Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth hormone (hGH) responses to centrally acting dopamine agonists were used as indices of CNS dopaminergic function in order to test hypotheses implicating dopaminergic alteration in the etiopathology of schizophrenia. Apomorphine, a direct acting dopamine receptor agonist, and L-Dopa, an indirect agonist dependent upon presynaptic conversion to dopamine for its action, both elicited elevations in plasma hGH in most young male schizophrenic- and control-subjects. A highly significant difference was seen between the distribution of hGH responses to apomorphine for schizophrenics and that for controls. Unusually high hGH response to apomorphine was seen in schizophrenics who subsequently failed to respond to neuroleptic therapy; intermediate hGH response was seen in controls; and low hGH response was seen in subsequent neuroleptic responders; differences in hGH response were statistically significant for all intergroup comparisons. No such differences were seen between responses of individuals to L-Dopa and to apomorphine. The findings suggest that the variability of hGH response to apomorphine is a reflection of dopamine receptor sensitivity, and that this variability may be an index of non-endocrine related dopaminergic sensitivity. They are consistent with hypotheses relating schizophrenia to alteration in dopamine receptors, although the type of receptor and the direction of alteration may be complex.
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PMID:Dopamine receptor alteration in schizophrenia: neuroendocrine evidence. 82 70

The dopamine (DA) autoreceptor agonist (-)-3PPP (preclamol) was tested in male schizophrenic volunteers for safety. The drug was administered intramuscularly in a single rising dose design, crossed with a similar "rising dose" placebo period; all evaluations and raters were blind to drug or placebo administration. Pharmacokinetic, endocrine, safety, and mental status outcome measures were completed before and after each single dose of drug or placebo. Pharmacokinetic analysis showed blood levels between 200-500 pmoles/ml after the intramuscular drug doses of 30-40 mg. Drug half life is 2-2.5 hrs. Growth hormone (GH) levels were elevated in a linear fashion to the 30 mg dose; whereafter, the drug failed to affect GH at all. All safety evaluations were negative, including any untoward effects on the major organ systems. After single dose drug administration, evidence of antipsychotic action occurred in two of the four subjects. This study suggests that (-)-3PPP/preclamol is a safe drug for study in the treatment of schizophrenia and may have antipsychotic efficacy.
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PMID:Pharmacologic properties of (-)-3PPP (preclamol) in man. 135 19

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.
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PMID:Schneider's first-rank symptoms of schizophrenia. An association with increased growth hormone response to apomorphine. 649 65

The hormonal effects of apomorphine, a direct-acting dopamine receptor agonist, in schizophrenic patients are of interest in view of the therapeutic efficacy of dopamine receptor antagonists. In this study, apomorphine (0.75 mg s.c.) and placebo were administered to unmedicated acute and chronic schizophrenics and controls. Apomorphine-induced prolactin suppression did not discriminate between the groups. However, an inverse relationship between basal prolactin levels and the severity of positive symptoms was detected in the patients with acute schizophrenia, consistent with a role for dopamine in the genesis of these symptoms. Growth hormone increments after apomorphine administration were blunted in the chronic schizophrenic patients, particularly those with 'negative' symptoms. It is argued that this blunting is not due to previous neuroleptic therapy and may represent evidence of structural change in the hypothalamus in this group of patients.
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PMID:Hormonal effects of apomorphine in schizophrenia. 672 95

Growth hormone has been investigated in numerous studies involving patients with schizophrenia but has been measured only by radioimmunoassay (RIA). There have been no consistent abnormalities differentiating patients with schizophrenia from normal controls. In the current study, growth hormone (GH) variants were measured by Western blotting techniques, which resulted in the quantitation of 4 GH size variants: 27K (27,000 Daltons), 22K, 20K, and 17K. In the entire sample of 17 schizophrenic subjects, all GH variants were significantly higher than in the 14 normal controls. While there were no significant differences between the 2 groups in RIA GH values, the RIA values were generally higher in the schizophrenic group. In a subset of 12 schizophrenic patients whose RIA values were approximately equal to the controls, both the 27K and 22K GH variants remained significantly higher in the patient group. In the schizophrenic group, none of the GH variants or RIA GH changed significantly after 1 week of treatment with neuroleptic medication. These preliminary results suggest that certain GH forms may be elevated in schizophrenia, but further studies are needed.
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PMID:Potential abnormalities in molecular forms of growth hormone in schizophrenia: a pilot study. 790 55

Acetylcholine is a neurotransmitter that has been implicated in the pathophysiology of major depression. This is supported by the enhanced growth hormone (GH) release in response to pyridostigmine (PYD) challenge in depressed subjects relative to healthy comparison subjects. The aim of this study is to examine the specificity of the PYD/GH challenge in the diagnosis of depression. Pyridostigmine 120 mg orally, was administered to a total of 116 physically healthy subjects. Growth hormone responses were studied in 38 patients with (DSM-III-R) major depression, 13 subjects with panic disorder, 9 subjects with schizophrenia, 10 recently detoxified alcoholics, and a comparison group of 46 healthy volunteers. Mean delta GH (the difference between basal and maximal GH following PYD) was significantly greater than comparison subjects in patients with major depression. Responses observed in patients with schizophrenia and alcohol dependence syndrome did not differ from the comparison group. Those patients with panic disorder and a high Hamilton depression score had an enhanced delta GH. The sensitivity of the PYD/GH test was 63% for major depression. These results indicate that the PYD/GH test may help distinguish depression from schizophrenia, alcohol-dependence syndrome, or panic disorder with a low Hamilton depression score.
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PMID:Specificity of the pyridostigmine/growth hormone challenge in the diagnosis of depression. 934 32

The dopaminergic system has been implicated in the pathogenesis and treatment of a variety of neuropsychiatric disorders, such as schizophrenia, depression, and addiction. (Dys)function of the dopaminergic system may be studied by combining [15O]H2O PET with a dopaminergic drug challenge. In this pilot study we investigated the suitability of the dopamine reuptake blocker methylphenidate (MP) as a dopaminergic probe. Measurements of regional cerebral blood flow (rCBF) were made at 10 and 30 min after placebo and MP (0.25 mg/kg) injection to seven healthy volunteers. During scanning the behavioral condition of the subjects was standardized using a continuous performance task. Growth hormone levels were assessed and subjective ratings were obtained. MP significantly elevated growth hormone levels. After receiving MP, the subjective experience varied from neutral to highly pleasurable. Ten minutes after MP administration, significant relative increases in rCBF were found in the rostral anterior cingulate (AC), temporal poles, and the supplementary motor area. Significant reductions were seen in the superior temporal gyri, right medial frontal gyrus, and right inferior parietal cortex. At 30 min after MP administration, increases were seen in the AC, temporal pole, and right cerebellum. No changes were observed in the striatum. The activation in the right rostral AC was significantly higher in the subjects with the highest euphoria scores compared to the subjects with minimal MP-induced changes in euphoria. We suggest that the combined MP challenge with functional imaging, as described in our study, may be a useful tool to study the functional integrity of the dopaminergic system in psychiatric disorders.
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PMID:Methylphenidate-induced activation of the anterior cingulate but not the striatum: a [15O]H2O PET study in healthy volunteers. 1708 Apr 42

The functional significance of hypothalams-pituitary axis as a neurohormonal link between endocrine glands and target organs is well established. It has also been demonstrated that three hormones of anterior pituitary viz. Prolactin (PRL), Lutenising hormone (LH) and Growth hormone (GH) have definite link with Dopamine (DA), the latter being implicated in the pathogenesis of schizophrenia. Radio immune assay technique was employed in estimation. Significantly low PRL level was found in majority of cases. However there was no significant corelation with effects of therapy or with L-DOPA administration. Similarly LH level was also found low indicating increased DA activity but the low level persisted even after therapy. GH level did not show any alteration in the patients, even when compared to different blood sugar levels and L-DOPA administration.
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PMID:Dopamine related hormone levels in acute schizophrenia: (a study of 84 patients). 2192 77