Stereospecificity of the dopamine receptor mediating the growth hormone response to apomorphine in man

Summary The stereospecificity of the D-2 receptor mediating the growth hormone (GH) response to apomorphine (Apo) and the D-2 receptor regulating prolactin (PRL) secretion were investigated in 10 normal men by examining the effects of cis-flupenthixol (cis-Fx) and trans-flupenthixol (trans-Fx). cis-Fx (1 mg six hourly times four doses) antagonized the GH response to Apo HCl (0.5 mg sc) and increased basal serum PRL concentrations whereas the transisomer showed no effect. These findings (a) provide further evidence that the GH response to Apo is mediated by stimulating dopamine (DA) receptors, and, (b) demonstrate stereospecificity of the DA receptor mediating the GH response to Apo and the DA receptor regulating PRL secretion.     

Failure of naloxone to reverse apomorphine effects in humans

Twelve male volunteers given apomorphine (20 micrograms/kg/hr) for 40 min by i.v. infusion had significant changes in growth hormone, prolactin, vasopressin, pulse rate, sedation and nausea. Naloxone, (20 mg i.v.) or placebo given in a double-blind manner 10 min before the end of the apomorphine infusion as a concealed bolus did not alter the effects of apomorphine. Vasopressin rise correlated significantly with nausea intensity. We conclude that acute opiate receptor blockade does not reverse most apomorphine effects.     

Growth hormone response to growth hormone-releasing hormone in schizophrenic patients

Ten schizophrenic patients and five normal control subjects were challenged with growth hormone-releasing hormone in a pilot study investigating growth hormone secretion from the pituitary. The results suggest suprapituitary dysfunction in schizophrenia, but replication in a larger study is needed.     

Bombesin inhibits growth hormone response to insulin-induced hypoglycemia in humans

Intravenous administration of bombesin (5 ng/kg/min X 2.5 h) significantly reduced growth hormone (GH) response to insulin-induced (0.15 U/kg, i.v.) hypoglycemia in 8 male volunteers without affecting its basal plasma levels. These data, together with the presence of bombesin-like immunoreactivity in the human brain, suggest that--as in experimental animals--this neurogastrointestinal peptide may be of physiological significance in the control of GH secretion also in man.     

Effect of enhancement of cholinergic tone on the growth hormone response to acute hyperglycaemia or thyrotropin-releasing hormone in dogs

The effect of enhancement of cholinergic tone by pyridostigmine on the growth hormone (GH) response to thyrotropin-releasing hormone (TRH) or glucose-induced acute hyperglycaemia was tested in six adult unanaesthetized beagle dogs. Both TRH (5μg/ kg iv) and glucose (2 g/kg orally) did not significantly alter baseline GH levels but reduced the GH response to GH-releasing hormone (GHRH) (2 μg/kg iv), although this effect was more clear-cut with TRH than with glucose. Pretreatment with pyridostigmine (2 mg/kg orally) counteracted the inhibitory effect of hyperglycaemia on the GHRH-induced GH release, but had no effect on the inhibition induced by TRH. In summary, these results indicate that: 1) acute hyperglycaemia and TRH play an inhibitory role on GHRH-stimulated GH secretion in dogs; 2) the inhibitory effect of acute hyperglycaemia is mediated via hypothalamic cholinergic neurotransmission, whereas other neurotransmitter pathways would be. involved in the effect of TRH.     

Neuromorphological abnormalities in schizophrenic patients with good and poor outcome

OBJECTIVE: The present study was designed specifically to assess the relationship between brain morphology and outcome in schizophrenia. METHOD: Fifty-six schizophrenic patients and a matched group of 32 healthy subjects were studied with magnetic resonance (MR) imaging scans. Clinical assessment included the Krawiecka-Manchester Scale (K-MS) and the Outcome scale by Strauss and Carpenter. RESULTS: Along several neuromorphological measures the patients differed from controls only for right and left ventricular volumes. The 'poor outcome' patients had a left and right ventricular enlargement when compared to the 'good outcome' patients and healthy controls. A regression analysis showed that right ventricle volume, left temporal lobe volume and left hippocampal volume entered into the regression equation, accounting for a 27% of the outcome measure. CONCLUSION: The outcome does not seem to be predicted by one particular morphological site but involves different brain regions; however, the ventricular enlargement identifies a subgroup of patients with poor outcome.     

Reduced anterior hippocampal formation volume in hyponatremic schizophrenic patients

Diminished hippocampal volume occurs in the anterior segment of some schizophrenic patients, and in the posterior segment in others. The significance of hippocampal pathology in general and these segmental differences in specific is not known. Several lines of evidence suggest anterior hippocampal pathology underlies the life-threatening hyponatremia seen in a subgroup of patients with schizophrenia; therefore our goal was to determine if this region was preferentially diminished in hyponatremic patients. We studied seven polydipsic hyponatremic, ten polydipsic normonatremic, and nine nonpolydipsic normonatremic schizophrenic inpatients, as well as 12 healthy controls. All underwent structural scanning on a high resolution (3.0 T) magnetic resonance imaging (MRI) scanner. Hippocampal formation, amygdala, and third ventricle volumes were manually traced in each subject. The hippocampus was divided at the posterior extent of the uncus, and all structural volumes were corrected for whole brain volume and other significant recognized factors (i.e., age, gender, height, parental education). Despite being overhydrated, anterior hippocampal formation volume was diminished in those with polydipsia and hyponatremia relative to each of the other three groups. Third ventricle volume was larger in this group than in healthy controls but similar to the two patient groups. Posterior hippocampal and amygdala volumes did not differ between groups. Other potential confounds (e.g., water imbalance) either had no effect or accentuated these differences. We conclude the anterior hippocampal formation is smaller in hyponatremic schizophrenic patients, thereby linking an important and objective clinical feature of schizophrenia to a neural pathway that can be investigated in animal models. The findings strengthen the hypothesis that anterior hippocampal formation pathology disrupts functional connectivity with other limbic structures in schizophrenia.     

Clonidine-induced growth hormone secretion in chronic schizophrenia

Clonidine (0.15 mg intravenously), an alpha-adrenergic receptor agonist, was administered to 13 male chronic schizophrenics, who had been withdrawn from chronic neuroleptic therapy, and to 18 normal male controls. There was no significant difference in growth hormone (GH) response between the two groups. There was no significant correlation between duration of psychosis, duration of neuroleptic therapy or length of neuroleptic withdrawal and GH response. These results suggest that postsynaptic alpha-adrenergic receptor function in the hypothalamic-pituitary axis is unaltered in chronic schizophrenia or by prior chronic neuroleptic therapy.     

精神分裂症患者共情能力与社会功能

目的：比较稳定期精神分裂症患者与正常对照者的共情能力,探讨患者共情能力与社会功能的关系。方法：采用人际反应指针量表（IRI-C）对103例稳定期精神分裂症患者（患者组）和88名正常对照者（对照组）进行评估,比较二者的共情能力;同时采用社会功能缺陷筛选量表（SDSS）、个体和社会功能量表（PSP）及阳性与阴性症状量表（PANSS）对患者组进行评估。结果：患者组IRI-C共情性关心分及共情总分平均为（14.7±4.0）分和（44.2±11.3）分,均较对照组的（16.0±4.5）分和（46.3±11.9）分显著为低（P〈0.01或P〈0.05）。控制年龄、症状后的IRI-C与SDSS偏相关分析显示,患者组IRI-C共情性关心分与SDSS中社会性退缩分（r=-0.421,P〈0.01）、责任心和计划性分（r=-0.344,P〈0.05）及总分（r=-0.335,P〈0.05）分别呈负相关。控制症状后的IRI-C与PSP偏相关分析显示,患者组IRI-C观点采摘分（r=0.288,P〈0.01）、共情性关心分（r=0.301,P〈0.01）及IRI-C总分（r=0.268,P〈0.01）与PSP总分均呈正相关。结论：精神分裂症患者存在共情能力障碍,其共情能力与其社会功能存在正相关。     

Failure of chronic antidepressant treatment to alter growth hormone response to clonidine

The effect of 4 to 6 weeks of treatment with the antidepressants, desmethylimipramine and amitriptyline, on the growth hormone response to clinidine was studied in 12 depressed patients. In contrast to the reported effects of clonidine in healthy subjects, clonidine did not significantly increase growth hormone secretion in the depressed patients before treatment. The antidepressant treatments did not alter the growth hormone response to clonidine in either treatment responders or nonresponders.     

Prolactin response to single and multiple doses of haloperidol in schizophrenic patients

Serum prolactin and blood levels of haloperidol were assessed in schizophrenic patients after single acute oral doses of haloperidol and during fixed dose treatment with this medication. Although significant intrapatient correlations between prolactin responses to different doses of haloperidol were found, no statistically significant interpatient relationship between haloperidol dose and prolactin response emerged. There were statistically significant relationships between steady-state plasma and red cell haloperidol levels (measured by radio- receptor or gas liquid chromatographic techniques) and serum prolactin response, but not between blood levels after the acute haloperidol dose and prolactin response.     

Evolution of plasma homovanillic acid (HVA) in chronic schizophrenic patients treated with haloperidol

In a 4-week study of 14 drug-free schizophrenic patients (according to DSM-III-R), free and conjugated fractions of plasma homovanillic acid (pHVA) were repeatedly measured. Free HVA levels decreased during the first 2 h of haloperidol intake (P<0.03). Conjugated HVA levels slowly decreased during the following weeks (P<0.05), while free HVA levels remained stable. After 4 weeks, free HVA levels remained unchanged 2 h after morning haloperidol intake, but conjugated HVA levels tended to increase. In haloperidol responders, at baseline the free/total HVA ratio was significantly higher than that in non-responders (P<0.01). Tolerant patients, i.e. those whose post-treatment free HVA levels decreased below pre-treatment levels, were not found to respond better to haloperidol than non-tolerant patients. The balance between free and conjugated pHVA may be a better reflection of the action of haloperidol than free pHVA levels and it may be of prognostic value in terms of drug response.     

Enhanced growth hormone response to clonidine after repeated electroconvulsive shock in a primate species

(1) The plasma growth hormone response to clonidine, 0.02 mg/kg, i.v., is enhanced 15 days after a course of 7 electroconvulsive shocks (ECS) in baboons, Papio papio. (2) This supports the hypothesis, based on behavioural observations in rodents, that the therapeutic action of electroconvulsive treatment (ECT) in depressive illness is associated with enhanced responses to monoamines.     

Poor neuroleptic response in acutely exacerbated schizophrenic patients

Poor neuroleptic response is a major unresolved clinical problem. Precise data concerning the frequency of poor neuroleptic response are not available. The implementation of treatment modalities that are specifically recommended for non-responders (such as clozapine) increases the desirability of such data. This study evaluated the proportion of acutely exacerbated schizophrenics who remained unimproved by consecutive administration of haloperidol, chlorpromazine and perphenazine, in randomly determined order. The overall improvement rate was 95%. The frequency of good responses to the first, second and third drug were 67%, 55%, and 67% respectively. Differences in receptor affinity profile might explain the added beneficial effect of a second or third drug.     

Increased growth hormone response to apomorphine in Parkinson disease compared with multiple system atrophy

BACKGROUND: Parkinson disease (PD) is often difficult to distinguish from parkinsonian syndromes of other causes in early stages of the disease. In search of a suitable endocrinologic challenge test, we investigated dopaminergic sensitivity in patients with de novo parkinsonian syndromes. OBJECTIVE: We measured the growth hormone (GH) response to a subthreshold dose of the dopamine 1-dopamine 2 receptor agonist apomorphine hydrochloride to differentiate parkinsonian syndromes from PD. PATIENTS AND METHODS: Seventeen patients with a clinical diagnosis of PD, 16 patients with a clinical diagnosis of multiple system atrophy, and 11 healthy controls. The GH response to a subthreshold dosage of apomorphine and to somatorelin (GH-releasing factor) was tested in a randomized order; on the third day the protocol was repeated with a clinically effective dose of apomorphine. RESULTS: The GH response to the low dose of apomorphine was significantly increased in patients with PD when compared with patients with multiple system atrophy or the control subjects (multivariate analyses of covariance; univariate F test, all P<.05). In contrast, there were no significant group differences with use of the higher dose of apomorphine or in the somatorelin-induced GH release. CONCLUSIONS: The GH response to a subthreshold dose of apomorphine appears to be a useful tool to identify patients with PD vs multiple system atrophy. The enhanced GH response to a subthreshold dopaminergic stimulus may reflect a hypersensitivity of the extrastriatal dopamine receptors in PD.     

Effect of hypthalamic ventromedial lesions on plasma growth hormone response to growth hormone-releasing factor in rats

The effect of ventromedial-arcuate (VMH-ARC) nuclei lesions on plasma growth hormone (GH) response to human growth hormone-releasing factor (GRF, 1 μg/kg b.wt., i.v.) was studied in conscious rats after they had received chlorpromazine (CPZ) or CPZ plus antiserum against somatostatin (ASS). When rats were pretreated with CPZ alone, there was no difference in basal plasma GH level between VMH-ARC lesioned rats and controls. The magnitude of plasma GH response to GRF in 5 out of 6 VMH-ARC lesioned rats exceeded that of controls. When the same observation was repeated using the same rats after they had received ASS and CPZ, basal plasma GH levels of controls were significantly higher than those of VMH-ARC lesioned rats, and the magnitude of the plasma GH response to GRF was augmented in both groups of rats. The plasma GH response to GRF was comparable between two groups, though the peak plasma GH response to GRF was slightly but significantly lower in VMH-ARC lesioned rats as compared to controls. Pituitary GH content was reduced significantly in VMH-ARC lesioned rats as compared to controls. The results demonstrate that the pituitary responsiveness to GRF does not appear to be altered significantly in rats bearing bilateral VMH-ARC lesions. In addition, the placement of electrolytic lesions in VMH-ARC regions causes reduced SS secretion into the hypophyseal portal vessels and leads to an augmentation of plasma GH response to GRF.