Is MAO‐B activity in platelets associated with the occurrence of suicidality and behavioural personality traits in depressed patients?

Objective: Low platelet monoaminoxidase B (MAO‐B) activity has been associated with various forms of impulsive behaviour and suicidality. The present study investigated the relationship between MAO‐B activity in platelets and aspects of suicidality in depressed patients and controls. Method: In 87 patients with affective spectrum disorders (58% suffering from a major depressive episode – MDE) the potential association between platelet MAO‐B activity and suicidality was examined. Fifty‐nine of the patients had committed suicide attempt recently (SA –‘suicide attempters’), 28 patients were acutely depressed without having shown suicidal thoughts or suicidal behaviour in the past (NA –‘non‐suicide attempters’). Results: The SA and NA were comparable as to their diagnoses and general demographic and psychopathological parameters. MAO‐B activity did not differ between SA and NA. No systematic correlations existed between MAO‐B activity and any dimensions of suicidal behaviour or psychopathology. As a single finding only a weak positive association of higher MAO‐B activity in SA with a fatal intention of the SA was observed. Conclusion: Our findings do not support a consistent association of platelet MAO‐B activity and suicidal behaviour in general, but specific facts of suicidality might be associated.     

Monoamine Oxidase Activity in Blood Platelets From Manic and Depressed Patients

To evaluate the possible abnormality in MAO activity in affective disorders, blood platelet samples were obtained from 80 patients with mania and depression. Blood-platelet MAO activity was measured by a newly developed assay procedures using serotonin as substrate. MAO activities in 121 normal adult subjects were in a range of 2.49-12.05 nM/mg protein/hour, with the mean values of 4.91 ±1.72 (±S.D.) for men and 6.88±1.99 for women. (p<0.001) MAO activities in the manic and depressed patients were in a range of 0.65–13.40 nM/mg protein/hour, and both manic and depressed patients showed the mean value very similar to that in the normal subjects. Bipolar depressed patients did not exhibited lower MAO activity in the blood platelets than other clinical subtypes of depressive illness, including unipolar, involutional, neurotic and chronic characterological, and first-episode depressions. No significant differences were established between these five subcategories of depression, while significant higher values were evident in female than male patients (p<0.001). No correlation was found between the MAO activity and serotonin levels in the blood platelets either in the normal subjects or in the depressed patients.     

Platelet monoamine oxidase activity in elderly depressed outpatients

Platelet monoamine oxidase (MAO) activity was assayed in 42 unmedicated, elderly, RDC depressed, unipolar outpatients over 60 years of age, 17 nondepressed controls, and 17 younger volunteers without psychiatric illness. Elderly depressed women (n = 22) had significantly higher MAO activity than sex- and age-comparable controls. No significant relationships between MAO activity and duration of current depressive episode, duration of illness, or family history of affective disorder were obtained. These results extend to elderly female outpatients the finding that depression is associated with increased platelet MAO activity, exceeding the normal age-related increase.     

Platelet monoamine oxidase and sex hormones in a population of depressed patients

The association between changes in platelet MAO activity and Major Depressive Episode have been demonstrated. Cyclical changes in sex hormones serum levels had never been related with changes of MAO activity in depressed patients. Platelet MAO activity, oestrogen serum levels, progesterone serum levels and testosterone serum levels, have been measured in drug free depressed patients: 22 men and 42 women. This study demonstrates no relationship between serum levels hormons and platelet MAO activity, measured in men and in women. If young women are separated from menopaused women, platelet MAO activity is negatively correlated with oestrogen serum levels, in non menopaused women. Significance of this variation in studies about the use of MAO as a biochemical marker in depression is discussed.     

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.     

Platelet MAO activity in clinical subtypes of depression and DST suppression

Platelet MAO activity was measured in 75 hospitalized depressed patients and in 31 healthy subjects. Plasmas post dexamethasone cortisol levels were examined in 73 patients. Results indicate that higher platelet MAO activity does not occur in all, but only in male major depressed patients. No relationship between changes of MAO activity and specific clinical subtypes was found. Platelet MAO activity is not different between DST suppressors and DST non suppressors. The authors suggest that platelet MAO activity may be related to non specific factors such as sex, age, but not to diagnosis of depression.     

Monoamine oxidase and cortisol response in depression and schizophrenia.

The relationship between hypothalamic-pituitary-adrenal (HPA) axis function and platelet monoamine oxidase (MAO) activity was examined in drug-free depressed (n = 32) and schizophrenic (n = 36) inpatients. HPA function was measured by determining plasma cortisol levels at 8:30 a.m. and 11 p.m. before, and 8:30 a.m., 4 p.m., and 11 p.m. after administration of 1 mg of dexamethasone (DEX). There was a significant correlation between platelet MAO activity and all post-DEX cortisol levels (8:30 a.m., 4 a.m., and 11 p.m.) in depressed patients, and MAO activity and pre-DEX cortisol levels (11 p.m.) in schizophrenic patients. MAO activity was significantly higher in depressed DST nonsuppressors than in suppressors, and there were more DST nonsuppressors in high-MAO groups as compared with low-MAO groups. Our results thus suggest a strong relationship between platelet MAO activity and HPA function in depressed patients. These biochemical markers are potentially useful in the identification of biochemically and clinically homogeneous subgroups of depressed patients.     

Platelet MAO deamination of serotonin in depressed patients. Changes after imipramine treatment and clinical correlations

Monoamine oxidase (MAO) in blood platelets has been used as a model to study MAO in the central nervous system, where disorders in serotonergic systems are thought to occur in depression. Inconsistent changes in platelet MAO of depressed patients have been reported when several substrates other than serotonin (5-HT) have been used. To correlate changes in platelet MAO activity with the enzyme activity in central serotonergic systems, the platelet MAO activity of depressed patients (first unmedicated and then after 3 weeks and 2 months of imipramine treatment) and normal controls was measured using 5-HT as substrate. The results showed that there is a steady, measurable platelet MAO activity with that substrate. This activity was significantly higher in unmedicated depressed patients than in controls, and it decreased progressively with imipramine treatment, reaching a normal level when the patients were clinically recovered from depression after 2 months of therapy.     

Platelet MAO activity in geriatric patients with depression and dementia

The authors studied platelet MAO activity in psychiatrically hospitalized geriatric patients with depression and dementia. Platelet MAO activity was higher in demented patients with and without depression and in depressed patients with reversible dementia than in nondemented depressed patients. The data suggest that abnormally high platelet MAO activity may reflect a predisposition to the development of a dementia syndrome.     

Platelet monoamine oxidase activity and trace acid levels in plasma of agoraphobic patients

ABSTRACT - Platelet monoamine oxidase activity and plasma trace acid levels in 29 patients classified as agoraphobics was estimated. MAO activity towards p-tyramine and β-phenylethylamine was found to be significantly higher in agoraphobics than in non-agoraphobic depressed patients and healthy controls. In addition plasma p-hydroxyphenylacetic acid levels were low in both agoraphobic and depressed patient groups. All patients were also assessed by Spielberger State Anxiety and the short form of the Beck Depression Inventory scales. No significant correlations could be found between platelet MAO activity or plasma trace acid levels and the psychological scores.     

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.     

Platelet MAO activity and monoamine metabolites in cerebrospinal fluid in depressed and suicidal patients and in healthy controls

Platelet monoamine oxidase (MAO) activity and cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5HIAA), homovanillic acid (HVA), and 4-hydroxy-3-methoxyphenylglycol (HMPG) were simultaneously measured in 20 currently depressed patients, 11 recovered depressed patients, 15 nondepressed suicide attempters, and 42 healthy control subjects. Both 5HIAA and HVA were positively and significantly correlated to platelet MAO activity in the healthy subjects, but not in any of the patient groups. Suicide attempters had significantly lower CSF 5HIAA than nonsuicidal patients.     

Longitudinal effect of amitriptyline and fluoxetine treatment on plasma phenylacetic acid concentrations in depression

Unconjugated (U-PAA), conjugated (C-PAA), and total phenylacetic acid (T-PAA) concentrations in blood plasma and monoamine oxidase (MAO) activity in platelets towards phenylethylamine (PE) were determined in 40 drug-free, depressed patients (23 melancholic, 17 nonmelancholic) from five psychiatric treatment centers, and in 34 normal healthy volunteers. No significant differences were found between controls and all depressed patients or between melancholic and nonmelancholic depressed patients. Treatment of the depressed patients with amitriptyline or fluoxetine over a 6-week period resulted in clinical improvement and in a significant increase in plasma PAA concentrations. A decline in the Beck and Hamilton rating scores during treatment correlated significantly with increases in the concentrations of unconjugated, conjugated, and total phenylacetic acid but not with MAO activity, which did not change during treatment. At each of the three assessment times, however, plasma PAA concentrations and psychiatric rating scores were not significantly correlated. Except for higher end-of-study T-PAA concentrations in the amitriptyline-treated subjects, no significant differences were found between the effects of the two drugs with regard to plasma phenylacetic acid levels, MAO activity, or rating scores.     

Toward a biochemical classification of depressive disorders—VIII. Platelet monoamine oxidase activity in subtypes of depressions

Platelet monoamine oxidase (MAO) activity was examined in 77 depressed patients (40 males and 37 females) and 28 controls (14 males and 14 females). Patients were compared across increasingly specific diagnostic groupings in a four-step data analytic procedure. In step 1, MAO activity in the total sample of depressed patients was compared with that of control subjects. In step 2, Unipolar depressed patients were compared with Bipolar (Bipolar I and Bipolar II) depressed patients. In step 3, Unipolar depressed patients with and without schizotypal features were compared. In step 4, both the nonschizotypal Unipolar patients and nonschizotypal Bipolar patients were separated into those who met RDC criteria for a definite Endogenous depression and those who did not; and platelet MAO activity was compared in the resulting four groups.

Results indicated significantly higher platelet MAO activity in nonschizotypal Unipolar Endogenous depressed patients than in nonschizotypal Bipolar Endogenous depressed patients or nonschizotypal Unipolar Other patients. In addition, the presence of a definite Endogenous depressive syndrome was associated with greater overall symptom severity in both Unipolar and Bipolar depressed patients. Findings are discussed with respect to the conflicting results reported in previous studies of MAO activity in patients with depressive disorders.     

Psychotic and nonpsychotic depressions: II. Platelet MAO activity, plasma catecholamines, cortisol, and specific symptoms

Preliminary data are presented on levels of plasma cortisol, dopamine (DA), epinephrine (EPI), and norepinephrine (NE) before and after dexamethasone in 22 depressed patients (of whom 4 were psychotic). Platelet monoamine oxidase (MAO) activity, determined in 19 of the depressed patients, was significantly higher in the 4 psychotic patients than it was in the 15 nonpsychotic patients. Positive correlations were observed before and after dexamethasone among cortisol, DA, EPI, and platelet MAO. After dexamethasone, plasma NE correlated negatively with DA, EPI, and cortisol. The various correlations were due largely to the inclusion of the psychotic depressive subgroup. Data are also presented on the relationships between these biological measures and specific signs and symptoms.     

Relationship of platelet MAO activity to characteristics of major depressive illness

Sixty-seven patients (greater than or equal to 55 years of age) with major depressive disorder had pretreatment assays of platelet monoamine oxidase (MAO) activity. As in previous studies, women had higher MAO activity than men, and MAO activity was positively correlated with age. Patients with melancholia (DSM-III) had significantly higher MAO activity than those without melancholia. This finding may reflect the higher MAO activity associated with the symptoms of anhedonia and mood autonomy. Anxiety also was correlated with higher MAO activity, as was a positive family history of depression. In addition, postdexamethasone cortisol levels were correlated with platelet MAO activity.     

Long-term sertraline treatment and peripheral biochemical markers in female depressed patients

Serotonergic system is implicated in the pathogenesis of depression. Peripheral biochemical markers, platelet serotonin (5-HT) and platelet monoamine oxidase (MAO) activity were determined spectrofluorimetrically at baseline and after 4 and 24 weeks of sertraline (a selective serotonin reuptake inhibitor (SSRI)) treatment in 15 female nonsuicidal, nonpsychotic patients with major depression and compared with 15 drug-free healthy women. The aim of the study was to determine the effects of 4 and 24 weeks of sertraline treatment on platelet 5-HT concentration and platelet MAO activity in depressed patients subdivided according to the treatment response into remitters, responders and nonresponders after 4 and 24 weeks of sertraline treatment based on the 70%, 50-69% and <49% reductions in baseline Montgomery-Asperg Depression Rating Scale (MADRS) scores, respectively. Platelet 5-HT concentration was significantly lower in all depressed patients at baseline than in healthy subjects. Among patients, platelet 5-HT concentration or platelet MAO activity did not differ before treatment. There was no significant correlation between MADRS scores and peripheral biochemical markers. The limitation of the study was in a small number of patients, but its advantage was in a long-term (24 weeks) follow-up of both patients and healthy controls. Our results show that long-term sertraline treatment induced remission and response in 87% patients, decreased platelet 5-HT concentration after 4 and 24 weeks of treatment and decreased platelet MAO activity after 24 weeks and suggest that pretreatment values of platelet 5-HT and platelet MAO might not predict therapeutic outcome to sertraline treatment in female depressed patients.     

Central catecholamine metabolism in vivo and the cognitive and motor deficits in Parkinson''s disease.

Cerebrospinal fluid levels of homovanillic acid (HVA) in unmedicated patients with Parkinson's disease were 45% of levels in control subjects. Levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) and platelet monoamine oxidase activity (MAO) did not differ. Within the Parkinson's disease group platelet MAO B activity correlated with HVA (an MAO B substrate) but not MHPG (an MAO A substrate). A mild global dementia was found that did not correlate with the more severe motor deficit. There was a negative correlation between the motor deficit and HVA levels but not with MHPG. Cognitive functioning correlated positively with platelet MAO, and the ratio of HVA to MHPG levels and negatively with MHPG alone. It is postulated that dopaminergic and noradrenergic activity or the functional balance between these systems may contribute to the observed cognitive dysfunction.     

Prediction of response to nortriptyline and phenelzine by platelet MAO activity

Thirty-seven depressed patients over the age of 55 were treated for 5-7 weeks with either nortriptyline, a tricyclic antidepressant, or phenelzine, a monoamine oxidase (MAO) inhibitor. Patients' platelet MAO activity was measured following a drug washout period before treatment. Patients with higher MAO activity had a better response to treatment, regardless of which drug was used.     

Platelet MAO activity and the dexamethasone suppression test in bipolar depression

The correlation between postdexamethasone cortisol levels after the dexamethasone suppression test (DST) and platelet monoamine oxidase (MAO) activity was studied in 31 depressed female inpatients with Research Diagnostic Criteria primary, endogenous, bipolar depression (12 bipolar 1 and 19 bipolar 11). Out of the 31 patients, 25 showed abnormal DST results. Platelet MAO activity did not differ significantly from the matched control group. There was a trend that patients with higher MAO activity had lower postdexamethasone cortisol levels, but it was significant only for the 0800 hr cortisol levels.