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)

This paper describes the use of serial neuroendocrine challenge studies in the assessment of depressive disorder, specifically the dexamethasone suppression test (DST) and thyrotropin-releasing hormone (TRH) stimulation test. The combined use of these challenge tests revealed high sensitivity (67%) and high predictive value for the identification of endogenous depression in contrast to schizophrenia (p less than 0.025) or nondepressed patients (p less than 0.005). Further, normalization or persistence of dysregulation of these tests was correlated with clinical outcome at 6 months. Normalization of the DST occurred in 26 of 32 patients (82%) and was significantly correlated with the timing of symptomatic improvement (p less than 0.01). Five of six patients (84%) who never normalized the DST suffered an early relapse in contrast to 4 of 26 patients who did normalize (p less than 0.005). Unlike the DST, normalization of the blunted thyrotropin (TSH) response to TRH injection was not significantly correlated with the timing of symptomatic improvement. Only 8 of 19 patients (42%) ever normalized the TSH response. However, none of these 8 normalized patients suffered relapse within 6 months in contrast to 7 of 11 patients (64%) who did not normalize (p less than 0.025). Thus, failure of normalization of either the DST or TRH test was associated with a group of patients at high risk for early relapse. In this study, the use of prophylactic antidepressant medications did not avert relapse in 9 of 11 relapsed patients who had persistent neuroendocrine dysregulation.
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PMID:The application of serial neuroendocrine challenge studies in the management of depressive disorder. 640 62

The levels of neurotensin and thyrotropin-releasing hormone (TRH) in normal post mortem human amygdala have been compared with those in cases of schizophrenia, Alzheimer's disease and depression. Amongst various factors which can influence post mortem human brain biochemistry (including age, sex, post mortem delay, time of death, disease status and severity), sex difference appeared to be responsible for the most extensive variation. The levels of both peptides were nearly doubled in males compared with females and this increase was significant in the case of neurotensin. There was also a positive correlation between neurotensin and TRH levels. Although levels of neurotensin and TRH tended to be lower in the disease groups these trends did not reach significance.
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PMID:Post mortem levels of thyrotropin-releasing hormone and neurotensin in the amygdala in Alzheimer's disease, schizophrenia and depression. 640 15

Fifteen patients with a primary diagnosis of borderline personality disorder were studied with the thyrotropin-releasing hormone (TRH) test. Twelve carried the additional diagnosis of depression, substance abuse, or both. A blunted thyroid-stimulating hormone (TSH) response to TRH was found in seven patients, two of whom were neither depressed nor had the additional diagnosis of depression and/or substance abuse. TSH blunting was unrelated to such factors as thyroid status, serum cortisol, weight, height, or body surface. Since TSH blunting occurs in about 25% of patients with major depression but not in schizophrenia, the findings suggest that some patients with borderline personality disorder share a neuroendocrine abnormality with some affective disorder patients.
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PMID:The TRH test in patients wih borderline personality disorder. 641 92

Measures of neuroendocrine function--plasma cortisol and its response to dexamethasone, and plasma thyroid-stimulating hormone (TSH) and its response to thyrotropin-releasing hormone (TRH)--were employed in 50 hospitalized male veteran psychiatric patients with diagnoses of unipolar or bipolar melancholia, secondary depression, or schizophrenia. Of 20 cases of unipolar melancholia, 17 (85%) exhibited hypercortisolism; 14 (70%) failed to suppress plasma cortisol after dexamethasone; and 4 (31%) of 13 tested had an abnormal TSH response to intravenous TRH. Two patients with secondary depression also exhibited hypercortisolism; no other patients evinced abnormal neuroendocrine test results. These measures were repeated in 14 unipolar depressed patients after a course of electroconvulsive therapy (ECT). Improvement in psychopathology was directly related to normalization of measures of hypothalamic-pituitary-adrenal (HPA) function. The TSH response to TRH was not systematically altered. After a followup period of 1 to 9 months, there was a good correlation between the measures of HPA function and the clinical outcome. These findings encourage further study of HPA function measures as outcome criteria for depressed patients receiving ECT.
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PMID:Neuroendocrine measures in psychiatric patients: course and outcome with ECT. 678 39

We utilized quantitative autoradiography to determine the distribution of receptors for thyrotropin-releasing hormone (TRH) throughout the human temporal lobe and to examine the distribution of these receptors in discrete subregions of the temporal lobe from patients diagnosed premortem with schizophrenia. When compared to non-neurologic controls, schizophrenic patients demonstrated an increase of 51% in the concentration of TRH receptors in the molecular layer of the dentate gyrus. Within nuclei of the schizophrenic amygdala, marked decreases were found in the central (44%), medial (38%), cortical (36%), accessory cortical (52%), lateral (54%), and medial basal (22%) nuclei. We also examined postmortem brain samples from patients with Huntington's disease, amyotrophic lateral sclerosis, and Alzheimer's disease for alterations in the distribution of TRH receptors. No significant differences from non-neuropsychiatric controls were noted within the hippocampus in any of these disease states; however, slight alterations were noted in the central and medial basal amygdala in Huntington's disease and in the cortical amygdala in Alzheimer's disease. These disease-specific findings suggest that TRH may play a role in the neurochemical dysfunction of schizophrenia.
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PMID:Alterations in TRH receptors in temporal lobe of schizophrenics: a quantitative autoradiographic study. 788 24

Brain asymmetry is understood as an anatomical, functional or neurochemical difference between the two hemispheres. It is not a static but rather a dynamic phenomenon in which both environmental and endogenous factors act as modulators. Aging modifies brain asymmetry, and an imbalance in specific asymmetries characterizes some brain disorders such as schizophrenia, depression, infantile autism or Alzheimer's disease. However, it is not clear whether these changes are a cause or a consequence of these disorders. Although this phenomenon has been extensively studied, its functional significance is not yet clear, and the neurochemical basis underlying anatomical or functional asymmetries in the brain is still poorly understood. In recent decades intensive research on the behaviour of neuropeptides has revealed asymmetries in their distribution in the brain, and there is evidence that the lateralized patterns of distribution are involved in the regulatory control of some neuropeptidase activities. Therefore, if these enzymatic activities are distributed asymmetrically, their endogenous substrates would presumably be affected in an asymmetrical way, as would the functions they are involved in. Here we review the most significant literature regarding human and animal brain asymmetry involving neuropeptides such as corticotropin-releasing hormone, cholecystokinin, luteinizing hormone-releasing hormone, thyrotropin-releasing hormone and angiotensin II, as well as their neuropeptidases.
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PMID:Neuropeptides, neuropeptidases and brain asymmetry. 1558 19

Neuropeptides are heterogeneously distributed throughout the digestive, circulatory, and nervous systems and serve as neurotransmitters, neuromodulators, and hormones. Neuropeptides are phylogenetically conserved and have been demonstrated to regulate numerous behaviors. They have been hypothesized to be pathologically involved in several psychiatric disorders, including schizophrenia. On the basis of preclinical data, numerous studies have sought to examine the role of neuropeptide systems in schizophrenia. This chapter reviews the clinical data, linking alterations in neuropeptide systems to the etiology, pathophysiology, and treatment of schizophrenia. Data for the following neuropeptide systems are included: arginine-vasopressin, cholecystokinin (CCK), corticotropin-releasing factor (CRF), interleukins, neuregulin 1 (NRG1), neurotensin (NT), neuropeptide Y (NPY), opioids, secretin, somatostatin, tachykinins, thyrotropin-releasing hormone (TRH), and vasoactive intestinal peptide (VIP). Data from cerebrospinal fluid (CSF), postmortem and genetic studies, as well as clinical trials are described. Despite the inherent difficulties associated with human studies (including small sample size, variable duration of illness, medication status, the presence of comorbid psychiatric disorders, and diagnostic heterogeneity), several findings are noteworthy. Postmortem studies support disease-related alterations in several neuropeptide systems in the frontal and temporal cortices. The strongest genetic evidence supporting a role for neuropeptides in schizophrenia are those studies linking polymorphisms in NRG1 and the CCKA receptor with schizophrenia. Finally, the only compounds that act directly on neuropeptide systems that have demonstrated therapeutic efficacy in schizophrenia are neurokinin receptor antagonists. Clearly, additional investigation into the role of neuropeptide systems in the etiology, pathophysiology, and treatment of schizophrenia is warranted.
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PMID:Involvement of neuropeptide systems in schizophrenia: human studies. 1734 66

Schizophrenia affects approximately 1% of the world population, and the majority of pharmacologically based treatments for this disorder are ligands that interact with monoaminergic transmission. However, there is a wealth of evidence that various neuropeptides are often co-released with monoamine neurotransmitters, and that ligands acting at neuropeptide receptors modulate monoaminergic transmission as well as schizophrenia-related behaviors in preclinical animal models. Such neuropeptide systems include neurotensin, cholecystokinin, corticotropin releasing factor, neuropeptide Y, oxytocin, opioid peptides, tachykinins, thyrotropin-releasing hormone, and orexins. The purpose of this review will be to summarize the existing preclinical and clinical literature on the role of various neuropeptide systems as modulators of schizophrenia-related behaviors, and the potential of targeting these systems for the development of novel antipsychotic medications.
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PMID:Neuropeptide systems and schizophrenia. 2357 75

Evidence-based psychopharmacological algorithms for the treatment of patients with schizophrenia have been developed in many countries in the last decade. While it would be of interest to consider a common algorithm based on international consensus, algorithms and information on antipsychotics available in each country are limited. Inspired by the algorithm generated by the International Psychopharmacology Algorithm (IPA) Project, this algorithm for the treatment of schizophrenia has been developed by the Japan Psychophamacology Algorithm (JPA) Project. New antipsychotics, such as clozapine, olanzapine and quetiapine, are excluded from this algorithm, being currently unavailable in Japan. In the end there was no essential difference between the algorithms for the treatment of acute schizophrenic episodes. However, combined use of antipsychotics appears to be more common in Japan and the adjunctive use of L-DOPS or thyrotropin-releasing hormone is included in the JPA algorithm for the treatment of drug-refractory schizophrenia.
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PMID:Algorithm for the treatment of schizophrenia in Japan. 2492 Dec 31


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