B-endorphin response to a low dosage of human corticotropin releasing hormone during metyrapone administration in depression.

This study defines the pituitary B-endorphin (BE) secretory response to a low dosage (0.3 ug/kg) of human corticotropin releasing hormone (CRH) in depressed patients and normal controls pretreated with metyrapone. We find no difference in the B-endorphin response to CRH in depressed subjects without evidence of HPA overactivity, compared with controls. This finding is contrasted with other data demonstrating a blunted B-endorphin response to CRH in depressives. The influence of metyrapone pretreatment on the pituitary B-endorphin response to CRH through a mechanism that minimizes the impact of cortisol negative feedback is discussed. Future studies which include low dose CRH infusion both in the presence and in the absence of metyrapone pretreatment will help investigate alterations in the regulation of pituitary B-endorphin secretion in depression including the possibility of increased pituitary sensitivity to the negative fast feedback of cortisol.

Augmented pituitary corticotropin response to a threshold dosage of human corticotropin-releasing hormone in depressives pretreated with metyrapone.

We studied pituitary corticotropin response to exogenous corticotropin-releasing hormone infusion and attempted to control for the confounding effect of variable serum cortisol levels between depressed and control subjects. If metyrapone was given during the time of day when hypothalamic pituitary adrenal activity was otherwise low, the relative increase in the corticotropin concentration was small. Pituitary response to exogenous corticotropin-releasing hormone can be defined under conditions in which the amount of glucocorticoid-mediated negative feedback present at the level of the pituitary gland is equal in all subjects. When the ambient cortisol level was equalized (and suppressed) in all subjects at the time of study with a threshold dosage of corticotropin-releasing hormone, we found an augmented response to corticotropin-releasing hormone in depressives. This raises the possibility that either increased pituitary sensitivity to corticotropin-releasing hormone or an increased intracellular pool of corticotropin is available for release in subjects with major depressive illness.

Prolactin, cortisol, and antidepressant treatment.

In four depressed patients with abnormal dexamethasone suppression test results before treatment, plasma prolactin levels significantly increased after successful amitriptyline therapy. Such an increase did not take place in five depressed patients with normal dexamethasone suppression test findings.

Nocturnal prolactin and cortisol secretion and recovery from melancholia.

Spontaneous prolactin and cortisol patterns were determined at 20 min intervals over 3 hr during the night in eight patients with melancholia, both during illness and after treatment with amitriptyline. Mean plasma prolactin levels were greater after recovery in the seven patients who responded to treatment. Mean cortisol secretion decreased upon recovery from melancholia, and such changes in two patients paralleled normalization of dexamethasone suppression test responses. The influence of assumptions of lack of interaction on the statistical significance of the analysis of variance with repeated measures for prolactin and cortisol values was evaluated.

Rating depression in normals and depressives: observer versus self-rating scales.

Different methods of assessing depression and anxiety were tested in 20 patients suffering from a major depressive disorder with melancholia and 20 matched control subjects. Depressives were assessed before and after treatment with amitriptyline and normals were retested at the same interval. The scales used were: Paykel's Clinical Interview for Depression--which is an expanded version of the Hamilton Depression Rating Scale; the Brief Depression Rating Scale; and Symptom Questionnaire (SQ). All scales discriminated sensitively between patients and normals and the scores changed substantially with treatment. Except for the well-being subscales of the SQ, the scales showed an adequate test-retest reliability in normals. Although all scales were suitable for the measurement of depression, they differed in psychometric properties. For example, the Depression subscale of the SQ showed an unusually high test-retest reliability in normals, whereas the Contentment subscale was unreliable. Yet, the latter has been found to be highly sensitive in detecting differences between the effects of psychotropic drugs and placebo in drug trials, so it appears to measure sensitively a fleeting mood. The combined use of all three scales in patients with affective disorders yields information that might not be revealed if only one scale is used.

Hostility and recovery from melancholia.

Twenty inpatients suffering from major depressive illness with melancholia were administered the hostility subscale of the Kellner Symptom Questionnaire and Paykel's Clinical Interview for Depression before and after treatment with amitriptyline. A matched control group of normal subjects had the same assessments at two points in time. Hostility decreased and friendliness increased in depressives after amitriptyline; upon recovery, there were no significant differences in hostility between depressed patients and control subjects, whereas such differences were striking during the illness. Patients who had reported losses before onset of illness rated themselves as more friendly than the other depressives; their hostility did not significantly decrease with recovery. The results suggest that hostility improves with the treatment of depression; life events appear to influence the degree of hostility in depressive illness as well as the response to treatment.

Hypochondriacal fears and beliefs in DSM-III melancholia. Changes with amitriptyline.

The authors administered the Illness Attitude Scales, which identify hypochondriacal patients, to 20 nonpsychotic inpatients with DSM-III diagnosis of melancholia before and after 4 weeks of treatment with amitriptyline, and to a matched group of normals. Before treatment characteristic hypochondriacal responses occurred in over one-third of melancholics whereas after treatment the number was the same as in normals. The findings are in accord with the clinical observation that melancholia is one of the causes of hypochondriacal fears and beliefs and these tend to remit with recovery from depression.

Treatment responses in primary and secondary melancholia: a preliminary report.

Ten patients suffering from primary affective illness and melancholia were compared to 10 melancholic subjects whose depression was chronologically superimposed on a preexisting nonaffective psychiatric disturbance. Both groups displayed a satisfactory response to treatment with amitriptyline. Similar patterns of improvement were reported in the two groups, and there was a concordance of subjective and objective rating methods.

The dexamethasone suppression and metyrapone tests in depression.

The dexamethasone suppression test (DST) and the metyrapone test (MT), a useful and reliable procedure for assessing the integrity of the hypothalamic-pituitary-adrenal (HPA) axis, were performed in 28 patients suffering from major depressive illness with melancholia. The relationship between the DST and MT appeared to be complex. Patients who failed to suppress cortisol secretion after dexamethasone administration had higher postmetyrapone cortexolone levels and cortexolone/cortisol ratios than suppressors. However, there was a wide range of metyrapone responses in patients exhibiting abnormal DST results. This suggests that failure of adequate suppression after 1 mg of dexamethasone in depressed patients does not necessarily reflect homogeneity in the HPA axis disturbances of such patients.

Effects of tricyclic antidepressants on platelet monoamine oxidase activity.

The eight subjects in this study were diagnosed as having primary or secondary depression and were treated with amitriptyline, 100 to 300 mg/day. Activity of platelet monoamine oxidase (MAO), an enzyme responsible for the degradation of biogenic amines, was determined before and after treatment with amitriptyline. Pretreatment values for MAO activity ranged from 17.94 to 44.89 U. After amitriptyline the values ranged from 0.66 to 41.94 U, a mean decrease of 50.2%. These results are consistent with the hypothesis that the tricyclic antidepressants act, at least in part, by inhibition of MAO.

Prolactin, amitriptyline, and recovery from depression.

Spontaneous prolactin patterns were determined at 15-min intervals over 5 h in 13 patients, who were suffering from melancholia, during illness and after treatment with amitriptyline. Plasma prolactin levels were significantly greater at most sampling points after patients had recovered than during their illnesses. One patient, who did not recover, showed the opposite trend.

Psychosomatic aspects of hyperprolactinemia.

A review of some recent studies on the psychosomatic aspects of hyperprolactinemia is presented. Women seem to be more prone to suffer from the behavioral effects of prolactin than males. Women with hyperprolactinemic amenorrhea rated themselves significantly more hostile, more depressed and more anxious than women with amenorrhea only and other control groups. Hyperprolactinemic males did not rate themselves more hostile and depressed than matched controls. Psychological distress and hostility appear to remit upon treatment with bromocriptine. Postpartum patients matched for prolactin levels with hyperprolactinemic women showed significantly less depression and anxiety but about the same levels of hostility. Hostility, depression and loss of libido may coexist in the same hyperprolactinemic patient but they may be also present independently.