Lower serum zinc in major depression is a sensitive marker of treatment resistance and of the immune/inflammatory response in that illness.

The aims of the present study were to examine i) serum zinc (Zn) and copper (Cu) in treatment resistant depression (TRD); ii) the effects of subchronic antidepressant therapy on these trace elements; and iii) the relationships between serum Zn and Cu and immune/inflammatory markers. Serum Zn was significantly lower in TRD than in normal controls. There was a significant inverse correlation between baseline serum Zn and staging of depression based on severity of prior treatment resistance. There were no significant effects of antidepressive treatment on serum Zn, whereas serum Cu was significantly reduced. There were highly significant correlations between serum Zn and the CD4+/CD8+ T-cell ratio (negative), and total serum protein, serum albumin, and transferrin (all positive). The results suggest that lower serum Zn is a marker of TRD and of the immune/inflammatory response in depression. It is suggested that treatment resistance may bear a relationship with the immune/inflammatory alterations in major depression.

Acute phase proteins in schizophrenia, mania and major depression: modulation by psychotropic drugs.

Recently, an acute phase (AP) protein response has been reported in major depression. In order to examine whether an AP response occurs in other psychiatric disorders, such as schizophrenia and mania, the authors measured plasma AP reactants, such as haptoglobin (Hp), immunoglobulin G (IgG), IgM, fibrinogen (Fb), complement component 3 (C3C), C4, alpha 1-antitrypsin (alpha 1 AT), alpha 1-acid-glycoprotein (alpha 1S) and hemopexin (Hpx), in 27 schizophrenic, 23 manic, 29 major depressed and 21 normal subjects. Schizophrenic patients had significantly higher plasma Hp, Fb, C3C, C4, alpha 1S and Hpx than normal controls. Manic subjects showed significantly higher plasma Hp, Fb, alpha 1S and Hpx than normal volunteers. Depressed subjects had significantly higher plasma Hp, Fb, C3C, C4 and alpha 1S than normal controls. Overall, the above disorders in AP reactants were more pronounced in schizophrenic than in depressed subjects. No significant differences in the above AP reactants could be found between normal volunteers, and schizophrenic, manic or depressed patients who underwent chronic treatment with psychotropic drugs. Plasma Hp, Fb, C3C, C4, alpha 1S, and Hpx were significantly higher in schizophrenic, manic and depressed patients who were non-medicated than in those who were treated with antidepressants, antipsychotics or lithium. The results suggest that not only major depression but also schizophrenia and mania are accompanied by an AP response, and that the latter may be suppressed by (sub)chronic treatment with psychotropic drugs.

Efficacy of treatment with trazodone in combination with pindolol or fluoxetine in major depression.

Fluoxetine, a selective serotonin (5-HT) reuptake inhibitor (SSRI), and trazodone, a heterocyclic antidepressant, are effective in the treatment of major depression and treatment resistant depression (TRD). Chronic treatment with both drugs causes increases in extracellular 5-HT through 5-HT reuptake inhibition and desensitization of inhibitory 5-HT1A autoreceptors. It has been shown that pindolol, a serotonin (5-HT)1A-receptor antagonist, may shorten the latency of onset of SSRIs in depression. The aim of the present study was to examine whether pindolol may increase the efficacy of a subtherapeutical dosage of trazodone in the treatment of major depression and TRD, defined according to the Thase and Rush criteria (1995). Thirty-three major depressed inpatients of whom 26 with TRD participated in this study. Ten days after hospitalization, treatment with trazodone 100 mg/day was started. After 1 week trazodone treatment, patients were randomized-using a double blind placebo controlled design-to receive trazodone 100 mg/day+placebo; trazodone 100 mg/day+pindolol 7.5 mg/day: or trazodone 100 mg/day+fluoxetine 20 mg/day and treated during 4 weeks. The 17-item Hamilton Depression Rating Scale (HDRS) was used as outcome measure. It was found that trazodone+pindolol was as effective as trazodone+fluoxetine in the treatment of major depression and TRD and significantly more effective than trazodone+placebo. Using an outcome measure of 50% reduction in the HDRS, we found that 72.5% of the depressed patients treated with trazodone+pindolol and 75% of depressed patients treated with trazodone+fluoxetine showed a clinically significant response compared with 20.0% of trazodone+placebo-treated patients.

Increased serum soluble CD8 or suppressor/cytotoxic antigen concentrations in depression: suppressive effects of glucocorticoids.

There is now some evidence that depression and, in particular, major depression, is accompanied by signs of an immune response, and that there are reciprocal relationships between immune function and increased hypothalamic-pituitary-adrenal (HPA) axis activity in depression. To further examine the above phenomena, this study has assayed serum soluble CD8 (sCD8) concentrations in 22 normal controls, 27 minor depressed, 37 major depressed, and 26 melancholic depressed patients. Serum sCD8 was significantly higher in depressed patients versus normal controls. Thirty-five percent of the depressed subjects had increased sCD8 serum levels (i.e., > 560 U/mL) with a specificity of 95.4%. Dexamethasone administration (1 mg PO) had a significant suppressive effect on serum sCD8. In depressed subjects, there were significant and negative relationships between serum sCD8 and postdexamethasone cortisol values. The results suggest the presence of an ongoing lymphocyte activation in depression, which may be down-regulated by increased HPA axis activity in that illness.

Biological variability in serum vitamin E concentrations: relation to serum lipids.

The components of biological variation in serum vitamin E in relation to serum cholesterol, triglycerides, high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), apolipoprotein A-I (apo A-I), and apo B were examined in 26 healthy volunteers who had monthly blood samplings during one calendar year. The estimated CVs for vitamin E were: interindividual, 19.9%, and intraindividual, 11.9%; the index of individuality (I-index) was 0.59. The I-indices for all lipid variables were < 0.51. Serum concentrations of vitamin E, cholesterol, triglycerides, HDL-C, LDL-C, and apo B were lower in spring than in the other seasons. The peak-trough differences in the yearly variations, expressed as a percentage of the mean, were for vitamin E 14.5%, cholesterol 16.2%, triglycerides 14.5%, and LDL-C 24.3%. A significant common annual rhythm was expressed in vitamin E or lipid variables and in the changes in ambient temperature the weeks before blood sampling (inverse relations). There were highly significant positive time relations between serum vitamin E and cholesterol, triglycerides, and apo B. Subjects with higher homeostatic setpoints of cholesterol showed higher homeostatic setpoints of vitamin E, triglycerides, LDL-C, and apo B.

Stimulatory effects of L-5-hydroxytryptophan on postdexamethasone beta-endorphin levels in major depression.

Recently it has been shown that acute administration of 200 mg L-5-hydroxytryptophan (L-5-HTP) PO may increase post-dexamethasone (DST) adrenocorticotropic hormone (ACTH) and cortisol levels in major, but not minor, depressed subjects. This study aimed to examine the effects of 200 mg L-5-HTP PO on post-DST beta-endorphin levels in the same depressed subjects. It was found that in major, but not minor, depressed subjects, L-5-HTP significantly increased post-DST beta-endorphin concentrations as compared to placebo. The L-5-HTP-induced post-DST beta-endorphin responses were significantly higher in major than in minor depressed subjects. There was a significant and positive relationship between L-5-HTP-induced post-DST beta-endorphin and ACTH or cortisol responses. There was a significant and positive relationship between L-5-HTP-induced post-DST beta-endorphin values and the Hamilton Depression Rating Scale (HDRS) score. The results show that the acute administration of L-5-HTP may increase the escape of beta-endorphin secretion from suppression by dexamethasone in major, but not minor, depression.

Lower serum L-tryptophan availability in depression as a marker of a more generalized disorder in protein metabolism.

Recently, it has been reported that major and melancholic depression are accompanied by a lower availability of total L-tryptophan (L-TRP) to the brain and by significant changes in electrophoretically separated protein fractions, such as albumin and alpha 2-globulin. The aim of this study was to examine the relationships between serum L-TRP availability and total serum protein, albumin, and alpha 2-globulin in 42 depressed and 24 normal subjects. In depressed and normal subjects, alone and together, there were significant and positive correlations between serum L-TRP and total serum protein or albumin concentrations. In the depressed subjects, but not in normal controls, there were significant inverse relationships between the L-TRP/competing amino acid ratio and the alpha 2-globulin fraction. Serum L-TRP and albumin were significantly lower in melancholic subjects than in normal and minor depressed subjects. Depressed subjects had a significantly lower L-TRP/competing amino acid ratio and significantly higher serum alpha 2-globulin than normal controls. Total serum protein was significantly lower in major depressed subjects than in normal controls. The results suggest that lower L-TRP availability to the brain in depression is related to lower serum albumin and to increased alpha 2-globulin fraction, which are both hallmarks of the acute phase response in depression. the results further corroborate the hypothesis that lowered L-TRP availability in depression is related to the acute phase response in that illness.

Blood coagulation and platelet aggregation in major depression.

Recently, it was found that the plasma of depressed patients significantly reduced the primary and secondary platelet aggregation to aggregating agents, such as ADP and collagen, in platelet rich plasma (PRP) of normal volunteers. Other authors found significantly decreased maximum amplitudes of adrenaline-induced platelet aggregation in major depressed patients versus normal controls. The aim of the present study was to examine platelet aggregation and blood coagulation in depression. Toward this end, the authors have measured secondary platelet aggregation to ADP and collagen, and the activated partial thromboplastin time (APTT) and prothrombin time (PT) in 16 normal volunteers, 16 minor, 40 simple major and 23 melancholic subjects. There were no significant differences in ADP- or collagen-induced platelet aggregability, APTT or PT between normal controls, minor, simple major or melancholic depressed patients. There were no significant relationships between severity of depression and APTT, PT or platelet aggregability to ADP or collagen. It is concluded that blood coagulation and platelet aggregability to ADP and collagen are probably not disordered in major depression.

Seasonal variation in platelet [3H]paroxetine binding in healthy volunteers. Relationship to climatic variables.

Recently, our laboratory has reported significant seasonal differences in [3H]paroxetine binding to platelets in depressed subjects. This study aimed to examine the seasonal variation in [3H]paroxetine binding to platelets and the relationships between [3H]paroxetine binding and climatic variables in healthy volunteers. We took monthly blood samples during one calendar year from 26 healthy volunteers for assay of [3H]paroxetine binding and analyzed the data by means of univariate and multivariate spectral and cosinor analyses. There was a statistically highly significant seasonal pattern in [3H]paroxetine binding to platelets with significant annual, 4-monthly, and bimonthly rhythms, which were expressed as a group phenomenon. [3H]Paroxetine binding to platelets was significantly lower in fall and summer than in winter and spring; lows occurred in summer and peaks in spring. The peak-trough difference in this yearly variation, expressed as a percentage of the mean, was as large as 83.7%. A large part of the variance, that is, 32.5%, in [3H]paroxetine binding could be explained by weather variables, such as ambient temperature, relative humidity, and air pressure. Highly significant common annual rhythms were expressed in [3H]paroxetine binding and ambient temperature or humidity (both inversely related) and changes in temperature the 2 weeks preceding blood samplings (positively related).

Lower plasma CC16, a natural anti-inflammatory protein, and increased plasma interleukin-1 receptor antagonist in schizophrenia: effects of antipsychotic drugs.

Recently, it was suggested that in vivo activation of the monocytic and T-lymphocytic arms of cell-mediated immunity (CMI) may occur in schizophrenia and that antipsychotic drugs may modify CMI. The aim of the present study was to examine plasma soluble interleukin-2 receptor (sIL-2R), soluble suppressor/cytotoxic antigen (sCD8), interleukin-1 receptor antagonist (IL-1RA), and Clara cell protein (CC16) concentrations in normal controls, nonmedicated schizophrenic patients, and schizophrenic patients treated with risperidone or loxapine. Plasma concentrations of IL-1RA were significantly higher in nonmedicated schizophrenic patients than in normal controls. Plasma CC16 was significantly lower in nonmedicated and loxapine-treated schizophrenic patients than in normal controls, whereas risperidone-treated patients had plasma CC16 levels which were not significantly different from normal controls. Plasma CC16 levels were significantly and positively related to age at onset of schizophrenia. Plasma sIL-2R was significantly higher in schizophrenic patients who were treated with risperidone than in normal controls and nonmedicated schizophrenic patients. The results show that (i) schizophrenia is accompanied by an activation of the monocytic arm of CMI (i.e., increased plasma IL-1RA) and lower plasma levels of a natural anti-inflammatory and immunosuppressive agent, i.e. CC16, and that the latter may constitute a trait market of schizophrenia; and that (ii) chronic treatment with atypical antipsychotic agents, i.e., risperidone, may normalize lower plasma CC16 and increase plasma sIL-2R.

Lower serum transcortin (CBG) in major depressed females: relationships with baseline and postdexamethasone cortisol values.

This study has been carried out to examine (i) transcortin or corticosteroid binding globulin (CBG), the major glucocorticoid transport protein, in major depressed versus minor depressed and normal subjects; and (ii) the relationships between CBG and basal and postdexamethasone cortisol or adrenocorticotropic hormone (ACTH) values. Serum CBG was significantly lower in major depressed than in minor depressed subjects and normal controls. The significant decrease in serum CBG was observed in major depressed women but not in major depressed men. In depressed subjects, there was a significant and negative relationship between serum CBG and severity of illness. There were significant positive relationships between serum CBG and basal 8:00 a.m. plasma cortisol in normal volunteers (r = 0.87, P < 10(-4)) and depressed subjects (r = 0.40, P = 0.0002). There was no significant relationship between serum CBG and 24-h urinary cortisol. In depressed patients, there was a positive relationship between serum CBG and postdexamethasone cortisol (r = 0.31, P = 0.003). It is concluded that, in depression, serum CBG levels should be taken into consideration for the interpretation of baseline and postdexamethasone plasma total cortisol levels.

Fatty acid composition in major depression: decreased omega 3 fractions in cholesteryl esters and increased C20: 4 omega 6/C20:5 omega 3 ratio in cholesteryl esters and phospholipids.

Recently, there were some reports that major depression may be accompanied by alterations in serum total cholesterol, cholesterol ester and omega 3 essential fatty acid levels and by an increased C20: 4 omega 6/C20: 5 omega 3, i.e., arachidonic acid/eicosapentaenoic, ratio. The present study aimed to examine fatty acid composition of serum cholesteryl esters and phospholipids in 36 major depressed, 14 minor depressed and 24 normal subjects. Individual saturated (e.g., C14:0; C16:0, C18:0) and unsaturated (e.g., C18:1, C18:2, C20:4) fatty acids in phospholipid and cholesteryl ester fractions were assayed and the sums of the percentages of omega 6 and omega 3, saturated, branched chain and odd chain fatty acids, monoenes as well as the ratios omega 6/omega 3 and C20:4 omega 6/C20:5 omega 3 were calculated. Major depressed subjects had significantly higher C20:4 omega 6/C20:5 omega 3 ratio in both serum cholesteryl esters and phospholipids and a significantly increased omega 6/omega 3 ratio in cholesteryl ester fraction than healthy volunteers and minor depressed subjects. Major depressed subjects had significantly lower C18:3 omega 3 in cholesteryl esters than normal controls. Major depressed subjects showed significantly lower total omega 3 polyunsaturated fatty acids in cholesteryl esters and significantly lower C20:5 omega 3 in serum cholesteryl esters and phospholipids than minor depressed subjects and healthy controls. These findings suggest an abnormal intake or metabolism of essential fatty acids in conjunction with decreased formation of cholesteryl esters in major depression.

Acute administration of buspirone increases the escape of hypothalamic-pituitary-adrenal-axis hormones from suppression by dexamethasone in depression.

Recently, our laboratory found a significant enhancing effect of L-5-hydroxy-tryptophan (L-5-HTP) on post-dexamethasone (DST) plasma adrenocorticotropic hormone (ACTH) and cortisol levels in major-but not in minor-depression. To further elucidate the effects of central serotonin (5-HT) activity on the negative feedback of glucocorticoids on hypothalamic-pituitary-adrenal (HPA)-axis function in depression, this study investigates the effects of buspirone, a 5-HT1A receptor agonist, on post-DST ACTH and cortisol levels in 75 depressed subjects. Plasma post-DST ACTH and cortisol concentrations were significantly increased by the acute administration of buspirone (30 mg PO) compared to placebo. There were no differences in buspirone-induced post-DST ACTH or cortisol responses between minor and major depression. There were significant correlations between post-DST ACTH and cortisol, and between post-DST-buspirone ACTH and cortisol. The buspirone-induced post-DST cortisol responses were significantly higher in depressed women than men. It is concluded that buspirone may augment ACTH and, consequently, cortisol escape from suppression by dexamethasone in major as well as in minor depression.

Alterations in plasma dipeptidyl peptidase IV enzyme activity in depression and schizophrenia: effects of antidepressants and antipsychotic drugs.

Recently, our laboratory reported that the activity of dipeptidyl-peptidase IV (DPP IV) was significantly lower in the peripheral blood of major depressed patients than in normal controls. The present study examines plasma DPP IV activity in 43 major depressed and 13 schizophrenic subjects versus 21 normal controls and the effects of antidepressants and antipsychotic drugs on plasma DPP IV activity. DPP IV activity was significantly lower in major depressed subjects than in normal controls and schizophrenic subjects. There was a trend towards higher DPP IV activity in schizophrenic patients than in normal controls. There were no significant effects of antidepressants or neuroleptics on plasma DPP IV activity in depressed and schizophrenic patients, respectively. There were no significant relationships between plasma DPP IV activity and plasma cortisol or immune-inflammatory markers, such as serum interleukin-6 (IL-6) or soluble IL-2 receptor. A significant and positive correlation was found between plasma DPP IV and prolyl endopeptidase (PEP) enzyme activity in the study group as a whole and in schizophrenic subjects. The results support the hypothesis that lower and higher plasma DPP IV activities are trait markers of major depression and schizophrenia, respectively. It is concluded that alterations in the enzyme activity of peptidases, such as DPP IV and PEP, play a role in the pathophysiology of major depression and schizophrenia.

Increased serum interleukin-1-receptor-antagonist concentrations in major depression.

Recently, it has been shown that major depression may be accompanied by an increased production of interleukin-1 beta (IL-1 beta), an acute phase (AP) response and simultaneous signs of activation and suppression of cell-mediated immunity. The interleukin-1-receptor antagonist (IL-1-rA) is released in vivo during an AP response and serum levels are increased in many immune disorders. The release of IL-1-rA may limit the pro-inflammatory effects of IL-1. This study has been carried out to examine serum IL-1-Ra in 68 depressed subjects (21 minor, 25 simple major and 22 melancholic subjects) vs. 22 normal controls. Depressed subjects showed significantly higher serum IL-1-rA concentrations than healthy controls. 29% of all depressed subjects had serum IL-1-rA levels higher than the mean value +2 standard deviations of normal controls; 44% depressed subjects had IL-1-rA values greater than 0.215 ng/ml with a specificity of 90%. In depressed subjects, there was a significant and positive relationship between serum IL-1-rA and severity of illness. In depression, there were no significant relationships between serum IL-1-rA concentrations and indicants of hypothalamic-pituitary-adrenal (HPA)-axis activity, such as 24-h urinary cortisol and postdexamethasone cortisol values. Women had significantly higher serum IL-1-rA levels than men. The findings support the thesis that depression is accompanied by an immune-inflammatory response.

Alterations in plasma prolyl endopeptidase activity in depression, mania, and schizophrenia: effects of antidepressants, mood stabilizers, and antipsychotic drugs.

The activity of prolyl endopeptidase (PEP), a serine proteinase, has been found to be significantly lower in the blood of patients with major depression than in normal volunteers. The present study investigates plasma PEP activity in 25 major depressed, 10 manic, and 14 schizophrenic subjects versus 30 normal volunteers. It also examines the effects of antidepressants, valproate, and neuroleptic drugs on plasma PEP activity. PEP activity was significantly lower in major depressed subjects than in normal volunteers and in patients with mania and schizophrenia. In depressed subjects, plasma PEP activity was significantly increased during treatment with antidepressant drugs, such as fluoxetine. Plasma PEP activity was significantly increased in manic and schizophrenic subjects compared with normal volunteers. In manic subjects, short-term treatment with valproate had a significant suppressive effect on PEP activity. No significant effects of neuroleptics on PEP activity could be found in the schizophrenic patients. The results support the hypothesis that lower PEP activity could play a role in the pathophysiology of major depression, while increased PEP activity may be related to psychotic conditions, such as mania and schizophrenia.

An augmented escape of androstenedione from suppression by dexamethasone in melancholia: relationships to intact ACTH and cortisol nonsuppression.

To further examine the association between basal and postdexamethasone (DST) pituitary and adrenal activity in depression, the authors measured intact adrenocorticotropic hormone (ACTH), androstenedione and cortisol, both in baseline and post-DST conditions, in 63 depressed subjects (14 minor, 33 simple major and 16 melancholic subjects). It was found that post-DST androstenedione, cortisol and ACTH values were significantly higher in melancholic than in minor depressed subjects. There were highly significant correlations between plasma androstenedione and ACTH both in baseline and post-DST conditions. The significant intercategory differences in post-DST androstenedione were determined by differences in post-DST ACTH. Basal and post-DST androstenedione values were significantly higher in men than in women and both values were significantly and negatively related to age. There were highly significant, positive relationships between cortisol and ACTH and between cortisol and androstenedione both in baseline and post-DST conditions. The results corroborate our hypotheses that, in depression, pituitary (ACTH) and adrenal (cortisol and androstenedione) hormonal secretion are tightly coupled in post-DST conditions and that the augmented escape of ACTH-target hormones in melancholia is, in part, related to that of pituitary ACTH.

Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression.

Recently, it was found that major depression may be accompanied by significant changes in cell-mediated and humoral immunity. The purpose of this study was to investigate the plasma concentrations of interleukin (IL)-6, soluble IL-6 receptor (sIL-6R), sIL-2R and transferrin receptor (TfR) in patients with major depression in an acute phase of illness, in remission and during antidepressive treatment. Plasma concentrations of IL-6, sIL-6R, sIL-2R and TfR were significantly higher in major depressed subjects than in healthy controls. In major depressed subjects, but not in normal controls, there were significant positive correlations between the plasma concentrations of IL-6 and sIL-6R, IL-6 and sIL-2R, IL-6 and TfR, and between sIL-2R and TfR. Subchronic treatment with antidepressive drugs, such as fluoxetine or tricyclic antidepressants, did not significantly affect plasma IL-6, sIL-6R, sIL-2R or TfR. The latter did not significantly differ between major depressed patients in an acute phase of illness or in complete clinical remission. It is suggested that: (1) a coordinated and upregulated production of IL-6, sIL-6R, sIL-2R and TfR may constitute a trait marker of major depression; and that (2) an upregulated production of IL-6 may represent a contributing factor to the various immune disorders encountered in major depression and maybe to the pathophysiology or pathogenesis of that illness.

Total serum protein and serum protein fractions in depression: relationships to depressive symptoms and glucocorticoid activity.

Recently, it has been reported that major depression is accompanied by changes in plasma protein concentrations indicative of an acute-phase protein (APP) response. The purpose of the present study was to examine total serum protein (TSP) and the electrophoretically separated major fractions of serum proteins (SP), i.e., albumin (Alb), alpha 1, alpha 2, beta and gamma globulin, in depression. Highly significant differences were found in TSP and the separated SP fractions between major depressed patients and normal controls and between melancholic and minor depressed patients. Major depressed subjects showed significantly lower TSP and Alb concentrations and a higher percentage of the alpha 1 globulin fraction than normal controls and minor depressed subjects. Major depressed subjects had significantly higher and lower percentages, respectively, of alpha 2 and gamma globulin fractions than normal controls. In depressed subjects, there were significant negative correlations between TSP or Alb concentrations and severity of illness. Psychomotor retardation and anorexia were psychopathological correlates of lower TSP and Alb concentrations while middle insomnia and psychomotor retardation were related to changes in the alpha 2 globulin fractions. Basal plasma cortisol values were significantly and positively related to serum alpha 2 globulin. The results support the view that major depression is accompanied by an APP response.

Plasma soluble interleukin-2-receptor in depression: relationships to plasma neopterin and serum IL-2 concentrations and HPA-axis activity.

The present study examined the plasma concentration of the soluble interleukin-2-receptor (sIL-2R) in depressed subjects in relation to hypothalamic pituitary adrenal (HPA) axis function and plasma neopterin and serum IL-2 concentrations. Plasma sIL-2R concentration was significantly higher in depressed patients (n = 47) than in controls (n = 19). There were no significant correlations between plasma sIL-2R and severity of illness. In the depressed subjects, there was a highly significant relationship between plasma sIL-2R and neopterin concentrations. Depressed patients with pathologically increased plasma neopterin levels had significantly higher plasma sIL-2R values than those with normal serum neopterin. There were no significant relationships between plasma sIL-2R and indices of HPA-axis function in depression. There was no significant effect of dexamethasone administration on sIL-2R levels. Significantly more depressed subjects had measurable serum IL-2 levels than normal controls. Our data support the notion that a moderate activation of cell-mediated immunity may play a role in the pathophysiology of depression.