Platelet Monoamine Oxidase Activity Levels Research Articles

Neuropsychological Function and Platelet Monoamine Oxidase Activity Levels in Type I Alcoholic Patients

To explore neuropsychological function in two differentiated patterns of platelet monoamine oxidase B (MAO B) activity in alcoholic patients. Neuropsychological examination and platelet MAO B activity extracted from blood were collected from 42 alcohol-dependent patients recruited in the alcoholism unit (NETER) of the Psychiatric Service of Santa Maria University Hospital. Alcoholics presented significantly low levels of platelet MAO B activity, when compared with control subjects; platelet MAO B activity in alcoholics classified as "under average subgroup" showed significant lower scores in the Raven Progressive Matrix and higher scores in hostility dimension, when compared with platelet MAO B activity in "above average subgroup." Results suggested platelet MAO B as a trait marker also to type I alcohol-dependent patients and the two observed associations between platelet MAO B activity with neurocognitive measures of executive functions (nonverbal reasoning) and psychopathological dimension such as hostility may support the notion about the effect of platelet MAO B activity in the further development of an impulsive cognitive style.

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 in association with adolescent inattentive and hyperactive behaviour: A prospective longitudinal study

Platelet monoamine oxidase (MAO) activity is a peripheral marker of central serotonergic activity, and has been associated with psychiatric vulnerability. This longitudinal investigation studied the relationship between aggressive and hyperactive behaviour and platelet MAO activity in adolescents at age 15 and 18 years. The psychological data were obtained from teachers by using the Hyperactivity Scale ( af Klinteberg, 1988) and, at the age of 18 years, the teacher-report version of the SNAP-IV. Female subjects had significantly higher platelet MAO activity levels than males, and regular smokers had significantly lower MAO activity levels than nonsmokers. Low levels of platelet MAO and smoking at the age of 15 years were independently associated with Motor Restlessness and Inattention symptoms at the age of 18 years. These longitudinal data suggest that specific aspects of hyperactivity and attention deficit are associated with platelet MAO activity independently of smoking.

Relationships Between Effects of Smoking, Gender, and Alcohol Dependence on Platelet Monoamine Oxidase-B: Activity, Affinity Labeling, and Protein Measurements

Background Many studies have reported apparent associations between platelet monoamine oxidase (MAO) activity and susceptibility to alcoholism and other psychiatric conditions. Alcohol-dependent individuals generally exhibit lower platelet MAO activity compared with controls, and on this basis, platelet MAO has been proposed as a potential genetic marker for predisposition to alcoholism. However, several lines of evidence also suggest that MAO activity is reduced in both the brain and platelets of smokers. Many alcohol-dependent individuals are also tobacco users, and few studies have attempted to dissociate the effect of alcohol and tobacco use on MAO activity. Methods Platelet MAO-B activity in 629 subjects recruited as part of the WHO/ISBRA Study of State and Trait Markers of Alcohol Use and Dependence was assayed by using a high throughput fluorescence assay. Platelet MAO-B protein concentrations were measured by analysis of immunoblots probed with a polyclonal antibody selective for MAO. Quantitative measurements of affinity labeling of platelet MAO were made by using the selective MAO-B catalytic site antagonist [3H]Ro 19–6327. Results Multiple regression analysis revealed that subjects’ gender, cigarette smoking, lifetime alcohol dependence, and recruitment site each contributed independently to the variance in platelet MAO activity levels. Female subjects had significantly higher MAO activity levels than males, whereas heavy smokers had significantly lower MAO activity levels than nonsmokers. Immunoblot measurement of platelet MAO-B protein demonstrated that females had significantly higher MAO-B protein concentrations. Platelet MAO-B protein concentrations did not differ significantly between smokers and nonsmokers but were lower in subjects with a diagnosis of lifetime alcohol dependence (DSM-IV) compared with subjects who were never alcohol dependent. Measurements of affinity labeling by [3H]Ro 19–6327 of platelet MAO correlated significantly with MAO activity levels (i.e., the lower MAO-B activity in smokers was mirrored by lower levels of [3H]Ro 19–6327 binding). Conclusions In this international population, gender, cigarette smoking, lifetime history of alcohol dependence, and recruitment site were associated with lower platelet MAO activity levels. Differences in MAO activity associated with gender and lifetime alcohol dependence can be attributed largely to differences in MAO-B protein concentration, whereas those associated with smoking behavior may be the result of binding of an inhibitor contained in cigarette smoke to platelet MAO-B at catalytic site of MAO.

Relationships Between Effects of Smoking, Gender, and Alcohol Dependence on Platelet Monoamine Oxidase‐B: Activity, Affinity Labeling, and Protein Measurements

Many studies have reported apparent associations between platelet monoamine oxidase (MAO) activity and susceptibility to alcoholism and other psychiatric conditions. Alcohol-dependent individuals generally exhibit lower platelet MAO activity compared with controls, and on this basis, platelet MAO has been proposed as a potential genetic marker for predisposition to alcoholism. However, several lines of evidence also suggest that MAO activity is reduced in both the brain and platelets of smokers. Many alcohol-dependent individuals are also tobacco users, and few studies have attempted to dissociate the effect of alcohol and tobacco use on MAO activity. Platelet MAO-B activity in 629 subjects recruited as part of the WHO/ISBRA Study of State and Trait Markers of Alcohol Use and Dependence was assayed by using a high throughput fluorescence assay. Platelet MAO-B protein concentrations were measured by analysis of immunoblots probed with a polyclonal antibody selective for MAO. Quantitative measurements of affinity labeling of platelet MAO were made by using the selective MAO-B catalytic site antagonist [3H]Ro 19-6327. Multiple regression analysis revealed that subjects' gender, cigarette smoking, lifetime alcohol dependence, and recruitment site each contributed independently to the variance in platelet MAO activity levels. Female subjects had significantly higher MAO activity levels than males, whereas heavy smokers had significantly lower MAO activity levels than nonsmokers. Immunoblot measurement of platelet MAO-B protein demonstrated that females had significantly higher MAO-B protein concentrations. Platelet MAO-B protein concentrations did not differ significantly between smokers and nonsmokers but were lower in subjects with a diagnosis of lifetime alcohol dependence (DSM-IV) compared with subjects who were never alcohol dependent. Measurements of affinity labeling by [3H]Ro 19-6327 of platelet MAO correlated significantly with MAO activity levels (i.e., the lower MAO-B activity in smokers was mirrored by lower levels of [3H]Ro 19-6327 binding). In this international population, gender, cigarette smoking, lifetime history of alcohol dependence, and recruitment site were associated with lower platelet MAO activity levels. Differences in MAO activity associated with gender and lifetime alcohol dependence can be attributed largely to differences in MAO-B protein concentration, whereas those associated with smoking behavior may be the result of binding of an inhibitor contained in cigarette smoke to platelet MAO-B at catalytic site of MAO.

A four-year follow-up study of male alcoholics: factors affecting the risk of readmission

This study is based on a consecutive series of 52 male alcoholics who have been followed up for 4 years after inpatient detoxification. The aim was to identify risk factors for readmission for alcohol detoxification. Information was collected individually, and psychiatric status, physiologic conditions at admission, personality profile, platelet monoamine oxidase (MAO) activity level, current psychosocial living conditions, as well as those during childhood/adolescence, and a history of alcohol and drug abuse were comprised. This information was supplemented by register data on hospital admissions covering the period of 4 years before the admission in question to 4 years after it. The main findings of this follow-up study revealed five risk factors for readmission; namely, heavy drinking before admission, a high gamma-glutamyltransferase level at admission, previous somatic care, and a sensation-seeking behavior in combination with a low platelet MAO activity level (odds ratios ranging from 4.2 to 10.2). The second year after admission seemed to be the most critical time for readmission.

A bootstrapped commingling analysis of platelet monoamine oxidase activity levels corrected for cigarette smoking.

Monoamine oxidase (MAO) activity levels have been suggested as a possible biological marker for alcohol dependence and abuse, as well as for schizophrenia and other psychiatric conditions. Using platelet MAO activities in the Collaborative Study on the Genetics of Alcoholism data set, we applied bootstrapping methods as a novel way to test for admixture in families. This bootstrapping involved resampling in family units and hypothesis testing of the resampled datasets for commingling in the distribution of MAO activity levels. Prior to commingling analysis, we used linear models to find covariates of greatest effect on MAO activity levels. While an alcoholism diagnosis was significant in men (n = 1151, P < 0.0001) and women (n = 1254, P = 0.0003), the effect lost significance after controlling for cigarette smoking, indicating alcoholism and smoking behavior to be highly confounded. When smoking histories were compared, former smokers had levels (mean = 7.1) closer to those who never smoked (mean = 7.0) than to current smokers (mean = 5.4). Furthermore, current daily smoking and time since smoking cessation were significantly related to MAO levels, indicating smoking probably has a direct effect on MAO levels, rather than the reverse. These results suggest that studies using MAO levels as a biological marker should consider smoking as an important covariate. Finally, admixture was found in MAO levels controlled for smoking and sex, possibly indicating a major genetic locus; this confirms previous evidence for admixture.

Relationships between attempted suicide, temperamental vulnerability, and violent criminality in a Swedish forensic psychiatric population

The relationship between suicide attempts and different vulnerability factors was investigated in 61 male subjects during forensic psychiatric examination. Personality traits and psychopathy were determined by means of the Karolinska Scales of Personality (KSP) and the Psychopathy Checklist-Revised (PCL-R). Clinical diagnoses were determined by the use of Structured Clinical Interview for DSM-III-R (SCID). Platelet monoamine oxidase (MAO) activity was investigated in 58 subjects. Suicide attempters had extremely low socialization and high impulsive aggression. This was independent of a history of repeatedly criminal violence or not. They had higher PCL-R scores and lower levels of platelet MAO activity than non-attempters. No relationship was found between suicide attempts and repeated violent criminality. However, among the subjects with repeated criminal violence there was a highly significant difference between suicide attempters and non-attempters, indicating different personality profiles in violent offenders with and without suicidal behavior. Suicidal behavior was significantly associated with borderline personality disorder, but not with any other single DSM-III-R disorder. The results show a far more severe personality disturbance in suicide attempters than in other violent patients in this type of population. Suicidal behavior should therefore be evaluated and treated per se.

Platelet monoamine oxidase activity in subgroups of alcoholics and controls: results from the Collaborative Study on the Genetics of Alcoholism.

Platelet monoamine oxidase (MAO) B activity levels were evaluated to determine whether low platelet MAO activity is a marker for alcoholism, correlates of alcoholism (e.g., cigarette smoking), or a subtype of alcoholism. Adult women (n = 788) and men (n = 685) participating in the Collaborative Study on the Genetics of Alcoholism study were evaluated with a semistructured interview, and blood samples were obtained for determination of platelet MAO activity using tryptamine (0.1 mM) as substrate. DSM-III-R alcohol-dependent individuals were subgrouped using four currently available methods (e.g., two variations of the type 1/type 2 scheme, primary versus secondary typology, type A/type B dichotomy). In the overall sample, subjects' gender, cigarette smoking status, and the Collaborative Study on the Genetics of Alcoholism site at which their platelets were prepared explained 22% of the variance in platelet MAO activity levels, and multivariate analysis showed that carrying a broad diagnosis of alcohol dependence did not uniquely explain any additional variance in platelet MAO activity levels. Furthermore, within each of the alcoholic subgrouping methods tested, there were no significant differences in platelet MAO activity for type 1 versus type 2, type A versus type B, or primary versus secondary alcoholics. Cigarette smoking and male gender are associated with decreased platelet MAO activity levels. After considering these factors, a diagnosis of alcohol dependence does not predict any additional variance in MAO-B activity. Phenotypes of alcoholics (e.g., type 1 versus type 2, type A versus type B, primary versus secondary) do not differ in platelet MAO activity. The results suggest that decreased platelet MAO activity is not a trait marker of alcoholism or one of its subtypes; but, rather, is a state marker of cigarette smoking.

Platelet monoamine oxidase activity as a biological marker in a Swedish forensic psychiatric population

Platelet monoamine oxidase (MAO) activities were determined in 58 non-psychotic males at forensic psychiatric examinations. The aim of the study was to investigate the role of platelet MAO activity as a biological marker in forensic psychiatry, a clinical field with growing need of safe predictors for both treatment outcome and behavior. The study population was heterogeneous with respect to clinical and personality disorders and personality traits. Theresults confirmed the role of platelet MAO activity as a biological marker for stable personality traits such as impulsiveness, monotony avoidance and aggressiveness. Disorders with high frequencies of these personality traits such as borderline personality disorder and type II alcoholism could secondarily be associated with low levels of platelet MAO activity, whereas no such associations could be found regarding other clinical or personality disorders. Neither psychopathy as assessed by the means of PCL-R nor behavior such as abuse or criminality could be associated with platelet MAO activity. The conclusion is that, due to its close relationship with stable personality traits, platelet MAO activity serves a marker for vulnerability also in forensic psychiatric populations. On the other hand it is not a marker for clinical or personality disorders, or behavior per se.

Monoamine Oxidase Molecular Activity in Platelets of Parkinsonian and Demented Patients

Platelet monoamine oxidase activity levels have been evaluated in several neuropsychiatric disorders, to identify biochemical markers for pathological brain functioning. In the present work, we assayed both total and molecular monoamine oxidase activity in platelets of parkinsonian and demented patients: both showed significantly higher enzyme activity values than healthy controls. Thus, high platelet monoamine oxidase activity levels seem to be related to an increased intrinsic activity of single enzyme molecules. A significant positive correlation was found between platelet monoamine oxidase activity and severity of illness in both disorders: monoamine oxidase activity, therefore, may be considered as a state-dependent marker for neuro-degeneration. Such findings are discussed with reference to central nervous system biochemical abnormalities in parkinsonian and demented subjects; it might be that in both Parkinson's Disease and in dementia of Alzheimer type some central biochemical changes are reflected in certain peripheral tissues (thrombocytes, for instance), or that a systemic derangement accompanies the cerebral involvement.

Platelet monoamine oxidase activity in patients with winter seasonal affective disorder

The aim of the present study was to examine whether high or low levels of platelet monoamine oxidase (MAO) activity were associated with an increased risk of winter seasonal affective disorder (SAD) or of developing characteristic vegetative symptoms during episodes of the disorder. We also investigated the relationship between MAO activity and the Global Seasonality Scale (GSS), a measure of seasonal variation in sleep length, social activity, mood, weight, appetite, and energy level. Patients with SAD ( n = 49), patients with subsyndromal SAD ( n = 11), and normal volunteers ( n = 25) participated in the study. We found significantly higher levels of platelet MAO activity in females but did not observe significant differences across age groups or between groups of patients tested in different seasons or mood states. MAO activity (whether high or low) was not associated with a significant increase in risk of SAD or of developing hypersomnia, hyperphagia, or carbohydrate craving during episodes of winter depression. We found no significant relationship between GSS and MAO activity. Patients who had made suicide attempts during an episode of SAD had significantly lower mean levels of platelet MAO activity than other patients.

Monoamine oxidases and alcoholism. II. Studies in alcoholic families

Thirty-five alcoholic families have been studied to investigate the relationship between DNA markers at the monoamine oxidase (MAO) loci and 1) platelet activity levels and 2) alcoholism. A quantitative linkage analysis failed to reveal any evidence that the variation in activity levels cosegregates with the DNA markers. A sib-pair analysis did not reveal a significant excess of MAO haplotype sharing among alcoholic sibs, although the deviation from random sharing was in the direction consistent with an X-linked component. A reanalysis of platelet MAO activity levels in a subset of these families revealed that the lower levels previously found in alcoholics is more likely due to the differences between males and females. Only among males and only when a "broad" definition of alcoholism is used (and MAO activity levels are transformed to normality) does it appear that alcoholics have depressed activities compared to nonalcoholics. Finally, when the confounding due to gender difference is removed, no differences between type I and type II alcoholics are found in these families.

Platelet monoamine oxidase activity levels in subgroups of alcoholics: Diagnostic, temporal, and clinical correlates

Platelet monoamine oxidase (MAO) activity levels were measured in 47 male inpatient alcoholics to determine whether this biological marker might be useful in differentiating subtypes of alcoholics. Of the subgrouping methods tested, only type 2 alcoholics defined by the criteria of Gilligan et al had significantly lower platelet MAO activity than type 1 alcoholics at intake, but this finding was not stable over time in a subset of subjects. Neither separating male veteran alcoholics into either of two other variations of the type 1/type 2 subtypes, nor classifying the sample into primary alcoholics versus primary ASPD with secondary alcoholism categories, yielded significant differences between subgroups. Generally, enzyme activity levels (Vmax) were higher about 10 days after stopping drinking compared to platelet MAO values determined in thrombocytes obtained after approximately 4 weeks abstinence; these levels remained relatively stable 3 months later in a cohort of subjects. Tobacco smoking was significantly negatively correlated to platelet MAO activity levels.

Platelet Monoamine Oxidase activity and Tardive Dyskinesia

A few studies of chronic psychiatric inpatients have reported an inverse association between platelet monoamine oxidase (MAO) activity level and tardive dyskinesia (TD). In contrast to these earlier findings, we found no significant or consistent association between platelet MAO activity level and TD occurence when we controlled for other TD predictors in a case-control study of 80 outpatients maintained on neuroleptic medications. We did find, however, that black subjects had significantly lower levels of MAO activity than did whites in an analysis controlling for age, sex, and neuroleptic dose.

Morbidity risk for psychiatric disorders in families of probands with affective disorders divided according to levels of platelet MAO activity

In a series comprising 166 subjects with affective disorders, the lowest and highest quartiles in the male and female platelet monoamine oxidase (MAO) distribution, respectively, were included. The morbidity risk in the first-degree relatives (parents and siblings) of these low and high platelet MAO subjects was determined. First-degree relatives of low platelet MAO probands were found to have an increased morbidity risk for neurotic-reactive depressions and for alcoholism. The results seem to be in line with the biological high-risk paradigm, indicating that platelet MAO could be a biological marker for increased vulnerability. First-degree relatives of high platelet MAO probands were found to have an increased morbidity risk for bipolar affective disorders.

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. V max was 38% lower in the patients ( n = 14) than in normal controls ( n = 22), but the enzyme affinity ( K m) 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.

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.

The effects of testosterone on plasma and platelet monoamine oxidase (MAO) an plasma dopamine-beta-hydroxylase (DBH) activities in the male rhesus monkey.

Dopamine-beta-hydroxylase (DBH) and monoamine oxidase (MAO) in plasma and platelets were studied in male rhesus monkeys to evaluate the effects of changes in endogenous testosterone on the activity of these enzymes. High plasma testosterone concentrations attained at the end of the mating season were associated with relatively low levels of platelet MAO activity. When testosterone levels fell, platelet MAO increased significantly. Mean differences in platelet MAO activity between a group of castrated and control males were in the direction expected, with the highest MAO activity in the castrated monkeys, but these differences did not attain statistical significance. No significant mating season or castration effects were seen in plasma DBH or MAO enzyme activities. These data support the hypothesis of a link between testosterone and some monoamine systems, and possibly the monoamine-related behaviors linked to testosterone in primates.