Endogenous Depressive Patients Research Articles

HPA Axis Function as Biomarker for Atypical and Melancholic Depression

HPA Axis Function as Biomarker for Atypical and Melancholic Depression

Defense mechanisms in endogenous depression

Objectives: Defense mechanisms may be directly related to psychiatric diagnoses. There is an association between depression and maladaptive defenses, especially, the immature defenses. The aim of this study was to evaluate the defense mechanisms used by endogenous and non-endogenous patients by comparing those used by controls. Methods: The sample was composed of 92 treatment-naive patients with major depressive disorder (MDD; 46 endogenous type and 46 non-endogenous type) and 40 controls. The diagnosis of MDD in each participating patient was confirmed by means of the Structured Clinical Interview for DSM-IV, Turkish version, conducted by trained interviewers. Endogeneity of depression was assessed with Newcastle Depression Diagnostic Scale. Defense mechanisms were evaluated by using the Defense Style Questionnaire 40. Results: Immature defense mechanisms differentiated controls from all patients as well as they distinguished endogenous depressive patients from non-endogenous patients. The analyses indicated that endogeneity is characterized by passive-aggression, acting out, isolation, autistic fantasy, rationalization and somatization. Additionally, total scores of the immature defenses had a positive correlation with severity of depression in the endogenous group. Conclusions: The results of the present study showed evidence of some differences in defense mechanisms among endogenous depression and non-endogenous depression diagnoses, specifically the maintenance of a high immature defense style in endogenous depression patients when compared with non-endogenous depression patients.

Hormonal responses to the 5-HT1A agonist buspirone in remitted endogenous depressive patients after long-term imipramine treatment

The serotonin-1A (5-HT1A) receptor subtypes are considered as targets of a variety of antidepressant drugs. Previous studies have suggested different adaptive changes in pre- and post-synaptic 5-HT receptors in the brain after treatment with non-selective tricyclic antidepressants (TCA) and selective 5-HT re-uptake inhibitors (SSRIs). The present study aimed to investigate the adaptive effect of the TCA imipramine on the post-synaptic 5-HT1A receptor function in the hypothalamus. A longitudinal design was used in 14 patients with major depressive disorder (DSM-IV) with endogenous features (Newcastle Scale) in order to assess the functional status of post-synaptic 5-HT1A receptors before and after successful antidepressant treatment with imipramine. The effect of the 5-HT1A receptor agonist, buspirone, on ACTH, cortisol, and prolactine (PRL) plasma levels was used to assess the functional status of hypothalamic 5-HT1A receptors. A group of 15 concurrent normal subjects were used as control. Endogenous depressed patients in remission and currently receiving treatment with imipramine (mean length of treatment 145 days, SD=27) presented significantly lower buspirone responses to ACTH and cortisol than in the pre-treatment condition (Deltamax p< or =.05; AUC p<.001) and to ACTH in comparison with healthy controls (Deltamax p<.01; AUC p<.05). No significant differences were found between the post-treatment and pre-treatment PRL responses, or between patients in both conditions and controls; nevertheless, the PRL response in patients in remission and receiving treatment almost reached the values seen in controls. This study extends previous findings from our group using the SSRI citalopram as an antidepressant. Imipramine and citalopram induce similar changes in the endocrine response to buspirone in depressed patients. As the direction of change in ACTH-cortisol and PRL responses after treatment is the opposite, we cannot substantiate increases or decreases in the sensitivity of post-synaptic 5-HT1A receptors in the hypothalamus by long-term imipramine treatment and/or resolution of illness. Therefore, the hormonal changes may result from different or multiples unknown mechanisms.

Dimension of Typus melancholicus on Kasahara’s Inventory for the Melancholic Type Personality

Background: Traditionally, Typus melancholicus (TM) was considered, a priori, to represent unidimensionality. Recent studies have suggested that TM is not a personality trait, but rather a constellation of personality traits. The purpose of this study was to examine whether TM on Kasahara’s Inventory for the Melancholic Type Personality (KIMTP), considered to represent one of the valid TM questionnaires, is comprised of personality dimensions, and if so, which dimension is essential for distinguishing depressive subjects from control subjects. Subjects and Methods: To clarify the dimensionality of TM scores on KIMTP, factor analysis of the TM scores was conducted using principal factor analysis followed by varimax rotation. Comparisons were then made between endogenous depressive patients (n = 38), nonendogenous depressive patients (n = 20), and healthy volunteers (n = 81) for total KIMTP score and factor scores using analysis of covariance, adjusting for sex and age. Results: Factor analysis of KIMTP revealed 2 distinct clusters of items, i.e. ‘harmony in personal relationships’ (factor 1) and ‘social norms’ (factor 2). Endogenous and nonendogenous depressive patients showed significantly higher KIMTP total and factor 1 scores than did control subjects. However, no significant differences were observed for KIMTP total score and scores of individual factors between endogenous and nonendogenous depressive patients. Conclusions: The present results indicate that TM on KIMTP represents a constellation of personality traits, and that the factor ‘harmony in personal relationship’ possesses the essential meaning for assessing TM.

Typus melancholicus is not the premorbid personality trait of unipolar (endogenous) depression.

The present paper aims to examine whether Typus melancholicus is a distinguishing premorbid personality of unipolar (endogenous) depressive patients vis-à-vis psychiatric patients with different diagnoses and healthy control subjects. Two observer-rated scales for Typus melancholicus were administered to a consecutive series of psychiatric patients (n = 140) and a group of control subjects (n = 84). To the authors' own surprise, the only statistically significant finding was the low Typus melancholicus score among unipolar (endogenous) depressives in comparison with normal controls but not with other psychiatric patients. In addition, this finding held only for one of the two rating scales and among women only. According to the other rating scale for Typus melancholicus, there was no difference between unipolar (endogenous) depressives and the normal control or other psychiatric patients. These findings are discussed with particular emphasis on the methodological aspects of studies of premorbid personality of psychiatric disorders, a favored subject in the psychiatric science for decades.

Relationship between the Newcastle scale and sleep polysomnographic variables in major depression: a controlled study

In order to investigate the reliability of the endogenous concept of depressive illness with some sleep EEG parameters, we studied 39 male inpatients suffering from a nonbipolar major depressive episode (15 endogenous (MDDE) and 24 nonendogenous (MDDNE)) and 20 age and sex matched normal controls (C). All patients were diagnosed according to the Research Diagnostic Criteria (RDC) and the endogenous character of the episode was assessed with the Newcastle Endogenous Depression Diagnostic Index. We found significant differences for the following variables between the three groups (MDDE, MDDNE and C): sleep period time (SPT), REM latency, stage II, slow wave sleep (SWS), REM latency expressed as a continuous variable and REM latency expressed as a dichotomizing variable with a threshold of 50 min. These variables were used to compare the endogenous and the nonendogenous depressed patients and also the major depressed patients and the normal controls. Significant differences were observed between all depressed patients and control subjects for amount of SWS and REM latency which were both reduced in endogenous and nonendogenous depressed patients. No significant difference was observed between endogenous and nonendogenous depressed patients, except for the REM latency expressed with a threshold of 50 min (more frequently observed in endogenous depressed patients). Our data support the observation that SWS and REM latency are decreased in major depressive patients. However, in this age and sex controlled study, subtyping nonbipolar major depressive disorder for an endogenous character by the Newcastle Endogenous Depression Diagnostic Index (NEDDI) did not reveal further significant differences for sleep EEG variables, except for the shortening of the REM latency expressed as a dichotomizing variable.

Brofaromine in endogenous depression

1. Recently, a new generation of monoamine oxidase (MAO) inhibitors has been developed which selectively and reversibly inhibit MAO-A activity. 2. One of these compounds, called brofaromine, has been administered in subjects suffering from endogenous depression, revealing antidepressive efficacy in a majority of them without inducing serious adverse events. 3. The results obtained so far suggest that brofaromine might be effective in endogenous depressed patients who failed to respond to tricyclic antidepressants.

Cortisol reaction in success and failure condition in endogenous depressed patients and controls

The authors studied differences in cortisol response to controllable and uncontrollable stress and its relationship to Seligman's theory of learned helplessness in hospitalized unipolar depressed patients (11 nontreated, acutely depressed; 11 treated patients) and 11 age and sex matched controls hospitalized for traumatic surgery. Control and lack of control were achieved by induction of success and failure in a simple number addition test and applied in balanced order on 2 consecutive days. Saliva cortisol samples were collected before and after the test. No group differences in baseline cortisol levels were observed. Cortisol increased after uncontrollable and decreased after controllable stress in control patients, whereas cortisol decreased after both conditions in the acutely depressed group and less so in the treated group, although they were as emotionally upset after failure as controls. Thus, the normally observed ability of the neuroendocrine system to discriminate between controllable and uncontrollable stress deteriorates with increasing severity of depression.

Effects of tricyclic antidepressant treatment on tyramine-O-sulfate excretion in depressed patients

The urinary excretion of tyramine-O-sulfate following an oral load of tyramine (Tyramine Challenge Test, ‘TCT’) was measured in a group of fourteen inpatients with unipolar and bipolar major depressive episode. TCT was done both during a pretreatment baseline period and following four weeks of treatment with tricyclic antidepressants. The change in TCT values after treatment correlated with improvement in depression. The previously described ability of TCT to discriminate between endogenous and nonendogenous depressed patients was confirmed at baseline. However, following tricyclic antidepressant treatment, TCT values were not significantly different between endogenous and nonendogenous patients.

Psychomotor disturbances in psychiatric patients as a possible basis for new attempts at differential diagnosis and therapy. V. Evaluation of psychomotor training programs in depressed patients.

Parts I-III of this series used psychometric assessment of motor performance in psychiatric patients and indicated a "psychotic-motor syndrome" (PMS) in schizophrenic and affective psychoses, which was not found in "neurotic"/reactive or healthy persons. Part IV yielded signs of concomitant brain dysfunction in these patients, demonstrated by EEG mapping as well as other (SPECT/PET) neuroimaging methods. Apart from this "basic science" interest into the pathophysiology of endogenous psychoses we engaged in the development of motor training programs using the PMS as "target" syndrome. We hypothesized, that motor training would not only improve disturbed motor behaviour, but ameliorate other symptoms of psychopathology also. These assumptions were supported in the first two independent studies involving n = 45 and n = 31 ICD-9 mono- and/or bipolar endogenous depressed patients, respectively (the studies on schizophrenic patients being reported finally as part VI of this series, along with the final version of our modified motor test battery). Examples of the motor training programs are provided in this paper, although the final version of the complete programs will be published separately for space reasons and for better availability for routine clinical use.

24-hour profiles of cortisol and melatonin and sleep parameters in endogenous depressive patients and healthy controls

24-hour profiles of cortisol and melatonin and sleep parameters in endogenous depressive patients and healthy controls

BROFAROMINE IN ENDOGENOUS DEPRESSION

Abstract 1. Recently, a new generation of monoamine oxidase (MAO) inhibitors has been developed which selectively and reversibly inhibit MAO-A activity. 2. One of these compounds, called brofaromine, has been administered in subjects suffering from endogenous depression, revealing antidepressive efficacy in a majority of them without inducing serious adverse events. 3. The results obtained so far suggest that brofaromine might be effective in endogenous depressed patients who failed to respond to tricyclic antidepressants.

Antidepressive effects of the selective MAO-inhibitor brofaromine:an open trial

SummaryIn an open prospective study, the antidepressive effects of the selective and reversible MAO-A inhibitor, brofaromine, were investigated in nine endogenous depressed patients, who had failed to respond to cyclic antidepressants. In three patients a clinically relevant improvement was observed, although for the total group, no statistically significant treatment effect could be demonstrated. In two subjects, postural hypotension and sleep disturbances occurred temporarily.

Zur Tagesschwankung der Depressionssymptomatik

New symptom-statistical, chronobiological and experimental investigations concerning diurnal variation in endogenous depression (melancholia) are reported and interpreted referring to psychopathological, biological and phenomenological aspects. According to recent studies, the so-called typical diurnal variation of mood (with morning low) is not as frequent, as it was assumed before, and even intraindividually unstable. Although more frequent than other daily rhythmus, the so called typical diurnal variation should not be used for diagnostic purposes, because it is quite frequent in different depressive states as well. During their healthy intervals endogenous depressive patients show not rarely an analogous diurnal variation of mood; this was also found in healthy subjects. Therefore the so called typical variation in mood is not specific, and it is questionable whether it is a marker of endogenous depression at all. Concerning circadian rhythm biological functions were examined more often than the depressive symptomatology itself (especially temperature, heart rate, cortisol and other neuroendocrine parameters). Unexpectedly there were only slight variations of the circadian diurnal curves in melancholic patients compared to healthy subjects. The circadian rhythm in endogenous depression does not seem to be very different from the physiological diurnal course. Comparing the biological circadian curves in endogenous depression to the curves of the depression symptomatology, the similarities outline the differences. Sleep research didn't show any results, supporting the suggestion of a specific rhythm variation either. Therefore the opinion, that the circadian rhythm is altered basically in melancholia, cannot be maintained, neither psychopathologically nor biologically. Experiments of time estimation in the course of the day could'nt explain the diurnal variation in mood either.

Decreased seasonal mesor of platelet 3H-imipramine binding in depression

Seasonal cycles of platelet 3H-imipramine binding were compared in 49 endogenous unipolar depressed patients and 20 normal volunteers. A significant sinusoidal component was detected in the B max of binding in both patients and controls with similar amplitudes and seasonal peaks. However, the yearly average (mesor) of the patient group was significantly lower (20.0%) than that of the normal controls. The results support earlier claims of a diminished platelet binding in endogenous depression and indicate that this decrease was still evident in the presence of a 48.2% (controls) to 65.8% (patients) seasonal variation. Control B max values were normally distributed about a best-fit mean (cosinor fit). In contrast, patient values appeared to be bimodally distributed with one mode that was similar to controls and one mode that was substantially lower. In general, psychiatric symptoms failed to distinguish between patients with high and low platelet binding and no correlation was found between B max and severity of illness (HAM-D).

Biological clocks in depression: phase-shift experiments revisited

SummaryFive endogenous depressed patients were asked to participate in a phase-shift experiment consisting of advancing, by 5 hours, the time-schedule of the major external synchronizers such as light/dark cycle, sleep/wake, meal-time and social activity cycles. Clinical and biological parameters (body temperature, plasma cortisol, TSH and norepinephrine (NE) circadian rhythms) were observed throughout this two week period. The circadian rhythms were severely altered in the pre-treatment period, with a significant reduction of amplitude. During the phase shift experiment, the clinical state of the patients improved significantly. Their circadian rhythms were dramatically impaired in the first days of the procedure and were then restored after the first week, with higher amplitude. However, the TSH circadian rhythm remained unentrained by the phase shift leading to an internal desynchronization. Our findings suggest that entrainment of internal clocks by environmental information may be impaired in depression.

Time Estimation and the Experience of Time in Endogenous Depression (Melancholia): An Experimental Investigation

The importance of disturbances in time experience in endogenous depression (melancholia) has long been under discussion. In the present study alterations of time experience were examined by means of time estimation experiments. 25 endogenous depressive patients (according to ICD-9) underestimated prospectively a 30-second interval by 6 s, whereas 12 healthy controls overestimated this interval by more than 10 s. The results are based on eight successive measurements over a period of 2 days. In the endogenous depressives, a feeling of being unwell was accompanied by a more pronounced time estimation error than a relatively good state of well-being. The influence of various patient data on the results of time estimation is also discussed in detail. The findings show clearly that time estimation provides a satisfactory delineation between depressive patients and healthy controls.

Effects of chronic imipramine treatment on subclasses of platelet 3H-imipramine binding sites and plasma cortisol

A decreased density of platelet 3H-imipramine ( 3H-IMI) binding sites has been proposed as a putative trait marker of major depressive illness. However, subsequent studies have demonstrated that the number of such sites is increased so as to be more like normal controls upon chronic treatment with antidepressant drugs. In addition, there is some evidence to suggest that altered 3H-IMI binding may be secondary to elevated plasma cortisol levels which are common in depressed patients and which normalize with remission. The present study compares platelet 3H-imipramine binding, plasma cortisol levels, and clinical improvement of 10 endogenous depressed patients before and after 6 weeks of treatment with imipramine-HC1. Total high affinity 3H-IMI binding sites were further differentiated into two subclasses on the basis of their relative sensitivities to cyanoimipramine (CNIMI) inhibition. Treatment was associated with a significant increase (134%) in CNIMI resistant binding but a decrease (45.2%) in CNIMI sensitive binding. While the former was significantly correlated with posttreatment cortisol levels, no significant correlation was found between cortisol and CNIMI specific binding. Neither site appeared to be directly related to mood state. The significance of these findings to the evaluation of platelet binding as a trait dependent marker is discussed.

Platelet imipramine binding in endogenous depressed patients and controls: Relationship to platelet MAO and 5HT uptake during successful imipramine treatment

Platelet imipramine binding was measured in 25 unmedicated depressed patients and 25 age- and sex-matched healthy controls. In the patients, the measurement was repeated after 3 weeks and 2 months of imipramine treatment leading to clinical recovery. No significant differences in imipramine binding were found between controls and unmedicated patients. In the latter, imipramine administration produced a progressive change in the binding characteristics, increasing the apparent K d and decreasing the number of binding sites ( B max). The results suggest that platelet imipramine binding is not altered in depression and that changes in this parameter are the consequence of the presence of imipramine in the blood stream. However, such changes accompany changes in other biological parameters, such as platelet monoamine oxidase and serotonin uptake, seen in the same patients througout imipramine treatment, suggesting that the drug acts on a wide range of normal or altered serotonin-related cellular mechanisms while it accelerates the clinical recovery from depression.

Moclobemide versus clomipramine in the treatment of depression: a double‐blind multicentre study in Belgium

Moclobemide and clomipramine were compared for efficacy, tolerance and safety in 63 mixed endogenous and nonendogenous depressed patients. Treatment was given for at least 4 weeks in a double-blind, randomized, parallel-group design. The mean Hamilton Rating Scale for Depression score decreased gradually during treatment with no differences between groups. Two patients on clomipramine and none on moclobemide were withdrawn for lack of efficacy, and poor tolerance caused 3 patients on moclobemide and 7 on clomipramine to stop treatment prematurely. Patients with endogenous depression responded better to clomipramine, whereas nonendogenous disorders did better on moclobemide. Adverse events were more frequent in the clomipramine group and more of these were severe or very severe than for moclobemide. Thus, although no significant difference in efficacy was seen, moclobemide appeared to be tolerated better than clomipramine. The numbers were small, however, and many patients received concomitant medication, and the results are therefore difficult to interpret.