Plasma levels of homovanillic acid, 5-hydroxyindoleacetic acid and cortisol, and serotonin turnover in depressed patients

Plasma levels of ACTH, cortisol and monoamines were examined in 23 depressed patients and 31 healthy subjects. Patients showed increased plasma cortisol levels, but not plasma adrenocorticotropic hormone (ACTH) levels. The plasma levels of a dopamine metabolite, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), were significantly decreased in the patients. In contrast, the plasma levels of a serotonin (5-HT) metabolite, hydroxyindoleacetic acid (5-HIAA), and 5-HT turnover (5-HIAA/5-HT) were increased in the depressed patients. Therefore, plasma levels of HVA and 5-HIAA are proven to be dissociable. Furthermore, plasma levels of 5-HIAA and L-DOPA have positive relationships with severity of depression. On the basis of this and the previous studies, we speculate that an increase in the plasma 5-HIAA levels might be a compensatory mechanism for stress, whereas 5-HT turnover might reflect depressive state. Taken together, plasma levels of HVA and 5-HIAA, and 5-HT turnover (5-HIAA/5-HT) could be good markers for evaluating depression.     

Fluctuation of tPA and PAI-1 antigen levels in plasma: difference of their fluctuation patterns between male and female

The circadian fluctuation of the fibrinolytic activity and the antigen levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) in plasma were analyzed in normal male and female volunteers. Samples were obtained at 8:30, 10:30, 12:30, 14:30 and 16:30 h. Euglobulin clot lysis time (ECLT) showed the longest time at 8:30 to 10:30 h and the shortest time at 16:30 h. The highest level of tPA was obtained at 8:30 h and the lowest at 14:30 h in men, whereas the highest value was at 8:30 h and the lowest was at 16:30 h in females. Free PAI-1 showed highest value at 10:30 h in men and at 8:30 h in women. The lowest values obtained at 16:30 h in both men and women and were about one third of the highest values. ECLT was always shorter in females than in males and parameter such as tPA and PAI-1 were also lower in females than in males. The phase of the circadian rhythm of the fibrinolytic parameters may be advanced in females than in males.     

CSF monoamine metabolites of depressed patients during illness and after recovery

Repeated lumbar punctures in 16 healthy volunteers showed reproducible concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in cerebrospinal fluid (CSF). In seven depressed patients, studied during two or three illness periods, the metabolite concentrations were also fairly stable. In 11 patients CSF concentrations of 5-HIAA, but not of HVA, were higher after recovery than during depression. This increase of 5-HIAA after recovery was confined to patients whose initial serotonin metabolite levels were low. The finding constitutes further evidence of a biochemical heterogeneity within the depressive disorders, and suggests that patients whose CSF 5-HIAA is low during a depressive episode may have a less stable serotonin system than other patients with depressive illness.     

Fluctuation of TPA and PAI-1 antigen levels in plasma: difference of their fluctuation patterns between male and female

The daytime fluctuation of the fibrinolytic activity and the antigen levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) in plasma were analyzed in normal male and female volunteers. Samples were obtained at 8:30, 10:30, 12:30, 14:30 and 16:30 h. Euglobulin clot lysis time (ECLT) showed the longest time at 8:30 to 10:30 h and the shortest time at 16:30 h. The highest level of tPA was obtained at 8:30 h and the lowest at 14:30 h in men, whereas the highest value was at 8:30 h and the lowest was at 16:30 h in females. Active free PAI-1 showed highest value at 10:30 h in men and at 8:30 h in women. The lowest values obtained at 16:30 h in both men and women and were about one third of the highest values. ECLT was always shorter in females than in males and parameter such as tPA and PAI-1 were also lower in females than in males. The phase of the circadian rhythm of the fibrinolytic parameters may be advanced in females than in males.     

24-h Monitoring of plasma norepinephrine, MHPG, cortisol, growth hormone and prolactin in depression

Depression is associated with alterations in hormone and catecholamine circadian rhythms. Analysis of these alterations has the potential to distinguish between three neurobiological models of depression, the catecholamine model, the phase advance model and the dysregulation model. Although a number of studies of 24-h rhythms have been reported, inconsistencies among the findings have complicated efforts to model the chronobiology of depression. The present study takes advantage of frequent plasma sampling over the 24-h period and a multioscillator cosinor model to fit the 24-h rhythms. METHOD: Plasma levels of norepinephrine, cortisol, prolacatin and growth hormone were sampled at 30-min intervals, and MHPG at 60-min intervals, over a 24-h period in 22 patients with major depressive disorder and 20 healthy control volunteers. RESULTS: The depressed patients had phase advanced circadian rhythms for cortisol, norepinephrine and MHPG, phase advanced hemicircadian rhythms for cortisol and prolactin, and a phase advanced ultradian rhythm for prolactin compared to healthy control subjects. In addition, the rhythm-corrected 24-h mean value (mesor) of norepinephrine was lower in the depressed patients compared to the healthy controls. There also was a poorer goodness-of-fit for norepinephrine to the circadian oscillator in the depressed patients relative to the healthy controls. CONCLUSIONS: These findings provide partial support for the dysregulation model of depression and are consistent with those studies that have found phase advances in cortisol, norepinephrine and MHPG rhythms in depression.     

Insulin, cortisol and catecholamines do not regulate circadian variations in fibrinolytic activity

To evaluate possible hormonal regulators of the diurnal rhythm in fibrinolytic activity, we measured tissue plasminogen activator (t-PA) activity, plasminogen activator inhibitor activity (PAI-1), t-PA antigen, insulin, cortisol, and catecholamines in 6 healthy males (age 34 +/- 5) every 2 hours for 24 hours. Fibrinolysis was characterized by a peak in PAI-1 activity and a trough in t-PA activity at 0600 h. PAI-1 activity increased 92% and t-PA activity decreased 56% between 2400 h and 0600 h. t-PA antigen (principally a measure of t-PA/PAI-1 complex), peaked at 0800 h. In comparison, insulin levels were lowest at night when PAI-1 activity was rising. The weak inverse correlation between insulin and PAI-1 activity (r = -0.28, p less than 0.02), was not sufficient to explain the diurnal change in fibrinolysis. While cortisol demonstrated the expected circadian change, the increase in cortisol did not occur until 0400 h, 4-6 hours after the rise in PAI-1 and decrease in t-PA activity started. Supine resting plasma epinephrine and norepinephrine showed no circadian rhythm. From this data, we hypothesize that the increased level of PAI-1 in the morning consumes t-PA, leading to decreased t-PA activity and increased t-PA/PAI-1 complex. Further, we conclude that insulin, cortisol, and catecholamines are not responsible for the circadian rhythm of fibrinolysis.     

Fluoxetine treatment of depression. Clinical effects, drug concentrations and monoamine metabolites and N-terminally extended substance P in cerebrospinal fluid

In an open study of depressed inpatients, the effects of the selective serotonin uptake blocker fluoxetine on 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), 4-hydroxy-3-methoxyphenyl glycol (HMPG) and N-terminally extended substance P (SP) in cerebrospinal fluid (CSF) were measured. Thirteen unmedicated patients who met the DSM-III criteria for major depressive episode were included, and 9 completed the study. During treatment the 5-HIAA concentration decreased by 46%. The HVA and HMPG concentrations also decreased significantly, but to a lesser degree. The mean level of N-terminally extended SP was unaffected by fluoxetine treatment, but the pretreatment level correlated significantly with the pretreatment level of HMPG. The pretreatment level of HVA was the only biochemically variable that appeared to predict therapeutic outcome. The plasma concentrations of both fluoxetine and its metabolite norfluoxetine increased significantly between 3 and 6 weeks. Plasma and CSF levels of both the parent drug and its active metabolite were correlated.     

Oxidative stress effects fibrinolytic system in dialysis uraemic patients

INTRODUCTION: Enhanced oxidative stress (SOX) and changes in the fibrinolytic system are common in end-stage renal failure patients undergoing maintenance dialysis. This study attempted to verify the existence of a relationship between SOX documented by Cu/Zn superoxide dismutase (Cu/Zn SOD) and fibrinolysis analyzed by tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor 1 (PAI-1) and plasmin/antiplasmin (PAP) complexes in dialysis patients. MATERIALS AND METHODS: Twenty-seven patients on maintenance haemodialysis (HD) and 16 on maintenance peritoneal dialysis (CAPD) were examined together with 18 healthy controls. Pre-dialysis blood levels of all the parameters were determined using commercially ELISA kits. RESULTS: Cu/Zn SOD, uPA and PAP levels were increased in both groups of dialyzed patients compared to the controls. PAI-1 was significantly lower in CAPD subjects compared to HD subjects and control group. PAI-1/uPA ratio and PAI-1/tPA ratio were significantly decreased in CAPD and HD compared to controls, being significantly lower in CAPD patients relative to HD patients. In the patients, increased Cu/Zn SOD levels directly correlated with those of uPA (r=0.565, p<0.0001) and PAP (r=0.335, p<0.05); the fibrinolytic markers were also positively associated with each other (r=0.377, p<0.05). CONCLUSIONS: The positive association between Cu/Zn SOD and both uPA as well as PAP levels suggests a link between SOX and the fibrinolytic activity in dialysis patients. We hypothesize that increased SOX-mediated fibrinolytic activity may be a part of the counter-system against activation of blood coagulation in these patients.     

THE LEVEL AND DIURNAL RHYTHM OF SERUM SEROTONIN IN MANIC-DEPPESSIVE PATIENTS

The serum levels and diurnal rhythm of serotonin before and during treatment were investigated in 65 manic-depressive patients, comparing with those in 34 normal controls and 13 schizophrenics. 1. The serum serotonin level in 40 newly admitted depressive patients who had not been medicated (127±58 ng/ml) was significantly lower than that in normal controls (221±96ng/ml). 2. The serum serotonin level in 24 recovering patients with depression had the tendency to return to normal while under treatment with imipramine type antidepressants (281±189 ng/ml). 3. The serum serotonin level in 10 manic patients (365±85 ng/ml) was significantly higher than that in normal controls. 4. After the injection of imipramine to depressive patients, serum serotonin level tended to increase (1.5 times). 5. Electroconvulsive shock did not appear to alter the serum serotonin level in depressive patients and normal dogs. 6. As for the diurnal rhythm of serum serotonin of depressive patients, the serotonin level in the morning was the lowest, which seemed to be related to the worst depressed mood in the morning. In the manic patients, the serotonin level at 20.00 hours was the highest. This pattern of rhythm resembled that of normal controls. 7. The significance of serum serotonin levels in manic-depressive patients was discussed.     

Plasma levels of MHPG, HVA and total 5-HIAA in depression. Preliminary study]

This study was aimed at assessing monoamine catabolites plasma levels in depressed patients and healthy volunteers. Plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) of 21 control subjects and 26 depressed patients (according to DSM III-R criteria) were measured at baseline (day 0) and day 4, day 7, day 30 of prescribed antidepressant treatment. The clinical assessment, at baseline as well as during treatment, used the Hamilton depression rating scale and the BPRS. Our data show the interest of these results in predicting response. The respondent patients showed a significant decrease in plasma MHPG level at J7, contrary to non-respondent patients. Moreover, a positive correlation between plasma levels of MHPG and HVA before any prescribed antidepressants was found only with respondent patients. The lack of correlation for non-respondent patients can suggest that the relationships between this monoamine systems should be disrupted in these patients. Significant relationships appear between clinical symptoms and plasma catabolites, allowing us to consider new physiopathological aspects of the depressive picture. The 3 monoamines seemed involved in sleep disorders. Perturbations of norepinephrine and serotonin metabolism could intervene in suicidal ideation and behaviour. Motor activity was associated with a modification in dopamine and serotonin metabolism. Moreover significant correlations were observed between items referring to thought content and monoamine plasma catabolites such as MHPG and blunted affect, 5-HIAA and obsessions, HVA and guilt feelings, devalorization and without hope items.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fluctuations of euglobulin lysis time, tissue plasminogen activator, and free and total plasminogen activator inhibitor levels in plasma in daytime

Blood was taken from healthy 15 males and 10 females at 9:30 h, 10:00 h and 12:30 h. The euglobulin fraction was prepared and clotted by the addition of human thrombin. The clot lysis time shortened significantly from 9:30 h to 10:00 h (p less than 0.01) and further to 12:30 h (p less than 0.01). Plasma levels of tissue plasminogen activator (t-PA) antigens did not change from 9:30 h to 10:00 h, but slightly and significantly to 12:30 h (p less than 0.01). Plasma levels of free plasminogen activator inhibitor-1 (PAI-1) and complex of t-PA-PAI-1 decreased from 9:30 h to 10:00 h (p less than 0.02) and to 12:30 h (p less than 0.01). Plasma levels of total PAI-1 (free plus complex) decreased from 9:30 h to 10:00 h (p less than 0.01) and to 12:30 h (p less than 0.01). These results suggest that a major factor contributing to the enhanced fibrinolytic activity of the euglobulin fraction may be a level of PAI-1 (free and total).     

Circadian rhythm of plasma melatonin in endogenous depression

1. The circadian rhythm of plasma melatonin was investigated in normal men 18–30 years (N=5), normal men 50–70 years (N=5) and in six patients with endogenous depression.

2. The environmental photoperiod was 11 hours.

3. The subjects and patients were indoors with lights on from 07:00 until 23:00 hours.

4. Blood samples were obtained every 4 hours over a 24 hour period, with additional sampling at 22:00 and 02:00 hours.

5. Plasma melatonin was estimated by radioimmunoassay compared to both groups of controls.

6. In the depressed patients, the levels of melatonin were low throughout the 24 hour period.

7. The depressives had a delayed onset of the dark phase of the rhythm.

8. The patients also showed peak melatonin levels occurring earlier than in the controls.

9. Circadian rhythm of melatonin and therefore of its pacemaker may be altered in endogenous depression.     

Hypofibrinolysis in patients with a history of idiopathic deep vein thrombosis and/or pulmonary embolism.

An impaired fibrinolytic activity after a venous occlusion test is the most common abnormality associated with thomboembolic disease. To better characterize the causes of abnormal responses we have measured different fibrinolytic parameters, before and after 10 and 20 min of venous occlusion, in 77 patients with a history of idiopathic deep vein thrombosis and/or pulmonary embolism and in 38 healthy volunteers. The patients had a lower mean fibrinolytic response to venous occlusion than the controls and higher antigen levels of tissue-type plasminogen activator (t-PA:Ag) and plasminogen activator inhibitor type 1 (PAI-1:Ag). Before venous occlusion, PAI-1 levels were at a molar excess over those of t-PA in all patients and controls. After 20 min of venous occlusion, the release of t-PA from the vascular endothelium resulted in a molar excess of t-PA over PAI-1 in the majority of controls (72%) but only in a minority of patients (39%). To identify patients with fibrinolytic abnormalities, reference intervals (RI) for fibrinolytic activity, t-PA:Ag and PAI-1:Ag were established in healthy controls. None of the patients had low levels of t-PA:Ag, but 17 (22%) had elevated PAI-1:Ag levels before venous occlusion and 12 (16%) exhibited low fibrinolytic activity after 20 min of venous occlusion. Ten of these were among the 17 subjects with high PAI-1:Ag levels before venous occlusion. Thus, the measurement of PAI-1:Ag levels before venous occlusion (i.e. in samples taken without any stimulation) is a sensitive (83%) and specific (89%) assay for the detection of patients with an impaired fibrinolytic response to venous occlusion.     

CSF neurochemistry in depressed, manic, and schizophrenic patients compared with that of normal controls

A total of 114 subjects (41 depressed, 20 schizophrenic, 15 manic, and 38 normal controls) underwent lumbar puncture and their CSF was analyzed for levels of tyrosine, tryptophan, homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylglycol (MHPG), choline, gamma-aminobutyric acid (GABA), and calcium. Results showed that depressed patients, particularly those over 40 years of age, had lower levels of GABA than did controls, and that their level of HVA increased with age, while controls' decreased. Schizophrenic subjects tended to have higher levels of 5-HIAA and manic subjects tended to have higher levels of HVA and MHPG. Age-associated changes were found in HVA, 5-HIAA, MHPG, GABA, and choline concentrations.     

Daytime fluctuations of plasminogen activator inhibitor 1 (PAI-1) in populations with high PAI-1 levels.

The mechanism underlying diurnal variations in PAI-1 as well as the cellular origin of PAI-1 in subjects with high PAI-1 levels are unknown. We evaluated diurnal changes (8:00 am vs 4:00 pm) in PAI-1 (functional and immunological assays), t-PA Ag and t-PA/PAI-1 complex levels in controls and subjects with high PAI-1 levels. Three test groups were recruited among obese hyperinsulinemic subjects, emergency care unit patients with inflammatory syndrome or infection and pregnant women. The classical afternoon decrease of PAI-1 level was observed in controls and obese subjects but its amplitude was greater in the latter. The decrease in t-PA Ag and t-PA/PAI-1 complex levels was the same in controls and in obese. As, in previous studies, elevated PAI-1 levels have been correlated with insulin resistance and a decrease in insulin sensibility has been described in the early morning, it is proposed that this "dawn phenomenon" could be implicated in the circadian variations of PAI-1 in controls and could be amplified in obese subjects. Great variability in PAI-1, t-PA Ag or t-PA/PAI-1 complex levels was observed in patients with acute inflammatory syndrome or infection for whom classical biorhythms are suppressed. No diurnal changes in PAI-1 and other fibrinolytic parameters were observed in patients with inflammatory syndrome or in pregnant women suggesting that other sources and/or other regulatory mechanisms of PAI-1 production are involved.     

Growth hormone, cortisol and prolactin responses to physical exercise: higher prolactin response in depressed patients

This study was designed to compare growth hormone, cortisol and prolactin responses to physical exercise in depressed patients and healthy comparison subjects. Patients fulfilled the DSM-IV diagnostic criteria for current major depressive disorder; subjective depressive symptoms were rated with Montgomery-Asberg Depression Rating Scale (MADRS) immediately before the experiment. Growth hormone, cortisol and prolactin were measured before and immediately after physiologically stressful bicycle cardiopulmonary exercise test. After exercise, there were three additional hormone measurements, with 30-min intervals. No significant difference was found in baseline growth hormone, cortisol or prolactin levels between patients and the control group. Plasma growth hormone and cortisol levels increased significantly during physical exercise in both patients and controls and returned to baseline in 90 min. There was no significant difference in growth hormone or cortisol responses to physical exercise between the two groups. However, prolactin levels increased only in the depressed patients group during the exercise. We hypothesize that acute exercise may have a stronger effect on serotonin (5-HT) release in depressed patients, which is reflected in increased plasma prolactin concentration.     

Pulsatile growth hormone,prolactin, and thyrotropin secretion in rats with hypothalamic deafferentation

Rats submitted to regular 12 h cycles of light and darkness for three weeks were sacrificed at various times of the day. 5-HT, 5-HIAA and tryptophan levels were estimated in the fronto-parietal cerebral cortex. Tyrosine and free and total tryptophan levels in serm were estimated in parallel. Significant circadian variations in 5-HT and 5-HIAA levels were found in cerebral tissues. The peaks of 5-HT and 5-HIAA levels were detected during the light and dark periods respectively, the maximal fluctuations being seen between 17.00 h and 21.00 h, two times separating the light off. Important significant circadian variations in free and total serum tryptophan levels were also observed. In both cases, the maximal levels were found during the middle of the dark phase after the peak of 5-HIAA levels. The circadian rhythm of tyrosine levels in serum was in opposite phase with that of tryptophan (free or total). The diurnal changes in tryptophan content in cerebral tissues seemed thus related to those found in serum. Taking in consideration results obtained in previous studies^16,17 carried out in similar experimental conditions, it was concluded that the parallel increase in serum free tryptophan and in tissues 5-HIAA levels seen during the night were not related to a stimulation of 5-HT turnover. Indeed 5-HT synthesis is minimal at this time¹⁶.     

Reduction of Blood Platelet Serotonin Levels in Manic and Depressed Patients

Blood platelet serotonin levels were measured in unmedicated 12 manic and 74 depressive patients with 118 normal control subjects employed. Blood platelets were separated by multiple centrifugation in the medium of Naz-EDTA solution, and the loss of serotonin during collecting procedures was about 11%). The mean value of blood platelet serotonin levels in depressed patients was 594±288 ng/mg platelet protein (±S.D.), which was significantly lower than that for normal controls, 780±253 ng/mg protein (p<0.001). Age does not account for the reduction of serotonin levels both in depressed and in normal population. Unipolar and involutional depressed patients exhibited to have the most pronounced reduced levels of serotonin of various subtypes of depression, while bipolar depressed patients, neurotic and chronic characterological depressed patients as well as patients with first-episode depression had the values which were comparable with those in normal controls. Manic patients did not show enhancement but did reduction of serotonin levels, the mean being 5802±152 ng/mg protein, which made a contrast with their clinical manifestations of exhilaration and hyperactivity. Changes in blood platelet serotonin levels were determined before, during and after administration of L-5–HTP with a maintenance dose of 300 mg daily in nine depressed patients. Serotonin levels in all subjects were lifted to normal levels during the L-5–HTP treatment, while clinical symptoms were not improved with the treatment. Reduction of blood platelet serotonin levels in depressed patients may be due to their psychobiological distinction, which involves abnormal biogenic amine metabolism in the brain.     

Reduction of blood platelet serotonin levels in manic and depressed patients.

Blood platelet serotonin levels were measured in unmedicated 12 manic and 74 depressive patients with 118 normal control subjects employed. Blood platelets were separated by multiple centrifugation in the medium of Na2-EDTA solution, and the loss of serotonin during collecting procedures was about 11%. The mean value of blood platelet serotonin levels in depressed patients was 594 +/- 288 ng/mg platelet protein (+/- S.D.), which was significantly lower than that for normal controls, 780 +/- 253 ng/mg protein (p less than 0.001). Age does not account for the reduction of serotonin levels both in depressed and in normal population. Unipolar and involutional depressed patients exhibited to have the most pronounced reduced levels of serotonin of various subtypes of depression, while bipolar depressed patients, neurotic and chronic characterological depressed patients as well as patients with first-episode depression had the values which were comparable with those in normal controls. Manic patients did not show enhancement but did reduction of serotonin levels, the mean being 580 +/- 152 ng/mg protein, which made a contrast with their clinical manifestations of exhilaration and hyperactivity. Changes in blood platelet serotonin levels were determined before, during and after administration of L-5-HTP with a maintenance dose of 300 mg daily in nine depressed patients. Serotonin levels in all subjects were lifted to normal levels during the L-5-HTP treatment, while clinical symptoms were not improved with the treatment. Reduction of blood platelet serotonin levels in depressed patients may be due to their psychobiological distinction, which involves abnormal biogenic amine metabolism in the brain.     

The daily rhythm of HVA,VMA, (VA) and 5-HIAA in depressionsyndrom

Summary The daily rhythm (8–14 h, 14–20 h, 20–2 h, 2–8 h) of HVA, VMA, (VA) and 5-HIAA was studied in 21 depressed patients and was compared to the values of 13 healthy subjects. In healthy subjects all compounds trend to high values during day-time and significant lower values in the nightphase (2–8 h). Depressed patients did not show a significant rhythm during the four fractions; the values of HVA and VMA were significant lowered in the morning-phase (8–14 h). This demonstrates a good connexion to the clinical feature with the morning listlessness. Normal concentrations were reached in the night-phase (2–8 h). 5-HIAA did not show any significance between healthy subjects and depressed patients during the circadian rhythm. The ratio VMA/HVA in healthy subjects fell significant from morning-phase (8–14 h) to night-phase (20–2 h, 22–8 h). In depressed patients the ratio was approximately equal in all fractions. Whereas the ratio 5-HIAA×100/ VMA>+HVA increased from the morning-phase to the night-phase in healthy persons, this ratio did not show any significance in the four fractions of depressed patients.Also these results suggest some importance in explaining the lost of drive in the activity of depressed patients during morning hours and the remission of these patients often observed in the evening. A very good correlation to the clinical feature is emphasized.Preliminary studies on 6 patients with different depressive diagnosis during depression- and remission-phase gave a different biochemical pattern. Further extended studies have to be carried out to differentiate exactly between nosological different depressions.