Estradiol treatment decreases type A and increases type B monoamine oxidase in specific brain stem areas and cerebellum of ovariectomized rats

Diurnal variations in activities of both type A and type B monoamine oxidase (MAO) in specific areas of the brain stem were investigated in male rats maintained on a 12 h light-12 h dark schedule (06.00 to 18.00 h light). A significant diurnal variation in the activity of both type A and type B MAO was observed in the areas A₁, A₂ and in the locus coeruleus, but not in the cerebellar cortex. For both type A and type B MAO lowest activities were found during the morning, while highest activities occurred in the late afternoon and the beginning of the night. These results may reflect a role of MAO in the circadian variation of the concentrations of catecholamines in the brain stem.     

Correlation of platelet MAO activity with introversion: A study on a German rural population

Platelet monoamine oxidase (MAO) activity and personality characteristics were correlated in a sample of 52 men (37 ± SD 13 years) and 54 women (37 ± SD 15 years) from a rural community. Personality characteristics were measured by using the Freiburger Persönlichkeitsinventar (FPI-A). In the males, weak but significant linear correlations (Pearson product-moment and Spearman rank correlations) were found between platelet MAO activity (p-tyramine and benzylamine as substrates) and the extraversion/introversion dimension. In the females, however, there were no consistent significant correlations between MAO activity and FPI test scores. Comparing the top and bottom 25% of the platelet MAO distribution resulted in a significant difference for the second order factor extraversion in the group of men but not in the group of women. The significant correlation between MAO and introversion could not be attributed to cigarette smoking, food consumption, alcohol, or drugs. In accord with previous biochemical-behavior research, it is suggested that reduced platelet MAO activity may, to some extent, reflect an impulsive personality type.     

Serotonergic mechanism underlying tranylcypromine enhancement of nicotine self-administration

Although nicotine is generally considered to be the main psychoactive component of tobacco, growing evidence highlights the importance of nonnicotine compounds in smoking reinforcement. Monoamine oxidase (MAO) inhibition is a major consequence of smoking and MAO inhibitors, such as tranylcypromine, increase nicotine reinforcement. Tranylcypromine has multiple pharmacological effects, increasing monoamine release for a few hours immediately after its administration and blocking MAO activity for several days. To assess the relative role of these two actions, adult male rats were tested in consecutive daily 3‐h sessions for self‐administration of nicotine (3 μg kg^?1 inj^?1, i.v.) either 20 or 1 h following administration of tranylcypromine (3 mg kg^?1). Both paradigms were shown to produce highly significant inhibition of MAO activity. However, whereas animals readily acquired self‐administration when pretreated with tranylcypromine 1 h prior to testing, they did not with the longer pretreatment interval. Such animals did immediately acquire nicotine self‐administration when the tranylcypromine pretreatment interval was switched to 1 h prior to testing on Day 4, indicating that an acute effect of the MAO inhibitor was responsible for enhanced nicotine reinforcement. Several lines of evidence implicate serotonin (5‐HT) as the mediator of this enhancement: (1) Tranyclypromine‐enhanced nicotine reinforcement was blocked by the 5‐HT₂ receptor antagonists, ritanserin and ketanserin; (2) parachloroamphetamine (PCA), a 5‐HT releaser, also enhanced nicotine self‐administration in animals in which MAO activity was inhibited; (3) pretreatment with tranylcypromine increased PCA‐induced 5‐HT overflow in the nucleus accumbens. These findings suggest that MAO inhibition enhances serotonergic transmission, which serves a critical role in the reinforcing effects of nicotine. Synapse, 2011. © 2010 Wiley‐Liss, Inc.     

Platelet monoamine oxidase activity in obsessive-compulsive disorder

Response to SSRIs suggests the implication of the serotonergic system in obsessive-compulsive disorder (OCD). However, biological studies on serotonergic function in OCD have yielded contradictory results. Platelet monoamine oxidase (MAO) activity has been proposed as an index of cerebral serotonin activity. The aim of this study was to examine platelet MAO activity in 29 OCD patients and 29 healthy controls matched by age, sex and tobacco use. We also explored the relationship between platelet MAO activity and aggressive obsessions in OCD patients. There were no differences in platelet MAO activity between OCD patients and healthy controls. We found a significant correlation between platelet MAO activity and Y-BOCS scores in the group of patients with Y-BOCS scores >15. OCD patients with aggressive obsessions had significantly lower levels of platelet MAO activity than patients without aggressive obsessions. Our results suggest that platelet MAO activity may be a marker of OCD severity, and that low platelet MAO activity may be associated with aggressive obsessions in OCD patients.     

Platelet monoamine oxidase activity and schizophrenia —A myth that refuses to die?

Summary Platelet monoamine oxidase (MAO) activity was determined using kynuramine as a substrate in a group of schizophrenic patients (n =107), a group of healthy individuals (n =100), and a group of psychiatric patients who were neither schizophrenics nor alcoholics (n =110). No significant difference emerged between the schizophrenics and the other two groups, while a significant reduction in platelet MAO activity in a group of alcoholics (n = 60) was confirmed. Breaking down the schizophrenic group according to course of illness, phenomenology (paranoid-hallucinatory or not) and drug use did not lead to a significant deviation in platelet MAO activity in any of these subgroups. It can also be demonstrated from the literature that the results reached by most research teams question the usefulness of platelet MAO activity as a genetic marker for psychiatric illness.     

Commonly used L-amino acid decarboxylase inhibitors block monoamine oxidase activity in the rat

Summary. The effects of the peripheral aromatic amino acid decarboxylase (AADC) inhibitors, carbidopa and benserazide, and the central AADC inhibitor, 3-hydroxybenzylhydrazine (NSD-1015) on peripheral and brain monoamine oxidase (MAO) A and B activity were investigated in the rat. In vitro, carbidopa, benserazide and NSD-1015 all potently inhibited hepatic MAO A and B activity (IC₅₀ 10–50 μM). In ex vivo studies following systemic drug administration, NSD-1015 (100 mg/kg ip) produced 88% and 96% inhibition of hepatic and striatal MAO A and B activity respectively. Carbidopa (12.5 mg/kg i.p.) and benserazide (50 mg/kg i.p.) had no effect on striatal MAO A activity or hepatic MAO B activity. However, they inhibited striatal MAO B activity by 45 ± 10% and 36 ± 10% respectively. In conclusion, carbidopa and benserazide may not only protect L-DOPA from peripheral decarboxylation, but also increase striatal dopamine content through MAO inhibition. NSD-1015 should not be used to investigate the neuromodulatory role of L-DOPA as it potently inhibits rat striatal MAO. Received March 8, 2002; accepted July 15, 2002 Published online November 22, 2002 Authors' address: Prof. P. Jenner, Neurodegenerative Disease Research Centre, Guy's, King's and St Thomas' School of Biomedical Sciences, King's College, London SE1 1UL, United Kingdom, e-mail: div.pharm@kcl.ac.uk     

Measurement of Platelet Monoamine Oxidase Using Three Different Substrates in Patients with Alcoholism and Schizophrenia

Abstract: The platelet monoamine oxidase (MAO) activities in alcoholism and schizophrenia were investigated by means of the simultaneous determination, using β-phenyl-ethylamine, tryptamine and serotonin as substrates. No significant difference was found between the MAO levels in the alcoholic and schizophrenic groups, when tryptamine was used as a substrate, but both groups showed lower values than the controls. On the other hand, β-phenylethylamine, a specific substrate for MAO B used as a substrate, showed no significant difference between the alcoholic and control groups in the activities. These two groups showed higher values in MAO activity than the schizophrenic group, whereas when MAO activity was estimated using serotonin, platelet enzyme was found to be inhibited significantly in alcoholism, and the level of activities in the schizophrenics was similar to that of the controls. Moreover, the β-phenylethylamine inhibition curve obtained serotonin as the substrate in the pooled platelets of 50 normal human subjects, and the MAO activity could not be inhibited by higher concentrations than the Km value of serotonin. These findings suggested that there might be two interacting catabolic sites having different substrate affinities in blood platelet MAO. Thus, it could be speculated that serotonergic catabolic sites of MAO in the platelets are disturbed in the alcoholics, while β-phenylethylaminergic catabolic sites of platelet MAO are inherently vulnerable in schizophrenia.     

Monoamine Oxidase Activity in Blood Platelets From Manic and Depressed Patients

To evaluate the possible abnormality in MAO activity in affective disorders, blood platelet samples were obtained from 80 patients with mania and depression. Blood-platelet MAO activity was measured by a newly developed assay procedures using serotonin as substrate. MAO activities in 121 normal adult subjects were in a range of 2.49-12.05 nM/mg protein/hour, with the mean values of 4.91 ±1.72 (±S.D.) for men and 6.88±1.99 for women. (p<0.001) MAO activities in the manic and depressed patients were in a range of 0.65–13.40 nM/mg protein/hour, and both manic and depressed patients showed the mean value very similar to that in the normal subjects. Bipolar depressed patients did not exhibited lower MAO activity in the blood platelets than other clinical subtypes of depressive illness, including unipolar, involutional, neurotic and chronic characterological, and first-episode depressions. No significant differences were established between these five subcategories of depression, while significant higher values were evident in female than male patients (p<0.001). No correlation was found between the MAO activity and serotonin levels in the blood platelets either in the normal subjects or in the depressed patients.     

Monoamine oxidase‐A and B activities in the cerebellum and frontal cortex of children and young adults with autism

Monoamine oxidases (MAOs) catalyze the metabolism of monoamine neurotransmitters, such as serotonin, dopamine, and norepinephrine, and are key regulators for brain function. In this study, we analyzed the activities of MAO‐A and MAO‐B in the cerebellum and frontal cortex from subjects with autism and age‐matched control subjects. In the cerebellum, MAO‐A activity in subjects with autism (aged 4–38 years) was significantly lower by 20.6% than in controls. When the subjects were divided into children (aged 4–12 years) and young adults (aged 13–38 years) subgroups, a significant decrease by 27.8% in the MAO‐A activity was observed only in children with autism compared with controls. When the 95% confidence interval of the control group was taken as a reference range, reduced activity of MAO‐A was observed in 70% of children with autism. In the frontal cortex, MAO‐A activity in children with autism was also lower by 30% than in the control group, and impaired activity of MAO‐A was observed in 55.6% of children with autism, although the difference between the autism and control groups was not significant when all subjects were considered. On the contrary, there was no significant difference in MAO‐B activity in both the cerebellum and frontal cortex between children with autism and the control group as well as in adults. These results suggest impaired MAO‐A activity in the brain of subjects with autism, especially in children with autism. Decreased activity of MAOs may lead to increased levels of monoaminergic neurotransmitters, such as serotonin, which have been suggested to have a critical role in autism. © 2017 Wiley Periodicals, Inc.     

Relationship of auditory hallucinations and paranoia to platelet MAO activity in schizophrenics: sex and race interactions

Platelet monoamine oxidase (MAO) activity was determined in 37 female and 64 male patients with Research Diagnostic Criteria diagnoses of paranoid or undifferentiated schizophrenia, or schizoaffective disorder, mainly schizophrenic, and for 71 female and 65 male normal controls (NCs). Female NCs had significantly higher adjusted mean platelet MAO activity than male NCs and female, paranoid, nonhallucinating schizophrenics. Male NCs had significantly higher adjusted mean platelet MAO activity than male, paranoid, hallucinating schizophrenics. Examination of main and interactive effects of diagnostic subtype, presence/absence of auditory hallucinations, gender, and race within the group of schizophrenic patients revealed no statistically significant main effect but, rather, significant interactive effects of auditory hallucinations with gender, with diagnostic group and gender, and with diagnostic group and race in the prediction of platelet MAO activity. The interaction of diagnostic subtype with race and gender in the prediction of platelet MAO activity was also statistically significant. In general, significantly decreased platelet MAO activity was associated with both paranoid subtype and presence of auditory hallucinations in male and in black schizophrenics; and with paranoid subtype alone in white male schizophrenics. These interactive relationships with platelet MAO activity in schizophrenics may account for discrepancies in previous reports of the activity of this enzyme in schizophrenics, and are consistent with reduced platelet MAO activity in subgroups of schizophrenics.     

Type A personalities tend to have low platelet monoamine oxidase activity

This study investigated whether there are relations between type A behaviours and the activity of monoamine oxidase (MAO) in blood platelets. Forty male nonsmokers completed the Jenkins Activity Survey (JAS) and had a blood sample drawn while at work. The JAS was scored in the traditional manner, yielding scores for ambitiousness (factor A), impatience (factor S), competitiveness (factor H) and job involvement (factor J). High scores on JAS scales were associated with low MAO activity in blood platelets; the correlation between platelet MAO activity and job involvement was significant. The findings agree with previous reports in showing relationships between MAO activity and certain personality traits and support the notion that low activity of MAO may contribute to sympathetic hyperreactivity in type A individuals.     

Platelet monoamine oxidase activity and evoked response as predictors of anxiety and depression derived from the content analysis of speech

Platelet MAO activity has been reported by several investigators to differentiate schizophrenia, schizophrenia related depressive disorders, alcoholism, unipolar and bipolar depression from normal controls. Evoked potentials likewise have differentiated schizophrenic and affective patients. However, the precise relationship between MAO activity, evoked potentials (EP), and psychiatric illness has not been clarified. A possible association between psychopathology and high MAO activity/EP reducing and low MAO activity/EP augmenting has been reported. Such a bidirectionality further confounds results. This study was undertaken to determine the association of psychopathological dimensions found in a group of subjects whose platelet MAO activity and evoked responses were obtained two years earlier. Utilizing the Gottschalk-Gleser verbal behavior scales of Anxiety, Depression, Social Alienation-Personal Disorganization and Cognitive Impairment a significant correlation was revealed between low platelet MAO activity and high Total Anxiety scale and Shame Anxiety subscale scores. Additionally, a significant correlation was demonstrated between reducing evoked potentials and elevated Death Anxiety, Somatic Concerns, and Total Death and Mutilation Depression subscales scores, combined and separately. Furthermore, a significant positive correlation was found between augmenting evoked potentials and Overt Hostility Outward scores. No significant correlations were demonstrated between platelet MAO activity or evoked potentials and Social Alienation-Personal Disorganization or Cognitive Impairment scores. These findings lend support to the position that biological markers may predict predispositions to anxiety and depression.     

Criminality and platelet monoamine oxidase activity in former juvenile delinquents as adults

Platelet monoamine oxidase (MAO) activity was estimated in 70 former delinquent boys and 40 controls now aged 38–46 years. Platelet MAO activity was compared with their early criminal behaviour (before the age of 15) and their late registered criminality from the age of 15). Mean platelet MAO activity in subjects with both early and late criminality was significantly lower than that in former delinquents without late criminality. There was no significant difference in mean platelet MAO activity between controls and delinquents with early but no late criminality. When delinquents with early criminality were divided into a low and a high MAO group, the relative risk to be registered for late criminality was about 3.1 times higher for the subjects in the low MAO group. Thus, individuals with low platelet MAO activity run an increased risk of continued criminal behaviour.     

Early morning awakening in unipolar depressives with higher levels of platelet MAO activity

Platelet monoamine oxidase (MAO) activity was analyzed in 51 patients with Major Depressive Disorder. The enzyme activity was correlated univariately and multivariately using split-half techniques with affective subdiagnosis, sex, body measures, and a great many depressive symptoms. The results indicate that unipolarly depressed patients with higher levels of platelet MAO activity woke up earlier in the morning than they had before becoming depressed. Waking up early appeared to be one least common denominator behind higher MAO activities and a unipolar subdiagnosis. Earlier reports on univariately significant differences in MAO activity between affective subdiagnoses or between the sexes were not replicated. Positive trend correlations were found between homovanillic acid and 5-hydroxyindoleacetic acid in cerebrospinal fluid and platelet MAO activity. Urinary free cortisol correlated significantly with platelet MAO activity, but only in unipolars.     

Psychopathy,platelet MAO activity and criminality among former juvenile delinquents

Psychopathy-related personality traits as well as platelet monoamine oxidase (MAO) activity and criminality from the age of 15 years were studied in a group of 68 male former juvenile delinquents and 32 control subjects. The former juvenile delinquents registered for crime as adults were found to have higher Psychopathy Check List (PCL) scores and lower platelet MA0 activity than either juvenile delinquents who were not registered criminals from the age of 15 years or non-criminal controls. Although PCL scores and platelet MAO activity were unrelated, a configural frequency analysis showed a significant interaction. Individuals with PCL scores, low platelet MAO activity and persistent criminal behaviour constituted a significant ‘type’. Among the 27 former juvenile delinquents who developed persistent criminality, 21 subjects (78%) had PCL scores greater than 0 and low platelet MAO activity, while none of these persistent criminals were characterized by a combination of zero PCL score and high platelet MAO activity.     

Personality correlates of platelet monoamine oxidase (MAO) activity in female and male subjects

Associations between platelet monoamine oxidase (MAO) activity and scale scores from the Eysenck Personality Questionnaire, the Impulsiveness-Venturesomeness-Empathy inventory and the Karolinska Scales of Personality were studied in 32 female and 29 male students (age range 17-19 years). There were significant negative correlations between MAO activity and extraversion-related scales for male subjects; in the female group the correlations were also negative but nonsignificant. When comparing subgroups with low, intermediate, and high platelet MAO activity subjects, consistent trends were observed in the direction of higher scores in the impulsivity scales, the sensation seeking-related Monotony avoidance scale, and the Indirect Aggression scale for both female and male low MAO activity groups.     

Evidence that brain MAO A activity does not correspond to MAO A genotype in healthy male subjects.

BACKGROUND: A functional polymorphism in the promoter region of the monoamine oxidase A (MAO A) gene has two common alleles that are referred to as the high and low MAO A genotypes. We report the first in vivo human study to determine whether there is an association between MAO A genotype and brain MAO A activity in healthy male subjects. METHODS: Brain MAO A activity was measured with positron emission tomography and [(11)C]clorgyline in 38 healthy adult male nonsmokers genotyped for MAO A polymorphism. RESULTS: There was no significant difference in brain MAO A activity between the high (n = 26) and low (n = 12) MAO A genotypes. CONCLUSIONS: The lack of an association between the high and low MAO A genotype and brain MAO A activity suggests that this polymorphism by itself does not contribute to differences in brain MAO A activity in healthy adult male subjects.     

Reduction of blood platelet monoamine oxidase activity in schizophrenic patients on phenothiazines.

A newly developed assay for monoamine oxidase (MAO) activity in blood platelets (serotonin used as substrate) was applied for the measurement of the enzyme activity in 76 schizophrenic patients. No significant reduction was found in the blood platelet MAO activity in a group of 33 untreated schizophrenic patients, as compared to that in the normal controls. Male patients revealed to have lower enzyme activity than females in the schizophrenic group, as we described previously in the normal subjects. Treatment with phenothiazines caused significant reduction of blood platelet MAO activity, while platelet serotonin content and platelet count appeared to be not affected by the drug treatment. The authors suggest that blood platelet MAO activity may be related to hormonal factors but not to psychiatric diagnosis of schizophrenia or constitution liable to schizophrenic illnesses.     

Platelet MAO activity during treatment with pegylated interferon-alfa in melanoma patients

Depression and cognitive disturbance are well-known neuropsychiatric side effects of therapy with interferon-alfa (IFN-alfa). Aggression and irritability are also reported as side effects. Probably, central nervous system (CNS) serotonergic dysfunction is one of the underlying pathophysiological mechanisms of IFN-alfa-induced neuropsychiatric toxicity. Platelet activity of monoamine oxidase-B (MAO; EC1.4.3.4) is a possible indicator of central serotonergic function. Moreover, low platelet MAO activity is linked to impulsiveness, addiction and personality disorder. In this exploratory study in 17 high-risk melanoma patients, platelet counts, whole blood MAO, and platelet MAO activity were measured before and during therapy with IFN-alfa. Patients were randomized to treatment either with pegylated IFN-alfa (PEG-IFN-alfa) once a week at a dose of 6 microg/kg/week subcuteanously (s.c.) during 8 weeks, followed by a maintenance treatment of 3 microg/kg/week s.c. for a total of 5 years, or to observation only. Blood samples were taken at baseline, 4 and 8 weeks and 3 months. During treatment with IFN-alfa, platelet counts decreased at 4 and 8 weeks and 3 months, while platelet MAO activity increased, both compared to baseline and compared to non-treated controls. Compared to non-treated controls, platelet MAO activity increased with 86.4% (95 CI: 52.9-127.2). No significant changes in platelet MAO activity were observed in the control group. This indicates that platelet MAO activity is influenced by IFN-alfa. Since platelet MAO activity is a model for CNS MAO-B activity, it may be speculated that CNS MAO-B activity will also be increased. This could influence serotonin (5-HT) metabolism and thereby contribute to the development of psychiatric disturbance. However, a preferential inhibition of platelet production cannot be ruled out. Hypothetically, the antiproliferative effects of IFN-alfa could interfere more strongly with the synthesis of platelets than with the synthesis of mitochondria. In that case, increased platelet MAO activity reflects an increased number of mitochondria per platelet.     

Psychiatric morbidity, platelet monoamine oxidase and tribulin output in headache

A significantly higher proportion of patients with headache showed scores in the psychopathological range of the General Health Questionnaire (GHQ) compared with controls, with ratings particularly high on the anxiety and depression subscales. Across the whole group, there was a significant negative correlation between platelet monoamine oxidase (MAO) activity and GHQ score overall, and with the anxiety and depression subscales. There was a significant positive correlation between platelet MAO activity and urinary output of the endogenous MAO inhibitor, tribulin. Within the migraine group, there was a significant negative correlation between tribulin output and GHQ score. These findings suggest that the biochemical nature of the anxiety associated with migraine may differ from that in other conditions such as generalized anxiety disorder where high platelet MAO activity and high tribulin output have been reported.