Monoamine Metabolism in Human Brain Robinson, MD; Theodore L. Sourkes, PhD; Alexander Nies, MD; Sydney Spector, PhD; Diantha L. Bartlett, MS; Irwin S. Kaye, MD Donald S.
\s=b\ Norepinephrine (NE), dopamine (DA), tyrosine hydroxylase (TH), catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) levels were measured in human brain tissue obtained at autopsy from a series of 39 patients dying of various medical and accidental causes. The nine following brain areas were studied: globus pallidus, thalamus, hypothalamus, hippocampus, substantia nigra, floor of the fourth ventricle, orbital cortex, caudate nucleus, and mammillary bodies. Enzyme activity correlated positively with age in all brain areas for MAO (with both benzylamine and tryptamine substrates) but no consistent of correlation was found for COMT and TH. Mean MAO was significantly higher in women than men. There is increased brain MAO activity during late childhood and adolescence. These data are consistent with previous evidence suggesting that age and sex are important determinants of amine metabolism in the human central nervous system.
pattern
activity
(Arch Gen Psychiatry 34:89-92, 1977)
is widespread interest in biogenic amine metabo¬ lism in the central nervous system (CNS) because of the established physiologic importance of amine neurotransmitters. Of particular interest have been studies of human brain in suicide victims, for such studies have been able to explore the biogenic amine hypothesis of affective illness'" directly by determining brain amine levels,1" and brain monoamine oxidase (MAO).''"1 Other brain studies have dealt with MAO and monoamines to determine their interrelationships in aging""" and with various neurotransmitters and enzymes in brains from schizophrenic patients.14""! Fluctuations in brain monoamine metabolism
There '
Accepted
for publication Sept 13, 1976. From the Departments of Medicine, Psychiatry, Pathology, and Epidemiology and Community Medicine, University of Vermont College of Medicine, Burlington, Vt (Drs Robinson, Nies, Harris, Kaye, and Ms Bartlett); Department of Psychiatry, McGill University, Montreal (Dr Sourkes); and the Department of Pharmacology, Roche Institute of Molecular Biology, Nutley, NJ (Dr Spector). Dr Nies is now with the Department of Psychiatry, Dartmouth Medical School, Hanover, NH. Reprint requests to Given Medical Bldg, University of Vermont College of Medicine, Burlington, VT 05401 (Dr Robinson).
Lawrence S.
Harris, MD;
associated with the oestrous cycle and hormone adminis¬ tration have also been reported in animal studies.'7"' More recently, Gruen et al,-'" have described altered aminemediated neuroendocrine function in depressed patients. These various studies provide additional evidence for biological theories of the pathogenesis of many neuro¬ psychiatrie disorders. The present study pursues these important topics through investigation of 39 human brains obtained at autopsy. It was undertaken in order to examine further the effects of age and sex on CNS amine metabolism, to provide normative data for human brain, and to explore the possible link between altered amine neurotransmitters and neuropsychiatrie disorders. The causes of death in¬ cluded a spectrum of medical, neurologic, and psychiatric disorders as well as several sudden accidental deaths. Data reported here are consistent with preexisting evidence that biologic factors such as aging play a part in modifying brain amine metabolism. METHODS Brains were obtained for dissection at the time of autopsy. Patients ranged in age from 4 to 83 years and included 14 women, 19 men, and six children. Brains were obtained from both the State Medical Examiner and the Medical Center Hospital of Vermont, and causes of death included accidental sudden death (n 8), homicide (n 1), suicide (n 2), and various medical conditions (n 17). In addition, there were five neuropsychiatrie patients and six minors who died from medical causes. Time from death to postmortem ranged from 2 to 30 hours and averaged 16 hours. Nine separate brain regions were dissected within minutes after the dura mater was opened. Dissections were carried out by two neuropathologists (L.S.H and I.K.) using standard anatomical landmarks to obtain uniform sections. The nine regions examined were the following: globus pallidus, thalamus, hypothalamus, hippocampus, substantia nigra, floor of the fourth ventricle (retic¬ ular formation, reticular activating system [RAS]), orbital cortex, caudate nucleus, and mammillary bodies. Bilateral sections were obtained and stored separately at —20 C in airtight containers flushed with 1009? nitrogen before sealing. Specimens from one side of the brain were randomly selected for monoamine assay and =
=
=
=
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the contralateral sections for enzyme assays, including mono¬ amine oxidase (MAO), tyrosine hydroxylase (TH), and catechol-Omethyltransferase (COMT). Evidence from these laboratories and other studies" have shown that brain levels of norepinephrine (NE), dopamine (DA), and MAO activity are stable over a storage period of several weeks when tissues are collected and stored in this fashion. Similar evidence for stability of TH and COMT with storage at low temperatures is less well established; recent studies of brain TH activity in animals maintained at room temperature for varying periods after death suggests that there are significant changes in TH with time."22
Table
1.—Enzyme
Activities in Nine Areas of Human Brain*
'214'""
Assay
of
Enzyme
activities were assayed in crude whole tissue homogenates. The MAO was determined with benzylamine tagged with carbon 14 and tryptamine tagged with carbon 14 as substrates by the method of Robinson et al.-' The TH was assayed by the method of Nagatsu et al 24 and COMT by the method of Creveling and Daly.2' Protein was determined by the procedure of Lowry et al.-'" Enzyme activities were expressed as nanomoles per milligram of protein per hour.
Substrate
pallldus Thalamus
Hypothalamus Hippocampus
51 68 91 50
Substrate
±3 ±7 ±6 ±3
32
4
1.1 ±.1
44± 4 37+4
1.6±.2 0.9+ .2
nigra
65 ±4
RAS Cortex Caudate
57 ±3 49 + 3
19 ±1 17 ±1
27 28
0.9
15
34 ± 4 40± 4
67±5
+
Analysis
All demographic and laboratory data were recorded for each patient in machine-readable form and stored for analysis by computer. Standard univariate techniques, such as the Student
i-test were used to test for difference in means and the Wilcoxon test for difference in medians. The nonparametric test of correla¬ tion (Kendall's tau)2* and the F-test of analysis of covariance2" were used to examine for age and sex-related differences in MAO activity in the adult sample. Exclusion of the juvenile group permitted assumption of linearity of the age-MAO relationship in the remaining sample for the purposes of covariance analysis. The substrate, benzylamine, was selected because of the sub¬ stantial previous experience with benzylamine in human platelet and brain MAO studies. Tryptamine was selected because of its forms of high activities as substrate for the MAO A and the brain enzyme.
RESULTS
The activities of the enzymes MAO, COMT, and TH in the nine brain areas are shown in Table 1. It is evident that the specific activity of MAO is greatest in the hypothal¬ amus and mammillary bodies for both substrates, benzyl¬ amine, and tryptamine, and lowest in cortex, globus pallidus, and hippocampus. Highest specific activity for COMT was in hypothalamus. The TH activity was greatest in the mammillary bodies and hypothalamus.
Enzyme
Activities and
+
41
17±2
Mammillary bodies
'Enzyme
85 ±5
activities (mean ±
1
26
±
2
Age
Table 2 shows correlations (Kendall's tau) of COMT, TH, and MAO, respectively, with age for each of eight brain areas. The MAO correlation computations excluded the juvenile group because there is an elevation of plasma, platelet, and brain MAO activity in individuals under 20 years of age compared to young adults. A typical example of the age relationship is shown for two areas, globus
5 4
± ±
1.5: ±
.1
1.0 ±.2 0.9±.1
32 ±12
SEM) expressed
Table 2.—Correlations of Brain
Data
TH
COMT
14±1 20 ±2 29±2 16 ±1
of Monoamines
The NE and DA were determined in seven regions of brain, but for the smaller brain areas (hypothalamus, substantia nigra), only one monoamine determination was carried out in an individual brain. Catecholamines were determined by a minor modification of the method of Laverty and Taylor.27
Correlations of
Tryptamine
Benzylamine Area Globus
Substantia
Activities
Enzyme
Assay
MAO
as
nmole/mg/hr.
Enzymes
vs
Age
Correlation Coefficient
(Kendall's T) MAO (n 33) ,-«-, =
Benzylamine
COMT
Tryptamine (n
=
TH
(n)
32)
Globus
pallidus
+
+.28Í
-.05
Thalamus
+
+.17
+.24$
-.16 +.03
+.15
—.21J
+.09(14)
-.13
+.22(7) +.10(15) -.03(17) -.04(18)
Hypothalamus Hippocampus
.37s 20i + .26Í +.34+
+.02(16) +.14(18)
-.11(9)
Substantia
nigra
+
.32+
+
+.11
RAS Cortex Caudate
+.27+ +.21 i
.25+.
+.12 +.09 +.08
-.13 -.12 -.10
*P £ .001. +P < .01. IP S .05.
pallidus and hypothalamus, (Figure).
with
tryptamine
as
substrate
It can be seen that for MAO the correlation coefficient is
positive for all areas with both substrates (Table 2). With benzylamine as substrate, Kendall's tau is significantly positive for seven out of eight areas. With tryptamine as substrate, the positive correlation is statistically signifi¬ cant for only three of the eight individual areas. To get a measure of overall correlation of MAO activity with age, the multiple correlation coefficient2" was computed for age with MAO levels in the eight areas. This correlation was significant with both substrates, ie, for benzylamine .64 (P .67 (P .001) and tryptamine r r .001). =
=
=
=
For COMT, the coefficients of correlation for seven of eight areas were negative, but only in the case of the hippocampus does this achieve statistical significance. This contrasts with the positive correlation of MAO with age.
Relationship
of Sex and MAO
Activity
The MAO activity was adjusted for age before analysis for possible sex differences. This was necessary because of the positive correlation between age and MAO activity and because in the adult sample the women were older than the
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60 Table
of MAO Activities of Men Women in Nine Brain Areas
3.—Comparison
Hypothalamus
vs
Mean MAO Activities*
Tryptamine, nmoles/mg/hr
Benzylamine, nmoles/mg/hr
40
Men
Area_(n
=
Women
19) (n
=
14)
Men
P+
(n
=
Women
19) (n
=
14) P+
Globus
20
pallidus
47.4
54.2
Thalamus
50.5 80.7 42.9
84.7 101.1 54.2
60.2
Hypothalamus Hippocampus
NS .01
13.1 17.1
15.3
NS
24.4
.07
.03 .12
27 9
33.7
14.2
19.0
NS NS
66.4
NS
19.4
21.1
NS
53.1
62.5
NS
16.8
18.8
NS
41.0
53.6
57.3
76.9
.09 .07
13.5 12.9
18.9 21.6
.06 .10
67.4
94.9
.02
22.6
29.6
NS
Substantia
nigra Floor fourth ventricle
J_ 20
J
40
60
70
AGE (decade) Mean MAO activities ( and globus pallidus with
SEM) by age tryptamine as
hypothalamus
(the mean age for women was 62.6, as opposed to 50.3 for the men). The age adjustment was made by means of men
linear regression of MAO activity on age decade for each brain area separately. Table 3 shows mean MAO activities after adjustment for age for men and women over 20 years of age for each of nine brain areas. Women have higher mean activities than men for each area and with both substrates, a pattern more pronounced with benzylamine than tryptamine. Because of significant interarea correla¬ tions and variability among persons, analysis of variance was used to test for overall sex difference in age-adjusted MAO, taking into account area and person effects. This analysis showed a significant sex difference in brain MAO .02 for benzylamine and .07 for tryp¬ activity at tamine. =
Correlation of Brain Amines With
Age of hypothalamus and
As shown in Table 4, NE content hippocampus has a significant negative correlation with age and tends to negative in all areas except substantia nigra. There is no overall pattern for DA. There are slight negative correlations between DA and age in the thalamus -.47, < .1), -.25, < .1) and hypothalamus ( ( and positive, though nonsignificant, correlations between DA and age in several areas. =
=
Correlations of Monoamines With
Enzyme Activities
None of the correlations of NE or DA levels with COMT TH was significant. However, there are strong negative correlations of MAO with DA in hypothalamus ( —.87), thalamus ( -.27) and MAO with -.42) and RAS ( NE in hippocampus ( -.28) (Table 4). or
=
=
=
(orbital) Caudate
decade in substrate
=
(RAS) Cortex
=
COMMENT
There is a growing interest in brain catecholamine metabolism in man because of the implied role of monoamines in neuropsychiatrie disorders, especially such agerelated conditions as depressive illness and parkinsonism.
Mammillary bodies!
•Mean MAO activities adjusted individually by brain area for age. +P probability that the difference in age-adjusted means for men and women for each brain area is due to chance as measured by the F-test from analysis of covariance. Because of significant ¡nterarea correlations of MAO, an overall sex difference in MAO was tested adjusting for age, area, and individual within sex, using analysis of variance. This analysis showed .02 for benzyl¬ a significant sex difference in brain MAO activity at amine and .07 for tryptamine as substrates. 10 each for men and women. iSample size: =
=
=
=
Table 4.—Correlations (Kendall's ) of Brain Amines With Age and With MAO Activity Amines Area Globus
vs
Age
Amines
vs
MAO
NE
DA
NE
DA
(n)
(n)
(n)
(n)
+.07(14) -.25(14)* -.47(6)* -.18(18)
+.12(16) +.15(19) -.20(10) -.28(19)+
+.14(14) -.42(14)+ -.87(6) -.24(18)
+.18(10) +.02(19) +.18(19)
+.03(9) -.19(19) -.10(19)
+.36(10) -.27(19)+ +.05(19)
-.02(16) -.09(19) Hypothalamus -.51 (10)+ Hippocampus -.29(19): pallidus
Thalamus
Substantia
nigra RAS Caudate
*P
\s=b\ Norepinephrine (NE), dopamine (DA), tyrosine hydroxylase (TH), catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) levels were measured in human brain tissue obtained at autopsy from a series of 39 patients dying of various medical and accidental causes. The nine following brain areas were studied: globus pallidus, thalamus, hypothalamus, hippocampus, substantia nigra, floor of the fourth ventricle, orbital cortex, caudate nucleus, and mammillary bodies. Enzyme activity correlated positively with age in all brain areas for MAO (with both benzylamine and tryptamine substrates) but no consistent of correlation was found for COMT and TH. Mean MAO was significantly higher in women than men. There is increased brain MAO activity during late childhood and adolescence. These data are consistent with previous evidence suggesting that age and sex are important determinants of amine metabolism in the human central nervous system.
pattern
activity
(Arch Gen Psychiatry 34:89-92, 1977)
is widespread interest in biogenic amine metabo¬ lism in the central nervous system (CNS) because of the established physiologic importance of amine neurotransmitters. Of particular interest have been studies of human brain in suicide victims, for such studies have been able to explore the biogenic amine hypothesis of affective illness'" directly by determining brain amine levels,1" and brain monoamine oxidase (MAO).''"1 Other brain studies have dealt with MAO and monoamines to determine their interrelationships in aging""" and with various neurotransmitters and enzymes in brains from schizophrenic patients.14""! Fluctuations in brain monoamine metabolism
There '
Accepted
for publication Sept 13, 1976. From the Departments of Medicine, Psychiatry, Pathology, and Epidemiology and Community Medicine, University of Vermont College of Medicine, Burlington, Vt (Drs Robinson, Nies, Harris, Kaye, and Ms Bartlett); Department of Psychiatry, McGill University, Montreal (Dr Sourkes); and the Department of Pharmacology, Roche Institute of Molecular Biology, Nutley, NJ (Dr Spector). Dr Nies is now with the Department of Psychiatry, Dartmouth Medical School, Hanover, NH. Reprint requests to Given Medical Bldg, University of Vermont College of Medicine, Burlington, VT 05401 (Dr Robinson).
Lawrence S.
Harris, MD;
associated with the oestrous cycle and hormone adminis¬ tration have also been reported in animal studies.'7"' More recently, Gruen et al,-'" have described altered aminemediated neuroendocrine function in depressed patients. These various studies provide additional evidence for biological theories of the pathogenesis of many neuro¬ psychiatrie disorders. The present study pursues these important topics through investigation of 39 human brains obtained at autopsy. It was undertaken in order to examine further the effects of age and sex on CNS amine metabolism, to provide normative data for human brain, and to explore the possible link between altered amine neurotransmitters and neuropsychiatrie disorders. The causes of death in¬ cluded a spectrum of medical, neurologic, and psychiatric disorders as well as several sudden accidental deaths. Data reported here are consistent with preexisting evidence that biologic factors such as aging play a part in modifying brain amine metabolism. METHODS Brains were obtained for dissection at the time of autopsy. Patients ranged in age from 4 to 83 years and included 14 women, 19 men, and six children. Brains were obtained from both the State Medical Examiner and the Medical Center Hospital of Vermont, and causes of death included accidental sudden death (n 8), homicide (n 1), suicide (n 2), and various medical conditions (n 17). In addition, there were five neuropsychiatrie patients and six minors who died from medical causes. Time from death to postmortem ranged from 2 to 30 hours and averaged 16 hours. Nine separate brain regions were dissected within minutes after the dura mater was opened. Dissections were carried out by two neuropathologists (L.S.H and I.K.) using standard anatomical landmarks to obtain uniform sections. The nine regions examined were the following: globus pallidus, thalamus, hypothalamus, hippocampus, substantia nigra, floor of the fourth ventricle (retic¬ ular formation, reticular activating system [RAS]), orbital cortex, caudate nucleus, and mammillary bodies. Bilateral sections were obtained and stored separately at —20 C in airtight containers flushed with 1009? nitrogen before sealing. Specimens from one side of the brain were randomly selected for monoamine assay and =
=
=
=
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the contralateral sections for enzyme assays, including mono¬ amine oxidase (MAO), tyrosine hydroxylase (TH), and catechol-Omethyltransferase (COMT). Evidence from these laboratories and other studies" have shown that brain levels of norepinephrine (NE), dopamine (DA), and MAO activity are stable over a storage period of several weeks when tissues are collected and stored in this fashion. Similar evidence for stability of TH and COMT with storage at low temperatures is less well established; recent studies of brain TH activity in animals maintained at room temperature for varying periods after death suggests that there are significant changes in TH with time."22
Table
1.—Enzyme
Activities in Nine Areas of Human Brain*
'214'""
Assay
of
Enzyme
activities were assayed in crude whole tissue homogenates. The MAO was determined with benzylamine tagged with carbon 14 and tryptamine tagged with carbon 14 as substrates by the method of Robinson et al.-' The TH was assayed by the method of Nagatsu et al 24 and COMT by the method of Creveling and Daly.2' Protein was determined by the procedure of Lowry et al.-'" Enzyme activities were expressed as nanomoles per milligram of protein per hour.
Substrate
pallldus Thalamus
Hypothalamus Hippocampus
51 68 91 50
Substrate
±3 ±7 ±6 ±3
32
4
1.1 ±.1
44± 4 37+4
1.6±.2 0.9+ .2
nigra
65 ±4
RAS Cortex Caudate
57 ±3 49 + 3
19 ±1 17 ±1
27 28
0.9
15
34 ± 4 40± 4
67±5
+
Analysis
All demographic and laboratory data were recorded for each patient in machine-readable form and stored for analysis by computer. Standard univariate techniques, such as the Student
i-test were used to test for difference in means and the Wilcoxon test for difference in medians. The nonparametric test of correla¬ tion (Kendall's tau)2* and the F-test of analysis of covariance2" were used to examine for age and sex-related differences in MAO activity in the adult sample. Exclusion of the juvenile group permitted assumption of linearity of the age-MAO relationship in the remaining sample for the purposes of covariance analysis. The substrate, benzylamine, was selected because of the sub¬ stantial previous experience with benzylamine in human platelet and brain MAO studies. Tryptamine was selected because of its forms of high activities as substrate for the MAO A and the brain enzyme.
RESULTS
The activities of the enzymes MAO, COMT, and TH in the nine brain areas are shown in Table 1. It is evident that the specific activity of MAO is greatest in the hypothal¬ amus and mammillary bodies for both substrates, benzyl¬ amine, and tryptamine, and lowest in cortex, globus pallidus, and hippocampus. Highest specific activity for COMT was in hypothalamus. The TH activity was greatest in the mammillary bodies and hypothalamus.
Enzyme
Activities and
+
41
17±2
Mammillary bodies
'Enzyme
85 ±5
activities (mean ±
1
26
±
2
Age
Table 2 shows correlations (Kendall's tau) of COMT, TH, and MAO, respectively, with age for each of eight brain areas. The MAO correlation computations excluded the juvenile group because there is an elevation of plasma, platelet, and brain MAO activity in individuals under 20 years of age compared to young adults. A typical example of the age relationship is shown for two areas, globus
5 4
± ±
1.5: ±
.1
1.0 ±.2 0.9±.1
32 ±12
SEM) expressed
Table 2.—Correlations of Brain
Data
TH
COMT
14±1 20 ±2 29±2 16 ±1
of Monoamines
The NE and DA were determined in seven regions of brain, but for the smaller brain areas (hypothalamus, substantia nigra), only one monoamine determination was carried out in an individual brain. Catecholamines were determined by a minor modification of the method of Laverty and Taylor.27
Correlations of
Tryptamine
Benzylamine Area Globus
Substantia
Activities
Enzyme
Assay
MAO
as
nmole/mg/hr.
Enzymes
vs
Age
Correlation Coefficient
(Kendall's T) MAO (n 33) ,-«-, =
Benzylamine
COMT
Tryptamine (n
=
TH
(n)
32)
Globus
pallidus
+
+.28Í
-.05
Thalamus
+
+.17
+.24$
-.16 +.03
+.15
—.21J
+.09(14)
-.13
+.22(7) +.10(15) -.03(17) -.04(18)
Hypothalamus Hippocampus
.37s 20i + .26Í +.34+
+.02(16) +.14(18)
-.11(9)
Substantia
nigra
+
.32+
+
+.11
RAS Cortex Caudate
+.27+ +.21 i
.25+.
+.12 +.09 +.08
-.13 -.12 -.10
*P £ .001. +P < .01. IP S .05.
pallidus and hypothalamus, (Figure).
with
tryptamine
as
substrate
It can be seen that for MAO the correlation coefficient is
positive for all areas with both substrates (Table 2). With benzylamine as substrate, Kendall's tau is significantly positive for seven out of eight areas. With tryptamine as substrate, the positive correlation is statistically signifi¬ cant for only three of the eight individual areas. To get a measure of overall correlation of MAO activity with age, the multiple correlation coefficient2" was computed for age with MAO levels in the eight areas. This correlation was significant with both substrates, ie, for benzylamine .64 (P .67 (P .001) and tryptamine r r .001). =
=
=
=
For COMT, the coefficients of correlation for seven of eight areas were negative, but only in the case of the hippocampus does this achieve statistical significance. This contrasts with the positive correlation of MAO with age.
Relationship
of Sex and MAO
Activity
The MAO activity was adjusted for age before analysis for possible sex differences. This was necessary because of the positive correlation between age and MAO activity and because in the adult sample the women were older than the
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60 Table
of MAO Activities of Men Women in Nine Brain Areas
3.—Comparison
Hypothalamus
vs
Mean MAO Activities*
Tryptamine, nmoles/mg/hr
Benzylamine, nmoles/mg/hr
40
Men
Area_(n
=
Women
19) (n
=
14)
Men
P+
(n
=
Women
19) (n
=
14) P+
Globus
20
pallidus
47.4
54.2
Thalamus
50.5 80.7 42.9
84.7 101.1 54.2
60.2
Hypothalamus Hippocampus
NS .01
13.1 17.1
15.3
NS
24.4
.07
.03 .12
27 9
33.7
14.2
19.0
NS NS
66.4
NS
19.4
21.1
NS
53.1
62.5
NS
16.8
18.8
NS
41.0
53.6
57.3
76.9
.09 .07
13.5 12.9
18.9 21.6
.06 .10
67.4
94.9
.02
22.6
29.6
NS
Substantia
nigra Floor fourth ventricle
J_ 20
J
40
60
70
AGE (decade) Mean MAO activities ( and globus pallidus with
SEM) by age tryptamine as
hypothalamus
(the mean age for women was 62.6, as opposed to 50.3 for the men). The age adjustment was made by means of men
linear regression of MAO activity on age decade for each brain area separately. Table 3 shows mean MAO activities after adjustment for age for men and women over 20 years of age for each of nine brain areas. Women have higher mean activities than men for each area and with both substrates, a pattern more pronounced with benzylamine than tryptamine. Because of significant interarea correla¬ tions and variability among persons, analysis of variance was used to test for overall sex difference in age-adjusted MAO, taking into account area and person effects. This analysis showed a significant sex difference in brain MAO .02 for benzylamine and .07 for tryp¬ activity at tamine. =
Correlation of Brain Amines With
Age of hypothalamus and
As shown in Table 4, NE content hippocampus has a significant negative correlation with age and tends to negative in all areas except substantia nigra. There is no overall pattern for DA. There are slight negative correlations between DA and age in the thalamus -.47, < .1), -.25, < .1) and hypothalamus ( ( and positive, though nonsignificant, correlations between DA and age in several areas. =
=
Correlations of Monoamines With
Enzyme Activities
None of the correlations of NE or DA levels with COMT TH was significant. However, there are strong negative correlations of MAO with DA in hypothalamus ( —.87), thalamus ( -.27) and MAO with -.42) and RAS ( NE in hippocampus ( -.28) (Table 4). or
=
=
=
(orbital) Caudate
decade in substrate
=
(RAS) Cortex
=
COMMENT
There is a growing interest in brain catecholamine metabolism in man because of the implied role of monoamines in neuropsychiatrie disorders, especially such agerelated conditions as depressive illness and parkinsonism.
Mammillary bodies!
•Mean MAO activities adjusted individually by brain area for age. +P probability that the difference in age-adjusted means for men and women for each brain area is due to chance as measured by the F-test from analysis of covariance. Because of significant ¡nterarea correlations of MAO, an overall sex difference in MAO was tested adjusting for age, area, and individual within sex, using analysis of variance. This analysis showed .02 for benzyl¬ a significant sex difference in brain MAO activity at amine and .07 for tryptamine as substrates. 10 each for men and women. iSample size: =
=
=
=
Table 4.—Correlations (Kendall's ) of Brain Amines With Age and With MAO Activity Amines Area Globus
vs
Age
Amines
vs
MAO
NE
DA
NE
DA
(n)
(n)
(n)
(n)
+.07(14) -.25(14)* -.47(6)* -.18(18)
+.12(16) +.15(19) -.20(10) -.28(19)+
+.14(14) -.42(14)+ -.87(6) -.24(18)
+.18(10) +.02(19) +.18(19)
+.03(9) -.19(19) -.10(19)
+.36(10) -.27(19)+ +.05(19)
-.02(16) -.09(19) Hypothalamus -.51 (10)+ Hippocampus -.29(19): pallidus
Thalamus
Substantia
nigra RAS Caudate
*P
