Salivary cortisol levels and their correlation with plasma ACTH levels in depressed patients before and after the DST.

OBJECTIVE: The aim of this work was to study the clinical utility of salivary cortisol concentrations in a group of depressed patients undergoing the dexamethasone suppression test (DST) and the correlation of these concentrations with plasma ACTH levels. METHOD: Twenty outpatients from the psychiatric department of a Barcelona hospital who were diagnosed as having nonendogenous (N = 9) or endogenous (N = 11) depression according to DSM-III criteria and the Newcastle scale participated in the study. The comparison group consisted of 12 healthy volunteers. Blood and saliva samples were taken before and after administration of 1 mg of dexamethasone Salivary cortisol and plasma ACTH concentrations were determined by direct iodine-125 radioimmunoassay with commercial kit reagents. RESULTS: Predexamethasone salivary cortisol concentrations were significantly higher in the group with endogenous depression than in the comparison group. A significant correlation was obtained between plasma ACTH and predexamethasone salivary cortisol levels in the group with nonendogenous depression and in the comparison subjects. CONCLUSIONS: These preliminary findings indicate that salivary cortisol could substitute for plasma cortisol in clinical studies in which the DST and hypercortisolemia are evaluated. The lack of correlation between ACTH and cortisol levels in saliva in the group of endogenously depressed patients could indicate a disturbance in the regulation of cortisol secretion in major depression.     

The dexamethasone suppression test: importance of dexamethasone concentrations

Plasma dexamethasone concentrations and cortisol response to dexamethasone were measured in 29 normal healthy volunteers, 23 depressed patients, and 10 patients with anorexia nervosa at 4:00 PM postdexamethasone. In each of the 3 groups, nonsuppressors had lower dexamethasone concentrations than suppressors. Of the subjects with plasma dexamethasone at or below 0.7 ng/ml, a significantly higher proportion (48%) were nonsuppressors compared to the proportion above 0.7 ng/ml (14%), all of whom were patients. Plasma dexamethasone concentrations in a subgroup of depressed nonsuppressors were high (mean 1.35 ng/ml), whereas the remainder were low (0.42 ng/ml) and were similar to the normal nonsuppressors (0.35 ng/ml), suggesting different mechanisms for nonsuppression in the subgroups. Plasma dexamethasone concentrations were similar in nonendogenous and endogenous depressives, in men and women, and in medicated and drug-free patients. None of the variables of age, weight, history of weight loss, Hamilton depression rating score, predexamethasone cortisol, or postdexamethasone cortisol were significantly correlated with plasma dexamethasone, except for body weight and a history of weight loss in the depressed group only. Mean plasma dexamethasone concentrations increased significantly from week 1 to week 2 in 7 depressed patients, whereas plasma cortisol decreased; however, the relationship between dexamethasone and cortisol varied considerably for individual patients.     

Blunting of ACTH response to human CRH in depressed patients is avoided by metyrapone pretreatment

The current concept that blunted adrenocorticotropic hormone (ACTH) response to human corticotropin-releasing-hormone (h-CRH) in depression is primarily determined by elevated circulating plasma cortisol levels is still unproven. We tested this hypothesis by comparing ACTH release following intravenous administration of 100 micrograms h-CRH in 10 normal controls and in 21 inpatients with a major depressive episode. Eleven of these depressed patients were pretreated with an oral dose of 2 g metyrapone, which inhibits cortisol biosynthesis by blocking C-11 beta-steroid-hydroxylase. This intervention deprives the entire system of cortisol, which is the major feedback signal for the regulation of ACTH secretion at various pituitary and limbic sites. ACTH responses, assessed as areas-under-time-course-curves, were: in normal controls, 6.8 +/- 2.4 (SD) pg/ml/min x 10(3); in unmedicated patients, 2.6 +/- 1.1 pg/ml/min x 10(3); and in metyrapone pretreated patients, 9.0 +/- 6.7 pg/ml/min x 10(3). Thus, ACTH release in unmedicated depressed patients was significantly (p less than 0.001, Mann-Whitney U-test) blunted when compared with normal controls. In contrast, this blunting was completely avoided after metyrapone pretreatment, which resulted in net ACTH responses that were indistinguishable from those of the controls.     

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 degree of endogeneity correlated moderately (r = 0.27) but significantly (p = 0.02) with absolute DST values; 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); mean values for maximum DST concentrations increased steadily with categorical endogeneity (nonendogenous, 1.44 microgram/dl; probable endogenous, 7.65 micrograms/dl; definite, 10.93 micrograms/dl; p = 0.01); 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.     

Effect of dexamethasone on cortisol and prolactin responses to meals in bulimic and normal women

In normal individuals, serum cortisol and prolactin concentrations have been shown to rise following a mid-day meal. To determine whether abnormalities of the hypothalamo-pituitary-adrenal axis in bulimics lead to a disrupted hormonal response to eating, cortisol and prolactin responses to meals (600 kcal, 30% protein, 30% fat, 40% carbohydrate) were studied on two consecutive days in six normal weight bulimics and six normal volunteers. Dexamethasone (1 mg orally) was administered at 2330 h after baseline sampling. During baseline sampling, cortisol concentrations were significantly higher in the bulimics (18.2 +/- 0.9 micrograms/dl, mean +/- SEM) than in the normals (12.1 +/- 0.4 micrograms/dl) (p less than 0.001). Post-dexamethasone cortisol concentrations also were higher in the bulimics (5.7 +/- 0.3 micrograms/dl) than in the normals (1.2 +/- 0.2 micrograms/dl) (p less than 0.001). The three bulimics with a major depressive disorder had higher peak post-dexamethasone cortisol concentrations than the nondepressed bulimics. Dexamethasone significantly enhanced the prolactin response to meals among both bulimics (at 90 min post onset of eating) and normals (at 60, 75 and 90 min post onset of eating). This enhancement of the prolactin response to meals by dexamethasone is opposite to the inhibitory effect of dexamethasone on stress-induced prolactin release and suggesting that stress-induced and meal-induced prolactin release involve different neuroendocrine mechanisms.     

Dexamethasone suppression test and the levels of serum growth hormone, plasma vasopressin and plasma homovanillic acid in depressed in- and outpatients

A total of 206 depressive patients (176 outpatients and 30 inpatients) underwent a dexamethasone suppression test (DST). Resting levels of serum growth hormone (GH), plasma vasopressin (AVP) and plasma homovanillic acid (HVA) were also measured in a proportion of the patients. Fifty-seven per cent of the endogenous patients showed nonsuppression of cortisol in the DST, while 92% in the nonendogenous group showed normal suppression. The diagnostic confidence of a positive test was 83%. The sensitivity and specificity of the test was slightly higher among inpatients than out-patients, and serum cortisol value at 4 p.m. was more useful than the morning value. No significant correlation was found between severity of the depression as measured by the Hamilton Rating Scale for Depression and serum cortisol. In single subjects there was, however, an obvious correlation. The levels of serum GH, plasma AVP and plasma HVA did not differ in the endogenous and nonendogenous groups, and there was no correlation between serum cortisol in the DST and the concentrations of the other hormones or HVA in plasma.     

Schizophrenic patients who develop postoperative confusion have an increased norepinephrine and cortisol response to surgery

The purpose of this study was to investigate the relationship between postoperative confusion and the plasma norepinephrine (NE), adrenocorticotropin (ACTH) or cortisol response to surgery in schizophrenic patients. We studied 50 schizophrenic patients and 35 control patients who underwent orthopedic surgery and perioperatively measured plasma NE, ACTH and cortisol levels. Postoperative confusion during 72 h after the end of the operation occurred in 14 of 50 schizophrenic patients (28%) and in 2 of 35 control patients (6%). Plasma NE levels 15 min after skin incision, the next day, the second day and the third day after operation in schizophrenic patients with postoperative confusion (668.0 +/- 59.2, 522.0 +/- 96.5, 463.2 +/- 71.2 and 398.9 +/- 56.2 pg/ml, respectively) were significantly higher than those in schizophrenic patients without confusion (524.1 +/- 62.6, 342.4 +/- 38.6, 311.2 +/- 58.3 and 314.1 +/- 77.1 pg/ml, respectively). Plasma cortisol levels 15 min after the skin incision and the next and second days after operation in schizophrenic patients with postoperative confusion (23.6 +/- 3.2, 21.1 +/- 4.3 and 19.9 +/- 4.4 microg/dl, respectively) were significantly higher than those in schizophrenic patients without confusion (15.2 +/- 4.5, 14.3 +/- 5.1 and 13.8 +/- 3.8 microg/dl, respectively). In conclusion, the occurrence of postoperative confusion in schizophrenic patients is associated with an increase in plasma norepinephrine and cortisol levels during and after surgery.     

Anterior pituitary, adrenal, and gonadal hormones during cocaine withdrawal

Plasma luteinizing hormone (LH), prolactin, testosterone, and cortisol levels were determined in 16 patients after hospital admission for cocaine abuse, during the course of 4 weeks of hospitalization, and before discharge. Hyperprolactinemia was found at admission (mean +/- SD, 27.5 +/- 10.2 ng/ml) and persisted until discharge (mean +/- SD, 28.7 +/- 10.8 ng/ml). Plasma LH, testosterone, and cortisol levels were within normal limits. These findings suggest that persistent elevation of plasma prolactin levels after cocaine withdrawal may reflect a chronic cocaine-induced derangement in neural dopaminergic regulatory systems.     

Repeated administration of the combined dexamethasone-human corticotropin releasing hormone stimulation test during treatment of depression.

Human corticotropin releasing hormone (h-CRH) was administered to 14 patients with major depression, after premedication with an overnight dose of 1.5 mg dexamethasone. Cortisol response, expressed as area under the time course curve (AUC), was significantly higher in the 14 patients than in a group of 13 age-matched control subjects (9.4 +/- 7.6 ng x min x 1,000/ml vs. 3.1 +/- 3.6 ng x min x 1,000/ml). Corresponding AUC values for plasma adrenocorticotropic hormone (ACTH) were also significantly higher in patients than in control subjects (4.9 +/- 1.4 pg x min x 1,000/ml vs. 2.6 +/- 0.9 pg x min x 1,000/ml). After patients were treated with trimipramine (200 mg/day) for 6 weeks, the combined dexamethasone/h-CRH test was repeated. At that time, depression scores were significantly improved and the patients' cortisol response pattern became indistinguishable from that of controls. While plasma cortisol output normalized during treatment with trimipramine, ACTH release remained exaggerated. The combined dexamethasone/h-CRH challenge test may be of particular value in the detection of state-dependent changes of pituitary-adrenocortical neuroregulation.     

A chronobiological study of melatonin and cortisol secretion in depressed subjects: plasma melatonin, a biochemical marker in major depression

The temporal organization of plasma melatonin and cortisol secretion was examined in healthy rested controls and in depressed patients: 11 patients suffering from a primary affective disorder (10 female, 1 male) and 8 male controls were studied over a 24-hr period; blood was collected at 2-hr intervals during the day at 1-hr intervals at night. Plasma melatonin and cortisol levels were determined by radioimmunoassay. In addition, melatonin was determined in plasma sampled at 3 AM in older male controls (n = 8) and in females (n = 10) at ovulation. The controls showed low or undetectable (less than 5 pg/ml) diurnal plasma melatonin levels and a very marked nocturnal rhythm (acrophase: 2.27 AM, mesor: 34.4 pg/ml, amplitude: 58.7 pg/ml). For the three control groups, no significant difference was observed in the nocturnal melatonin peak at 3 AM. The depressed patients also showed a significant melatonin rhythm but with lower amplitude (14.5 pg/ml) and mesor (19.1 pg/ml). The latter rhythm was not significantly phase-advanced with respect to the controls (acrophase at 1.18 and 2.34 AM, respectively). In 9 of the 11 patients, nocturnal melatonin secretion was less marked and frequently associated with hypercortisolemia. An additional episodic melatonin secretion was observed in the late afternoon in only two patients. In depressed patients, there was an increase in the mean cortisol secretion level (mesor at 13.6 micrograms/100 ml against 9.1 micrograms/100 ml in the controls), but the amplitude and the acrophase were not significantly modified. These data are discussed in terms of both the hypothalamus-pituitary-adrenal-epiphysis and aminergic abnormalities.     

Cortisol response to surgery and postoperative confusion in depressed patients under general anesthesia with fentanyl

The purpose of this study was to investigate the relationship between postoperative confusion and plasma cortisol response to surgery in depressed patients. We studied 80 depressed patients and 40 control patients who had undergone orthopedic surgery and perioperatively measured plasma cortisol and adrenocorticotropin levels. Postoperative confusion in the first 3 postoperative days occurred in 5 (13%) depressed patients given fentanyl during anesthesia, 13 (33%) patients without fentanyl and 1 (3%) control patients. Plasma cortisol concentration (19.7 +/- 6.9 and 19.2 +/- 8.0 microg dl(-1)) 15 min after skin incision and 60 min after the end of surgery in depressed patients with fentanyl was significantly lower than that (24.2 +/- 7.2 and 23.5 +/- 8.1 microg dl(-1)) of depressed patients without fentanyl. Plasma cortisol levels during and after surgery in depressed patients with postoperative confusion were higher than those of depressed patients without postoperative confusion. We conclude that the occurrence of postoperative confusion in depressed patients is associated with an increase in plasma cortisol levels during and after surgery. The incidence of postoperative confusion in depressed patients with fentanyl was significantly lower than that of depressed patients without fentanyl.     

Cortisol response to clonidine in panic disorder: comparison with depressed patients and normal controls

Abnormalities in regulation of noradrenergic function have been proposed as part of the pathology of depressive and panic anxiety disorders. However, abnormalities in hypothalamic-pituitary-adrenal (HPA) axis function have largely been limited to patients with depressive disorders. Using the cortisol response to clonidine, an alpha 2-adrenergic receptor agonist, this study examined the relationship between the noradrenergic system and the HPA axis in 10 patients with major depression (4 unipolar, 6 bipolar), 10 patients with panic disorder, and 10 normal controls. Baseline cortisol was significantly elevated in depressed as compared with panic patients, but not with controls. Depressed patients also tended to exhibit a greater absolute fall in plasma cortisol (5.2 +/- 4.0 micrograms/dl) compared with panic patients (1.7 +/- 2.4 micrograms/dl) (p less than 0.06, t-test). When expressed as a percentage of baseline, however, the cortisol response to clonidine did not differ significantly between diagnostic groups (p greater than 0.10). Basal levels of cortisol were highly correlated with the degree of decrease in cortisol induced by clonidine in the group of 30 subjects (r = -0.81, p less than 0.0001). These findings are discussed in the context of the utility of clonidine as a probe of the functional relatedness of the noradrenergic system and the HPA axis in these disorders.     

Alzheimer's disease patients display gender dimorphism in circulating anorectic adipokines

Among neurodegenerative diseases, Alzheimer's disease (AD) is a leading cause of death in elderly individuals. AD is characterized, among other clinical findings, by unexplained weight loss, cachexia and altered immune function. To explore whether any relationship between gender and circulating levels of several eating-controlling metabolites exist, we evaluated leptin, tumor necrosis factor (TNF)-alpha, triiodothyronine (T(3)), free (F) thyroxine (T(4)), TSH, PRL, insulin (INS), and cortisol in 15 AD-treated patients (age range 55-82 years): 9 postmenopausal females (without hormone replacement therapy) and 6 males. The results (mean +/- SEM) indicated that circulating leptin levels were significantly (p < 0.05) higher in female AD (40.34 +/- 11.1 ng/ml) than in male AD (6.07 +/- 1.39 ng/ml) patients. The difference found in circulating leptin levels was noticed regardless of BMI (26.75 +/- 1.77 and 24.55 +/- 1.93 kg/m(2), in females and males, respectively) and waist:hip ratios (0.91 +/- 0.03 and 0.94 +/- 0.02, in females and males, respectively). Moreover, serum TNF-alpha concentrations were also significantly (p < 0.02) higher in AD females (12.24 +/- 1.47 pg/ml) than in AD males (6.62 +/- 1.44 pg/ml), regardless of TNF-alpha:BMI ratios (0.50 +/- 0.09 and 0.28 +/- 0.08, in females and males, respectively; p > 0.05). Finally, no differences were observed between gender (in female and male AD patients, respectively) in circulating levels of T(3) (151.33 +/- 9.91 vs. 116 +/- 17.04 ng/dl), FT(4) (1.26 +/- 0.08 vs. 1.24 +/- 0.06 ng/dl), TSH (1.28 +/- 0.16 vs. 2.46 +/- 0.67 microIU/ml), PRL (10.53 +/- 2.47 vs. 12.61 +/- 2.37 ng/ml), INS (11.76 +/- 1.95 vs. 8.59 +/- 1.34 microIU/ml) and cortisol (15.71 +/- 1.23 vs. 12.63 +/- 1.47 microg/dl). These results indicate that our AD group of patients, with normal corticoadrenal and thyroid functions and normoprolactinemia, displayed a gender-related characteristic in the circulating levels of two very important anorectic signals, leptin and TNF-alpha, being both higher in female than in male AD patients, regardless of BMI. Our study suggests that increased circulating levels of both anorexigenic adipokines may contribute to the metabolic changes observed in AD females.     

Function of the adrenal cortex in patients with major depression

Failure to suppress cortisol secretion after administration of dexamethasone occurs in up to 50% of depressed patients. To test whether this hypothalamic-pituitary-adrenal (HPA) overactivity is associated with adrenocortical hyperresponsiveness, we performed dexamethasone suppression tests (DSTs) and adrenocorticotropic hormone (ACTH) stimulation tests in depressed subjects and subjects with other psychiatric disorders. Three groups were defined: depressed nonsuppressors, depressed suppressors, and other suppressors. While predexamethasone and postdexamethasone cortisol concentrations were greater in the depressed nonsuppressor group, ACTH concentrations did not differ among groups. After receiving alpha-ACTH[1-24] (4.2 micrograms/kg), depressed nonsuppressors had greater increases in stimulated cortisol secretion than the other groups. These results demonstrate that in a subgroup of depressed patients, HPA overactivity is associated with adrenocortical hyperresponsiveness.     

Postdexamethasone prolactin and cortisol: a biological state variable in depression

In 70 inpatients with major depressive disorder postdexamethasone cortisol and prolactin, but not baseline cortisol and prolactin, was found to correlate significantly with various state variables of depression. Postdexamethasone prolactin appeared to be a more specific state variable of depression compared with postdexamethasone cortisol. While prolactin was decreased following dexamethasone in controls and nonendogenous depressed patients, in endogenous depressed patients prolactin was increased by 30%. Due to this inverse prolactin response to dexamethasone, the sensitivity of this test should be considerably increased by using a higher dexamethasone dosage. The DST failed to be a diagnostic marker for any subgroup of depression.     

Relative insulin insensitivity and cortisol secretion in depressed patients

Relative insulin insensitivity occurs in a substantial portion of patients with major endogenous depressions, and about half such cases also hypersecrete cortisol in the afternoon and evening. This study assessed the relation between these two abnormalities in 16 patients with major endogenous depression. Over several days, insulin tolerance tests (ITTs) were performed in the morning and evening, and measures of cortisol secretion taken: plasma cortisol at 0800, 1600, and 2300 hours, both before and after dexamethasone; baseline cortisol before ITTs; and mean 24-hour plasma cortisol concentrations (in 10 cases). After clinical recovery, some of these patients had repeat ITTs (n=10) and repeat predexamethasone and postdexamethasone cortisol assessments (n=9). Additionally two control groups of 15 normal subjects and of 12 schizophrenic patients received morning ITTs. None of the control subjects manifested insulin insensitivity. However, during illness, 8 of the 16 depressed patients manifested relative insulin insensitivity (glucose drop <50%, glucose nadir > 50 mg/dl); compared to the insulin responsive depressed group, the insensitive group had insignificantly greater afternoon and evening cortisol secretion by nearly all indices. After clinical recovery, hypoglycemic response for the entire group was significantly greater than during illness; this improvement was accounted for by the increased insulin responsivity of the previously insulin resistant subgroup. There was also substantial plasma cortisol reduction in the previously insulin resistant group after clinical recovery, but not in the insulin sensitive group.     

Hypothalamic-pituitary-adrenal axis function and suicidal behavior in depression.

Hypothalamic-pituitary-adrenal (HPA) axis function was examined in relation to suicidal behavior in depression. There were no significant differences between depressed patients who had or had not attempted suicide for either cerebrospinal fluid concentrations of corticotropin-releasing hormone, plasma cortisol levels predexamethasone or postdexamethasone, or for urinary-free cortisol outputs. However, depressed patients who had made a violent suicide attempt had significantly higher 4 PM and maximum postdexamethasone plasma cortisol levels, and significantly more of them were cortisol nonsuppressors than patients who had made nonviolent suicide attempts. A 5-year follow-up was carried out. There were no significant differences on indices of HPA function between depressed patients who did or did not reattempt suicide during the follow-up or who had never attempted suicide. These results suggest the possibility that dysregulation of the HPA axis may be a determinant of violent suicidal behavior in depression.     

The effect of the cold pressor test on vasopressin secretion in man

Stress has been thought to induce the release of arginine vasopressin (AVP). We evaluated this claim by studying the effects of a modified cold pressor test on plasma AVP, plasma cortisol, blood pressure, pulse rate, and a number of variables known to affect AVP secretion. In a cross-over study design, test and control values were obtained in seven male subjects. The pressor test was found to induce painful stress as evidenced by subjective reports and the objective findings of increased mean arterial pressure (13.9 +/- 3.1 mm Hg; p less than 0.004), pulse rate (9.2 +/- 2.8 beats/min; p less than 0.02), and plasma cortisol (3.5 +/- 0.8 micrograms/dl; p less than 0.005). In contrast, there were no significant changes in plasma AVP that could be attributed to the cold pressor test. There also were no changes in plasma osmolality, measured plasma solutes, hematocrit or body temperature. An unexpected finding was a premonitory drop in plasma AVP occurring just prior to the pressor test (2.5 +/- 2.0 pg/ml; p less than 0.04) and at the comparable time point in the control study (3.1 +/- 1.2 pg/ml; p less than 0.001). There were no changes in any of the other measured variables which could account for this drop. We conclude that the cold pressor test is not a stimulus to AVP release and that anticipation of stress may inhibit secretion of this hormone.     

The dexamethasone suppression test: identification of subtypes of depression

In this study mean 4 p.m. cortisol levels were significantly higher in patients with major depression than in control subjects or in patients with bipolar depression or dysthymic-related disorders. Moreover, the distribution of values differed significantly among groups. Eighteen of 45 patients with major depression had cortisol levels of 10 micrograms/dl or more, compared with 2 of 20 bipolar depressed patients and 0 of 31 controls. Patients with very high cortisol levels (15 micrograms/dl or more) tended to fulfill criteria for major depression with mood-congruent psychosis. The distribution of values in the major depression group also suggested the existence of three major subgroups. The authors discuss the implications of these data.     

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.