| 1 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2002 Apr 26: 579-84 |
|---|---|
| PMID | 11999911 |
| Title | Different neuroendocrine profiles of remitted and nonremitted schizophrenic patients. |
| Abstract | Thyrotropin-releasing hormone (TRH) test and Dexamethasone Suppression Test (DST) are two neuroendocrine tests that have been extensively used in an attempt to predict treatment response and outcome in schizophrenia. The objectives of this study were to investigate (1) the relationship between TRH test and DST and various psychiatric symptoms and (2) the potential value of these tests in prediction of short-term outcome in schizophrenic patients. TRH test and DST were administered to 58 patients with schizophrenia. All patients were evaluated with a battery of rating scales before neuroendocrine test procedures and at regular intervals for 1 year. Patients were divided into two groups as remitted (RP; n = 30) and nonremitted patients (NRP; n = 28). Baseline results of these two groups were compared with each other and 30 healthy controls. Basal levels of total T3 (T3T) and free T3 (T3F) were higher in RP group than controls. Basal prolactin (PRL) level was higher in RP group, but not in NRP, compared to controls. Basal growth hormone (GH) and thyroid-stimulating hormone (TSH) levels of NRP were significantly higher than those of RP. DST nonsuppression was observed at a significantly higher rate in RP than NRP and control group. Blunted TSH response rate in RP group was higher significantly compared to other two groups. The data implicate that higher basal TSH and GH levels may be associated with a poorer treatment response, whereas higher total and free T3 levels, a blunted TSH response to TRH and nonsuppression on the DST may indicate a better response in schizophrenics. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 2 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2002 Apr 26: 579-84 |
| PMID | 11999911 |
| Title | Different neuroendocrine profiles of remitted and nonremitted schizophrenic patients. |
| Abstract | Thyrotropin-releasing hormone (TRH) test and Dexamethasone Suppression Test (DST) are two neuroendocrine tests that have been extensively used in an attempt to predict treatment response and outcome in schizophrenia. The objectives of this study were to investigate (1) the relationship between TRH test and DST and various psychiatric symptoms and (2) the potential value of these tests in prediction of short-term outcome in schizophrenic patients. TRH test and DST were administered to 58 patients with schizophrenia. All patients were evaluated with a battery of rating scales before neuroendocrine test procedures and at regular intervals for 1 year. Patients were divided into two groups as remitted (RP; n = 30) and nonremitted patients (NRP; n = 28). Baseline results of these two groups were compared with each other and 30 healthy controls. Basal levels of total T3 (T3T) and free T3 (T3F) were higher in RP group than controls. Basal prolactin (PRL) level was higher in RP group, but not in NRP, compared to controls. Basal growth hormone (GH) and thyroid-stimulating hormone (TSH) levels of NRP were significantly higher than those of RP. DST nonsuppression was observed at a significantly higher rate in RP than NRP and control group. Blunted TSH response rate in RP group was higher significantly compared to other two groups. The data implicate that higher basal TSH and GH levels may be associated with a poorer treatment response, whereas higher total and free T3 levels, a blunted TSH response to TRH and nonsuppression on the DST may indicate a better response in schizophrenics. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 3 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2002 Apr 26: 579-84 |
| PMID | 11999911 |
| Title | Different neuroendocrine profiles of remitted and nonremitted schizophrenic patients. |
| Abstract | Thyrotropin-releasing hormone (TRH) test and Dexamethasone Suppression Test (DST) are two neuroendocrine tests that have been extensively used in an attempt to predict treatment response and outcome in schizophrenia. The objectives of this study were to investigate (1) the relationship between TRH test and DST and various psychiatric symptoms and (2) the potential value of these tests in prediction of short-term outcome in schizophrenic patients. TRH test and DST were administered to 58 patients with schizophrenia. All patients were evaluated with a battery of rating scales before neuroendocrine test procedures and at regular intervals for 1 year. Patients were divided into two groups as remitted (RP; n = 30) and nonremitted patients (NRP; n = 28). Baseline results of these two groups were compared with each other and 30 healthy controls. Basal levels of total T3 (T3T) and free T3 (T3F) were higher in RP group than controls. Basal prolactin (PRL) level was higher in RP group, but not in NRP, compared to controls. Basal growth hormone (GH) and thyroid-stimulating hormone (TSH) levels of NRP were significantly higher than those of RP. DST nonsuppression was observed at a significantly higher rate in RP than NRP and control group. Blunted TSH response rate in RP group was higher significantly compared to other two groups. The data implicate that higher basal TSH and GH levels may be associated with a poorer treatment response, whereas higher total and free T3 levels, a blunted TSH response to TRH and nonsuppression on the DST may indicate a better response in schizophrenics. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 4 | Int. Rev. Neurobiol. 2007 -1 78: 327-76 |
| PMID | 17349866 |
| Title | Involvement of neuropeptide systems in schizophrenia: human studies. |
| Abstract | 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. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 5 | Schizophr. Res. 2010 Jun 119: 41-6 |
| PMID | 20347273 |
| Title | An abnormal relation between basal prolactin levels and prolactin response to 12.5 microg TRH i.v. in drug-naïve patients with first-episode schizophrenia. |
| Abstract | At doses lower than those needed to stimulate prolactin release directly, TRH almost completely antagonizes the inhibitory effect of dopamine on prolactin release. We have previously reported that prolactin response to administration of 12.5 microg TRH i.v. correlates with prolactin response to 0.5 mg i.m. haloperidol and negatively with 24-h urinary excretion of HVA in normal subjects, suggesting that the response reflects dopamine activity. An association between central dopamine hyperactivity and SANS scores relating to poverty of content of speech and inattention has been suggested by studies utilizing methylphenidate administration in patients with first-episode schizophrenia. The hypothesis that small plasma prolactin responses to administration of 12.5 microg TRH i.v. (Delta prolactin) correlate with SANS scores for these symptoms was tested in 19 drug-naïve patients with first-episode schizophrenia. Significant negative correlations were found between the response and scores relating to poverty of content of speech (r = - 0.55, p = 0.014) and inattention (r = - 0.52, p = 0.022), supporting the hypothesis of increased dopamine activity in association with disorganization symptoms. A significant positive correlation between basal prolactin levels and prolactin response to stimulation by 12.5 microg TRH was also found (r = + 0.61, p = 0.0058). Our previous study in normal subjects found a similar positive correlation between basal prolactin levels and prolactin response to stimulation by 200 microg TRH i.v., but not by 12.5 microg TRH i.v. As far as we know, this is the first study to report an abnormality in TRH-induced prolactin release in acute schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 6 | Expert Opin Ther Pat 2011 Nov 21: 1673-91 |
| PMID | 22017410 |
| Title | Novel thyrotropin-releasing hormone analogs: a patent review. |
| Abstract | The potential therapeutic applications of thyrotropin-releasing hormone (TRH) have attracted attention, based on its broad-spectrum neuropharmacological action rather than its endocrine properties. These central nervous system (CNS)-mediated effects provide the rationale for use of TRH and its analogs in the treatment of brain and spinal injury, and CNS disorders like schizophrenia, Alzheimer's disease, epilepsy, amyotrophic lateral sclerosis, Parkinson's disease, depression, shock and ischemia. This review summarizes the patent literature and advances in the discovery and development of novel TRH analogs over the past 20 years. It provides a comprehensive overview of the development of new TRH analogs, giving emphasis to their pharmaceutical profile. The use of TRH in the treatment of various CNS disorders has been proven clinically. However, TRH itself is a poor drug candidate due to its short plasma half-life (5 min), poor biopharmaceutical properties (low intestinal and CNS permeability) and endocrine side effect. Nevertheless, researchers have come up with metabolically stable, more potent and selective TRH analogs and prodrugs. Taltirelin, one of the TRH analogs, has been approved under the trade name of Ceredist(®) in Japan for the treatment of spinocerebellar degeneration. Several other TRH analogs are in various stages of preclinical or clinical development. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 7 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2014 Jan 48: 287-94 |
| PMID | 23085507 |
| Title | Immune system and glucose metabolism interaction in schizophrenia: a chicken-egg dilemma. |
| Abstract | Impaired glucose metabolism and the development of metabolic syndrome contribute to a reduction in the average life expectancy of individuals with schizophrenia. It is unclear whether this association simply reflects an unhealthy lifestyle or whether weight gain and impaired glucose tolerance in patients with schizophrenia are directly attributable to the side effects of atypical antipsychotic medications or disease-inherent derangements. In addition, numerous previous studies have highlighted alterations in the immune system of patients with schizophrenia. Increased concentrations of interleukin (IL)-1, IL-6, and transforming growth factor-beta (TGF-?) appear to be state markers, whereas IL-12, interferon-gamma (IFN-?), tumor necrosis factor-alpha (TNF-?), and soluble IL-2 receptor (sIL-2R) appear to be trait markers of schizophrenia. Moreover, the mononuclear phagocyte system (MPS) and microglial activation are involved in the early course of the disease. This review illustrates a "chicken-egg dilemma", as it is currently unclear whether impaired cerebral glucose utilization leads to secondary disturbances in peripheral glucose metabolism, an increased risk of cardiovascular complications, and accompanying pro-inflammatory changes in patients with schizophrenia or whether immune mechanisms may be involved in the initial pathogenesis of schizophrenia, which leads to disturbances in glucose metabolism such as metabolic syndrome. Alternatively, shared underlying factors may be responsible for the co-occurrence of immune system and glucose metabolism disturbances in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |