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.     

Psychological characteristics corresponding to low versus high platelet monoamine oxidase activity.

From an original sample of 375 college students and employees studied for platelet MAO activity, 66 subjects representing the lower and upper deciles of the sample were contacted for further study, including administration of the booklet form of the MMPI. We analyzed what psychological characteristics might be associated with differences in MAO activity and attempted to cross-validate these characteristics by using them to predict the separability of low vs. high MAO subjects. Each subject was randomly assigned to one of two groups in which the low and high MAO subjects were balanced for sex. For 16 women in group A, a MAO scale discriminated low and high subjects with 100% accuracy. For 18 men in group A, a separate MAO scale discriminated with 94% accuracy. To cross-validate these results, the two scales were applied to another population; both discriminated low and high MAO women and men with a combined 97% accuracy. The thematic content of the two scales is discussed in the light of other reports on the psychological characteristics of low and high MAO subjects, including the apparent relationship between the scale content and the clinical features of bipolar affective disorder.     

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.     

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.     

Psychoeducational and impulsivity correlates of platelet MAO in normal children

The authors examined the relationship between the activity of platelet monoamine oxidase (MAO) and a variety of psychoeducational measures, as well as the scores on the Matching Familiar Figures Test (MFF), a psychological test of reflection-impulsivity, in 21 normal children (12 boys, 9 girls) who were admitted to a clinical research center and placed on a low monoamine diet. The children were divided into three equal groups (n = 7) based on their values of platelet MAO. There were no significant differences among the three groups in the psychoeducational measures. However, the high and low MAO groups made significantly more errors and had shorter latency periods on the MFF than the middle MAO group. These findings suggest that normal children with platelet MAO activity values in the high and low ends of the MAO distribution are more impulsive than the children with platelet MAO values in the middle range on the MFF Test of Impulsivity. The findings further suggest that there is no relationship between platelet MAO levels and intellectual abilities or scholastic achievement in normal children.     

Pentametric distribution of platelet monoamine oxidase activity

The distribution of catalytic activity of platelet monoamine oxidase (MAO) with both tryptamine and phenylethylamine as substrates was examined in 1,129 Swedish men at age 18 years. A mixture of five components was needed to describe the distribution, even when the original scale was transformed to remove skewness. The proportions of admixture were 2% for the extremely low component with a mean of -2.3 sigma, 29% for moderately low MAO (mean -0.8 sigma), 51% for intermediate MAO (mean 0.0 sigma), 15% for moderately high MAO (mean + 1.3 sigma), and 3% for extremely high MAO (mean + 3.0 sigma). Thus, the upper and lower deciles each contain contributions from two extreme components that differ from a much larger intermediate component with activity near the mean of the general population. This is compatible with a minimum of three alleles at a single major locus or with at least two polymorphic loci. The hypothesis that MAO activity is controlled by two alleles at a single locus was tested and rejected. The demonstration of at least five distinct components to the distribution of MAO warrants further research to characterize the biochemical structure and function of MAO enzyme variants as well as study of the behavioral correlates of the components.     

Platelet MAO activity and the cortisol response to dexamethasone in major depression

Previous studies have sometimes found a positive relationship between platelet monoamine oxidase (MAO) activity and dexamethasone nonsuppression in depressed patients. To assess this relationship in more detail, we examined the association between these two biological variables in unmedicated depressed patients. A positive correlation between platelet MAO activity and 8:00 AM serum cortisol levels following an overnight dexamethasone test (1 mg) was observed. The relationship between high and low platelet MAO activity (median split) and suppression of serum cortisol levels was also significant. These relationships were stronger in bipolar patients. Multiple regression revealed that postdexamethasone 8:00 AM dexamethasone levels and platelet MAO activity were independent predictors of the 8:00 AM cortisol levels following dexamethasone. The possibility that platelet MAO activity may be a peripheral marker of brain serotonergic activity which in turn may affect various aspects of the hypothalamo-pituitary-adrenal axis activity, is discussed. We also found that all nine depressed patients studied greater than or equal to 15 days after admission were suppressors. Platelet MAO activity, but not 8:00 AM pre- or postdexamethasone serum cortisol, was related to the severity of depression.     

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.     

Suicide attempts, platelet monoamine oxidase and the average evoked response.

The relationship between suicides and suicide attempts and two biological measures, platelet monoamine oxidase levels (MAO) and average evoked response (AER) augmenting, was examined in 79 off-medication psychiatric patients and in 68 college student volunteers chosen from the upper and lower deciles of MAO activity levels. In the patient sample, male individuals with low MAO and AER augmenting, a pattern previously associated with bipolar affective disorders, showed a significantly increased incidence of suicide attempts in comparison with either non-augmenting low MAO or high MAO patients. Within the normal volunteer group, all male low MAO probands with a family history of suicide or suicide attempts were AER augmenters themselves. Four completed suicides were found among relatives of low MAO probands where as no high MAO proband had a relative who committed suicide. These findings suggest that the combination of low platelet MAO activity and AER augmenting may be associated with a possible genetic vulnerability to psychiatric disorders.     

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.     

Exploring the connections between platelet monoamine oxidase activity and behavior: relationships with performance in neuropsychological tasks

Platelet MAO activity has been found to have behavioral (psychiatric and personality) correlates. The purpose of the present study was to explore the nature of the connections between platelet MAO activity and behavior by analyzing performance in neuropsychological tasks in relation to platelet MAO activity, measured in 37 male subjects. The following neuropsychological tests were given: a finger tapping and alternation test, a reaction time test, a perceptual maze test, a perspective fluctuation task (the Necker cube), and a lexical decision task. The reaction time tasks comprised a motor disinhibition task, in which auditory stimuli given simultaneously with light stimuli were signals for response inhibition. Significant relationships were obtained between low MAO activity and short response times and small variations in response times to left-sided visual stimuli, suggesting a readiness for higher right hemisphere activation in low MAO subjects, and between low platelet MAO activity and many perspective reversals, in line with expectations. Furthermore, high MAO subjects had equal tapping speed for both hands, which has been found in schizophrenic patients. Of special interest in the present results is the strong negative relationship obtained between platelet MAO activity and number of failed inhibitions in the motor disinhibition task, which in a multiple regression analysis highly significantly contributed to the prediction of platelet MAO activity. This finding is in line with the poor passive avoidance performance associated with serotonergic deficiency and syndromes of disinhibition, and thus supports the assumption that platelet MAO activity may be considered as a genetic marker for some properties of the central serotonergic system.     

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.     

Platelet monoaminooxidase activity and behavioural characteristics in humans

We investigated the possible relationship between platelet MAO activity and behavioural characteristics, measured by MMPI, in a group of 19 healthy volunteers. The results showed that high MAO activity tended to be typical of subjects with inhibitory characteristics and that low MAO activity was more typical of uninhibited subjects.     

Platelet monoamine oxidase activity in the psychoses: relationship to symptoms and lithium response

The kinetics of platelet monoamine oxidase (MAO) were studied in 100 psychotic and manic patients and 36 controls. No relationship was found between MAO activity and response to lithium in the schizophrenic-like illnesses. However, the data do suggest there is an association between enzyme affinity (Km) and specific symptom clusters. Patients with the low Km variant of platelet MAO are enriched in depressive symptoms, while those with the high Km variant are enriched in manic symptoms.     

Platelet MAO activity and the dexamethasone suppression test in depressed patients

Platelet monoamine oxidase (MAO) activity and postdexamethasone cortisol levels were determined in 26 depressed patients. The incidence of cortisol nonsuppression and the mean postdexamethasone cortisol levels were significantly higher in patients with high MAO activity than in those with low MAO activity.     

Psychological correlates of monoamine oxidase activity in normals

This study replicates and extends earlier work by finding that low levels of platelet monoamine oxidase (MAO) activity correlate with sensation seeking, high ego strength, positive affect, and high leisure time activity levels, somewhat similar psychological correlates also being found for plasma amine oxidase activity. Although there are several ways in which a schizophrenia/MAO relationship may exist and still be congruent with the present data, these results pose difficulties for theories which link low MAO activity levels specifically to schizophrenia. Nothing in the present findings, however, is incongruent with the possibility of an association between low platelet MAO activity and bipolar affective disorder.     

Frontal midline theta activity and platelet MAO in human subjects

The distinctive theta rhythm that appears at the frontal midline during the performance of mental tasks has been designated as frontal midline theta (Fm theta). Fm theta shows individual differences and seems to be related to certain personality traits. In several studies, it has been indicated that low platelet monoamine oxidase (MAO) activity is also associated with certain personality traits. In the present study, we found a negative correlation between the appearance of Fm theta and platelet MAO activity. Subjects with marked extroversion show a high amount of Fm theta and low MAO activity. It is therefore suggested that Fm theta, an electrophysiological marker, may be useful in the investigation of monoamine functions in the central nervous system (CNS) by way of platelet MAO activity, a biochemical marker.     

Lymphocyte monoamine oxidase activity and chronic schizophrenia

Lymphocyte monoamine oxidase (MAO) activity was assayed in 62 chronic schizophrenic patients, 113 normal volunteers, and 23 first-degree relatives of schizophrenic patients. Mean lymphocyte MAO activity was significantly lower (p < 0.001) in the chronic schizophrenic group than in controls; first-degree relatives had a mean lymphocyte MAO activity midway between the schizophrenics and normals. No relationship was found between lymphocyte MAO activity and sex or age of subjects. When subjects were subgrouped by race, blacks had significantly lower MAO activity than whites (p < 0.001).     

Markers for vulnerability to psychopathology: temperament traits associated with platelet MAO activity

The functional linkage between platelet MAO activity and psychopathology was explored by analyzing temperamental correlates in 40 male subjects by means of scales from the Eysenck Personality Questionnaire (EPQ), the Zuckerman Sensation Seeking Inventory, and the Karolinska Scales of Personality (KSP). Linear correlations were found with two sensation seeking scales, replicating earlier findings. However, nonlinear correlations predominated. Subjects with intermediate platelet MAO activity had higher scores in conformity scales and lower scores in anxiety and hostility scales than low and high MAO subgroups. Low MAO subjects showed a pattern of higher scores in KSP Impulsiveness, EPQ Neuroticism, and KSP Somatic Anxiety and Irritability and lower scores in KSP Socialization, in line with personality profiles found in alcoholics, psychopaths, and suicide attempters who also tend to have low platelet MAO activity. High MAO subjects scored lower in sensation seeking and conformity scales and higher in KSP Psychasthenia, Muscular Tension and Suspicion scales, consistent with clinical links between high platelet MAO activity and anxiety and paranoia.     

Elevated platelet MAO is related to impulsivity in disruptive behavior disorders

Platelet monoamine oxidase (MAO) activity was measured in 32 drug-free prepubertal boys with externalizing symptoms of disruptive behavior disorders and 47 boys with no DSM-III-R diagnoses, and correlated to questionnaire and laboratory performance measures of impulsivity. A subgroup of boys with high MAO activity exhibited significantly poorer performance (i.e., more impulsivity) than a subgroup of low MAO activity on laboratory tasks requiring response inhibition. High MAO patients were more impulsive than high MAO controls on some performance tasks and elevated platelet MAO was unrelated to personality questionnaire measures of impulsivity or to patient status. These data suggest that biological markers such as MAO activity may correlate better with performance than clinical questionnaire measures. Abnormally high platelet MAO activity may not be sufficient to produce externalizing symptoms in children, perhaps interacting with an underlying behavioral dimension of impulsivity.