1% w/v. M A 0 activity. This was determined according to WUKTMAN & AXELROD(1963) as applied by FULLER & ROUSH (1972). The substances used were [14CJphenylethylamine (~-[1-14C]phenylethylaminehydrochloride, 7 mCi/mmol, New England Nuclear, Boston, MA); 80 PM and [14C]tryptamine ( [2-'4C]tryptamine bisuccinate, 60 mCi/mmol, New England Nuclear, Boston, MA). mixed with unlabclled tryptamine (tryptamine hydrochloride, Sigma
(TRYPTAMINE-OXIDIZING) IN DJFFERENT PARTS OF THE HUMAN BRAIN
IN CONTROLS AYD SUIClDES
Part o i brain
Control scrics n=20 M S.D.
Suiclde series n=15 M S.D.
Alcoholic suicides n = 8 M S.D.
Non-alcoholic suicides n = 7 M S.D.
Group differences (Students t analyses) Controls' Alcoholic, Controls! Controls! alcoholic nun-alcohohc nun-alcoholic suicides suicides suicides suicides P< P< P< P
Pcrgamon Press. Printcd m Great Brltain.
LOWERED MONOAMINE OXIDASE ACTIVITY IN BRAINS FROM ALCOHOLIC SUICIDES C. G. GOTTFRIES,L. ORELAND, A. WIBERGand B. WINBLAD
Department of Psychiatry (C.G.G.),Department of Pharmacology (L.O. & A. W.) and Department of Pathology (B.W.), University of Umeb, S-901 87 Umea, Sweden (Receiued 4 April 1975. Accepted 23 April 1975)
Abstract-Monoamine oxidase (MAO) activity in the brains of 15 suicides. of whom 8 were alcoholics, was compared to a control material of 20 individuals without known mental disorder. A t autopsy 13 dilferent parts of the brain were macroscopically dissected out and the M A 0 activity in the samples estimated with 8-phenylethylamine and tryptamine as substrates. The M A 0 activity in all parts of the brain investigated was found to be significantly lower in the alcoholic suicides as compared to the controls, while there was no significant difference between the non-alcoholic suicides and controls. Different variables which might have influenced the M A 0 activity werc investigatcd. There was no significant correlation between age and tryptamine-oxidizing activity, but a positive correlation between age and P-phenylethylamine-oxidi7ingactivity was found. There was also a significant difference between the series in the time lapse between death and autopsy and in the time during which the dead body was kept at room temperature. However, neither of these variables could cxplain the differences between the series. The results thus demonstrate a connection betwecn low M A 0 activity in the brain and suicidal behaviour among alcoholics.
ALTERATIONS in activity of the monoaminergic pathways in the CNS are believed to be involved in the aetiology of diseases such as Parkinsonism (EHRINGER & HORNYKI~WICS, 1960), affective psychoses (SHAW et al., 1967) and dementia states (GOTTFRIES et al., 1969). Monoamine oxidase (MAO) (monoamine: 0, oxidoreductase, EC 1.4.3.4) plays an important role in regulating the content of biogenic amines (see SCHILDKRAUT & KETY,1967). M A 0 is present in virtually all tissues, but is especially abundant in the liver and in the nervous system (PLETSCHER et al., 1960). Two types of M A 0 can be clearly dis.tinguished: soluble M A 0 in plasma, which probably has pyridoxal phosphate as a prosthetic group (MCEVEN, 1972), and FAD-containing M A 0 bound to mitochondria (TIPTON,1973). The high levels of plasma M A 0 found in older persons have been discussed in connection with the higher prevalence of depressive states in the elderly (ROBINSON et al., 1972), although the physiological function of plasma M A 0 is not yet known (see MCEVEN,1972). We were unable to verify such a connection between depressive states and altered levels of plasma M A O ; this study has been published elsewhere (MATTSSON et al., 1975). Mitochondria1 MAO, on the other hand, is of clearly established significance for the content of biogenic amines in various organs (for refs. see SCHILDKKAUT & KETY,1967). It has been directly shown that the content of norepinephrine and serotonin in the human brain increases after inhibition of the enzyme with M A 0 inhibitors, even at the therapeutic doses of such inhibitors that are used in antidepressive therapy (GANROTet al., 1963). A question of lively current 661
interest is whether mitochondria1 M A 0 occurs in multiple forms. Many reports suggest that such is probably the case (for reviews see SANDLER& YouDIM, 1972; YOUDIM,1973). The existence of multiple forms has not, however, been proved, and recent work has shown that the characteristics of the enzyme are highly dependent on the presence of phospholipids and other membrane components (ORELAND& & TIPTON,1973; TIPTONet EKSrEDT, 1972; HOUSLAY al., 1973). The occurrence of M A 0 in the human brain has been studied by WEINER(1960) among others, who found especially high activity in the regions of the thalamus and hypothalamus. He found no differences in substrate specificity between the enzyme from different regions of the brain, and thus no evidence for multiple forms of MAO. O n the other hand, such differences were observed by COLLINSet al. (1970~). For example, the latter found a six-fold difference in the ratio of M A 0 activities toward tryptamine and dopamine between the hypothalamus and the cerebral cortex, regions of the brain and substrates also investigated by WEINER(1960). Such discrepancies in the literature prompted us to use two substrates in analysing the M A 0 activity in different parts of the brain. As substrates we chose j-phenylethylamine and tryptamine, which are claimed, at least partly, to be deaminated by different forms of M A 0 (see NEFF et al., 1973). It has previously been shown both in certain animals (KUAYA& NAGATSU, 1969) and in man (ROBINSON et al., 1972) that M A 0 activity in the brain increases with advancing age. This increase has been
C. G. G O ~ R I E SL., OKELAND, A. WIBERGand B. WINRLAD
668
related to changes in the contents of biogenic mines cal or liver disease. The cases were also chosen to give and their metabolites associated with ageing. This a uniform spread with respect to age. Cause of death, age, finding has also been assumed to explain the in- sex and brain weight are given in Table 1. At autopsy creased frequency of depressive states in the elderly the degree of arteriosclerosis in the basal cerebral vessels (ROBINSONet al., 1972). The primary purpose of this was graded according to a three-step scale (United States Public Health Service, 1959) and the presence of encephastudy was to compare the M A 0 activity in the brains lomalacia was also noted (Table 1). Since the time elapsed of patients suffering from depressive states with that between death and autopsy could also be of importance in a control material to see whether differences could for M A 0 activity, this is also included in Table 1. The be detected. To this end, M A 0 activity was deter- time during which the dead body was kept in room temmined post mortem in the brains of persons who had perature was also rated as accurate as possible (Table 1). committed suicide. During the course of the investiga- The suicide material consisted of brains from 15 cases tion it became evident that the suicide group had to examined at the Department of Forensic Medicine, U m d be divided into two groups, one with and one without University Hospital. There was no doubt that death was due to suicide according to coroner’s inquest. Additional alcoholic abuse in their anarnnesis. MATERIALS AND METHODS Human brain. The control material consisted of brains from 20 persons with no history of psychiatric, neurologi-
Age
Sex
information was obtained from the autopsy findings including a statement concerning the chemical findings. Health insurance records and hospital records were collected if possible. If the information was considered insufficient an additional family interview was made.
TABLE 1. DIFFERENT DATA
ON PATIENTS IN CONTROL AND SUICIDE SEKlES
Cause of death
Time dead body in room temp. (h)
Control series (n = 20) 61 M Hcart Infarct 55 F Heart Infarct 65 F Heart infarct 60 M Pulmonary embolism 55 M Heart infarct 67 M Heart infarct 44 M Heart infarct 47 M Heart infarct 34 F Pulmonary embolism 22 M Ruptured aortic aneurysm 61 M Heart infarct 27 M Accident 41 M Heart infarct 46 M Heart infarct 87 M Heart infarct 74 M Heart infarct 25 M Accident 38 M Ruptured aortic aneurysm 61 M Heart infarct 55 M Heart infarct Suicide series (n = 15) 61 M Cut throat 47 M Hanging 59 M Drowning 47 M Carbon monoxide* 25 M Carbon monoxide 36 F Intoxication (neuroleptic) 25 M Intoxication* (barbiturate ethanol) 55 M Hanging* 27 M Intoxication (tri-cyclic antidepressant + ethanol) 53 M Hanging* 4 4 M Hanging* 69 F Stabbed chest 47 M Carbon monoxide* 45 M Carbon monoxide* 40 M Carbon monoxide*
* Indicates alcoholic abuse.
4 4 4 4 6 4 4 11
5 46 56 63 44 41 89 148 45 35 76 94 17 88 61 111 59
Brain weight
4
44 73
1.360 1.230 1.w 1390 1.620 1.480 1.620 1.550 1.200 1.940 1.540 1.490 1,450 1440 1,530 1.340 1.530 I.550 1.620 I ,480
11 6 9 5 17 42 17
65 82 80 71 28 82 54
1-480 1.620 1.590 1,340 1.640 1.400 1.350
19 16
93 106
1.610
10 6 16 4 11 14
98 82 110 23 34 103
1.430 1.430 1.540
9 4 8 14 9 5 8 4 24 16
4
+
Time deathautopsy (h)
x9
1,350
1-500
1.480 1.540
Arteriosclerosis cerebri
++
Ence~halomalacias
0
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0
0 0
0 0 0 0
0 0 0 0 0
0 0
0 0
0
0 0 0 0 0 0
+ + 0 0
+
+ 0 0 0
+ 0 + ++ ++
+ 0 0
+ +
0
+ + 0 0
Low brain M A 0 in alcoholic suicides
TABLE2. MEANSAND
STANDARD DEVIATION OF
669
iMAO* (,~-PHENYLETHYLAMINE-OXIDIZING) IN DIFFERENT
PARTS OF HE
HUMAN BRAIN IN CONTROLS AND SUICIDES
Part or hraint Hypothalamust Caudatus Putamen Pallidus Thalamus Mesencephalons Pons Medulla oblongata Hippocampus Cortcx lobus frontalis Cortcx lobus occipitalis Cortex gyrus cinguli Cortex gyrus hippocampus
Control series n=20 mean S.D.
Suicide series
Alcoholic suicide n=8 mean S.D.
Suicides not alcoholics n=7 mean S.D.
4396 i 1054 3601 f 1012 3288 f 444 3252 I 177 2447 11x2 2029 f 495 2959 f 1219 1921 f 856 1 6 0 7 i 684 3115 f 880 2141 783 1811 f 616 2589 ?- 810 1948 f 942 1588 i 526 2808 f 868 1 9 5 0 i 755 1716 f 654 2 2 9 4 i 699 1577 f 568 1366f 449 2701 i 637 1930 f 527 1755 f 538 2416 f 759 1705 k 664 1427 f 582 1569 592 1218 f 525 999 i 289 1315 f 450 884 i 443 692 i 283 1971 f 606 1514 f 709 1204 f 520 1943 f 593 1400 550 1177 i 396
3871 f 1368 292s 1370 2 2 8 0 i 1002 2519 f 881 2360 f 1234 2217 f 876 1819 f 667 2130 f 519 2023 f 697 I469 i 675 1104 541 I780 f 828 1655 f 656
n=lS
mean
+
S.D.
+
+
+
Group difcrences (Students I analyses) Controls! Controls Alcoliolic Controls/ alcoholic iron-8lcoholic ~~O~I-~~~COI~O~~ suicides suicides suicides suicides P i P< P< P< 0.05 0.05 001
0.005 0.05 0.005 0005 0.001 0-01 ns. 0.01 ns.
001
0.005 0001 0.0 I 0001 0.005 0-05 0.005
0005 0.005 0005 0.005 0.02 0.005
n.s. n s.
n.s.
ns. n.s. n s. n s. n.s. 0.05 ns. n.s. n.s.
n.s. n.s. n.s.
n.s. n.s.
IlS.
LS.
ns. n.s. n.s. n.s. ns. n.s. n s.
* Activity expressed in d.p.m. 1 d.p.m. corresponds to 19 x 10-6 nmol/mg wet wt. t The preparation of brain nuclei or brain parts were carried out macroscopically on
the basis of gross anatomical landmarks. To ensure that adjacent parts were not included in the sample, central parts, but as large as possible, of brain nuclei were dissected. $ After removal of the chiasma opticum, the infundibulum and hypophysis cerebri a block of tissue containing the hypothalamic nuclei was dissected out as follows: a transverse section behind the corpora mamillaria exposing the 3rd ventricle, thereafter sections just laterally of the corpora mamillaria on both sides, dorsally along the sulcus hypothalamicus and frontally behind the commisura anterior. $After removal of the pedunculi cerebellaris a transverse section at the level of the upper border of the corpora quadrigemina superior (es) was made followed by a longitudinal transverse section including the aquaeductus cerebri, the tegmentum and the substantia nigra but excluding the crura cerebri and pons. A transverse section distal to the pars superior fossa rhomboidea including locus caeruleus constituted the lower limit. The immediate cause of death and other data as for the controls are given in Table 1. Studying data from the suicide group it was obvious that 6 suicides before death had a heavy abuse of alcohol and could be considered chronic alcoholics. In two cases there had been abuse or alcohol to a certain extent. In these two cases the abuse was secondary to psychic factors. The suicide material could subsequently be divided into one group with alcohol abuse (n = 8) and one group with no alcohol abuse (n = 7). As shown in Table 1 there were three cases with death due to intoxication (barbiturates, neuroleptics and tricyclic antidepressant) of whom two wcre alcoholics. At autopsy 13 different parts of the brain were macroscopically dissected out (Tables 2 and 3). The material was frozen in air-tight packages and was stored for not more than 1
TABLE 3. MEANS AND STANDARD DEVIATION
OF
MAO*
week at -20°C until estimation of M A 0 activity. At the time of analysis, a representative part of each excised structure-usually the central third-was carefully removed, weighed and homogenized in 0.154 M-pOtaSSiUm phosphate (pH 7.4) in a Potter-Elvehjem homogenizer (Teflon pestle), three strokes at 1000 r.p.m. to a final concentration of 1% w/v. M A 0 activity. This was determined according to WUKTMAN & AXELROD(1963) as applied by FULLER & ROUSH (1972). The substances used were [14CJphenylethylamine (~-[1-14C]phenylethylaminehydrochloride, 7 mCi/mmol, New England Nuclear, Boston, MA); 80 PM and [14C]tryptamine ( [2-'4C]tryptamine bisuccinate, 60 mCi/mmol, New England Nuclear, Boston, MA). mixed with unlabclled tryptamine (tryptamine hydrochloride, Sigma
(TRYPTAMINE-OXIDIZING) IN DJFFERENT PARTS OF THE HUMAN BRAIN
IN CONTROLS AYD SUIClDES
Part o i brain
Control scrics n=20 M S.D.
Suiclde series n=15 M S.D.
Alcoholic suicides n = 8 M S.D.
Non-alcoholic suicides n = 7 M S.D.
Group differences (Students t analyses) Controls' Alcoholic, Controls! Controls! alcoholic nun-alcohohc nun-alcoholic suicides suicides suicides suicides P< P< P< P
