Growth hormone response to clonidine in untreated depressed patients

Growth hormone (GH) responses to i.v. clonidine administration (150 micrograms) were compared in untreated depressed patients and controls. There were 8 controls (6 males, 2 females), 16 patients with a major depressive episode (8 males, 8 females), and 16 matched patients with a minor depressive episode according to Research Diagnostic Criteria. Differences in the GH response to clonidine only occurred between male patients and controls. These results suggest that endocrinological variables are important in the interpretation of this neuroendocrine test. Findings in the subgroup of unmedicated male patients with a nonendogenous major depressive episode support the hypothesis of decreased noradrenergic receptor sensitivity.     

Differential patterns of psychomotor functioning in unmedicated melancholic and nonmelancholic depressed patients

Few studies examining psychomotor retardation (PR) in patients with major depressive disorder (MDD) included medication-free patients. The purpose of this study was (1) to examine whether unmedicated patients with MDD would exhibit PR, (2) to determine whether this retardation, if present, was more cognitive or motor in nature, and (3) to investigate whether any differences in PR could be established between melancholic and nonmelancholic depressed patients. Thirty-eight unmedicated inpatients with severe MDD (20 melancholic and 18 nonmelancholic patients) and 38 matched controls were compared on figure-copying tasks in which the cognitive task difficulty was manipulated. In addition, a simple motor task and the symbol digit substitution task (SDST) were administered. As a group, the patients were significantly slower performing all tasks and both initiation times (IT) and movement times (MT) were prolonged. However, when a distinction was made between the two subtypes, only the melancholic patients showed prolonged MTs compared to the controls. Furthermore, the melancholic patients differed significantly from the controls in IT in all tasks. The nonmelancholic patients had significantly longer ITs than the controls in two copying tasks. It can be concluded that there was clear cognitive and motor slowing in this group of unmedicated inpatients with MDD. The melancholic patients were more severely affected than the nonmelancholic patients and showed a slowing of cognitive as well as motor processes. Differences in psychomotor functioning between melancholic and nonmelancholic depressed patients could imply different underlying neurobiological disturbances in these subtypes of major depression.     

Multiple hormone responses to clonidine administration in depressed patients and healthy volunteers

Abnormalities in several hypothalamic-pituitary-target organ axes in depression may reflect alterations in central neurotransmitter receptor function. As the alpha 2-adrenergic receptor has been implicated in a variety of neuroendocrine abnormalities in depression, we assessed the role of alpha 2-adrenoceptor dysfunction in mediating response abnormalities of growth hormone, cortisol, and prolactin after intravenous clonidine administration (an alpha 2-adrenergic receptor agonist) in 18 patients with major depression (12 with melancholic features, 6 without melancholic symptoms) and 9 healthy volunteers. In particular, we examined the hypothesis that these abnormalities might be more evident in patients with DSM-III melancholic depression. After clonidine, the mean growth hormone response was significantly lower in melancholic depressives compared to controls (p = 0.02), and the shape of the growth hormone response profile was also significantly different in melancholic patients (p = 0.04). There was an overall decrease in the mean cortisol concentration after clonidine in melancholic patients and control subjects (p = 0.02), as well as a larger cumulative prolactin response in melancholic patients compared to those without melancholic features (p = 0.02). The present results confirm prior observations of a blunted growth hormone response after clonidine and suggest that alterations in alpha 2-adrenergic receptor activity might also contribute to several neuroendocrine abnormalities in patients with melancholic depression.     

Parental care and personality in melancholic and nonmelancholic depression

The authors hypothesized that low parental care is linked to nonmelancholic depression through depressive personality traits and personality dysfunction. This hypothesis was tested using path analysis with data provided from a sample of patients meeting DSM-IV criteria for major depression and distinguished on the basis of melancholic symptoms. The results supported their hypothesis. Lack of parental care was associated with self-critical traits, and higher levels of these traits were associated with personality dysfunction, which in turn was associated with nonmelancholic, but not melancholic, depression. Dependent traits were uniquely associated with the onset of an anxiety disorder before the first episode of depression. Researchers interested in the link between personality and depression are encouraged to focus their efforts on patients whose depressive episodes do not meet DSM-IV criteria for melancholia, and on the personality dimension of self-criticism rather than dependency.     

Noradrenergic responses to clonidine in acute and remitted depressed male patients.

To investigate noradrenergic function in depression, plasma 3-methoxy-4-hydroxyphenylglycol (MHPG), plasma norepinephrine (NE), mean arterial pressure (MAP), and heart rate responses to intravenous clonidine (2 micrograms/kg), an alpha 2-adrenergic agonist, were measured in 27 acutely depressed patients, 18 remitted depressed patients, and 27 normal control subjects; a placebo infusion was administered to a subgroup. Clonidine compared with placebo, over a 150-minute time course, decreased plasma NE, MAP, and heart rate, but not plasma MHPG, in the control subjects. Plasma MHPG, plasma NE, MAP, and heart rate at baseline or in response to clonidine and placebo over 150 minutes did not indicate any group differences. The only significant plasma MHPG response to clonidine in the normal control subjects occurred 60 minutes after the infusion. A significantly diminished plasma MHPG response to clonidine at 60 minutes was found in the acutely depressed group compared with the normal control subjects. These results suggest that peripheral inhibitory noradrenergic responses to clonidine are normal in depressed patients, while plasma MHPG responses to clonidine, which have a limited central contribution, appear to be a weak reflection of central noradrenergic function and appear insufficiently robust for a meaningful evaluation of hypothetical group differences in central inhibitory alpha 2-adrenergic activity in this population.     

Differences in nocturnal melatonin secretion between melancholic depressed patients and control subjects

The authors took multiple serum samples for measurement of melatonin between 4:30 p.m. and 7:30 a.m. in seven male depressed patients with melancholia and five healthy male control subjects and found that melancholic patients had a significantly lower rise of melatonin. They also compared a second, separate group of 14 women and five men suffering from melancholic depression with seven healthy male control subjects and nine depressed women without melancholia. The melancholic patients had a significantly lower concentration of serum melatonin at 11:00 p.m. than either the control subjects or the nonmelancholic depressed patients. These findings support the possibility that the functioning of the pineal gland is altered in these patients.     

Growth hormone, prolactin and thyrotropin responses to gonadotropin-releasing hormone in depressed patients and healthy volunteers

Growth hormone (GH), prolactin (PRL) and thyrotropin (TSH) release following gonadotropin-releasing hormone (GnRH) administration were examined in 56 patients with major affective disorder (37 unipolar, 19 bipolar) and 38 normal healthy subjects. There were no differences in GH, PRL or TSH responses after GnRH infusion between the patients and the normal subjects, in contrast to previously reported abnormalities in depressed patients. Serum GH concentration increased after GnRH in both normal and depressed men; serum TSH increased after GnRH in both normal women and bipolar women, but not in unipolar depressed women. Further studies comparing GnRH to saline infusion will be necessary to determine if the GH and TSH responses seen in this study are due to GnRH or result from the stress of the experimental procedures.     

Predicting the course of melancholic and nonmelancholic depression. A naturalistic comparison study.

We assessed improvement patterns and predictors of outcome over a 1-year period, in a sample of depressed patients receiving treatment from a specialized mood disorders unit. Patients with melancholia had a differential improvement pattern from the nonmelancholics in the first 20 weeks, but case rates and severity levels were comparable at 20 weeks and at 1 year. Only three variables (older age at first episode, less severe depression and extraversion) were predictors of improvement in both groups. Improvement was predicted by less psychomotor disturbance, absence of personality disorder, and higher social functioning in the melancholic patients. A reported absence of timidity and shyness in childhood, a briefer duration of depression, and receipt of individual psychotherapy predicted a better outcome in the nonmelancholic patients. Although significant predictors were few overall, the suggested differential relevance for most of the isolated predictors argues for outcome studies that examine melancholic and nonmelancholic depressive disorders separately.     

Growth hormone responses to growth hormone-releasing hormone, clonidine and insulin-induced hypoglycemia in normal weight bulimic women

The growth hormone (GH) responses to GH-releasing hormone (GHRH; 1 microgram/kg BW in an i.v. bolus), clonidine (150 micrograms in a single oral dose) and insulin (0.15 IU/kg BW in an i.v. bolus) induced hypoglycemia were evaluated in 7 normal weight bulimic women with regular menstrual cycles and in 7 age- and weight-matched normal women. In addition, the effect of thyrotropin-releasing hormone (TRH; 200 micrograms in an i.v. bolus) on serum thyroid-stimulating hormone (TSH) and GH levels was measured in the same subjects. Tests were carried out in random order on the 22nd days of the following menstrual cycles. A control test with the i.v. administration of normal saline instead of drugs was carried out 2 days after the TRH test. Basal GH levels were significantly higher in bulimic women than in normal controls; despite higher GH levels, bulimic women showed normal circulating concentrations of somatomedin-C (Sm-C). Serum GH levels remained unmodified during the control test. In contrast, the administration of GHRH, clonidine or insulin induced significant GH responses in all subjects. Bulimic and normal women showed comparable responses after GHRH, clonidine or hypoglycemia. The hypoglycemic response to insulin was similar in bulimic and control subjects. The administration of TRH was unable to increase the circulating levels of GH in the normal controls, whereas it significantly increased GH concentrations in 5 of 7 bulimic women.(ABSTRACT TRUNCATED AT 250 WORDS)     

Growth hormone (GH) response to clonidine and growth hormone releasing factor (GRF) in normal controls

To investigate the relationship between the plasma growth hormone (GH) response to provocative challenge with the hypothalamic peptide growth hormone-releasing factor (GRF) and the alpha 2-adrenergic agonist clonidine, we administered GRF (1 microgram/kg), clonidine (2 micrograms/kg), and placebo to 21 healthy normal controls (13 men and eight women). Both clonidine and GRF caused significant increases in plasma GH levels over baseline. The peak GH-responses to GRF and clonidine were similar (GRF = 8.7 +/- 6.7 ng/ml; clonidine = 6.5 +/- 5.9 ng/ml; Wilcoxon test: s = 361, z = -1.31, p = NS). The GH responses to GRF and clonidine were significantly correlated (rs = 0.62, n = 20, p = 0.004). Unexpectedly, we found that five of the 21 (26%) normal controls had no GH secretory response to either GRF or clonidine. There was a modest gender effect with clonidine (men greater than women; p less than 0.06) and a negative correlation between GH secretion and age with both GRF and clonidine. Neither GRF nor clonidine had an effect on cortisol levels (DRUG x TIME interaction: F(8,152) = 0.60, p = NS). These findings are consistent with animal studies suggesting that the GH response to clonidine is mediated by GRF. The age and gender effects underscore the importance of careful matching for these factors in studies measuring the GH secretory response.     

Serum haptoglobin levels in patients with melancholic and nonmelancholic major depression

Background

Major depression (MD) is accompanied by systemic immune activation or an inflammatory response with the involvement of phagocytic cells, T cell activation, B cell proliferation, and an acute phase response with increased levels of positive and decreased levels of negative acute-phase proteins. In this study, we aimed to determine any differences in serum haptoglobin (Hp) concentrations among patients with melancholic and nonmelancholic MD and the healthy controls.

Methods

This study involved 125 male patients who were admitted to the Department of Psychiatry, Gulhane Military Medical Academy (GMMA), in Ankara, Turkey. They were diagnosed with MD according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and agreed to participate in the study. The melancholic group consisted of 37 patients and the nonmelancholic group had 45 patients. A healthy control group of 40 subjects was selected from the staff of GMMA. These subjects had not had any lifetime psychiatric diagnosis or psychiatric treatment in their medical histories. Peripheral venous blood samples were obtained from the patients and the control group for a complete blood count, routine biochemistry, and the detection of serum Hp levels.

Results

There was no statistically significant difference among the melancholic MD, the nonmelancholic MD, and the healthy control groups in terms of age, level of education, and gender. Serum Hp concentrations are significantly higher in melancholic patients as compared with non-melancholic depressed patients and controls. However, there was no statistically significant difference between the nonmelancholic MD and the control group in terms of Hp concentrations.

Conclusion

The results of this study are important in terms of showing different serum Hp concentrations in patients with melancholic and nonmelancholic MD.     

Growth hormone responses to intravenous clonidine challenge correlate with behavioral irritability in psychiatric patients and healthy volunteers.

To explore the relationship between central noradrenergic receptor responsivity and indices of impulsive aggression, growth hormone responses to infusions with the alpha 2-adrenergic receptor agonist clonidine (GH[CLON]) and responses on the Buss-Durkee Hostility Inventory (BDHI) were examined in healthy male volunteers and male patients with major affective or personality disorder. GH[CLON] values were found to correlate significantly with the BDHI "Irritability" subscale in all subjects, but especially in healthy volunteer and personality disorder patients. GH[CLON] values did not correlate with the BDHI "Assault" subscale. These results suggest a role for central alpha 2-adrenergic receptor responsivity in the personality trait characterized by behavioral irritability, but not overt assaultiveness, in humans.     

Lymphocyte subsets and lymphokine production in patients with melancholic versus nonmelancholic depression

Several studies have reported immune changes during depression, but the results have not been fully consistent. Some of these changes could be related to the presence of melancholic features. A total of 42 depressed patients (melancholic [MEL] and nonmelancholic [non-MEL]) and 20 healthy controls participated in the study. We detected a higher CD4+ lymphocyte subset in MEL patients than in controls during the depressive state, which disappeared after clinical remission. We also found an increase in interleukin-2 (IL-2) production both in MEL and non-MEL patients, but these values did not differ from control values after clinical remission. Some of these changes may be related to the melancholic characteristics of depression.     

Hormonal responses to clonidine and urinary MHPG in delusional and nondelusional melancholic patients: a placebo-controlled study

Summary The growth hormone (GH) and cortisol responses to intravenous clonidine (0.15mg) treatment of 25 melancholic patients, 12 with and 13 without delusions, were studied with placebo control. The baseline concentrations of the main noradrenaline metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG) were also estimated in urine. Cortisol plasma levels decreased significantly and equally after both placebo and clonidine. Baseline cortisol levels correlated positively with urinary MHPG. Clonidine did not increase GH levels significantly over time compared with placebo. Delusional melancholic patients tended to have smaller GH responses to clonidine than nondelusionals (F=2.18,P=0.06). There were no differences in GH response to clonidine between high and low MHPG excretors.     

Growth hormone (GH) responses to GH-releasing hormone in depression: correlation with GH release following clonidine

Twenty subjects (10 patients with major depressive disorder and 10 controls matched for age, gender, and ovarian status) received 1 microgram/kg synthetic human growth hormone-releasing hormone (GHRH)-44 amide as an i.v. bolus dose. Compared to controls, depressed patients showed a significant attenuation of net growth hormone (GH) responses to GHRH associated with normal basal GH concentrations. The blunted GH responses occurred in the face of significantly higher somatomedin C (Sm-C) concentrations. Comparison of GH responses after GHRH with GH output following the alpha 2-agonist clonidine (CLON) revealed a significant positive correlation. The concordance between GH responses after specific challenges at different levels of the GHRH-GH-somatomedin axis indicates the integrity of the hypothalamic-pituitary-somatotropic system in depression and supports the view that altered GH secretory patterns in depression may primarily be due to a suprapituitary disturbance.     

Prolactin response to thyrotropin-releasing hormone in schizoaffective depressed compared to depressed and schizophrenic men and healthy controls

Biological tests may help clarify the relationship of schizoaffective disorder to major depressive disorder (MDD) and schizophrenia (SCZ). Thyrotropin-releasing hormone (TRH), 500 micrograms, was administered intravenously to eight schizoaffective depressed (SD), ten SCZ, 23 MDD patients and 43 healthy controls (HC), all males, ages 20-66 years and drug-free. Research Diagnostic Criteria (RDC) were utilized for establishing diagnoses, Hamilton Rating Scale for Depression (HRSD) total scores were used for assessing depressive symptoms. There were no differences in dmax PRL (post-TRH prolactin peak minus baseline, mean +/- SD) amongst SD, SCZ and HC groups (27.3 +/- 5.2, 28.8 +/- 5.4 and 31.5 +/- 5.6 ng/ml respectively). Mean dmax PRL in MDD was significantly lower than each of the other three groups (17.1 +/- 2.2 ng/ml, P less than 0.05 for all). The essentially normal PRL response to TRH in SD, significantly different from MDD but similar to SCZ parallels our previous observations on the pattern of thyrotropin (TSH) response to TRH in the same diagnostic groups. These biological findings may be taken to indicate that schizoaffective disorder, depressed subtype, is closer to schizophrenia than to major depressive disorder. However, they cannot be considered definitive evidence to that effect since schizoaffective disorders are known to be quite heterogeneous, and since the utilized biological tests lack specificity.     

Growth hormone response to clonidine as a probe of noradrenergic receptor responsiveness in affective disorder patients and controls

The growth hormone (GH) response to the alpha-adrenergic agonist clinidine was blunted in 19 depressed patients compared to 20 controls. The difference remained significant when age- and sex-matches pairs of patients and controls were compared from this sample, either including or excluding subjects with elevated GH baseline levels. Plasma levels of free 3-methoxy-4-hydroxyphenyl-glycol (MHPG) were assayed in blood samples drawn just before the clonidine infusion. A modest negative correlation was found between the plasma MHPG values and the magnitude of the GH responses to clonidine, although baseline plasma MHPG levels were not significantly different between patients and controls. The diminished GH response to clonidine observed suggests that many depressed patients may have decreased alpha-adrenoreceptor responsiveness. Decreased responsiveness may in some cases be associated with relatively increased indices of presynaptic noradrenergic availability. Such a model might have implications for understanding the functional status of the noradrenergic neurotransmitter system in depressed patients and the possible subtyping of affective disorder patients.