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.     

Noradrenergic function and the cortisol response to dexamethasone in depression

Abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis and the noradrenergic system have been reported in depression. To study possible interrelations between these two systems, plasma free 3-methoxy-4-hydroxyphenylglycol (MPHG) was compared with the cortisol response to dexamethasone in 64 depressed patients. Postdexamethasone cortisol nonsuppressors had higher baseline plasma free MHPG values than did cortisol suppressors. Increased severity of some depressive symptoms was associated with increased postdexamethasone cortisol levels. These results indicate that depressed patients with dexamethasone nonsuppression have increased noradrenergic turnover.     

Dopaminergic function and the cortisol response to dexamethasone in psychotic depression

1. It has been hypothesized that psychotic symptoms in depression may be due to increased dopamine activity secondary to hypothalamic-pituitary-adrenal (HPA) axis overactivity. 2. To test this hypothesis, the authors examined the cortisol response to dexamethasone suppression test (DST, 1 mg orally) and multihormonal responses to apomorphine (APO, 0.75 mg s.c.)--a dopamine agonist--in 150 drug-free hospitalized patients with DSM-IV major depressive episode with psychotic features (MDEP, n=35), major depressive episode without psychotic features (MDE, n=74), or schizophrenia paranoid type (SCZ, n=41), and 27 hospitalized healthy controls (HCs). 3. MDEPs showed increased activity of the HPA system (i.e. higher post-DST cortisol levels) than HCs, SCZs and MDEs. However, there were no differences in adrenocorticotropic hormone (ACTH), cortisol, prolactin and growth hormone (GH) responses to APO between MDEPs and MDEs and HCs. On the other hand, SCZs showed lower APO-induced ACTH stimulation and a higher rate of blunted GH than HCs, MDEs and MDEPs, suggesting a functional alteration of the hypothalamic dopamine receptors in SCZs. 4. In the total sample and in each diagnostic group, DST suppressors and non-suppressors showed no differences in hormonal responses to APO. 5. These results suggest a lack of causal link between HPA axis hyperactivity and dopamine dysregulation. In contrast to schizophrenia, psychotic symptoms in depression seem not to be related to dopamine function dysregulation.     

Platelet MAO activity and the dexamethasone suppression test in depressed patients

Platelet monoamine oxidase (MAO) activity and postdexamethasone cortisol levels were determined in 26 depressed patients. The incidence of cortisol nonsuppression and the mean postdexamethasone cortisol levels were significantly higher in patients with high MAO activity than in those with low MAO activity.     

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 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.     

Platelet MAO activity, TRH test, and dexamethasone suppression test in depressed patients

Platelet MAO activity, TRH test and DST results were compared in 23 normal subjects and 13 depressed patients. Patients as a group were older in age, had higher levels of FT4-index and T3-uptake, and lower levels of MAO activity. There was no association between thyroid hormones, including TSH response, and MAO activity. Five patients were DST positive. They showed a higher average age and a higher T3-uptake value than DST negative patients. Serum T4 and MAO activity levels were normal in both groups. These data suggest that MAO activity and TSH are independently regulated in both normal subjects and depressed patients. They also suggest a reduced binding capacity for thyroid hormones in patients with positive DST.     

Number of cortisol time-points and dexamethasone suppression test sensitivity for major depression

Failure to suppress cortisol secretion after administration of dexamethasone has been reported to be a diagnostic marker for major depression and to have prognostic implications when repeated after antidepressant treatment. The pulsatile pattern of cortisol secretion suggested to us that increasing the number of post-dexamethasone cortisol determinations might significantly increase the sensitivity of the dexamethasone suppression test (DST) for major depression. With a conventional two-point DST (1600 h and midnight), 5% of 20 normal volunteers, 8% of 13 inpatients with non-major depressions, and 31% of 65 inpatients with primary major depression failed to suppress. With six post-dexamethasone points (0800 h, 1200 h, 1600 h, 2000 h, 2200 h, midnight), the respective percentages were 10, 15 and 44%. The additional points increased the sensitivity from 31 to 44%, mostly by identifying more major depressives with a "late escape" pattern. If a clinician is using the DST to establish a marker for major depression that can be repeated to monitor response to treatment and the likelihood of relapse, then perhaps the increased sensitivity of the six-point DST would be helpful, despite a modest decrease in specificity from 94 to 88%.     

The dexamethasone suppression test and antidepressant response in major depression

We conducted a prospective open pilot study of 34 consecutively admitted patients with the DSM-III diagnosis of MD who were admitted to a general psychiatric unit. Patients underwent a 1 mg DST and were randomly assigned to treatment with either maprotiline or trazodone. Antidepressant dosages were increased as tolerated clinically and according to treatment response. Results: mean final oral doses were 193 mg for maprotiline and 328 mg for trazodone. The mean treatment duration was 4.5 weeks for maprotiline and 5.9 weeks for the trazodone group. Of these 34 patients 44% showed DST nonsuppression (41% maprotiline, 45% trazodone). Seventy-six per cent of the patients responded to treatment (76% for both drugs) as defined by GAS. Eighty-seven per cent of the nonsuppressors responded to treatment (86% maprotiline, 88% trazodone) and 68% of the suppressors responded (70% maprotiline, 67% trazodone). Of the eight treatment nonresponders six showed DST suppression. The implications of these findings are discussed.     

Lithium augmentation increases post-dexamethasone cortisol in the dexamethasone suppression test in unipolar major depression

Although considerable evidence exists on the efficacy of lithium as an augmenting agent in refractory depression, the underlying neurobiology of this phenomenon is unknown. In patients with major depression, changes of the hypothalamic-pituitary-adrenocortical (HPA) system have been detected by means of the dexamethasone suppression test (DST), when administered during treatment with tricyclic antidepressants. We investigated whether the DST also reveals alterations of the HPA system during lithium augmentation. We also sought to identify whether response to lithium augmentation can be predicted with the DST. Twenty-five patients with unipolar major depression, who did not respond to an adequate antidepressant monotherapy of at least 4 weeks, were measured for basal (pre-dexamethasone, 0800h) cortisol and ACTH levels and were administered the DST the day before initiation of lithium augmentation treatment. The same neuroendocrine procedures were repeated after 3 to 4 weeks. Criteria of response to lithium augmentation, defined as a reduction of the Hamilton Depression Rating Scale (HDRS17) score by > or =50% and an end point score of 9 or less, were determined by weekly HDRS ratings. The DST revealed a statistically significant increase of the post-dexamethasone cortisol values (P = 0.021) and an increase in the post-dexamethasone ACTH values (P = 0.051) during lithium augmentation as compared to pre-treatment baseline evaluations. The pre-dexamethasone hormone values were unchanged. The number of non-suppressors at baseline was one and increased to three at follow-up. Results of DST did not predict response to lithium augmentation, which occurred in 40% of subjects. Results suggest that lithium augmentation increases HPA system activity, as indicated by the increase of post-dexamethasone cortisol and ACTH levels measured by the DST. This is in contrast to the established decline of HPA system activity during treatment with tricyclic antidepressants.     

Basal hypersecretion of cortisol in relation to abnormal dexamethasone suppression test response in depression

1. The activity of the hypothalamus-hypophysis-adrenal axis was evaluated in a group of patients with primary affective disorder by correlation of basal cortisol hypersecretion and abnormal response to dexamethasone suppression test (DST).

2. The increase in basal cortisol was not found to be responsable for suppression failure.

3. Moreover, this -biochemical abnormality was common in the groups of psychiatric patients studied, although the psysiopathologic mechanisms involved are different. Further research is necessary to clarify the results.     

Platelet MAO activity and age at onset of depression in elderly depressed women

Platelet monoamine oxidase (MAO) activity was assayed in 38 elderly depressed women and 16 matched controls. The depressed women whose illness began at age 55 or earlier (N = 19) had significantly lower MAO activity than patients with later onset (N = 19) or controls.     

Platelet 3H-imipramine binding and response to minaprine in patients with major depression

Platelet 3H-imipramine binding was studied in 37 patients fulfilling Research Diagnostic Criteria for major depressive disorder, examined before and after four weeks of treatment with minaprine 200 mg/day, and in 19 healthy controls. Mean baseline Bmax values of depressed patients were found to be significantly lower than those of controls, while no significant difference between the two groups was observed with respect to mean Kd. Treatment with minaprine did not significantly affect Bmax or Kd in depressed patients. When patients who responded to treatment (n = 18) were compared with nonresponders (n = 19), mean baseline Bmax values were found to be significantly lower in the former group, whereas mean Kd values did not differ. It is hypothesized that reduced 3H-imipramine binding may represent a predictor of a favorable response to antidepressant drugs which potentiate serotonergic transmission.     

Platelet MAO activity and personality characteristics

Low levels of platelet monoamine oxidase have been found in schizophrenic and bipolar depressive patients. The enzyme activity seems to correlate negatively with certain personality traits (social activity, sensation seeking, hypomania, positive affect and monotony avoidance) which are correlated to some extent with the score “extraversion” from the Eysenck Personality Questionnaire (EPQ). The present study was carried out in an attempt to investigate further the possible correlation between platelet MAO activity and the personality traits measured by the EPQ. 41 schizophrenic patients and 20 healthy probands were blindly examined for platelet MAO activity and personality characteristics. The enzyme activity was found to correlate negatively with the extra-version score in patients and healthy probands, which is in agreement with the data from other studies. This correlation is discussed and a hypothesis suggested.     

Effects of trauma exposure on the cortisol response to dexamethasone administration in PTSD and major depressive disorder

OBJECTIVE: To evaluate cortisol suppression following 0.5 mg of dexamethasone (DEX) in trauma survivors (N=52) with posttraumatic stress disorder (PTSD), major depressive disorder (MDD), both, or neither disorder, and in subjects never exposed to trauma (N=10), in order to examine interactions between diagnosis and trauma history on cortisol negative feedback inhibition. METHOD: Lifetime trauma exposure and psychiatric diagnoses were assessed and blood samples were obtained at 8:00 a.m. for the determination of baseline cortisol. Participants ingested 0.5 mg of DEX at 11:00 p.m. and blood samples for determination of cortisol and DEX were obtained at 8:00 a.m. the following day. RESULTS: PTSD was associated with enhanced cortisol suppression in response to DEX. Among trauma survivors, the presence of a traumatic event prior to the "focal" trauma had a substantial impact on cortisol suppression in subjects with MDD. Such subjects were more likely to show cortisol alterations similar to those associated with PTSD, whereas subjects with MDD with no prior trauma were more likely to show alterations in the opposite direction, i.e. relative non-suppression. CONCLUSIONS: Cortisol hypersuppression in PTSD appears not to be dependent on the presence of traumatic events prior to the focal trauma. However, prior trauma exposure may affect cortisol suppression in MDD. This finding may have implications for understanding why only some depressed patients show non-suppression on the DST.     

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.     

Plasma cortisol, catecholamine and cyclic AMP levels, response to dexamethasone suppression test and platelet MAO activity in manic-depressive patients. A longitudinal study

Plasma cortisol, catecholamine and cyclic AMP levels, response to dexamethasone suppression test and platelet MAO activity have been determined in 15 patients suffering from bipolar affective psychosis, each examined during a depressive, a manic and an euthymic phase, and in 15 sex- and age-matched normal controls. Mean basal and post-dexamethasone cortisol levels have been found to be enhanced in patients during depression, but not during mania or free intervals. Non-suppression of cortisol secretion after dexamethasone has been observed in 46.7% of patients while in a state of depression, but in none of them during mania or euthymia. Mean plasma noradrenaline and adrenaline levels, which are thought to be the most reliable biochemical indices of emotional arousal, have been found to be increased in patients during mania, but not during depression. No significant difference has been observed between patients during any phase of their illness and controls with regard to mean plasma cyclic AMP levels and platelet MAO activity. These results confirm the state-dependent overactivity of HPA axis in endogenous depression, and suggest that it should not be regarded as a correlate of emotional hyperarousal. Moreover, they do not support the postulated role of plasma cyclic AMP as a state variable and of platelet MAO activity as a trait variable for manic-depressive illness.     

Cognitive impairment and cortisol resistance to dexamethasone suppression in elderly depression

The present study evaluates the relationship between cognitive impairment and the Dexamethasone Suppression Test (DST) in elderly persons suffering from depression. Twenty-nine subjects meeting DSM-III criteria for major depressive disorder (MDD) were assessed using the Global Deterioration Scale (GDS) and the DST. Plasma cortisol levels before and after receiving 0.5 mg dexamethasone were compared, and correlations were determined between GDS and postdexamethasone plasma cortisol levels. The results show that there is a positive correlation between the GDS scores and post-DEX cortisol levels (r = 0.57, p less than 0.005). It is suggested that increased activity of the HPA axis, seen in depression, could contribute to the cognitive impairments observed in this disorder.     

Influence of age on the cortisol response to dexamethasone

Controversy exists regarding the association of age with postdexamethasone serum cortisol levels. We evaluated this relationship in 95 patients with major depressive disorder and 49 healthy controls. Age and 8 a.m. postdexamethasone cortisol levels were not correlated among the healthy controls, but were positively associated among the depressives. There was also a trend for age and 4 p.m. postdexamethasone cortisol levels to be positively associated in depressives. Multiple linear regression analyses revealed that these associations could not be explained by other variables such as sex, psychotic features, or familial subtype of depression. Several hypotheses that might account for these associations are examined.