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.     

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.     

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.     

Platelet monoamine oxidase in chronic schizophrenic patients

The authors investigated platelet monoamine (MAO) activity in 40 chronic schizophrenic patients, 55 normal control subjects, and 16 hospitalized control subjects. The mean platelet MAO activity for the chronic schizophrenic patients was significantly lower than the mean in either control group. There were no significant differences between the mean platelet MAO activities in 21 chronic paranoid schizophrenic patients compared with 18 chronic undifferentiated schizophrenic patients.     

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.     

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.     

Platelet glutathione peroxidase and monoamine oxidase activity in schizophrenics with CT scan abnormalities: relation to psychosocial variables

We have previously reported that the activity in platelets of the important antioxidant enzyme glutathione peroxidase (GPx) is inversely correlated with computed tomographic (CT) measures of brain atrophy in a population of patients with chronic schizophrenia, suggesting that low GPx may be a vulnerability factor in those schizophrenic patients with structural brain abnormalities. The significance of this finding has now been explored in a larger clinical population by examining the relation of GPx and CT parameters to psychosocial variables and to the activity of platelet monoamine oxidase (MAO), which has also been reported to be altered in certain schizophrenic populations. In the present study, low platelet GPx and high brain atrophy were found to be associated with DSM-III diagnoses of nonparanoid schizophrenia, a high degree of chronicity, and a predominance of negative symptoms. Contrary to some literature reports, atrophy also correlated with age and length of illness among the schizophrenic patients, although the contribution of these factors was less than that of low GPx, which was itself not age dependent. The ventricle-brain ratio (VBR) and atrophy were highly correlated in a control group of affective disorder patients, but not in the schizophrenic group, where large VBRs were found predominantly in the DSM-III undifferentiated subgroup. The low-GPx/high-atrophy schizophrenic patients had normal platelet MAO levels, and MAO was significantly lower only in the paranoid subgroup, consistent with reported observations. There was no evidence for a neuroleptic-induced effect on either enzyme.     

Neuroleptic drug effect on platelet monoamine oxidase and plasma amine oxidase in schizophrenia

Activity levels of platelet monoamine oxidase (MAO) and plasma amine oxidase (PAO) were determined in eight chronic schizophrenic patients who had been treated with neuroleptic drugs for 3 months. The mean reduction in platelet MAO activity was 18.6%. The extent of decrease was statistically significant. The reduction in enzyme activity was unrelated to serum iron levels. PAO activity was unaltered. The implications for schizophrenia research are discussed.     

Influence of clozapine on platelet serotonin, monoamine oxidase and plasma serotonin levels

The purpose of this study was to investigate the influence of clozapine on plasma serotonin, platelet serotonin and monoamine oxidase (MAO) levels in schizophrenic patients and to compare their results with those of unmedicated healthy controls. Groups of 20 outpatients with schizophrenia and 20 healthy controls matched for age, sex and smoking status were recruited for the study. Psychopathology, neurocognitive functioning, plasma serotonin, platelet serotonin and MAO levels were assessed after 1-week drug free interval, and 8 weeks after initiation of clozapine treatment in an open design. The mean clozapine dose at week 8 was 382.5+/-96.4 (range: 250-600) mg/day. In the patient group, at baseline, plasma serotonin and platelet MAO levels were significantly lower, and platelet serotonin levels were significantly higher than in controls. After 8 weeks of clozapine treatment, plasma serotonin and platelet MAO levels increased significantly, while a significant decrease in platelet serotonin levels was detected compared with baseline values. Baseline platelet MAO levels explained 22% of the variance in Clinical Global Impression - Improvement (CGI-I) and improvement in attention, while baseline platelet serotonin predicted 23% of the variance in the improvement in positive symptoms during clozapine treatment. Our data indicate that clozapine may be reversing or compensating for a pre-existing alteration in serotonergic neurotransmission in schizophrenic patients. The prediction of response to clozapine through peripheral biochemical markers may have important clinical implications if repeated in larger samples.     

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.     

Effect of neuroleptic drugs on platelet monoamine oxidase in psychiatric patients

The authors determined the platelet MAO activity of 57 psychotic patients after a placebo period and after 3-65 days of neuroleptic treatment. Platelet MAO activity significantly decreased in both men and women after neuroleptic treatment. The platelet MAO activity of neuroleptic-treated schizophrenic women was significantly less than that of drug-free schizophrenic women, who did not differ from normal women. There were trends in the same direction for the schizophrenic men. Previous studies that reported lower platelet MAO activity in neuroleptic-treated schizophrenic patients than in normal controls may have been influenced by this neuroleptic effect.     

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.     

Biological studies of DSM-III psychotic disorders. I. Platelet measures and apomorphine-induced growth hormone response

The relationship between DSM-III schizophrenia, major affective disorders, and the psychotic disorders not elsewhere classified (PDNEC) can be explored through studies which attempt to determine whether these disorders can be differentiated from one another and normal controls by biological measures. Preliminary results of an ongoing project which utilizes measures of blood platelet monoamine oxidase (MAO), serotonin (5-HT) uptake, and 5-HT content, and the apomorphine-induced increase in growth hormone (GH) to accomplish these goals are reported here. DSM-III major affective disorders (bipolar disorder and major depression) can be differentiated from normal controls by the V max of platelet 5-HT. Platelet 5-HT V max of bipolar disorder, depressed type, is significantly different from that of schizophrenia and PDNEC. Elevated platelet 5-HT content is present in black schizophrenic patients compared to black normal controls. Platelet MAO was increased in a small group of schizophreniform female patients. There was no difference in the apomorphine-induced GH response between any of the diagnostic groups. If confirmed in a larger series of patients, these results tend to identify the PDNEC more closely with schizophrenia than the major affective disorders.     

Electrophoresis of platelet monoamine oxidase in schizophrenia and manic-depressive illness

Monoamine oxidase is an important enzyme in the catabolism of biogenic amines and can be measured in human platelets. Platelet MAO has been reported to be reduced in schizophrenic and manicdepressive patients, though other reports are contradictory. The present study evaluated the possibility that qualitative genetic enzyme abnormalities of MAO could be responsible for the different enzyme activities of platelet MAO in different populations. However, polyacrylamide gel electrophoresis of platelet MAO from 10 manic-depressive, 12 schizophrenic, and 11 normal individuals did not reveal any genetic mutant forms.     

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.     

Blood monoamine metabolism in Huntington's disease

In 25 patients with Huntington's disease (HD), the mean blood concentration of serotonin (5-HT) and percentage of plasma free tryptophan were significantly increased while plasma concentrations of total and protein-bound tryptophan were significantly decreased. The pattern of changes in tryptophan concentrations was related to clinical severity but not to 5-HT levels. Platelet monoamine oxidase (MAO) activity was significantly increased in patients with HD; kinetic and marker enzyme studies suggested an increased enzyme concentration. Offspring at risk for HD also had elevated platelet MAO activity but normal concentrations of blood 5-HT and plasma tryptophan. In ten patients, plasma epinephrine concentrations were significantly increased; plasma dopamine and norepinephrine concentrations were positively related to MAO activity. The finding of peripheral neurotransmitter abnormalities in HD raises the question of an interaction between CNS and peripheral processes or a systemic disorder of neurotransmitter metabolism.     

Platelet and fibroblast monoamine oxidase in alcoholism

Monoamine oxidase (MAO) activity has been reported to be low in platelets (MAO B) and brain (MAO A and B) of some patients with alcoholism compared to control subjects. Whether the decreased platelet MAO activity found in alcoholism is secondary to the effect of alcohol or exists before alcohol abuse is not clear. The hypothesis that altered MAO A activity is determined by an abnormality in the genetic regulation of the enzyme can be tested by measuring MAO A activity in human fibroblasts cultured under controlled conditions. We first studied the kinetic parameters of platelet MAO B activity in patients hospitalized for treatment of alcoholism. Vmax was 38% lower in the patients (n = 14) than in normal controls (n = 22), but the enzyme affinity (Km) for the substrate tyramine was unchanged. Patients with the five lowest levels of platelet MAO activity had MAO activity measured from fibroblasts cultured from skin punch biopsies. Their fibroblast MAO activity was within the normal range, showing a dissociation between platelet MAO B and fibroblast MAO A activities and suggesting that MAO A activity is not low for genetic reasons in alcoholic subjects who do have low platelet MAO B activity.     

Biochemical changes during clomipramine treatment of childhood obsessive-compulsive disorder

Peripheral measures of serotonergic and noradrenergic function were obtained in 29 obsessive-compulsive adolescents and 31 age- and sex-matched controls, as well as in a subsample of 22 patients after five weeks of treatment with clomipramine hydrochloride (134 +/- 33 mg/d) (mean +/- SD) given in a double-blind placebo-controlled trial. Drug-free obsessive-compulsive subjects did not differ from controls on measures of platelet serotonin and monoamine oxidase (MAO) activity, nor on plasma epinephrine or norepinephrine concentrations at rest and after a standard orthostatic challenge procedure. Compared with placebo, treatment with clomipramine was clinically effective and produced a marked decrease in platelet serotonin concentration, a trend toward a reduction in platelet MAO activity, and a rise in standing plasma norepinephrine. Clinical improvement during drug therapy was closely correlated with pretreatment platelet serotonin concentration and MAO activity, as well as with the decrease in both measures during clomipramine administration. This suggests that the effects of clomipramine on serotonin uptake may be essential to the antiobsessional action observed.     

Monoamine Oxidase Activity in Blood-Platelets From Autistic Children

In order to evaluate the possible abnormality in monoamine oxidase (MAO) activity in early infantile autism, blood platelet samples were obtained from 20 autistic children, aged 2–12 years. MAO activity, measured fluorometrically using serotonin as substrate, was 5.24 ± 1.65 (Mean ± Standard Deviation) nM/mg protein/hour in these autistic children. This value was not significantly different from either that in 30 age-matched normal children or that in 39 nonautistic children with various psychiatric and neurological disorders, although autistic children had higher platelet serotonin concentrations than these nonautistic individuals.     

Reduced platelet monoamine oxidase activity in a subgroup of schizophrenic patients.

Platelet monoamine oxidase (MAO) activity was significantly lower than control values in a subgroup of 16 schizophrenic patients (most of whom were paranoid) characterized by the presence of auditory hallucinations and delusions. Platelet MAO activity was not reduced in 16 other schizophrenic patients without auditory hallucinations. This finding suggests that reduced platelet MAO activity is not found in all schizophrenic patients but tends to occur in a clinically identifiable subgroup.