Low Platelet Monoamine Oxidase Activity Research Articles

Is low platelet MAO activity associated with antisocial behavior? evidence from representative samples of longitudinally observed birth cohorts

Lower platelet monoamine oxidase (MAO) activity has been associated with problem behaviors, including criminal behavior, but not all studies agree. We have examined platelet MAO activity and antisocial behavior involving police contact in a longitudinal birth cohort study. The sample included both birth cohorts (original n = 1238) of the Estonian Children Personality Behavior and Health Study. Platelet MAO activity was measured at ages 15, 18 and 25 radioenzymatically with β-phenylethylamine as the substrate. Police contacts were self-reported in an interview and drug use in a questionnaire filled in during a laboratory visit. In cross-sectional analyses, males with the record of antisocial behavior had lower platelet MAO activity. In longitudinal mixed-effect regression models, this association was found to be independent of smoking. Furthermore, including smoking in the model revealed lower platelet MAO activity also in females with past antisocial behaviour. A further exploratory regression analysis with antisocial behavior at two levels of frequency and consideration of self-reported use of illicit drugs either in a single occasion or repeatedly demonstrated some “dose-dependency” in the relationship of antisocial behavior and platelet MAO activity. Platelet MAO activity was lower in male but not female subjects with basic education level as compared to secondary and higher education, but it was not related to non-verbal intelligence. Neither was platelet MAO activity associated with socio- economic status. In conclusion, antisocial behavior as occurring in general population is associated with low platelet MAO activity that probably reflects low capacity of the serotonergic system.

Association between platelet MAO activity and lifetime drug use in a longitudinal birth cohort study.

Platelet monoamine oxidase (MAO) activity, a marker of central serotonergic capacity, has been associated with a variety of problem behaviours. However, studies on platelet MAO activity and addictive drugs have not consistently linked MAO activity with addiction or reported to predict illicit substance use initiation or frequency. Platelet MAO activity and illicit drug use was examined in a longitudinal birth cohort study. The sample included both birth cohorts (original n = 1238) of the Estonian Children Personality Behaviour and Health Study. Longitudinal association from age 15 to 25years between platelet MAO activity and lifetime drug use was analysed by mixed-effects regression models. Differences at ages 15, 18 and 25 were analysed by t-test. Cox proportional hazard regression analysis was used to assess the association between platelet MAO activity and the age of drug use initiation. Male subjects who reported at least one drug use event had lower platelet MAO activity compared to nonusers, both in cross-sectional and longitudinal analyses. Males with low platelet MAO activity had started to use drugs at a younger age. Moreover, in male subjects who had experimented with illicit drugs only once in lifetime, low platelet MAO activity was also associated with higher risk at a younger age. In females, platelet MAO activity was not associated with drug use. In males, low platelet MAO activity is associated with drug abuse primarily owing to risk-taking at early age.

Relapse of drunk driving and association with traffic accidents, alcohol-related problems and biomarkers of impulsivity.

Individual biological predispositions should play a role in risky driving behaviour. Platelet monoamine oxidase (MAO) activity, dopamine transporter gene (DAT1) and neuropeptide S receptor 1 (NPSR1) gene polymorphisms have been identified as markers of impulsivity, alcohol use and excessive risk-taking. We aimed to find out how this knowledge on neurobiology of impulsivity applies to drunk driving and traffic behaviour in general. We have longitudinally examined the behaviour of drunk drivers (n = 203) and controls (n = 211) in traffic, in association with their alcohol-related problems, personality measures and the three biomarkers. We analysed differences between the subjects based on whether they had committed driving while impaired by alcohol (DWI) violation in a 10-year time period after recruitment or not and investigated further, what kind of predictive value do the different biomarkers have in committing DWI and other traffic violations and accidents. The original drunk drivers group had lower platelet MAO activity but further DWI was not significantly associated with this measure. Being a NPSR1 T-allele carrier contributed to the risk of repeatedly committing DWI. DAT1 9R carriers in contrast were involved in more traffic accidents by their own fault (active accidents), compared to 10R homozygotes in the whole sample. All groups with DWI also had significantly more alcohol-related problems and higher scores in maladaptive impulsivity compared to controls without DWI. Established biological markers of alcohol use and impulsivity can be reliably associated with everyday traffic behaviour and help in contributing to the understanding of the need for more personalized prevention activities.

The association of measures of the serotonin system, personality, alcohol use, and smoking with risk-taking traffic behavior in adolescents in a longitudinal study

Studies on the neurobiological basis of risk-taking behavior have most often focused on the serotonin system. The promoter region of the gene encoding the serotonin transporter contains a polymorphic site (5-HTTLPR) that is important for the transcriptional activity, and studies have demonstrated its association with brain activity and behavior. Another molecular mechanism that reflects the capacity of the central serotonin system is the activity of the enzyme monoamine oxidase (MAO) as measured in platelets. The purpose of the present study was to examine how measures of the serotonin system (platelet MAO activity and the 5-HTTLPR polymorphism), personality variables, alcohol use and smoking are associated with risk-taking traffic behavior in schoolchildren through late adolescence. The younger cohort of the longitudinal Estonian Children Personality Behaviour and Health Study (originally n = 583) filled in questionnaires about personality traits, smoking status, alcohol use and traffic behavior at age 15 and 18 years. From venous blood samples, platelet MAO activity was measured radioenzymatically and 5-HTTLPR was genotyped. During late adolescence, subjects with lower platelet MAO activity were more likely to belong to the high-risk traffic behavior group. Male 5-HTTLPRs′-allele carriers were more likely to belong to the high-risk traffic behavior group compared to the l′/l′ homozygotes. Other variables predicting risk group were alcohol use, smoking and Maladaptive impulsivity.The results suggest that lower capacity of the serotoninergic system is associated with more risky traffic behavior during late adolescence, but possibly by different mechanisms in boys and girls.

A Biomarker of Risk-Prone Behavioral Phenotype Correlates With Winning in a Game of Skill

Abstract. The predisposition to take risk is a personality trait associated with dangerous or maladaptive behavior. Related to this, biomarkers associated with risk proneness such as low platelet monoamine oxidase (MAO) activity level are typically considered as prognostic for higher likelihood of undesirable behavior in real-life settings. In this study we explored whether this biomarker is also indicative of risk proneness in a game situation where serious real-life adaptations and motivations are absent or minimized and risk is more or less symbolic. We adapted a game of skill where in order to get a high score “risky” actions had to be taken by the players. Scores obtained in the game correlated with the (relatively low) platelet MAO activity. Our results show that (1) the same markers that are informative for real-life behavior and adaptations involving risk and/or sensorimotor skills based performance may be informative also in a game setting, (2) in specific circumstances biomarkers associated with predisposition to risk may be associated with success, and (3) the novel game of skill tested in this context has a potential to be developed to a model of risk-involving behavior allowing quantifiable dependent measures of performance and purposeful manipulation of variables without real adverse effects on health or social relations.

A New Risk Factor for Traumatic Spinal Cord Injury.

Several behavioral factors such as violence, impulsivity, and alcohol-related problems are associated with traumatic spinal cord injury (TSCI). Such factors have been associated with inherently low neuronal serotonergic capacity that in turn is reflected in low activity of monoamine oxidase (MAO) as measured in platelets. The aim of the study was to characterize platelet MAO activity and impulsivity in persons with TSCI. Data were collected from 93 patients with TSCI and compared with 93 age- and gender-matched control subjects. Platelet MAO activity was measured radioenzymatically and expressed as nanomoles of beta-phenylethylamine oxidized per 10 to the tenth power platelets per minute. Facets of impulsivity were self-reported using Barratt Impulsiveness Scale (BIS-11). Most of the patients were men (87%). The mean time from TSCI was 4.3 ± 3.7 years. Twenty-one (24%) patients reported social problems associated with alcohol, and 30 (39%) patients had consumed alcohol before the trauma. Platelet MAO activity was significantly lower among the patients with TSCI (6.4 ± 3.2 vs.10.8 ± 5.2, p < 0.0001). This difference was not affected by consideration of their smoking status. The patients with TSCI had significantly higher BIS-11 impulsivity compared with the controls (62.8 ± 10.0 vs. 55.4 ± 8.6, p = 0.0001). The patients with TSCI have lower platelet MAO activity, and they are more impulsive compared with the healthy controls. Our results indicate that both low platelet MAO activity and high impulsivity are important risk factors for TSCI that can have predictive value and aid in undertaking preventive measures.

Psychobiology of borderline personality traits related to subtypes of eating disorders: A study of platelet MAO activity

Increased and decreased levers of platelet monoamine oxidase (MAO) activity have been reported in patients with eating disorders, indicating abnormalities of the serotonin turnover. However, whether these findings are related to eating disorders or are rather reflecting the pathophysiology of borderline personality traits in these patients is still unknown. Platelet MAO activity and comorbid personality disorders were investigated in 72 patients with different subtypes of eating disorders (ED) and in a group of 28 healthy controls. ED patients comprised the following subtypes: 25 anorexia nervosa (AN) restrictive, 14 AN binge eating–purging (AN b-p), 3 anorexia nervosa not otherwise specified (AN NOS) and 30 bulimia nervosa (BN). Personality disorders and traits were assessed with the Structured Interview for Personality Disorders (SCID-II), the Zanarini Rating Scale for Borderline Personality Disorder, and the Barrat Impulsiveness Scale. Platelet MAO activity was significantly lower in ED patients with comorbid borderline personality disorder (BPD) than in ED without Borderline personality disorder (BDP). Platelet MAO activity was significantly and inversely correlated with the number and severity of BPD clinical features. In the subsample of patients with binge eating–purging symptoms (AN b-p, AN NOS and BN), platelet MAO activity was significantly lower in binge–purge patients with comorbid BPD than in binge–purge patients without BPD. The whole group of eating disorders had a significantly reduced lever of platelet MAO activity compared with the control group. The results suggest that low platelet MAO activity might characterize eating disorders with comorbid borderline personality traits, reflecting greater serotonin dysfunction in these patients. The role of decreased platelet MAO as an endophenotype with specific clinical manifestations should be explored in future studies.

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

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. 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. 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. 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.

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

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. The present study explores impulsivity and platelet MAO activity among people with driving violations. 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. 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. 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.

Platelet monoamine oxidase activity and psychometric correlates in male violent offenders imprisoned for homicide or other violent acts

Violent behavior has been associated with certain personality traits like poor impulse control, sensation seeking, and monotony avoidance, which predispose to increased risk for violent acts. Low platelet monoamine oxidase (MAO) activity has been found in subjects with such traits, as well as in imprisoned violent offenders. On the other hand, cigarette smoking is expected to inhibit MAO activity. We assessed impulse control, lifetime history of aggression, suicide risk, as well as platelet MAO activity in 82 male offenders (mean age 33.0+/-10.7 years) imprisoned for homicide or other violent acts, and in 54 control male subjects (mean age 35.1+/-6.6 years). General psychopathology was assessed by the Hopkins Symptom Check List (SCL-90) questionnaire. A high rate of smoking (89%),significantly higher than controls (63%), was observed in offenders, but there were no differences in MAO activities among nonsmokers, moderate, or heavy smokers in either group. Offenders showed significantly higher scores in Impulse Control, Past Feelings and Acts of Violence, Suicide Risk and SCL-90 scales. Offenders who had committed other violent acts than homicide had higher scores in the three psychometric scales and in the Depression, Obsessive-Compulsive, Hostility, and Anxiety subscales of the SCL-90, than offenders who had committed homicide. Platelet MAO activity was significantly lower (p=0.01) in the offenders' group (38.1+/-14.4) compared to controls (44.7+/-15.2). The difference could not be attributed to smoking, and seems to be related to personality traits and behaviors that characterize the offenders' group.

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

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. The authors compared platelet MAO activity and impulsivity in police-referred subjects caught driving while intoxicated and in control subjects, controlling for smoking. Platelet MAO activity was measured radioenzymatically and impulsivity scores obtained from questionnaires. Smoking status was self-reported. 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. 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.

Platelet Monoamine Oxidase, Personality and Alcoholism: The Rise, Fall and Resurrection

The history of research on the association between platelet monoamine oxidase (MAO) activity and personality traits, such as sensation seeking and impulsiveness, is reviewed. The effects of MAO-inhibiting compounds in cigarette smoke for the interpretation of this association are discussed. Recent results confirming a true association between platelet MAO activity and personality are presented. From a clinical point of view, this association has had its greatest impact on the understanding of the nature of constitutional factors making individuals vulnerable for e.g. substance abuse and the link between low platelet MAO activity and type 2 alcoholism, recently confirmed on non-human primates, is discussed. The molecular mechanisms underlying the association between platelet MAO and behaviour are discussed and evidence that common transcriptional factors, e.g. within the AP-2 family, regulating both the expression of platelet MAO and components of central monoaminergic systems, such as synthetizing enzymes, receptors and transporters, are presented. A hypothesis is put forward, that such common transcription factors may not directly regulate platelet MAO expression, but rather mitochondrial number or outer membrane surface.

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 a Swedish Male Criminal Population

Background: A Swedish male criminal population was grouped into personality disorder subgroups and investigated with regard to personality traits and platelet monoamine oxidase (MAO) activity. The main aim of the study was to examine the possibility of a risk factor combination by having low platelet MAO activity as well as belonging to a certain diagnostic DSM-IV axis I (drug abuse in the present series) and/or II subgroup. Methods: Personality disorders were grouped into clusters according to the cluster system used in DSM-IV axis II. The prisoners were grouped into five subgroups and each subject completed the Karolinska Scales of Personality self-report questionnaire. The comparison group for the personality data comprised 51 non-criminal males from a longitudinal Swedish project. Platelet MAO activity was assessed for the criminals as well as for a control group including 60 non-criminal healthy male Caucasians. For testing the existence of syndromes, a configuration frequency analysis (CFA) was used. Results: The results showed low scores on the socialisation and high scores on the sensation seeking-related traits impulsiveness and monotony avoidance, and the somatic anxiety-related muscular tension in the criminals with any DSM-IV mental disorder, however most markedly in cluster AB and cluster B subjects. In addition, cluster AB subjects had significantly lower platelet MAO activity than controls. Two significant ‘types’ were found among the criminals: one was characterised by low platelet MAO activity, cluster B personality diagnosis as well as drug abuse disorder diagnosis; and the other by a pattern of normal platelet MAO activity, no cluster B personality disorder and no drug abuse disorder diagnosis. Conclusion: The aggregation of certain risk factors in the same individual has been shown to contribute to the development of criminal behaviour.

Platelet monoamine oxidase activity in a nonhuman primate model of type 2 excessive alcohol consumption.

Low platelet monoamine oxidase (MAO) activity is associated with "type 2 alcoholism." MAO activity is also affected by cigarette smoking. Since most alcoholics are smokers, it is difficult to evaluate the possible effect of platelet MAO activity on alcoholism independently of the effects of smoking. The authors investigated the relationship between platelet MAO activity and excessive alcohol consumption in rhesus macaques. Platelet MAO activity and CSF metabolite concentrations were measured. The authors also investigated level of voluntary alcohol intake and social dominance rank. Subjects with low platelet MAO activity consumed alcohol to excess, had low CSF 5-hydroxyindoleacetic acid concentrations, and were less competent socially. These findings show that nonhuman primates that exhibit type 2-like alcohol features display low platelet MAO activity and support the notion that platelet MAO activity is a biologic marker for central serotonergic activity. The results also challenge the hypothesis that low platelet MAO activity in type 2 alcoholism is simply an artifact of smoking.

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.

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.

Monoamine oxidase: associations with alcohol dependence, smoking and other measures of psychopathology.

Many reports have appeared on associations between platelet monoamine oxidase (MAO) activity and susceptibility to psychiatric conditions; principally alcohol dependence but also conduct disorder, other drug use and depression. Recently, it has become apparent that MAO activity is inhibited by some component of cigarette smoke, and smokers have low platelet MAO activity. Since the prevalence of smoking is higher in many of the conditions in which MAO has been implicated, the MAO susceptibility associations may be partly, or entirely, false. We have measured platelet MAO in 1551 subjects, recruited from the Australian NHMRC Twin Registry, who have provided information on alcohol use and dependence, smoking, conduct disorder, depression, attempted suicide, panic disorder and social phobia. Current smoking reduced platelet MAO activity in a significant and dose-related manner, with no evidence of lower MAO in ex-smokers or in non-smoking subjects with co-twins who smoked. Alcohol use and lifetime DSM-III-R alcohol dependence history were not associated with MAO activity when smoking was taken into account. Depression, panic disorder and social phobia showed no significant associations with platelet MAO activity. Subjects with a history of serious attempts at suicide had low platelet MAO activity; but although the difference from controls was as great as the reduction associated with smoking it was not significant after correction for smoking effects. Although synaptic MAO activity undoubtedly plays a role in psychopathology, the concept that platelet MAO activity is a direct genetic marker of vulnerability to alcohol dependence cannot be sustained.

Low Platelet Monoamine Oxidase Activity in Sensation-Seeking Bullfighters

In this study, we attempt to demonstrate an association between low platelet monoamine oxidase (MAO) activity, as assessed by isotopic methods, and the stable behavioral pattern of sensation- and risk-seeking of professional bullfighters. Sixteen professional bullfighters were studied and compared with a control group of 46 healthy control subjects who did not engage in risky jobs or activities. The group of bullfighters had significantly reduced platelet MAO activity compared with the control group (P<0.05). Bullfighters were shown to be significantly more extroverted and sensation-seeking than controls on various temperament scales. A predisposition to engage in risky activities (eg, bullfighting) and sensation-seeking could be partly conditioned by the presence of biological components of personality manifested by a significantly decreased platelet MAO activity.