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 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.     

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.     

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.     

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.     

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.     

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.     

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 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.     

Early morning awakening in unipolar depressives with higher levels of platelet MAO activity

Platelet monoamine oxidase (MAO) activity was analyzed in 51 patients with Major Depressive Disorder. The enzyme activity was correlated univariately and multivariately using split-half techniques with affective subdiagnosis, sex, body measures, and a great many depressive symptoms. The results indicate that unipolarly depressed patients with higher levels of platelet MAO activity woke up earlier in the morning than they had before becoming depressed. Waking up early appeared to be one least common denominator behind higher MAO activities and a unipolar subdiagnosis. Earlier reports on univariately significant differences in MAO activity between affective subdiagnoses or between the sexes were not replicated. Positive trend correlations were found between homovanillic acid and 5-hydroxyindoleacetic acid in cerebrospinal fluid and platelet MAO activity. Urinary free cortisol correlated significantly with platelet MAO activity, but only in unipolars.     

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.     

Vitamin B12-induced reduction of platelet monoamine oxidase activity in patients with dementia and pernicious anaemia

Platelet monoamine oxidase (MAO) activity has previously been shown to be increased in patients with senile dementia of Alzheimer type (SDAT) and in patients with megaloblastic anaemia. Moreover, low serum B12 levels were found to be 4-5 times more frequent in SDAT compared with an unselected population of similar age. In the present investigation, platelet MAO activity was estimated in 14 SDAT patients with relatively low serum B12 levels and in 4 patients with pernicious anaemia. Before B12 therapy, platelet MAO activity was significantly increased in both patient groups compared with a control group. After B12 therapy, platelet MAO activity was significantly reduced in both patient groups to apparently normal levels. The present results show that B12 status is a controlling factor of platelet MAO activity and confirm that a significant connection exists between vitamin B12 deficiency and primary degenerative dementia disorders, such as SDAT.     

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.     

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 primary degenerative dementia

Platelet MAO activity was studied in 24 patients with primary degenerative dementia and 20 normal elderly controls. Demented patients had significantly higher platelet MAO activity than did controls. The increase was greater than that reported to occur in normal aging.     

Platelet MAO activity in anorexia nervosa patients with and without a major depressive disorder

Platelet MAO activity was determined in 33 anorexia nervosa patients. A subgroup of 15 patients who met Research Diagnostic Criteria for a concomitant major depressive disorder were found to have, both initially and after 5 weeks of treatment, significantly lower mean platelet monoamine oxidase (MAO) activity than 28 matched normal control subjects. In contrast, mean platelet MAO activity in the patients who did not meet criteria for major depressive disorder was similar to values in control subjects. The authors found that significantly more depressed patients had low MAO activity compared with nondepressed patients and controls. Platelet MAO activity may be useful in discriminating among subtypes of anorexia nervosa patients.     

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.     

Platelet MAO and amitriptyline treatment

Some tricyclic antidepressants have been reported to inhibit monoamine oxidase (MAO) activity in vitro in addition to blocking the reuptake of norepinephrine and/or serotonin. While the inhibition of MAO is reversible, platelet MAO activity in depressed patients responding to amitriptyline treatment has been reported to be reduced after drug treatment. In a reverse design, we measured platelet MAO activity and drug levels in patients chronically being treated with amitriptyline and again 2 and 4 weeks after stopping the medication. Although tricyclic drug concentrations were initially within the therapeutic range and undetectable on placebo treatment, platelet MAO activities were unchanged.     

Pain as a symptom in depressive disorders and its relationship to platelet monoamine oxidase activity

Summary 144 depressed in-patients were rated by means of the Comprehensive Psychopathological Rating Scale (CPRS) and platelet monoamine oxidase (MAO) was determined. 49 per cent of the patients were found to have pain as a symptom, and 21 per cent were found to have more severe pain. The patients with more severe pain were found to have lower platelet MAO activity than the patients without pain or with slight pain. As platelet MAO activity may reflect the turn-over in the serotinergic systems in CNS it is hypothesized that patients with depressive disorders with pain as a symptom may have more pronounced disturbances in the serotinergic systems than patients without pain as a symptom.     

The effects of paroxetine and tianeptine on peripheral biochemical markers in major depression

Depression is related to the alterations of the central serotonergic system and some antidepressants achieve their therapeutic effects through alteration of serotonin (5-HT) (re)uptake. Peripheral biochemical markers, platelet and serum 5-HT concentrations, platelet monoamine oxidase (MAO) activity, plasma levels of cortisol and prolactin (PRL), were investigated in patients with major depression before and after 4 weeks of treatment with paroxetine (an inhibitor of 5-HT uptake) or tianeptine (a stimulator of 5-HT uptake). Study was open, single center and included female depressed patients, 21 treated with tianeptine (37.5 mg/day) and 15 treated with paroxetine (20 mg/day), and 11 drug-free healthy women (controls). Before treatment, depressed patients as a group had significantly higher serum 5-HT and cortisol concentrations than healthy controls. There were no differences in the other biochemical markers. Response to antidepressant treatment was estimated according to the 50% fall in the initial scores of Hamilton Depression Rating Scale (HAMD) after 4 weeks of treatment. Good therapeutic response was observed in 47% and 45% patients treated with paroxetine and tianeptine, respectively. Paroxetine treatment induced significant decrease in platelet 5-HT concentrations in both responders and nonresponders, while no alterations in platelet 5-HT values were found in tianeptine-treated patients. There was a subgroup of depressed patients in paroxetine-treated group with high pretreatment platelet 5-HT concentration and later poor therapeutic response to paroxetine treatment. Serum 5-HT values, platelet MAO activity or plasma cortisol or PRL levels were unchanged after both treatments. The results suggest that pretreatment platelet 5-HT levels, but not other peripheral biochemical markers, might predict therapeutic outcome at least in paroxetine-treated patients.