Thyrotropin and prolactin responses to different doses of thyrotropin-releasing hormone in depression

The effects of low doses of thyrotropin-releasing hormone (TRH, 50 and 200 micrograms) on thyrotropin (TSH) and prolactin levels have been studied in depressed women and compared with the depressive condition and with the results of the dexamethasone suppression test (DST). TRH administration elicited blunted hormonal responses that were not correlated either with the age of the patients or with DST results. Different effects were observed in subgroups of depressive patients classified according to DSM III and ICD. No correlation was found between hormone responses and the scores of Hamilton Rating Scale and Montgomery Depression Scale. The effects of 50 micrograms on TSH were significant and inversely correlated with Anxiety Rating Scale scores. No dose-response effect was apparent of prolactin and TSH in depressed patients, suggesting an impaired function of pituitary TRH receptors.     

Relationship between prolactin responses to ECT and dopaminergic and serotonergic responsivity in depressed patients

The prolactin (PRL) increases in plasma, induced by the electrical stimulus during electroconvulsive therapy (ECT), is a consistent finding that can be studied in order to obtain information about its actions on the brain neurotransmitter systems, the most probable candidates being the serotonergic and the dopaminergic system. Central serotonergic and dopaminergic responsivity may also be assessed using neuroendocrine challenge tests. In this study, we measured the PRL responses during the first ECT of a therapeutic course in 15 male depressive patients, of mean age 49.2 ± 14.5 (range 22 to 68 years), and score in the HDRS of 29 ± 8 (range 18 to 43 points). Before the ECT course, we assessed the central serotonergic and dopaminergic responsivities, by measuring the PRL responses to the administration of the serotonin uptake inhibitor clomipramine (CMI) intravenously, and, two days later, the PRL responses dopamine receptor blocker haloperidol (HAL), administered intramuscularly. The CMI and HAL tests were also performed in 15 healthy male subjects. The PRL responses to CMI of the patients were blunted compared to healthy controls, while the PRL responses to HAL were not significantly different from controls. Searching for correlations among the maximal PRL responses to the three stimuli in the patient's group, we found that the PRL responses to ECT were significantly correlated to the PRL responses to i. m. HAL (r = 0.8205, N = 15, p < 0.001) and not to the PRL responses to i. v. CMI (r = 0.1713, n. s.). It is suggested that the rises in PRL during ECT reflect the responsivity of the hypothalamus-pituitary dopaminergic system, and seem to be the result of a transient decrease in the inhibitory dopaminergic input of the hypothalamus to the pituitary lactotrophs, caused by the electrical stimulus and the subsequent seizure. Received: 5 March 2002 / Accepted: 15 July 2002     

Thyrotropin, prolactin, and growth hormone responses to thyrotropin-releasing hormone in anorexia nervosa and bulimia

Serum thyrotropin (TSH), prolactin (PRL), and growth hormone (GH) levels were measured before and after stimulation with thyrotropin-releasing hormone (TRH) in 10 patients with bulimia, 7 with features of the restricting subtype of anorexia nervosa, and 6 with bulimic subtype of anorexia nervosa. The mean basal levels of TSH, PRL, and GH did not differ among the three groups. A delayed TSH response was found in 86% of the restricting anorectics, 80% of the bulimic anorectics, and 22% of the bulimics. The PRL response was normal in all patients, with no significant difference among the three groups. Elevated basal GH levels were found in 29% of the restricting anorectics, 33% of the bulimic anorectics, and 33% of the bulimics. An abnormal GH increase after TRH stimulation was observed in 50% of the restricting anorectics, 20% of the bulimic anorectics, and 13% of the bulimics. These results suggest that some patients with bulimia, and some with anorexia nervosa, have a hypothalamic dysfunction. These neuroendocrine abnormalities do not appear to be due solely to low weight or to metabolic changes resulting from binge eating and are not associated with depressive symptoms.     

Drug-induced growth hormone and prolactin responses in schizophrenia research

1. Interpretation of neuroendocrine studies in schizophrenia requires consideration of (a) the large number of variables that affect drug-induced endocrine responses (b) the effect of prior neuroleptic therapy (c) heterogeneity of schizophrenia (d) heterogeneity of receptors (e) uniqueness of the hypothalamic-pituitary axis (f) selectivity and pharmacokinetics of administered drugs. 2. Apomorphine increases growth hormone secretion by an effect on dopamine receptors that are not linked to adenylate cyclase and which are located outside the blood brain barrier. 3. Hypothalamic-pituitary histaminergic H2 and alpha-adrenergic function are unchanged in chronic schizophrenia. 4. Schizophrenic symptoms persist despite complete blockade of dopamine receptors modulating prolactin secretion. 5. Studies on dopamine receptors modulating prolactin secretion are unlikely to shed light on the pathophysiology of schizophrenia. 6. Screening for drugs which block apomorphine-induced growth hormone secretion but do not increase prolactin may provide a way of detecting anti-schizophrenic drugs which are devoid of side effects associated with hyperprolactinemia and which do not induce parkinsonism or tardive dyskinesia.     

Thyrotropin and Prolactin Secretion During ECT: Implications for the Mechanism of ECT Action

The effect of electroconvulsive therapy (ECT) on serum thyrotropin (TSH) and prolactin (PRL) was systematically investigated in two studies: a simulated ECT (SECT) versus real ECT controlled design, and one in which a more sensitive TSH assay was used. In addition to the expected PRL response, a small but consistent TSH increase was demonstrated, especially when the new TSH assay was used. The implications of these findings concerning the underlying ECT mechanisms mediating these effects are discussed and the involvement of thyrotropin-releasing hormone (TRH) and serotonin is stressed.     

Thyrotropin and prolactin responses to protirelin (TRH) prior to and during chronic imipramine treatment in patients with panic disorder

The effects of protirelin [thyrotropin-releasing hormone (TRH)] administration on the release of thyrotropin (TSH) and prolactin (PRL) were examined in 14 patients with panic disorder prior to and during chronic treatment with imipramine. During imipramine treatment, the patients exhibited an increase in their TSH response to TRH (Δ Δ_{max TSH = 3.65 ± 6.02 μIU/ml}, p0.05) and in their PRL response to TRH (Δ AUC_PRL = 734 ± 965 ng/ml/45 min, p < 0.005). Several behavioral measures correlated with the neuroendocrine measures during imipramine therapy. These preliminary findings might suggest a role for changes in dopaminergic function in the clinical effects of imipramine in patients with panic disorder.     

Thyrotropin and prolactin response to thyrotropin-releasing hormone in depressed and nondepressed alcoholic men

Thyrotropin-releasing hormone (TRH) stimulation tests were performed on 81 alcoholic men after at least 3 weeks of abstinence. Subjects were given 500 micrograms of TRH intravenously, and thyroid-stimulating hormone (TSH) and prolactin (PRL) were measured at baseline, and then 15 and 30 min later. Comparisons were made among alcoholics with (n = 27) and without (n = 54) a lifetime history of depression as determined by the Diagnostic Interview Schedule. Nine nondepressed, nonalcoholic subjects served as controls. Alcoholics with or without a depression history did not differ from each other or from control in TSH or PRL response area under the curve. Blunted TSH responses were present in 10 (12%) of the alcoholics and none of the controls when blunting was defined as a delta max TSH less than 5 microU/ml. When blunting was defined as a delta max TSH less than 7 microU/ml, 18 (22%) of the alcoholics and 1 (1%) of the controls were blunted. Conversely, 2 (2.5%) of the alcoholics had a delta max TSH greater than 32 microU/ml. All subjects were clinically euthyroid. Contrary to expectation, depressed subjects were slightly less likely to show blunted responses than nondepressed subjects. No relationship was found between neuroendocrine measurements and several measurements of alcoholism or depression. Some alcoholic subjects show a blunted TSH response to TRH injection, which may be a function primarily of the alcoholism itself. The precise mechanism remains unknown.     

ECT in primary and secondary depression

The response of depressive symptoms to ECT was studied in 58 subjects who met DSM-III criteria for major depression. For data analysis, the sample was divided by diagnosis into categories of primary unipolar depression, bipolar depression, and secondary depression. Only 56% of the secondary depression group had a partial or complete remission of depressive symptoms, but 91% of the primary unipolar group and 100% of the primary bipolar group improved. Subdividing the secondary depression group by primary diagnosis revealed a differential response, with alcoholism and schizophrenia having the most favorable outcomes.     

Catatonia with schizophrenia: From ECT to rTMS

Background

Electroconvulsive therapy is indicated in cases of catatonic schizophrenia following a failure of the challenge test with lorazepam or Zolpidem^®. Some patients need maintenance treatment with ECT. Repetitive Transcranial Magnetic Stimulation (rTMS) and anodal Transcranial direct-current stimulation (tDCS) might be effective against catatonia.

Increases in prolactin levels following bilateral and unilateral ECT

Plasma prolactin levels were studied after bilateral and unilateral ECT in eight female melancholic patients. Although prolactin levels were higher after both treatments, patients who received bilateral ECT had significantly higher prolactin levels than did those who received unilateral ECT.     

Studies on prolactin in major psychoses--with reference to prolactin response to stress in schizophrenia

The serum prolactin concentrations of schizophrenics with delusions or hallucinations, hypomanics, depressives, alcoholics with and without psychotic symptoms were examined. Among them, only the serum prolactin concentrations of alcoholics with psychotic symptoms were significantly higher when compared to the normal controls. In a stress experiment, the alterations of serum prolactin seen in schizophrenics were significantly greater when compared to the normal controls. The results are discussed in connection with the neurochemical mechanisms for the emotional states caused by stress.