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.     

Examination of circadian rhythmicity of blood serotonin and platelets in autistic and non-autistic children

A study was designed to determine whether circadian rhythmicity existed for blood serotonin concentrations and platelet counts in autistic and non-autistic children. Blood samples were drawn from hospitalized children, outpatients, and normal adults at varying times throughout the day and over prolonged periods. Circadian rhythmicity was not observed. The possibility remains that there existed very brief or prolonged rhythms which were not detectable by the methods used. The implications of these results in relation to previous findings on blood serotonin concentrations and platelet counts in autistic and non-autistic children are discussed.This research was supported by Public Health Service Grant HD 94612 to the UCLA Mental Retardation Center and the California Department of Mental Hygiene. The authors are indebted to Mrs. Rose Weisler, Miss Selma Plotkin, Miss Juli Wasserman and Mr. Joseph DeLee for administrative assistance and to Dr. J. Raymond and Miss Gwen McAfee of the UCLA Clinical Laboratory for help with platelet counts.     

Monoamine oxidase and other mitochondrial enzymes in density subpopulations of human platelets

Normal human platelets have been separated according to density on continuous Percoll gradients and the platelet distribution divided into five fractions containing approximately equal numbers of platelets. The mean volumes and protein contents of the platelets in each fraction were found to correlate positively with density while the protein concentration did not differ significantly between the fractions. Four mitochondrial enzymes (monoamine oxidase, glutamate dehydrogenase, cytochrome oxidase and NADP-dependent isocitrate dehydrogenase) were assayed and their activities per unit volume were found to increase in a very similar monotonic fashion with platelet density. When MAO and GDH were assayed on the same set of density fractions the correlation between the two activities was very high (r = 0.94-1.00, p less than 0.001) and a similar close correlation was found between MAO and ICDH. The results support the hypothesis that high density platelets either have a higher concentration of mitochondria or have larger mitochondria than low density platelets.     

Uptake and efflux of serotonin from platelets of autistic and nonautistic children

This study examined, in vitro, the uptake and efflux of serotonin by platelets from autistic children, nonautistic hospitalized comparison cases, and normal children. The autistic patients were carefully selected according to previously established diagnostic criteria. The hospitalized comparison children were utilized to assess possible environmental and dietary influences upon the results. Uptake methods were similar to those used by previous investigators. Two efflux procedures were utilized to explore the possibility that methodological factors accounted for previously reported differences between autistic and comparison groups. The results failed to indicate statistically significant differences in uptake or efflux between the autistic and the hospitalized comparison groups or the normals. Methodologic considerations which could possibly account for the failure to confirm previous findings are discussed in detail.     

Monoamine oxidase activity in several structures of rat brain

Spectrophotometric detection (at 327 nm) of a product of the kynuramine oxidation was used to study the distribution of the total activity of monoamine oxidase (MAO) in the hypothalamus, limbic system, dorsal raphe nucleus, locus coeruleus (with surrounding tissues), and hypophysis of female rats. The highest and lowest activities (8.03 ± 0.28 and 0.61 ± 0.05 nmol/min per mg of the protein, M ± m) were found in the median eminence (with its surrounding tissues) and in the hypophysis, respectively. Intermediate values were revealed in the dorsal raphe nucleus (3.10 ± 0.12), medial preoptic area (2.61 ± 0.07), locus coeruleus with its surrounding tissue (2.20 ± 0.22), mammillary body (2.00 ± 0.19), olfactory tubercle cortex (1.43 ± 0.05), and amygdalae(1.41 ± 0.11 nmol/min per mg of the protein). The activity levels of the MAO isoenzymes of types A and B were studied in the median eminence (with its surrounding tissue), dorsal raphe nucleus, medial preoptic area, and the locus coeruleus (with its surrounding tissue). These four structures displayed no significant differences in the activity of MAO A, whereas the MAO B activity decreased in order of the above list of the structures. This indicates that the regional differences in the total MAO activity are determined by the differences in the activity of MAO B.     

Monoamine oxidase activity and the puerperal blues syndrome

The puerperal blues syndrome has been examined prospectively in 38 women in relation to platelet M.A.O. activity using C¹⁴-tyramine and C¹⁴-P.E.A. as substrates and the Present State Examination to evaluate psychiatric symptoms. Of the eight main psychiatric variables which were found to comprise the syndrome, three, ‘depression’, ‘concentration loss’ and ‘obsessionalism’, correlated significantly with M.A.O. activity during the study but only depression has consistently significantly correlated with M.A.O. activity over the 6 days of the study. The significance of these changes in mood and the relationship to platelet M.A.O. activity is discussed.     

Serotonin and amino acid content in platelets of autistic children

The platelet levels of serotonin and the amino acids aspartic acid, glutamine, glutamic acid and gamma-aminobutyric acid were measured in 18 drug-free autistic (DSM-III criteria) and 14 age-matched healthy children. Serotonin was significantly increased while the amino acids aspartic acid, glutamine, glutamic acid and gamma-aminobutyric acid were significantly decreased in comparison with the controls. It is suggested that the decline of the amino acids in platelets from autistic children represents a biochemical marker related to infantile autism.     

Monoamine oxidase inhibitor toxicity

Monoamine oxidase inhibitor (MAOI) drugs are used in the treatment of depressive and anxiety disorders in adults. MAOIs are also used in high doses for the treatment of lymphomas and of central nervous system (CNS) tumors in children. Toxic effects resulted when procarbazine, a drug of this class, was used in treating a child with a CNS tumor. Psychotic reaction in the child may have been triggered by any of several factors, but arguments are for an organic cause. The implication of the MAOI procarbazine must be seriously considered. The case highlights potential serious problems associated with MAOIs and the interaction of this agent with other drugs.     

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.     

Monoamine oxidase inhibitor-responsive depression

Double-blind, placebo-controlled trials have documented the efficacy of some monoamine oxidase (MAO) inhibitors in treating certain depressed patients. This preliminary report of a 6-week, double-blind, placebo-controlled study of the MAO inhibitor isocarboxazid (Marplan) examines the time course of platelet MAO inhibitor isocarboxazid (Marplan) examines the time course of platelet MAO inhibition and treatment response, and describes symptoms that distinguish markedly improved from slightly improved responders. Thirty male outpatients, ages28–64, randomly divided into placebo (n=15) and active medication (n=15) groups, were followed weekly. Medication was started at 20 mg daily and increased to achieve 90% platelet MAO inhibition. Data were analyzed for 24 patients who completed at least 3 weeks of the study. A clinician's global change rating at the study's conclusion showed that 12 of 13 patients (92%) in the active medication group improved, while 3 of 11 (27%) patients in the placebo group improved. Significant symptomatic improvement occured in the active treatment group by week 3. Trends suggest that anxiety improved first (week 2), followed by depression (week 3), and finally cognitive outlook (week 6). Only minimal difficulties were observed with orthostatic hypotension, hypertensive crises, or other side effects. At baseline, the only significant difference between the markedly improved and slightly improved groups was greater psychomotor retardation in the markedly improved group. Trends suggest that the markedly improved group showed less depression, anxiety, sleep disturbance, and weight loss, fewer gastrointestinal complaints, and more helplessness and worthlessness.     

Monoamine oxidase and tobacco dependence

Tobacco smoking is a leading cause of preventable death around the world, and there are major public health and research efforts in many countries aimed at reducing its usage. However, the molecular mechanisms underlying tobacco dependence are still not completely understood. Nicotine's action on nicotinic acetylcholine receptors, and the downstream release of dopamine, is believed to be the major pathway underlying tobacco dependence. However there is mounting evidence indicating that non-nicotinic components of tobacco smoke also play a role by inhibiting monoamine oxidase (MAO) and subsequently altering neurotransmitter levels. This article provides a review of the current knowledge of the association between MAO and tobacco dependence and suggests that further research into this topic is likely to lead to more effective pharmacotherapies for smoking cessation.     

Monoamine oxidase and cigarette smoking

Current cigarette smokers have reduced monoamine oxidase (MAO) and there is evidence that this is a pharmacological effect of tobacco smoke exposure rather than a biological characteristic of smokers. This article summarizes human and animal studies documenting the inhibitory effects of tobacco smoke on MAO and discusses MAO inhibition in the context of smoking epidemiology, MAO inhibitor compounds in tobacco, reinvestigations of low platelet MAO in psychiatric disorders and smoking cessation.     

Disorders of regulation of cognitive activity in autistic children

Infantile autism is a pervasive developmental disorder characterized by disturbances concerning not only the areas of socialization and communication (aloneness) but also the ability to modify and change behavior (need for sameness). In most recent studies, various abnormal and deviant cognitive activities, such as the ability to regulate one's behavior, were considered as accounting for these signs. In this report, we examined the regulation of cognitive activity, from a developmental perspective in comparing autistic with mentally retarded children matched in a pairwise manner by global, verbal, and nonverbal developmental ages. All children were tested with tasks adapted from the Object Permanence Test which corresponds to Piaget's sensorimotor development Stages IV to VI. Results showed that autistic children had a pervasive difficulty in maintenance set, made more perseverative errors when the abstraction degree of task was higher, and were more variable in their behavioral strategies. Discussion is focused on the interests and limits of these tasks for the examination of regulation activity from diagnostic and developmental perspectives. Finally, interpretations about recent neuropsychological and neurophysiological works, and additional interdisciplinary studies are suggested.The authors gratefully acknowledge the helpful advice and encouragement of G. F. Lelord, E. M. Ornitz, and P. Tanguay. They thank C. Mahé and D. Lioret for their technical assistance with videotapes, G. Couturier and M. Boiron for their cooperation with the examination of children, and S. Roux for her statistical assistance. This study was supported by INSERM Unit 316 The Nervous System from the Foetus to the Child: Development, Circulation and Metabolism (L. Pourcelot), Grants C.R.E. INSERM No. 911102 (D. Sauvage) and INSERM Network No. 493001 (C. Barthélémy), convention INSERM—France Telecom 1993. This study could not have been conducted without the contribution of Fondation Langlois.     

Monoamine oxidase activity and tri-iodothyronine level in violent offenders with early behavioural problems

The focus is on evaluating the relationships between early behavioural problems and biochemical variables at adult age and their significance for early criminality and violent behaviour in a life perspective. In the present study, using prospective longitudinal data, a sample of males with a history of early criminal behaviour and male controls (n = 103) were investigated concerning (1) teacher-rated behaviours at age 11-14 years; (2) platelet monoamine oxidase (MAO) activity and tri-iodothyronine (T(3)) level at adult age; (3) registered early criminality (11-14 years); (4) records of violent offending up to age 35 years, and (5) interview data on smoking. The main finding was that a combined risk level pattern of low MAO activity and high T(3) level was found significantly more frequently than expected in violent offenders with an early behavioural risk pattern. Furthermore, there was a significant interaction effect between early attention difficulties and smoking on MAO activity, as well as an effect by smoking on MAO activity. The findings are discussed in terms of the possible influence of biological vulnerability to certain behaviours, which in combination with possible childhood stress, enhance the risk for antisocial behaviours and subsequent violence.     

Monoamine oxidase a polymorphism in brazilian patients

Different studies have attempted to find polymorphisms involved in the serotonergic pathway that could be involved in mood disorders and late-onset Alzheimer's disease (LOAD) symptoms. Here, we compared the frequency of two polymorphisms: monoamine oxidase A (MAOA) and serotonin transporter in LOAD patients versus controls. No evidence of association was observed when these polymorphisms were compared separately; however, the combination of the MAOA allele 1+the short allele of 5-HTTLPR+ApoE-epsilon4 was significantly more frequent in patients than in controls. It reinforces the hypothesis that different genes acting together might play a role in AD susceptibility. Based on these data, we suggest replicating these studies in larger samples of LOAD patients belonging to different ethnic groups.     

Monoamine oxidase a polymorphism in brazilian patients

Different studies have attempted to find polymorphisms involved in the serotonergic pathway that could be involved in mood disorders and late-onset Alzheimer’s disease (LOAD) symptoms. Here, we compared the frequency of two polymorphisms: monoamine oxidase A (MAOA) and serotonin transporter in LOAD patients versus controls. No evidence of association was observed when these polymorphisms were compared separately; however, the combination of the MAOA allele 1 + the short allele of 5-HTTLPR + ApoE-ɛ4 was significantly more frequent in patients than in controls. It reinforces the hypothesis that different genes acting together might play a role in AD susceptibility. Based on these data, we suggest replicating these studies in larger samples of LOAD patients belonging to different ethnic groups.