Decreased platelet monoamine oxidase activity in female anorexia nervosa

OBJECTIVE: To study if platelet MAO activity, previously described as a serotonergic index, is modified in a sample of pure restrictive anorectic patients. METHOD: Twenty-five female patients with DSM-IV anorexia nervosa restricting type were studied and compared with 30 healthy female controls. Platelet MAO activity was measured by isotopic methods using C-14 benzylamine. Impulsive personality features were measured with specific rating scales and temperament studied with Cloninger's TCI. RESULTS: Platelet MAO activity was significantly lower (4.3+2.7 nmol/h/ 108 platelets) in the anorectic patients than in the control group (6.7+2.8) (P<0.01). Platelet MAO was inversely correlated with scores on impulsivity scales and positively correlated with the dimension 'persistence' of Cloninger's TCI. CONCLUSION: Platelet MAO activity is lowered in a group of patients with anorexia nervosa and might involve some dysfunction in the regulation of impulse control.     

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.     

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.     

Low platelet monoamine oxidase activity in pathological gambling

Decreased platelet monoamine oxidase (MAO) activity has been reported in association with sensation-seeking personality type and in some mental disorders associated with a lack of impulse control. Pathological gambling itself has been related with both sensation-seeking and reduced impulse control. Platelet MAO activity was investigated in 15 DSM-III-R pathological gamblers from our outpatient clinic. Gamblers had a significantly lower platelet MAO activity than a group of 25 healthy controls. The range of MAO levels in gamblers was also significantly shorter than in controls. In controls, platelet MAO levels showed the previously described negative correlations with sensation-seeking scores but not in gamblers. The findings are consistent with previous studies showing an association of low platelet MAO activity with impulse control disorders and raise some interesting therapeutic alternatives for pathological gambling.     

Blood platelet monoamine oxidase activity, serotonin uptake and release rates in anorexia and bulimia patients and in healthy controls

Platelet monoamine oxidase (MAO) activity, serotonin uptake rate and serotonin efflux rate have all been suggested to be markers for central serotonergic mechanisms. Platelet MAO activity is associated with certain personality traits, with low activity linked to traits such as impulsiveness, sensation-seeking and avoidance of monotony, all possible expressions of low central serotonergic activity. Low platelet serotonin uptake rate has been connected to unipolar depression and the rate of efflux, in the presence of the ATP uncoupler CCP, higher in bipolar depressives than in controls. Platelet MAO was found to be lower in 16 consecutive female inpatients fulfilling the DSM-III criteria for bulimia nervosa than in 12 female controls. Rates of serotonin uptake and efflux in the presence of CCP were, on the other hand, similar to the controls. In the controls there were no correlations between platelet MAO activity and any of the other parameters estimated. Vmax for the platelet uptake of serotonin correlated positively with the Km for the uptake, but not with any other parameter. The uninfluenced rate of efflux of serotonin correlated positively with the efflux in the presence of the ATP uncoupler CCP.     

Type A personalities tend to have low platelet monoamine oxidase activity

This study investigated whether there are relations between type A behaviours and the activity of monoamine oxidase (MAO) in blood platelets. Forty male nonsmokers completed the Jenkins Activity Survey (JAS) and had a blood sample drawn while at work. The JAS was scored in the traditional manner, yielding scores for ambitiousness (factor A), impatience (factor S), competitiveness (factor H) and job involvement (factor J). High scores on JAS scales were associated with low MAO activity in blood platelets; the correlation between platelet MAO activity and job involvement was significant. The findings agree with previous reports in showing relationships between MAO activity and certain personality traits and support the notion that low activity of MAO may contribute to sympathetic hyperreactivity in type A individuals.     

Platelet monoamine oxidase activity is related to MAOB intron 13 genotype

Summary. Monoamine oxidases (MAO) play a critical role in the degradation of endogenous and exogenous amines throughout the body. There are two distinct MAO isoforms, MAO-A and MAO-B, which both are encoded in genes on the X chromosome. Alterations in MAO-B activity have previously been connected with several neurological disorders. Platelet MAO (trbc-MAO) is exclusively of the B-type and the catalytic activity of this enzyme is under strong, yet unknown, genetic control. Specific trbc-MAO activity has been reported to be increased in certain neurodegenerative diseases and to correlate with personality traits such as sensation seeking and impulsiveness. In the present study, we investigated if trbc-MAO activity is associated with genotype at a variable region (A/G dimorphism) in intron 13 of the human gene encoding MAO-B. The MAOB intron 13 allele status and levels of trbc-MAO were determined for 55 Caucasian non-smoking males. Individuals with the "A-allele" displayed significantly lower enzyme activity than individuals with the "G-allele", i.e. 11.4 ± 0.6 nmol/10¹⁰ platelets/min compared with 13.5 ± 0.6 (mean ± SEM, p = 0.019). The present results suggest that the MAOB genotype may be involved in determining trbc-MAO activity. Received July 1, 1999; accepted January 11, 2000     

Classification of patients with affective disorders using platelet monoamine oxidase activity,serum melatonin and post-dexamethasone Cortisol

Platelet monoamine oxidase activity (MAO), melatonin and Cortisol post-dexamethasone suppression test (DST) were examined in 28 patients with major affective disorder and in 20 controls. MAO activity was lower and Cortisol post-dexamethasone was higher in depressed patients. Platelet MAO activity and Cortisol in depressed and controls yielded high sensitivity (90%) and specificity (89%). The patients were re-examined after 10 years and categorized into affective psychosis or neurotic depression (ICD-9). Multidimensional analysis identified one subgroup coinciding in 92% with affective psychosis and another subgroup coinciding in 87% with neurotic depression. Combination of MAO, melatonin and post-DST Cortisol may be useful in the diagnosis of subgroups of depressed patients and in choice of therapy.     

Schizophrenic outcome in late life: symptom state and platelet monoamine oxidase activity

Reported here are the results of a study of symptom state, platelet monoamine oxidase (MAO) activity, and demographic variables in a group of elderly neuroleptic-free schizophrenics. Analyzed by both bivariate and multivariate techniques, the data from this sample indicate that after the effects of demographic variables upon the variance of enzyme activity have been controlled for, the patients most likely to continue to manifest schizophrenic symptomatology in the senium are those with low platelet MAO activity. The results are discussed with respect to other studies of platelet MAO and prognosis in schizophrenia and with respect to future studies.     

Low platelet monoamine oxidase activity: A possible biochemical correlate of borderline schizophrenia

Platelet monoamine oxidase (MAO) activity, psychiatric disorders, and family history of psychopathology were studied in 115 nonhospitalized, previously undiagnosed college student volunteers. Subjects were classified into two extreme groups: those with platelet MAO activity two standard deviations below the mean (“low-MAO” probands) and those with platelet MAO activity two standard deviations above the mean (“high”-MAO probands). Low-MAO probands were found to have a significant increase in the incidence of borderline schizophrenia and other psychiatric disorders compared to high-MAO probands. First-degree relatives of low-MAO probands were more often affected with psychiatric disorders and borderline schizophrenia than relatives of high-MAO probands. The data suggest that reduced platelet MAO activity is associated with psychiatric vulnerability and that the spectrum of schizophrenia may be more closely related to this vulnerability than other psychiatric disorders.     

Platelet monoamine oxidase B (MAO-B) activity and its relationship to DL-fenfluramine-induced prolactin response in healthy men

Summary. Several techniques are used to assess central serotonergic neurotransmission in man, e.g. challenge tests (hormonal and physiological responses to serotonin active drugs), platelet MAO-B activity as well as brain imaging techniques. Little is known about how these tests relate to each other. The aim of the present study was therefore to investigate if platelet MAO-B activity could be related to hormonal and temperature responses to the serotonin active drug DL-fenfluramine in healthy men. Twelve male subjects without any history of psychiatric disorders or drug abuse/dependencies were recruited. Prior to the challenge with 60 mg DL-fenfluramine, which was given orally, blood for determination of platelet MAO-B activity was drawn. Blood samples for determination of serum prolactin and serum cortisol were drawn at baseline and thereafter every hour for the following six hours. In addition, body temperature was measured at the same time-points. Δ-values were calculated as the difference between the baseline values and the highest (prolactin and cortisol) or lowest value (temperature) thereafter. There was a strong positive correlation (r = 0.75, p < 0.02) between platelet MAO-B activity and Δ-prolactin. No correlations were found to Δ-cortisol, Δ-temperature or any of the baseline values. The results support the notion that the peripheral marker platelet MAO-B activity is related to the function of the central serotonergic neurotransmitter system as assessed by the prolactin response to 60 mg DL-fenfluramin.     

Immunocytochemical localization of serotonin, monoamine oxidase and assessment of monoamine oxidase activity in human dental pulp

In the present study serotonin (5-hydroxytryptamine, 5-HT) and monoamine oxidase (MAO) were both found localized in the blood vessel walls of human dental pulp. Our discovery of MAO activity in human dental pulp suggests a functional relationship between serotonin and MAO in this region.     

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.     

The effect of lamotrigine on platelet monoamine oxidase type B activity in patients with bipolar depression

Lamotrigine is an anticonvulsant drug effective in the treatment of epilepsy and bipolar depression. Preclinical data showed that lamotrigine inhibited monoamine oxidase (MAO) activity in vitro. The aim of the study was to determine the effects of 6-weeks lamotrigine treatment on platelet MAO type B (MAO-B) activity in patient with bipolar depression. The study included 26 female patients with bipolar I disorder in depressive episode (DSM-IV criteria, Hamilton Depression Rating Scale (HAMD) and Young Mania Rating Scale). Platelet MAO-B activity was determined spectrofluorimetrically before and after 6 weeks of the treatment with a relatively low dose of lamotrigine (100 mg/day). Six weeks of treatment with lamotrigine significantly decreased platelet MAO-B activity in bipolar depressed patients. This inhibitory effect was not related to smoking status and was independent of the treatment combinations (lamotrigine alone or in combination with either lithium or antipsychotics). Lamotrigine treatment induced a decrease in total HAMD scores in bipolar depressed patients, which was not significantly correlated with reduction of platelet MAO-B activity. These findings provide in vivo insight of lamotrigine effect on platelet MAO-B activity in patients with bipolar depression. Its in vivo MAO-B inhibiting effect might have contributed in part to its antidepressant activity.     

Regional serotonin metabolism in the brain of transgenic mice lacking monoamine oxidase A.

The effect of a lack of the gene encoding monoamine oxidase A (MAO A) in transgenic Tg8 mice on the activity of tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin (5-HT) biosynthesis, and on the levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the midbrain, hypothalamus, hippocampus, striatum, amygdala, and frontal cortex was studied. It was shown that mice with a genetic MAO A knockout differed from mice of the initial C3H/HeJ strain in having a higher level of 5-HT and a lower level of its metabolite, 5-HIAA, in all brain regions but the frontal cortex, where the changes were insignificant. Although the 5-HIAA/5-HT ratio in various brain regions differed considerably, the decrease of the 5-HT oxidative deamination index in Tg8 mice was similar in different brain regions (to 41-45% of control values), with the exception of the frontal cortex, where the decrease of the 5-HIAA/5-HT was somewhat smaller (to 54%). The presence of the remaining 45% +/- 1.9% of the control ratio value indicates rather effective oxidative deamination of 5-HT in MAO A knockout mice and explains the lack of severe behavioral and pathological consequences in MAO A genetic deficiency. An increase of TPH activity in mice lacking MAO A was found in the frontal cortex, hippocampus, and amygdala. No significant changes were found in the striatum, hypothalamus, and midbrain. The data show an effect of the MAO A gene mutation on TPH and indicate a uniform decrease of 5-HT catabolism in different brain regions except for the frontal cortex, which is somewhat more resistant to the lack of MAO A than other brain structures.     

Platelet monoamine oxidase and plasma dopamine-beta-hydroxylase activities in patients with multiple sclerosis

Platelet monoamine oxidase (MAO) and plasma dopamine-beta-hydroxylase (DBH) activities were determined in a large group of multiple sclerose patients in relapse (49 patients) and in remission (28 patients), and compared with an age- and sex-matched control group (52 normal subjects). The activities of both enzymes did not differ from normal in both patient groups. Women had higher MAO activities both in normal and in patient groups. Multiple linear regression analysis revealed an association of low platelet MAO to the score in the mental subscale in the Kurtzke Disability Status Scale. Both male and female patients with mental symptomatology had significantly (p = 0.02) lower platelet MAO activities compared to the patients without. The possibility of a relationship between MAO activity and psychiatric vulnerability in MS is considered.     

Electrophoresis of platelet monoamine oxidase in schizophrenia and manic-depressive illness

Monoamine oxidase is an important enzyme in the catabolism of biogenic amines and can be measured in human platelets. Platelet MAO has been reported to be reduced in schizophrenic and manicdepressive patients, though other reports are contradictory. The present study evaluated the possibility that qualitative genetic enzyme abnormalities of MAO could be responsible for the different enzyme activities of platelet MAO in different populations. However, polyacrylamide gel electrophoresis of platelet MAO from 10 manic-depressive, 12 schizophrenic, and 11 normal individuals did not reveal any genetic mutant forms.     

Psychological traits and platelet monoamine oxidase activity in eating disorder patients: their relationship and stability

Self-reported behavior and attitudes towards eating [Eating Disorder Inventory-2; Garner DM (1991). Eating Disorder Inventory-2: Professional Manual. Odessa, Fl.: Psychological Assessment Resources; Estonian version Podar I, Hannus A, Allik J (1999). Personality and Affectivity Characteristics Associated With Eating Disorders: a Comparison of Eating Disordered, Weight-Preoccupied, and Normal Samples. J Pers Assess; 73(1), 133-147] and the activity of platelet monoamine oxidase (MAO) was studied in 11 patients with anorexia nervosa (AN), 43 patients with bulimia nervosa (BN) and a healthy control group (n=138). Nineteen patients filled in the EDI-2 questionnaire and donated blood samples three times with three month intervals in order to determine platelet MAO activity. Eating disordered (ED) patients scored higher on all EDI-2 subscales and had lower MAO activity compared to the control group. They also scored higher than the control group on the Neuroticism domain but lower on the Extraversion, Openness, and Conscientiousness domains of the NEO-PI-R questionnaire. The average stability of MAO on different occasions (r=.56) was slightly smaller than the stability of the EDI-2 scores (r=.70). The lack of correlations between personality dispositions and MAO activity indicates that they have independent influence on eating disorders. A possible relationship between neurochemical mechanisms and psychological symptoms of eating disordered behavior is discussed.     

Kinetic evaluation of platelet monoamine oxidase following relaxation in chronic anxiety

ABSTRACT - The effect of relaxation training, utilizing EMG biofeedback, on platelet monoamine oxidase (MAO) activity was examined in patients with a history of chronic anxiety. Anxiety scores and MAO activity were significantly lowered after 4 weeks of therapy. Kinetic studies, using phenylethylamine as substrate, indicated a significant increase of the K_m constant while the V. showed no significant or consistent variation. It is thought that this phenomenon represents an adaptive response by the individual to maintain a homeostatic level of the biogenic amines.     

Effects of clomipramine treatment on cerebrospinal fluid monoamine metabolites and platelet 3H-imipramine binding and serotonin uptake and concentration in major depressive disorder.

In an open study of 12 inpatients who met the DSM-III criteria for a major depressive episode, the effects of clomipramine (CI) on the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), 4-hydroxy-3-methoxyphenyl glycol (HMPG) in cerebrospinal fluid (CSF) were measured simultaneously with the effects on 3H-imipramine binding, serotonin (5-HT) uptake and 5-HT concentration in platelets after 3 and 6 weeks of treatment. Drug (CI and desmethylclomipramine) plasma concentrations were determined. The concentrations of 5-HIAA and HMPG decreased substantially, and the concentration of HVA remained unchanged. There was also a large and significant reduction of the number of imipramine binding sites (Bmax) and of the platelet 5-HT concentration. The 5-HT uptake was not measurable after 3 weeks of treatment. None of the parameters changed significantly between weeks 3 and 6. There were no significant correlations between antidepressant effect (measured by the Montgomery-Asberg Depression Rating Scale) and plasma drug concentrations, although a tendency to a significant correlation between antidepressant effect and CI was observed at 3 weeks. There were no significant intercorrelations between the different 5-HT parameters and no other significant correlations between the biochemical measures and clinical outcome.