Low platelet monoamine oxidase activity in Swedish imprisoned criminal offenders.

Numerous studies report a connection between low platelet monoamine oxidase activity (trbc MAO) and personality traits such as impulsiveness and sensation seeking. Generally, criminal offenders constitute a group of individuals that are high in such temperamental characteristics. In this study, we investigated trbc MAO activity in imprisoned criminal offenders and in controls where the confounding factor of smoking was under control. Radiometric MAO assays were performed in 99 male criminal offenders and in 60 non-criminal volunteers. Offenders had significantly lower trbc MAO activity than controls, i.e., 8.8 +/- 3.0 nmol/10(10) platelets/mm and 11.3 +/- 5.1, respectively (p<0.0001). When only smoking individuals were included in the analysis, the difference in trbc MAO was still statistically significant (p<0.05). Based on these data, we suggest that trbc MAO is related to mechanisms predisposing for development of specific personality characteristics that in turn increase vulnerability for criminal behaviour. The results also suggest that low trbc MAO activity in criminal offenders is not an artefact of cigarette smoking.     

Both low and high activities of platelet monoamine oxidase increase the probability of becoming a smoker.

Platelet monoamine oxidase (MAO) activity is a marker of personality and psychiatric vulnerability, but the direct inhibitory action of tobacco constituents on the enzyme distorts the association. In the present investigation, data from a prospective longitudinal study of smoking behaviour and platelet MAO activity in adolescents at ages 15 and 18 years were sequentially analysed using a second-order multiple logistic regression analysis. The odds of regular smoking at 18 years increased significantly with increasing absolute deviation of platelet MAO activity at 15 years from the mean. That is, both low and high platelet MAO activity at 15 years predicted a higher probability of becoming a smoker. These data suggest that smoking is associated with low platelet MAO activity not only because of the direct inhibitory effect of tobacco constituents on the enzyme, but also because subjects with low platelet MAO activity are more likely to become smokers. Furthermore, the possible association between above-average platelet MAO activity and behavioural phenotypes should be reexamined.     

Personality traits and platelet monoamine oxidase activity in alcoholic women

Twenty-nine women, sent to an inpatient treatment facility for rehabilitation and social training after treatment for heavy alcohol abuse, were compared with 29 female students of pharmacy or medicine with regard to platelet monoamine oxidase (MAO) activity and extraversion-impulsivity and anxiety-proneness personality traits. The alcoholic females were found to have slightly lower platelet MAO activity than the controls, the difference being considerably smaller than that previously found between male alcoholics and male controls. The personality pattern of the female alcoholics is in line with that previously found in alcoholic males. Thus, the female alcoholics were characterized by high anxiety proneness, impulsive acting-out behaviour, sensation seeking, social withdrawal, and a hostile attitude.     

Association between substance use, personality traits, and platelet MAO activity in preadolescents and adolescents

This study examined the relationship between alcohol/illicit drug use, the Five-Factor Model (FFM) personality traits, aggressiveness (Agg), and hyperactivity (Hyp), and platelet monoamine oxidase (MAO) activity in a population-derived representative sample of preadolescents and adolescents (n=1172). Alcohol and illicit drug use was self-reported. The FFM personality inventories were filled in by mothers of the participants, and Agg and Hyp were rated by their class teachers. Higher scores in extraversion (E), Agg, and Hyp and lower scores in conscientiousness (C) together with older age were significant predictors of more frequent alcohol use in adolescents. No significant association was found between alcohol illicit drug use, and platelet MAO activity.     

Platelet monoamine oxidase activity and personality traits in alcoholics and methamphetamine dependents

Personality traits of alcoholics and methamphetamine dependents were examined by Karolinska scales of personality (KSP). The two groups differed with respect to Aggression, but, they were basically same in Impulsiveness. The biological marker platelet monoamine oxidase (MAO) activity showed a significant difference between the two groups. The low platelet MAO activity in alcoholics may suggest a certain biological basis to be involved in the etiology of dependence whereas the higher platelet MAO activity observed in methamphetamine dependents may reflect the prolonged use of methamphetamine and/or treatment with neuroleptics, or some biological basis.     

Decreased platelet monoamine oxidase activity in female bulimia nervosa.

The involvement of brain serotonin systems in the pathophysiology of eating disorders has been repeatedly demonstrated in recent studies. Platelet MAO activity is an index of brain serotonin activity and lowered platelet MAO levels have been found in association with impulsive behaviors. In addition, some preliminary reports indicate that platelet MAO could be lowered in eating disorder patients. Methods: 47 patients with DSM-IV eating disorders were studied, including 30 with bulimia nervosa and 17 with anorexia nervosa binge eating-purging type. Platelet MAO activity was measured by isotopic methods using C-14 benzylamine and compared with a control group of 30 healthy subjects. Impulsive personality features were studied with specific rating scales. Results: Platelet MAO activity was significantly lower (4.4+/-2.4 nmol/h/10(8) platelets) in the bulimic patients than in the control group (6.9+/-2.5) (p<0.001). No significant differences were found between pure bulimics and binge eating-purging anorectics. Platelet MAO was inversely and significantly correlated with scores on impulsivity scales and with borderline personality disorder characteristics. Conclusions: Platelet MAO activity is lowered in patients with bulimia, which may reflect dysfunction in impulse control mechanisms. Since platelet MAO has a predominant genetic component, there is need for studies on the association of low platelet MAO and higher risk for developing eating disorders.     

Adaptive and maladaptive impulsivity, platelet monoamine oxidase (MAO) activity and risk-admitting in different types of risky drivers

Rationale Platelet monoamine oxidase (MAO) activity reflects serotonergic functioning associated with impulsive behaviour, but the significance of these associations to real-life impulsive behaviour in healthy subjects is not clear.Objectives The present study explores impulsivity and platelet MAO activity among people with driving violations.Materials and methods We compared facets of impulsivity and platelet MAO activity in 1,004 male drivers, out of whom 203 had been caught by the police driving drunk and 292 had been caught exceeding speed limits and committing other non-alcohol-related driving violations. Subjects with speeding and other non-alcohol-related violations were further divided according to their self-reported risk-admitting of exceeding speed limits.Results While drunk driving was associated only with maladaptive types of impulsivity, exceeding speed limits was associated with functional impulsivity and excitement seeking and, to a lesser degree, with dysfunctional impulsivity. Drunk drivers had lower platelet MAO activity. Risk-admitting high-risk drivers had higher platelet MAO activity, neuroticism-related impulsivity, dysfunctional impulsivity and excitement seeking compared to all other groups and higher functional impulsivity compared to controls. Risk-denying high-risk drivers had only higher functional impulsivity compared to controls.Conclusions This study demonstrates different expressions of functional and dysfunctional impulsivity in behaviour. While platelet MAO activity is lower in alcohol-related risky behaviour, non-alcohol-related self-acknowledged risky behaviour is related to higher platelet MAO activity. Thus, deviance towards lower as well as higher end of central serotonergic functioning may lead to impulsive behaviour. While self-reported impulsivity did not correlate with MAO activity, both MAO activity and impulsivity were related to risky behaviour.     

Low platelet MAO activity associated with high dysfunctional impulsivity and antisocial behavior: evidence from drunk drivers

Rationale Low platelet monoamine oxidase (MAO) activity is associated with problem drinking and other deviant behaviors. Since the majority of alcohol abusers are smokers, and tobacco smoke has a direct inhibitory effect on the enzyme, these associations may not be meaningful.Objective The authors compared platelet MAO activity and impulsivity in police-referred subjects caught driving while intoxicated and in control subjects, controlling for smoking.Methods Platelet MAO activity was measured radioenzymatically and impulsivity scores obtained from questionnaires. Smoking status was self-reported.Results Subjects caught driving while intoxicated had significantly higher dysfunctional impulsivity and lower platelet MAO activity than control subjects. This difference in platelet MAO activity between the two groups was significant in non-smokers and ex-smokers.Conclusions These findings demonstrate that platelet MAO activity is lower in subjects with socially deviant behavior, and the association of low platelet MAO and problem drinking is not an artifact of smoking.     

Psychopathology and personality characteristics in relation to blood serotonin in Tourette's syndrome and obsessive-compulsive disorder.

Family studies suggest an interrelationship between Gilles de la Tourette Syndrome (GTS) and some forms of obsessive-compulsive disorder (OCD). Some authors consider GTS to be part of a serotonergically mediated cluster of OCD spectrum disorders. The present study was undertaken to compare measures of psychopathology, personality and blood serotonin between GTS and OCD (without tics), and to investigate whether an OCD spectrum hypothesis is supported for GTS. Fifteen GTS without OCD subjects, 21 tic with (+) OCD subjects, 15 OCD without tic subjects and 26 controls (all without serotonergic medication) were evaluated with self-rated and clinician-rated measures of psychopathology and personality. Whole blood serotonin (5-HT) and platelet monoamine oxidase activity (MAO) was measured, and Spearman's correlations were calculated between whole blood 5-HT, MAO and rating scale scores within the entire sample and within subgroups. There were main effects of OCD on anxiety, obsessive-compulsive, neuroticism and extraversion scores. There were main effects of tics on depression, obsessive-compulsive, trait anxiety and neuroticism scores, and on platelet MAO. There were interaction effects on platelet MAO, 5-HT, Yale-Brown Obsessive-Compulsive Rating Scale severity, trait anxiety and Eysenck Personality Questionnaire neuroticism scores. Platelet MAO activity was elevated in tic-free OCD subjects when compared to tic + OCD, GTS without OCD and controls. Whole blood 5-HT was lowered in tic + OCD patients in comparison to GTS without OCD and tic-free OCD subjects. Whole blood 5-HT and obsessive-compulsive severity were negatively correlated within OCD without tic patients and MAO and Leyton Obsessive Inventory scores were negatively related within GTS without OCD patients. The biochemical data of this study suggest that in tic + OCD and in tic-free OCD patients, 5-HT dysregulations play a role, but not necessarily in pure GTS. Serotonergic dysregulations within tic + OCD and tic-free OCD patients are distinct, suggesting differences in underlying pathophysiology. The finding that obsessions and compulsions can be associated with either 5-HT hypofunctionality or hyperfunctionality reveals a major weakness in the OCD spectrum theory, i.e. that the associations between obsessive-compulsive behaviours and 5-HT abnormalities are less specific than suggested by the original obsessive-compulsive spectrum model.     

The 5-HT1A C(-1019)G polymorphism, personality and electrodermal reactivity in a reward/punishment paradigm

During past years the 5-HT(1A) C(-1019)G polymorphism has been associated with vulnerability to depression, anxiety-disorder and personality traits related to negative emotionality (e.g. neuroticism). Many of these studies focused on case-control comparisons or associations between genetic markers and personality traits assessed by the use of questionnaires. In contrast, overt behaviour and physiological measures in experimental paradigms, although very promising, have seldom been the focus of studies investigating the role of the 5-HT(1A) polymorphism for behaviour and psychopathology. To fill this gap, we examined the relationship between the 5-HT(1A) C(-1019)G polymorphism and reaction times (in a reward/punishment paradigm) as well as electrodermal activity, as a marker of autonomic arousal, in 123 healthy subjects. This paradigm seems very promising, as sensitivity to punishment in particular, is strongly associated to traits related to negative emotionality. Carriers of the GG genotype, which is related to increased expression of 5-HT(1A) autoreceptors, exhibited increased reaction times when they were able to win money (reward condition). In direct contrast to the reward condition, these subjects show faster reaction times in the punishment condition (losing money). Moreover, GG carriers are characterized by an enhanced electrodermal activity in all experimental conditions (win, lose and verbal feedback). Finally, the reaction-time pattern mentioned was related to higher scores on negative emotionality as revealed by self-reports. These findings demonstrate for the first time that the 5-HT(1A) polymorphism is related to personality on the level of a triadic approach including behaviour, physiology and self-reports.     

Monoamine oxidase activity in different density gradient fractions of human platelets

Monoamine oxidase (MAO) activity measured in human platelets is reportedly altered by such drugs as epinephrine, lithium carbonate, and imipramine, and also reduced in a number of clinical disorders. To evaluate whether MAO activity might differ in platelet supopulations, density gradient centrifugation with arabino-galactan was used to prepare four platelet fractions that differed in weight and volume. MAO activity in the lightest and smallest platelet subpopulation was approximately one-half that in the heaviest and largest subpopulation. Because platelet weight and size are thought to be related to platelet age, it is possible that some drug effects on platelet MAO activity might represent changes in platelet turnover. Factors other than platelet turnover rates may contribute to individual differences in platelet MAO activity, however, since one group of individuals with markedly reduced platelet MAO activity exhibited no shift in the proportion of lighter versus heavier platelets nor in the relative amount of MAO activity in each density gradient subfraction.     

The effects of adrenaline injections on human platelet monoamine oxidase and related measures

A double-blind, placebo-controlled, crossover study in ten normal volunteers assessed the effects of the subcutaneous administration of adrenaline on platelet MAO activity, in an attempt to replicate previous findings of increased MAO activity following adrenaline. Platelet counts, cortisol plasma concentrations, and uptake of metaraminol by the platelets were also determined to elucidate possible mechanisms of action. Blood pressure and heart rate were used as indices of the concentration of adrenaline effectively in circulation.MAO activity towards benzylamine was significantly increased by adrenaline. Non-significant increases were noted in the deamination of tyramine and tryptamine, in platelet counts, cortisol concentrations and metaraminol uptake. Increases in MAO activity were also noted early in the experimental sessions suggesting that other experimental variables such as venepuncture may affect platelet MAO activity.Possible mechanisms for this adrenaline effect are discussed and it is suggested that variables such as arousal and stress must be taken into account when interpreting clinical data on platelet MAO.     

Basic aspects of blood platelet monoamine oxidase activity in hospitalized men alcoholics

Platelet MAO activity (tryptamine as substrate) was assessed in 44 hospitalized men alcoholics to examine the relationships between MAO levels and variables related to alcohol misuse and physiological status. Mean MAO levels were lower in this population than in normal controls and hospitalized psychiatric patients. MAO activity correlated with age but was independent of variables derived from self-reported drinking histories and scales of alcohol dependence. Similarly, platelet MAO activity was not related to the misuse of other drugs. Of the variance in MAO activity, 38% could be accounted for by age, and the values of Mg++, low density lipoproteins and eosinophil combined. The significance of low platelet MAO activity in alcoholics is discussed.     

Inhibition of monoamine oxidases by haloperidol and its metabolites: pharmacological implications for the chemotherapy of schizophrenia

The effect of haloperidol and its metabolites on human platelet monoamine oxidase B (MAO-B) and human placenta monoamine oxidase A (MAO-A) in vitro has been investigated. We found that 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]-pyridinium (HP⁺), 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]-1,2,3,6-tetrahydropyridine (HTP) and 4-chlorophenyl-1,2,3,6-tetrahydropyridine (CPTP) are potent inhibitors of MAO. HP⁺ appeared to be a reversible, uncompetitive and selective MAO-B inhibitor with a Ki of 0.83 µM. HTP was found to be an irreversible, uncompetitive and selective MAO-B inhibitor (Ki of 1.84 µM). CPTP inhibits both MAO-A and MAO-B. Some other haloperidol metabolites, i.e. 4-(4-chlorophenyl)-4-hydroxypyridine (CPHP), 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]-1,2,3,6-tetrahydropyridine N-oxide (HTPNO) and reduced haloperidol (RHAL), do not inhibit MAO to any appreciable degree at concentrations up to 100 µM. The results suggest that haloperidol metabolites may contribute to the reduction of platelet MAO-B activity in schizophrenic patients undergoing neuroleptic chemotherapy. An examination of the literature reveals that schizophrenic patients with low platelet MAO activity exhibit a strong association with the use of haloperidol. Other possible pharmacological implications of the inhibition of MAO activity are discussed.     

Platelet MAO activity and the 5-HTT gene promoter polymorphism are associated with impulsivity and cognitive style in visual information processing

Rationale Low capacity of the central serotonergic system has been associated with impulsive behaviour. Both low platelet monoamine oxidase (MAO) activity and the short (S) allele of the serotonin transporter gene promoter region polymorphism (5-HTTLPR) are proposed to be markers of less efficient serotonergic functioning. Objectives The effect of the two markers for serotonin system efficiency on performance in a visual comparison task (VCT) and self-reported impulsiveness (Barratt Impulsiveness Scale, BIS-11) were investigated in healthy adolescents participating in the Estonian Children Personality Behaviour and Health Study. Possible confounding effect of general cognitive abilities on the performance in VCT was controlled for. Results Low platelet MAO activity and carrying of the S allele of 5-HTTLPR were both associated with higher error-rate and more impulsive performance in VCT. Platelet MAO activity and 5-HTTLPR S allele had a significant interactive effect on self-reported impulsivity (BIS-11). The effect of platelet MAO activity on both self-reported and performance impulsivity was significant only in the S allele carriers. The effect of 5-HTTLPR S allele on impulsive performance remained significant after controlling for general cognitive abilities. Conclusions The two markers of lower serotonergic capacity, 5-HTTLPR S allele and low platelet MAO activity, have a similar and partly synergistic influence on self-reported as well as performance measures of impulsivity.     

Beyond personality—Experimental investigations of the effects of personality traits on in situ alcohol consumption in social and solitary drinking contexts

Numerous studies have highlighted that personality traits are associated with alcohol problems and disorders; however, little is known on the link between personality and the quantities of alcohol actually ingested during given drinking episodes (i.e. in situ alcohol consumption, in grams of pure alcohol). Based on data of 123 young adults who participated in two wine-tasting assignments (one performed in group, the other individually; sequence of participation assigned at random), the results from regression models suggest that individual characteristics and personality traits are, to some extent, associated with in situ alcohol consumption, but contextual factors (e.g., in line with behavioral exposition and perceptions of norms) might overwhelm such associations in a social context, or later on in similar drinking contexts. These findings argue for the development of early preventive initiatives focusing on social influences and on specific drinking context.     

Salicylate and mitochondrial monoamine oxidase function in Reye's syndrome

The main objective of this investigation was to study the effect of salicylate on platelet mitochondrial monoamine oxidase (MAO) activity isolated from blood of two patients with Reye's syndrome. Comparative studies were made with hospitalized children without Reye's syndrome (n = 27) and healthy children (n = 19) serving as controls. Platelet MAO was measured by a radioenzymatic technique with [14C]tyramine as a substrate. The results of this study showed that salicylate (1.0 mM) caused an appreciable inhibition of the platelet MAO activity of patients with Reye's syndrome at the onset of the illness. This was demonstrated by a greater than 50% reduction in enzyme maximum velocity (Vmax) value. The salicylate MAO-inhibitory effect was maintained throughout the duration of the illness. Salicylate had only a minimal MAO-inhibitory effect on platelets isolated from blood of recovered Reye's syndrome patients, healthy controls, and non-Reye's hospitalized children, and no apparent effect on enzyme Vmax values. These preliminary findings suggest that salicylate-induced mitochondrial injury may affect MAO function in children with Reye's syndrome.     

Substrate and inhibitor selectivity of human heart monoamine oxidase.

The subcellular distribution, inhibitor sensitivity, thermostability and pH profiles of monoamine oxidase (MAO) from samples of human heart obtained at post mortem have been investigated with several substrates. A simple subcellular fractionation showed that, with either tyramine or benzylamine as substrate, about 50 per cent of the MAO activity was found in the mitochondrial fraction, with negligible quantities in the high speed supernatant. From the use of clorgyline, it appears that 5-HT is a substrate for MAO-A, benzylamine and β-phenethylamine are substrates for MAO-B, while tyramine and dopamine are substrates for both forms of the enzyme, d-Amphetamine was shown to be a selective competitive inhibitor of MAO-A, of similar potency to that observed with MAO from rat liver. No significant difference between the thermostability at 50° of the MAO activity towards 5-HT and benzylamine was observed. Preliminary results for the effect of pH on human heart MAO are presented. The results are discussed with respect to similar data obtained for MAO from other human and animal tissues.     

A comparative study of some kinetic and molecular properties of microsomal and mitochondrial monoamine oxidase

This experimental work tries to characterize the monoamine oxidase of microsomal origin through its kinetic and molecular properties, and to establish a comparative study with the enzyme present in rat liver mitochondria. The temperature effect upon this catalytic activity was examined and similar behaviour of MAO A and MAO B between both cellular fractions was found. The study of the pH dependence of initial velocity showed similar results both in mitochondria and in microsomes. The FAD cofactor is covalently attached to the MAO of microsomal origin. The FAD containing subunits corresponding to MAO A and MAO B, previous binding of the enzyme with [3H]pargyline and posterior SDS electrophoresis and fluorography, showed molecular weights of 65,900 and 62,400, respectively, in both cellular fractions. The inhibition curves with clorgyline, deprenyl, semicarbazide and KCN, measuring the remaining activity towards 1 microM of benzylamine, indicated that in mitochondria 5% of the total activity is due to the presence of SSAO activity whereas in microsomes this activity represents about 20%. From all these results it appears that mitochondrial and microsomal MAO are related enzymes, although further structural studies are necessary to confirm their possible identity.