Growth hormone response to growth hormone releasing hormone in depression and schizophrenia

Growth hormone releasing hormone, a 44-amino acid peptide (GHRH-44), was administered (1 micrograms/kg i.v.) to 6 normal controls, 10 schizophrenic subjects, and 7 depressed subjects. A significantly lower growth hormone (GH) response was found in the schizophrenic and depressed groups. Two molecular forms of GH, 22K GH and 20K GH, were also measured but did not further differentiate the three groups of subjects.     

Lymphocyte monoamine oxidase and plasma prolactin and growth hormone in tardive dyskinesia

Twelve elderly women with tardive dyskinesia were matched with 12 patients without dyskinesia. Lymphocyte monoamine oxidase (MAO) activity and plasma prolactin and growth hormone concentrations were determined "blind" in these 12 pairs of patients. Chronic schizophrenic patients with tardive dyskinesia had significantly lower lymphocyte MAO activity as compared to controls. Organic brain syndrome patients with dyskinesia did not differ from controls in the lymphocyte MAO activity. These results with lymphocyte MAO parallel our earlier findings on platelet MAO. No significant differences were found between dyskinesia group and controls in the plasma prolactin and growth hormone concentrations. Possible implications of our findings are discussed.     

The influence of psychotropic drugs and releasing hormones on anterior pituitary hormone secretion in healthy subjects and depressed patients

Pharmacoendocrinological studies have shown that psychotropic drugs with different actions have different effects on anterior pituitary hormone secretion in man. Substances with different effects on the central nervous system are characterized by a different pharmacoendocrinological profile. Studies with various receptor blockers have shown varying influences on the DMI-induced growth hormone, prolactin, and ACTH/cortisol secretion. Growth hormone stimulation was shown to be mediated by alpha 2-receptors and inhibited by beta-receptors. Investigations in male and female endogenous depressive patients demonstrated a significantly blunted growth hormone response to DMI compared with age- and sex-matched healthy subjects. A comparative study in male endogenous depressive patients showed a significantly diminished growth hormone stimulation both after DMI and after growth hormone-releasing hormone compared to healthy male subjects. In further tests a simultaneous application of four releasing hormones (GHRH, CRH, GnRH, TRH) was used. These investigations showed a significantly lower GH stimulation in endogenous depressive patients compared with age- and sex-matched healthy subjects, but not in neurotic depressive or schizophrenic patients. Cortisol stimulation was similar in all groups of patients and healthy subjects. TSH stimulation was significantly lower in endogenous depressive and schizophrenic patients than in healthy subjects. Somatomedin-C concentrations were significantly elevated in endogenous depressed patients compared with healthy subjects. The blunted growth hormone response in endogenous depression could be explained by inhibitory influences such as increased somatomedin-C concentrations or a hyperactivity of central beta-adrenergic-receptors.     

Long-term benzodiazepine administration blunts growth hormone response to diazepam

Growth hormone and prolactin responses to diazepam were measured in eight male patients who had been receiving long-term treatment with benzodiazepines and eight age-matched drug-free controls. The growth hormone response was significantly attenuated during benzodiazepine administration, but increased significantly after benzodiazepine treatment was discontinued. Growth hormone responses four days after the drug therapy withdrawal in patients, however, were still significantly less than in drug-free controls. Prolactin levels were unaltered after diazepam challenge, both in patients and in controls. The results clearly demonstrate tolerance to the growth hormone-releasing effect of diazepam, but do not suggest receptor supersensitivity after withdrawal of benzodiazepine therapy. It is possible that pituitary mammotropes lack benzodiazepine receptors.     

Schneider's first-rank symptoms of schizophrenia. An association with increased growth hormone response to apomorphine

Growth hormone and prolactin (PRL) responses to 0.75 mg of apomorphine hydrochloride were measured in 19 newly admitted psychotic patients who had been untreated by neuroleptic or antidepressant drugs for at least nine months. We compared hormonal responses between subgroups of patients who were distinguished using the diagnostic criteria of Feighner et al and Spitzer et al, and by the presence or absence of Schneider's first-rank symptoms of schizophrenia. We included nine healthy subjects who were matched by age and sex with the schizophrenic patients. Growth hormone responses to apomorphine were greater in patients with Schneider's first-rank symptoms than in those without first-rank symptoms, and were also greater than in control subjects. Suppression of plasma PRL was also greater in schizophrenic patients than in control subjects. These results support the dopamine hypothesis of schizophrenia.     

Thyroid stimulating hormone response after thyrotropin releasing hormone in depressed, schizophrenic and normal women.

(1) Thyroid stimulating hormone (TSH) response after injection of thyrotropin releasing hormone (TRH) was studied in 23 depressed, 9 schizophrenic and 40 normal women. (2) In no group was TSH response correlated with age. (3) In the depressed patients, no relationship was found between TSH response and (i) severity of illness, (ii) clinical subtypes (unipolar/bipolar) and (iii) clinical remission. (4) There were no statistically significant differences in TSH baseline values between the groups. (5) Neither of the two patient groups showed reliable differences from controls regarding TSH response. However, depressed patients tended to show lower values than controls, while schizophrenic patients tended to show higher values than normal controls. (6) Significant differences were found between depressed and schizophrenic patients in regard to TSH response. In three depressed patients a TSH response below 5 μU/ml was found. This deficient TSH response occurred in unipolar depressed patients and was not seen in bipolar depressed patients, schizophrenic patients or normal controls. (7) These data provide evidence for a fault in hypothalamic pituitary regulation in some depressed patients but not in schizophrenic patients.     

Neuroendocrine responses in chronic schizophrenia: Evidence for serotonergic dysfunction

Neuroendocrine and mood responses to a 60 mg oral dose of the serotonin-releasing agent, fenfluramine, were assessed in ten neuroleptic-free, chronic schizophrenic patients and in age- and sex-matched normal control subjects. The prolactin (PRL) response to fenfluramine was significantly blunted in the schizophrenic subjects. Growth hormone and cortisol levels were not differentially affected by the challenge. There was no significant effect of fenfluramine on mood in either group. The blunted PRL response in the schizophrenic group suggests serotonergic dysfunction; possible mechanisms of this finding and implications for treatment are considered.     

Reduced growth hormone response to apomorphine in schizophrenic patients with poor premorbid social functioning

Summary The apomorphine-induced growth hormone (GH) response of 16 drug-free schizophrenic patients and nine control subjects were studied. The sub-group of nine patients with poor premorbid psychosocial functioning had a significantly lower GH response than the controls. Additional evidence for state dependent effects is provided.     

Nocturnal levels of growth hormone in hyperactive children of small stature.

Growth disturbances have been demonstrated in hyperactive children treated with stimulant medication. This study examines sleep related growth hormone secretion in patients with hyperactive syndrome and relative short stature. Five such patients were compared with 9 age matched controls. There were no differences in sleep patterns, and growth hormone levels for the hyperactive children were within normal limits. This study suggests that hyperactive children with short stature have normal sleep patterns and normal sleep related growth hormone secretion.     

抑郁症患者血浆生长激素水平变化及临床意义

目的:探讨血浆生长激素(GH)水平与抑郁症之间的关系.方法:采用汉密尔顿抑郁量表对30例抑郁症患者及30例正常对照者进行评定,并采用酶联免疫吸附法测定患者和正常对照者的血浆GH水平.结果:抑郁症患者血浆生长激素水平[(7.2±1.3)ng/ml]显著高于对照组[(1.3±0.7)ng/ml],(t=21.830,P<0...     

Assessment of central noradrenergic functioning in irritable bowel syndrome using a neuroendocrine challenge test

Desipramine, the monoamine reuptake inhibitor, acts predominantly on noradrenergic neurones, and via alpha-2 receptors brings about the release of growth hormone in normal healthy subjects. Thirteen patients with a diagnosis of irritable bowel syndrome, 10 normal controls and eight patients with peptic ulcer disease were each given a challenge test of desipramine 1 mg/kg body weight. Growth hormone release over a 3 h period was monitored. A blunted response was defined as a failure of growth hormone levels to rise at least 5 mU/l above baseline. Of the 13 patients with irritable bowel syndrome 11 showed such a blunting. The results suggest abnormal central alpha-2 receptor functioning in irritable bowel syndrome.     

Dopaminergic function in two patients with catalepsy

Apomorphine HCI (2 mg subcutaneously), a dopamine receptor agonist, was administered to two schizophrenic patients with catalepsy. In one of these patients the clinical response to apomorphine was compared with that of sodium amytal and the growth hormone response to apomorphine (0.75 mg subcutaneously) was compared with that of 25 control subjects. Apomorphine had no effect whereas sodium amytal caused rapid disappearance of catatonic symptoms including catalepsy. The peak growth hormone response to apomorphine was similar to that of controls. These data suggest that unlike experimental catalepsy in animals, catalepsy associated with schizophrenia may not be dependent on impaired dopaminergic function. Further case studies as well as the use of other dopamine receptor agonists are required before definite conclusions can be drawn.     

Naloxone in chronic schizophrenic patients: neuroendocrine and behavioral effects

Naloxone produced improvement in abnormal thought content in medicated chronic schizophrenic patients, but not in drug-free patients. In contrast, drowsiness and increases in plasma prolactin concentrations were seen only in drug-free schizophrenic patients. Although growth hormone concentrations increased in drug-free and medicated schizophrenic patients, the time course was different in the two groups. Neuroleptics appear to alter naloxone's clinical and neuroendocrine effects in chronic schizophrenic patients.     

Melatonin and schizophrenia

Many research studies have been conducted with melatonin, a pineal hormone, in psychiatry. Studies with melatonin in schizophrenic patients are rare. Blood plasma samples were drawn at 24 hours and 12 hours in 23 schizophrenic subjects and 26 controls, during the same season. Plasma melatonin levels were obtained using a specific radioimmunoassay technique. The 24 hours levels significant decreased in schizophrenic patients compared with controls (p less than 0.01). Methodology, specificity of results and concomitant study of cortisol levels are discussed.     

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.     

Adverse effects of anticholinergic antiparkinsonian drugs in tardive dyskinesia. An investigation of mechanism

10 long-term schizophrenic patients with tardive dyskinesia were studied over 14 weeks and maintained on their usual neuroleptic medications while anticholinergic antiparkinson drugs were employed and then discontinued, and the cycle then repeated. Discontinuation of anticholinergic medications resulted in improvement in dyskinetic movements and vice versa. Estimation of haloperidol equivalents in serum at four times suggested that changes in severity of tardive dyskinesia were not caused by changes in blood levels of neuroleptics. Levels of pituitary hormones were also estimated at four times. Prolactin levels tended to diminish in men over the course of the experiment. Growth hormone and thyrotropin values were mainly stable. However, the growth hormone levels peaked during the final 'off anticholinergic' condition and thyrotropin levels were consistently elevated.     

Human platelet MAO in drug-free and medicated schizophrenic patients.

The authors compared platelet monoamine oxidase activity in drug-free chronic and acute schizophrenic patients, medicated chronic schizophrenic patients, and normal controls. A significant decrement in MAO activity was found only in medicated chronic schizophrenic patients. The possible mechanism for this finding is discussed.     

Circadian and sleep-related endocrine rhythms in schizophrenia.

Plasma levels of prolactin, growth hormone, corticotropin, and cortisol were measured at 15-minute intervals for 24 hours in nine unmedicated male schizophrenic patients and in nine age-matched normal male subjects. Each study was preceded by 3 days of habituation to the laboratory environment. Sleep was polygraphically recorded. The circadian and pulsatile variations present in each hormonal profile were quantitatively characterized with the use of computer algorithms specifically designed for analyses of hormonal fluctuations. The major abnormality of neuroendocrine release that was observed in the schizophrenic patients was an almost threefold enhancement of the sleep-related increase in the prolactin level, associated with an intensified frequency of nocturnal prolactin pulses. This increased stimulatory effect of sleep on prolactin secretion was evident immediately after sleep onset. The normal inhibition of cortisol secretion during early sleep was absent in schizophrenic patients. The major sleep abnormalities were a prolonged sleep latency and a reduction in total rapid eye movement stage sleep. During wakefulness, prolactin and cortisol levels were normal. The 24-hour profile of growth hormone was unaltered in schizophrenic patients, and a sleep-onset growth hormone pulse was observed in all patients. No abnormalities were noted in the levels or temporal organization of corticotropin secretion. Both the amplitude and the timing of the cortisol rhythm were normal. We conclude that, in schizophrenic men, pituitary-adrenal function and circadian time-keeping are normal but prolactin secretion is hyperresponsive to the physiologic stimulus of sleep onset. Schizophrenia thus appears to be characterized by a subset of neuroendocrine disturbances distinct from that observed in major endogenous depression.     

Blood protein fraction comparisons of normal and schizophrenic patients.

Whole blood, plasma, or serum levels of various components were measured in fasting, drug-free control subjects and drug-free schizophrenic patients. Compared to normal controls, chronic schizophrenic patients showed increased alpha2-globulins and decreased plasma cholinesterase activity and ceruloplasmin activity, and acute schizophrenic patients showed decreased alpha2-globulins. Compared to chronic patients, acute schizophrenics showed decreased alpha2-globulins and IgA. Compared to normal controls of similar age, chronic schizophrenic patients weighed less, were shorter, and had smaller body surface area. The acute schizophrenic patients were significantly younger than the normal subjects or chronic schizophrenics but there was no difference in the other physical measurements. The present study indicates no gross disturbances in the blood variables studied. That some differences are statistically significant from controls is of scientific interest, but of no clinical value in the diagnosis of schizophrenia.     

CSF corticotropin releasing hormone, somatostatin, and thyrotropin releasing hormone in schizophrenia.

Cerebrospinal fluid (CSF) corticotropin releasing hormone (CRH), somatostatin (SRIF), and thyrotropin releasing hormone (TRH) were measured by specific radioimmunoassay methods in 86 patients who met DSM-III-R criteria for schizophrenia or schizophreniform disorder and in 30 neurologic controls. The multivariate CSF peptide concentration was significantly different in patients compared with controls, but none of the individual variable differences reached statistical significance when analyzed separately. There were no significant CSF neuropeptide differences among patients with various schizophrenic subtypes. Neither global severity of illness nor individual symptoms were correlated with CSF neuropeptide concentrations. Although schizophrenic patients showed a pattern of mildly lower SRIF and TRH levels in their CSF, together with a weak tendency for higher CSF CRH values, these peptide changes did not appear to be specifically related to the core features of schizophrenia.