Platelet MAO in subtypes of alcoholism

A number of investigators have observed low platelet monoamine oxidase (MAO) activity in alcoholism. There is also preliminary evidence suggesting that low enzyme activity is principally associated with one of two putative subtypes of alcohol dependence, i.e., type II (male limited). The results of this study are consistent with two previous reports of reduced platelet MAO activity in type II male alcoholics as compared with type I male alcoholics and normal, healthy male controls. Type I (milieu-limited) alcoholics showed a smaller reduction in enzyme activity. The observed differences do not appear to be related to concurrent use of other psychoactive substances, characteristic differences in age between type I alcoholics and type II alcoholics, antisocial personality disorder, or variation in platelet size. Low platelet MAO activity in alcoholics is possibly related to both state and trait factors and may be a useful biochemical measure to assist with subtyping.     

Familial biochemical and clinical correlates of alcoholics with low platelet monoamine oxidase activity.

This study substantiates previous reports that low platelet MAO activity is associated with alcoholism. The results also indicate that low platelet MAO activity in alcoholic probands is associated with a higher prevalence of psychiatric hospitalization in first-degree family members as well as alcoholism and suicide attempts among alcoholics. Psychiatrically ill family members of the alcoholic probands with low platelet MAO activity also demonstrate low enzyme activity whereas the well family members have normal enzyme activity.     

Platelet MAO activity as a biological marker in subgroups of alcoholism

In the Stockholm Adoption Study, two types of alcoholism, "Type I" and "Type II", have been identified on the basis of genetic predisposition. In the present study, this classification has been applied to a clinical sample. The two types of alcoholism were clinically clearly identifiable. Type I alcoholism was characterized by late onset and few social complications. Type II alcoholism was characterized by early onset, use and abuse not only of alcohol, but also of glue, cannabis, amphetamine and opioids, together with several social complications. The subjects with Type II alcoholism had also more alcoholism and depression among their first-degree relatives than the subjects with Type I alcoholism. Furthermore, the two types of alcoholism were separable by means of the biological marker - platelet MAO activity. While platelet MAO activity was normal in Type I alcoholics, as compared with healthy controls, it was clearly low in the Type II alcoholics. This subclassification of alcoholism seems to be of value in future studies concerning the etiology, epidemiology and treatment of alcoholism.     

Platelet monoamine oxidase in alcoholism

We studied platelet monamine oxidase (MAO) activity using 14C-tyramine as substrate in hospitalized alcoholic patients in the early phases of abstinence and in nonhospitalized normal control volunteers. Platelet MAO was determined in 75 patients (67 men, 8 women) with alcoholism and 123 normal control volunteers (52 men, 71 women). The platelet MAO activity in alcoholic patients was significantly lower than in normal control volunteers. We also observed that the mean platelet MAO activity in male alcoholics was significantly lower than in normal males. The analysis of platelet MAO in alcoholics revealed a mixture of two normal distributions. Alcoholic patients falling into the low MAO component were younger in age, with a lower age of onset of alcoholism, and had higher frequencies of family history of alcoholism. They thus resembled type II alcoholics described by other investigators. Platelet MAO may thus serve as a useful biological marker for subtyping alcoholism and identifying high-risk groups at an early stage. The findings of this study are consistent with previous reports of low platelet MAO activity in alcoholic patients.     

Monoamine oxidase and catechol-o-methyltransferase activities in cultured fibroblasts and blood cells from children with autism and the Gilles de la Tourette syndrome

Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) activities were measured in cells from children with autism (n=5) and the Gilles de la Tourette syndrome (n=5). Monoamine oxidase activities in cultured skin fibroblasts (type A) and platelets (type B) from the same individual were not correlated. COMT activities in fibroblasts and red blood cells showed a negative but not significant correlation (r=-0.42). Fibroblast MAO and COMT activities from patients were similar to values from controls matched for age, race, and sex. Increasing clinical severity of illness in both disorders, however, correlated significantly with higher fibroblast MAO activity. Cultured fibroblasts provide a means of measuring enzyme activities independently of the individual's current physiological and psychological state.     

Measurement of platelet monoamine oxidase using three different substrates in patients with alcoholism and schizophrenia

The platelet monoamine oxidase (MAO) activities in alcoholism and schizophrenia were investigated by means of simultaneous determination, using beta-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, beta-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 beta-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 beta-phenylethylaminergic catabolic sites of platelet MAO are inherently vulnerable in schizophrenia.     

Monoamine oxidase-A polymorphisms might modify the association between the dopamine D2 receptor gene and alcohol dependence

OBJECTIVE: Low monoamine oxidase (MAO) activity and the neurotransmitter dopamine are 2 important factors in the development of alcohol dependence. MAO is an important enzyme associated with the metabolism of biogenic amines. Therefore, the present study investigates whether the association between the dopamine D2 receptor (DRD2) gene and alcoholism is affected by different polymorphisms of the MAO type A (MAOA) gene. METHODS: A total of 427 Han Chinese men in Taiwan (201 control subjects and 226 with alcoholism) were recruited for the study. Of the subjects with alcoholism, 108 had pure alcohol dependence (ALC) and 118 had both alcohol dependence and anxiety, depression or both (ANX/DEP ALC). All subjects were assessed with the Chinese Version of the Modified Schedule of Affective Disorders and Schizophrenia-Lifetime. Alcohol dependence, anxiety and major depressive disorders were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria. CONCLUSION: The genetic variant of the DRD2 gene was only associated with the ANX/DEP ALC phenotype, and the genetic variant of the MAOA gene was associated with pure ALC. Subjects carrying the MAOA 3-repeat allele and genotype A1/A1 of the DRD2 were 3.48 times (95% confidence interval = 1.47-8.25) more likely to be ANX/DEP ALC than the subjects carrying the MAOA 3-repeat allele and DRD2 A2/A2 genotype. The MAOA gene may modify the association between the DRD2 gene and ANX/DEP ALC phenotype.     

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 in Alcoholism

A newly developed assay for monoamine oxidase (MAO) activity in blood platelets was applied in 50 alcoholic patients. The assay is the direct measurement of serotonin oxidation by MAO employing a double microcolumn technique on Sephadex G-10 and Amberlite CG-50 for separating 5–HIAA formed, which is measured fluori-metrically. Rebound of MAO activity levels after withdrawal of alcohol was observed to be more pronounced in the patients with delirium tremens than those who exhibited no outstanding abstinent symptomatology. MAO activity levels measured in the 1st week of alcohol withdrawal were 3.49±1.15 (Mean±S.D.) nmol/mg protein/hour in the alcoholic patients with delirium tremens, a value significantly lower than that in the subjects without (p<0.01) and that in the male normal subjects (p<0.001). Four weeks after withdrawal of alcohol, the reduced MAO activity levels in the alcoholic population were restored to normal levels. These data demonstrate that physical dependency for alcohol occurred evidently in the alcoholic patients examined. Delirium tremens and other psychotic symptoms in alcoholism may be manifested as impaired serotonin metabolism in the brain, which may be due to MAO inhibition caused by excessive alcohol intake.     

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 concentration and molecular activity: I. New methods using an MAO B-specific monoclonal antibody in a radioimmunoassay

New methods for determination of specific concentration and molecular activity of monoamine oxidase (MAO) in platelets are described and evaluated in parallel with specific activity measures, performed in whole platelets and platelet extracts. Platelet MAO specific concentration is determined in platelet extracts by a radioimmunoassay, using a monoclonal antibody that recognizes human MAO B, the form that occurs in platelets, but not MAO A. All four platelet MAO measures are found to be reliable and stable, and thus are suitable for long-term comparisons of normal and clinical populations, such as those reported in Part II of this report. The new measures of enzyme concentration and molecular activity make available important information about the state of MAO B molecules in a given individual that reflects the genetic expression and control of the enzyme.     

Platelet monoamine oxidase, plasma dopamine beta-hydroxylase activity, dementia and family history of alcoholism in chronic alcoholics

The authors measured platelet monoamine oxidase (MAO) activity and plasma dopamine beta-hydroxylase activity in 36 male chronic alcoholics during a period of non-abstinence, and in 29 normal controls. The influence of family history, dementia, chronicity of drinking and liver injury on the enzyme activities was also examined by multiple regression analysis. Platelet MAO was significantly lower in the alcoholic group. Both enzyme activities were negatively related to the presence of dementia, while low MAO activity was associated with positive family history (parents, sibs) of alcoholism.     

Monoamine oxidase activity in blood platelets in alcoholism.

A newly developed assay form monoamine oxidase (MAO) activity in blood platelets was applied in 50 alcoholic patients. The assay is the direct measurement of serotonin oxidation by MAO employing a double microcolumn technique on Sephadex G-10 and Amberlite CG-50 for separating 5-HIAA formed, which is measured flourimetrically. Rebound of MAO activity levels after withdrawal of alcohol was observed to be more pronounced in the patients with delirium tremens than those who exhibited no outstanding abstinent symptomatolgy. MAO ACTIVITY LEVELS MEASURED IN THE 1ST WEEK OF ALCOHOL WITHDRAWAL WERE 3.49+/-1.15 (Mean+/-S.D.) nmol/mg protein/hour in the alcoholic patients with delirium tremens, a value significantly lower than that in the subjects without (p less than 0.001) and that in the male normal subjects (p less than 0.001). Four weeks after withdrawal of alcohol, the reduced MAO activity levels in the alcoholic population were restored to normal levels. These data demonstrate that physical dependency for alchol occurred evidently in the alcoholic patients examined. Delirium tremens and other psychotic symptoms in alcoholism may be manifested as impaired serotonin metabolism in the brain, which may be due to MAO inhibition caused by excessive alcohol intake.     

Platelet monoamine-oxidase activity in schizophrenia. Relation to genetic load of the illness and treatment with antipsychotic drugs

A significant decrease of mean platelet monoamine-oxidase (MAO) activity was observed in a sample of haloperidol-treated schizophrenic patients as compared with normal control subjects. The enzyme activity was not significantly reduced in drug-free schizophrenics. No significant difference was found between drug-free schizophrenics with and without a family history of the illness and between healthy relatives of schizophrenics and normal subjects without a family history of schizophrenia. MAO activity was significantly reduced after 14 and 21 days of treatment with haloperidol, in comparison with baseline values. It is suggested that neuroleptic intake may at least in part explain low MAO values repeatedly reported in schizophrenics.     

Platelet monoamine oxidase kinetics, alcoholism subtypes and cigarette smoking

In trying to dissociate the effect of alcohol and tobacco use on platelet monoamine oxidase-B (MAO-B) activity, we compared the enzyme kinetics in controls (n = 66) and alcohol-dependent patients (n = 81), subdivided according to the severity of both, alcohol and tobacco use. Platelet MAO-B kinetics was measured spectrophotofluorimetrically in chronic alcohol intoxication and after 3 weeks abstinence. In alcoholic patients, an increased Michaelis-Menten constant (16%, p < 0.01) was shown, notwithstanding smoking status. Maximal velocity did not differ between patients and controls when adjusted for smoking. In cigarette smokers, a highly significant dose-dependent reduction of platelet MAO velocity (40%, p < 0.001) was demonstrated, with a similar degree of reduction in patients and controls. Tobacco use itself had no influence on MAO affinity. No differences were shown between subtype 1 and 2 alcoholics, or between the day of admission and the 21st day of abstinence. In conclusion, it seems that both, alcohol and tobacco consumption, may contribute to the lowering of overall platelet MAO-B activity. The effect of alcohol is small, due to interference with substrate binding, and not alteration of catalytic activity. In contrast, the effect of cigarette smoking is pronounced and relates to the dose-dependent reduction of platelet MAO velocity, with no influence on its affinity.     

Reduced platelet MAO activity in healthy male students with blood group O

The association between the two genetic markers of affective disorders, ABO blood group system and platelet MAO (monoamine oxidase) activity was studied in 70 healthy young males. The platelet MAO activity of subjects with blood type O was significantly lower than that of subjects with blood type A and with blood types A + B AB + B together. This finding could constitute a "bridge" between the two genetic approaches to affective disorders.     

Platelet MAO deamination of serotonin in depressed patients. Changes after imipramine treatment and clinical correlations

Monoamine oxidase (MAO) in blood platelets has been used as a model to study MAO in the central nervous system, where disorders in serotonergic systems are thought to occur in depression. Inconsistent changes in platelet MAO of depressed patients have been reported when several substrates other than serotonin (5-HT) have been used. To correlate changes in platelet MAO activity with the enzyme activity in central serotonergic systems, the platelet MAO activity of depressed patients (first unmedicated and then after 3 weeks and 2 months of imipramine treatment) and normal controls was measured using 5-HT as substrate. The results showed that there is a steady, measurable platelet MAO activity with that substrate. This activity was significantly higher in unmedicated depressed patients than in controls, and it decreased progressively with imipramine treatment, reaching a normal level when the patients were clinically recovered from depression after 2 months of therapy.     

Platelet MAO activity in anorexia nervosa patients with and without a major depressive disorder

Platelet MAO activity was determined in 33 anorexia nervosa patients. A subgroup of 15 patients who met Research Diagnostic Criteria for a concomitant major depressive disorder were found to have, both initially and after 5 weeks of treatment, significantly lower mean platelet monoamine oxidase (MAO) activity than 28 matched normal control subjects. In contrast, mean platelet MAO activity in the patients who did not meet criteria for major depressive disorder was similar to values in control subjects. The authors found that significantly more depressed patients had low MAO activity compared with nondepressed patients and controls. Platelet MAO activity may be useful in discriminating among subtypes of anorexia nervosa patients.     

Platelet monoamine oxidase and plasma dopamine-beta-hydroxylase activities in patients with multiple sclerosis

Platelet monoamine oxidase (MAO) and plasma dopamine-beta-hydroxylase (DBH) activities were determined in a large group of multiple sclerose patients in relapse (49 patients) and in remission (28 patients), and compared with an age- and sex-matched control group (52 normal subjects). The activities of both enzymes did not differ from normal in both patient groups. Women had higher MAO activities both in normal and in patient groups. Multiple linear regression analysis revealed an association of low platelet MAO to the score in the mental subscale in the Kurtzke Disability Status Scale. Both male and female patients with mental symptomatology had significantly (p = 0.02) lower platelet MAO activities compared to the patients without. The possibility of a relationship between MAO activity and psychiatric vulnerability in MS is considered.     

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.