Nonendogenous Patients Research Articles

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.

Serum β-endorphin level in patients with depression on fluvoxamine

The main interest of the present study was to determine possible alterations in β-endorphin serum levels in healthy volunteers and in patients with depression, as well as changes in β-endorphin serum levels caused by fluvoxamine treatment. Fluvoxamine maleate (Fevarin®) was administered orally at a dose of 200 mg/day for 4 weeks. The serum levels of β-endorphin were lower in patients with ‘nonendogenous’ depression (104.68±5.29 pg/ml) and those with ‘endogenous’ depression (36.34±2.23 pg/ml) than in healthy volunteers (125.19±1.64 pg/ml). The endogenously depressed patients had significantly lower β-endorphin levels than the nonendogenous patients. A 4-week treatment of fluvoxamine (200 mg/day) caused a statistically significant increase in β-endorphin serum levels in all patients (nonendogenous depression 132.10±2.38 pg/ml and endogenous depression 50.09±2.45 pg/ml) in comparison to values found before the onset of the therapy. The efficacy of fluvoxamine was 11.0 (±9.0) evaluated by the Hamilton Rating Scale for Depression (HAMD) in the patients with a diagnosis of depression. These results indicate that determination of β-endorphin serum levels could be a valuable laboratory test in the diagnosis of depression.

Neuroendocrine and sleep variables in major depressed inpatients: role of severity

To evaluate the reliability of the endogenous concept of depressive illness according to the Newcastle Endogenous Depression Diagnostic Index (NEDDI), 155 major depressive inpatients with NEDDI scores ≥ 6 (endogenous) were matched for gender and age (± 5 years) to 155 major depressive inpatients with NEDDI scores ≤6 (nonendogenous). When sleep polygraphic variables, neuroendocrine parameters (dexamethasone suppression and thyrotropin-releasing hormone tests), and various clinical variables (unipolar/bipolar status, psychotic/nonpsychotic subtype, and severity of the depressive episode) were examined, statistically significant differences between endogenous and nonendogenous patients emerged for three variables: the thyroid-stimulating hormone response to the thyrotropin-releasing hormone test, the dexamethasone suppression test response at 16:00 h, and the percentage of time awake during the night. However, when the effects of age and severity of depression were controlled, those differences disappeared.

Frontal and parietal metabolic disturbances in unipolar depression

The authors investigated brain glucose utilization using positron emission tomography (PET) in 12 normal volunteers and 12 unipolar unmedicated depressed patients (six endogenous; six nonendogenous) following injection of [18F]fluoro-deoxyglucose (FDG). Compared by analyses of variance, absolute and relative regional glucose metabolic rates appeared different in depressed patients and control subjects, especially in parietal and frontal lobes. In patients with unipolar depression, metabolic rates were increased in the orbital part of the frontal lobe and decreased in a frontal dorsolateral area. The metabolic supero-basal gradient calculated in the frontal cortex was significantly lower in depressed patients than in normal subjects. Decreased glucose metabolism was also observed in the parietal cortex of depressed patients. No differences in glucose metabolic rates have been detected between endogenous and nonendogenous patients. No correlation has been found between the metabolic data and the Hamilton Rating Scale.

Regional cerebral blood flow in affective disorder.

The results of two-dimensional cerebral blood flow (CBF) studies in depression and the results of measurements of regional CBF (rCBF) using single photon emission computerized tomography (SPECT) are briefly reviewed. A technical outline of both types of method is described. The majority of SPECT studies point to a decreased CBF in untreated patients with a tendency towards normalization, but other studies suggest that, following treatment, there is an increase above normal either from a decreased or an abnormally high initial level. One study has pointed to unipolar patients having lower flow in the right temporal and parietal lobes relative to normals, whereas non-endogenous patients did not differ significantly from normal controls. Bipolar depressives have been found to have higher flow values than normals in the parietal and temporal lobes in the left hemispheres. This relevant aspect or a possible relationship between type of depression and hemispheric asymmetry needs further study for full classification. Thus, most investigations designed to determine which brain structures might be involved in regulating affect have not been very successful, which may be a consequence of the biological heterogeneity of these disorders or of the limited spatial resolution of the techniques used for investigation. Even if some of these technical difficulties can be overcome with measurements of receptor kinetics supplemented, other biological variables that have proved valuable in psychiatry (such as rapid eye movement latency and biogenic amines) should be studied to find more precise biological markers for depressive illness.

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.

Platelet α 2-adrenoceptors, defined with agonist and antagonist ligands, in depressed patients, prior to and following treatment

Saturation binding of the α 2-adrenoceptor antagonist, 3H-yohimbine, and displacement of 3H-yohimbine with the α 2-adrenoceptor agonist, UK-14,304, were performed concurrently in platelet membranes obtained from drug-free depressed patients and healthy volunteers. Where possible platelet binding was repeated in depressed patients following treatment. The number and affinity of 3H-yohimbine binding sites did not differ between controls and depressed patients, or when depressed patients were divided on the basis of endogenicity (Newcastle or RDC criteria) or dexamethasone test result. The proportion of α 2-adrenoceptor binding sites with high affinity for UK-14,304 and K D values for the two states of the receptor did not differ in the total sample of depressed patients compared to controls. The K D for both states of the receptor and the proportion of sites with high affinity for UK-14,304 was lower in RDC non-endogenous patients than RDC endogenous patients. Treatment did not alter the total number of α 2-adrenoceptors or the proportion of sites with high affinity for UK-14,304, but reduced the K D for 3H-yohimbine and the K D of UK-14,304 for the low affinity state of the α 2-adrenoceptor.

Serum postdexamethasone prolactin measures in depressive patients and control subjects

Recently, some researchers noted significant positive relationships between postdexamethasone serum cortisol and prolactin levels, whilst endogenous depressives exhibited a significantly lower suppression of prolactin by dexamethasone than non-endogenous patients or normal controls. To ascertain the extent of prolactin responses to dexamethasone in severely depressed patients, we measured 8 a.m. pre- and postdexamethasone prolactin levels in 104 depressed and 42 normal subjects. Serum cortisol levels were also determined in depressed patients before and after dexamethasone administration. We found a significant suppressive effect of dexamethasone on prolactin levels. There were no significant differences either in pre- or postdexamethasone prolactin, or in actual dexamethasone-induced decrements in prolactin between normal controls, melancholics, simple major or minor depressed subjects. We have not found any significant relationships between cortisol and prolactin, either under baseline or postdexamethasone conditions.

Responses of Growth Hormone to Desipramine in Endogenous and Non-endogenous Depression

Desipramine, a monoamine reuptake inhibitor, was used to stimulate release of growth hormone (GH) in 29 DSM-III major depressives and in 10 healthy controls. Eighteen of the depressives showed a blunted response. The GH-stimulation test was unable to distinguish endogenous from non-endogenous patients. The 13 dexamethasone non-suppressors were more likely to have a blunted GH response than the 14 suppressors. The results indicate that at least a subset of non-endogenous depressives have significant neuroendocrine abnormality.

Endogenous and non‐endogenous depressions: Relations to life events, dysfunctional attitudes and event perceptions

A comparison was made between endogenous and non-endogenous depressed patients on several characteristics on which they traditionally have been asserted to differ, and which play important roles in cognitive approaches to depression. The non-endogenous patients reported more dysfunctional attitudes and a greater number of recent life events than did endogenous patients. These results support the distinction between endogenous and non-endogenous depressions, and suggest that cognitive theories of aetiology may be more relevant for the latter group. However, both groups perceived their recent upsetting events in relatively maladaptive ways, consistent with the idea that biased perceptions are more related to the depressive state, whereas dysfunctional attitudes may represent a trait vulnerability.

Psychomotor disturbances in psychiatric patients as a possible basis for new attempts at differential diagnosis and therapy. IV. Brain dysfunction during motor activation measured by EEG mapping.

In parts I-III of this series psychometric evidence was reported of a "psychotic motor syndrome" (PMS) in schizophrenic and endogenous depressed patients, which was not found in non-endogenous depressed or healthy persons. An attempt is reported to establish signs of brain dysfunction in these patient groups during motor activation, using a 16-channel EEG mapping system. "Resting" conditions after a special relaxation procedure were compared with simple and complex motor tasks (and music perception/reproduction; to be reported separately). Two measurements, at least 2 weeks apart, were obtained for each subject, in order to obtain information on the influence of drug treatment and/or psychopathological improvement on brain dysfunction. In all, 23 male and 25 female schizophrenics, 11 male and 18 female non-endogenous depressed patients (not actually mediated, i.e. drug naive or wash-out period of 1 week to 17 years), and 26 male and 37 female endogenous depressed patients (medicated with tri- or tetracyclic antidepressants and/or benzodiazepines; no lithium treatment) were compared with 22 male and 17 female control persons (i.e. total n = 179). Major findings were obtained in the delta and alpha frequency bands yielding signs of "diffuse hyperactivation" in schizophrenic and endogenous depressed patients as compared with the patterns found in healthy persons. However, since in the non-endogenous patients a (less marked) hyperactivation of various EEG parameters was also found, unspecific effects such as anxiety/arousal may have influenced the results in psychotic patients, which was to be explored further. Drug treatment tended to "normalize" the activation pattern both in schizophrenics and endogenous depressed patients. Viewing the findings on schizophrenics using neuroimaging methods [single photon emission computerized tomography-(SPECT), magnetic resonance imaging-(MRI), positron emission tomography-(PET)], these results suggest pathological brain organization connected to an impaired motor performance (evident peripherally as PMS) in schizophrenic and endogenous depressed patients. If it is possible to further "externally validate" (by SPECT/MRI/PET) EEG mapping data this method may exclusively offer the possibility of innocuous long-term follow up of brain dysfunction in psychotic patients ("brain function monitoring"). This could enable the early recognition (and early therapy) of negative symptoms. Finally, the EEG mapping findings provide further neurophysiological basis for the use of motor training programs in the additional therapy of psychiatric patients.

Specificity of symptoms in RDC endogenous depression

The Research Diagnostic Criteria (RDC) define endogenous depression by the presence of a particular subset of depressive symptoms. This typological approach to classification implicitly assumes that endogenous and non-endogenous patients differ only or primarily in this subset of symptoms, rather than simply in severity of all depressive symptoms. We tested this assumption in a sample of 80 patients with a current episode of major depressive disorder. Whereas RDC endogenous patients ( n = 53) had significantly higher levels of most criterial symptoms than did non-endogenous patients ( n = 27), they differed on almost no non-endogenous symptoms. These findings support the concept of a specific endogenous symptom cluster.

Plasma levels of beta-endorphin, cortisol, prolactin and growth hormone in depressed patients.

Basal serum cortisol, growth hormone, prolactin and immunoreactive (IR) plasma beta-endorphin levels were measured in 31 depressed patients (14 endogenous, 17 nonendogenous) undergoing the dexamethasone suppression test. The endogenously depressed patients had significantly higher (22.55 +/- 1.34 micrograms/dl) predexamethasone cortisol levels than the nonendogenous patients (16.34 +/- 1.93 micrograms/dl). The mean serum prolactin and growth hormone values of these two groups were not significantly different, while plasma IR-beta-endorphin levels of the endogenous group (40.11 +/- 3.57 pg/ml) were significantly lower than those of the nonendogenous group (120.33 +/- 27.98 pg/ml). Neither group showed a significant correlation between plasma IR-beta-endorphin and serum cortisol values. These results indicate that measurement of predexamethasone serum cortisol values and plasma IR-beta-endorphin could be valuable laboratory tests in the diagnosis of depression.

Factors interfering with the 1 mg dexamethasone suppression test in depression.

The 1 mg dexamethasone suppression test (DST) was performed in 50 depressive inpatients in order to investigate factors which might interfere with its sensitivity and specificity for endogenous depression: improvement within one week after the test, recent admission to a psychiatric ward, and weight loss. Four out of five endogenous depressive patients whose depression improved within one week after the test had normal suppression, thus supporting the assumption that normalization of the DST may precede the improvement in depression. Nonendogenous depressive patients had an accumulation of pathologic test results on the day after admission that may be due to "admission stress". However, in endogenous depressives this effect was not observed. An influence of weight loss on the percentage of suppressors and nonsuppressors was not demonstrable. It is concluded that in the evaluation of DST results time parameters should be considered to a greater degree.

Trazodone: a 5-year review of antidepressant efficacy.

Results from double-blind studies reported since 1981 were reviewed to evaluate trazodone's relative antidepressant efficacy and its safety profile. Trazodone's therapeutic efficacy compared favorably with that of the tricyclic antidepressant (TCA) agents in both endogenous and nonendogenous patients. Data also suggested that trazodone had a more pronounced, earlier anxiolytic action than the TCA agents. Trazodone may be more effective at lower than maximal doses; some studies that used high dosages--starting at 200 mg/day and rapidly titrated doses to as high as 600 mg/day--reported poorer therapeutic responses than did those that employed more conservative dosages. Trazodone therapy generally produced less pronounced anticholinergic effects than did the comparison TCA agent and it is often as sedating as amitriptyline but more sedating than imipramine. Untoward side effects may be reduced by taking trazodone after meals, and by using bedtime dosing. Issues of possible cardiotoxicity and priapism are reviewed briefly. Overall, studies in the past 5 years point to trazodone as being an effective antidepressant agent with a relatively favorable safety profile.

Binding of yohimbine and imipramine to platelets in depressive illness.

Radioligand binding to intact platelets was carried out in antidepressant-free patients and the 1 mg dexamethasone suppression test (DST) was performed. There were no differences in binding characteristics between patients and controls for either [3H]yohimbine or [3H]imipramine. There were no differences in binding between patients classified as endogenous using the Newcastle Scale, compared with non-endogenous patients, and no difference between DST suppressors and non-suppressors. The severity of depression did not affect binding values. After 4-6 weeks antidepressant treatment [3H]yohimbine binding was significantly reduced but [3H]imipramine binding was unaffected.

Relationships of the dexamethasone suppression test to clinical severity and degree of melancholia

Investigators continue to debate whether the Dexamethasone Suppression Test (DST) reflects clinical severity or degree of melancholia (“endogeneity”). To evaluate this question, we studied 73 drug-free inpatients diagnosed with Schedule for Affective Disorders and Schizophrenia/Research Diagnostic Criteria (SADS/RDC) as having major depressive disorder (MDD). We compared absolute and dichotomous DST values (DST suppression versus nonsuppression) with absolute and dichotomous measures of endogeneity (as measured by operationally defined RDC items) and with Hamilton Rating Scale for Depression (HRSD) scores that were collected immediately prior to treatment. We found that (1) degree of endogeneity correlated moderately ( r = 0.27) but significantly ( p = 0.02) with absolute DST values; (2) DST nonsuppression increased proportionately with changes in categorical endogenous subtype (0% of the nonendogenous patients were nonsuppressives, 52% of probable endogenous, and 61% of subjects definitely endogenous); (3) mean values for maximum DST concentrations increased steadily with categorical endogeneity (nonendogenous, 1.44 μg/dl; probable endogenous, 7.65 μg/dl; definite, 10.93 μg/dl; p = 0.01); (4) HRSD scores correlated more strongly ( r = 0.45, p = 0.000) with maximum DST levels than did the degree of endogeneity. Age and weight changes did not account for the relationship of endogeneity to DST values. These data suggest that maximum postdexamethasone plasma cortisol levels reflect overall severity of depression and endogeneity and that endogeneity per se is highly confounded with severity.

Four definitions of endogenous depression and the dexamethasone suppression test

We examined the relationship between the DST and 4 definitions of endogenous depression: DSM-III, Feinberg and Carroll, Newcastle and RDC. Endogenous patients had a significantly higher rate of nonsuppression than nonendogenous patients according to the DSM-III and Newcastle definitions but not according to the RDC and Feinberg and Caroll criteria. Moreover, the relationship between the DST and the DSM-III and Newcastle definitions was significant even after individually controlling for age, psychosis and weight loss. We review the literature on the relationship between the DST and the RDC definition of endogenous depression and suggest that interstudy differences in criteria application may be partially responsible for the inconsistent results across studies.

Hypothalamic - Pituitary - Adrenocortical Function in Geriatric Depression: Diagnostic and Treatment implications

Extensive work in the field has indicated a state-dependent hyperactivity of the hypothalamic-pituitary-adrenocortical (HYPAC) functions and unresponsiveness to dexamethasone suppression in at least 50% of patients suffering from endogenous depression. In this study, elderly outpatients, 60-85 years of age, suffering from major depressive illness according to research diagnostic criteria (RDC) were studied with the dexamethasone suppression test (DST). Careful diagnostic evaluation included RDC, the Newcastle index, and clinical interviews focusing on "endogenomorphic features." The great majority (83.3%) of patients diagnosed as endogenous depressives were nonsuppressors (abnormal DST) as compared to 16.7% nonsuppressors amongst nonendogenous patients. In addition, DST tended to normalize the clinical recovery. The research and clinical implications of our findings in this population are further discussed.

Separation of subtypes of depression using discriminant analysis. I. Separation of unipolar endogenous depression from non-endogenous depression.

We derived a discriminant function based on clinical features to classify patients with endogenous depression ('melancholia') and non-endogenous ('neurotic') depression. The difference between the groups was not one of overall severity of illness alone. Bipolar melancholic patients were classified less well than were unipolars, supporting previous findings of clinical differences between these groups. The discriminant function (DF) was reduced to a discriminant index (DI) which classified a separate group of unipolar melancholic and non-endogenous patients with comparable accuracy. Approximately 80 per cent of all cases received a definite classification by the DI. The agreement between the 105 definite DI classifications and the clinical diagnoses was 90 per cent when results from the derivation and validation groups were combined. The DI classification was then validated against an objective biological marker, the dexamethasone suppression test (DST). The diagnostic discriminant index predicted the DST result with the same accuracy as the clinical diagnoses. The discriminant index can serve as an operational definition of the patients diagnosed as endogenous or nonendogenous unipolar depression in future studies by ourselves and other groups of investigators.