| 1 | Biol. Psychiatry 2005 Sep 58: 401-7 |
|---|---|
| PMID | 15978554 |
| Title | Association of an orexin 1 receptor 408Val variant with polydipsia-hyponatremia in schizophrenic subjects. |
| Abstract | Primary polydipsia is a common complication in patients with chronic psychoses, particularly schizophrenia. Disease pathogenesis is poorly understood, but one contributory factor is thought to be dopamine dysregulation caused by prolonged treatment with neuroleptics. Both angiotensin-converting enzyme (ACE) and orexin (hypocretin) signaling can modulate drinking behavior through interactions with the dopaminergic system. We performed association studies on the insertion/deletion (I/D) sequence polymorphism of ACE and single nucleotide polymorphisms within the prepro-orexin (HCRT), orexin receptor 1 (HCRTR1), and orexin receptor 2 (HCRTR2) genes. Genotypes were determined by polymerase chain reaction amplification, followed by either electrophoretic separation or direct sequencing. The ACE I/D polymorphism showed no association with polydipsic schizophrenia. Screening of the orexin signaling system detected a 408 isoleucine to valine mutation in HCRTR1 that showed significant genotypic association with polydipsic-hyponatremic schizophrenia (p = .012). The accumulation of this mutation was most pronounced in polydipsic versus nonpolydipsic schizophrenia (p = .0002 and p = .008, for the respective genotypic and allelic associations). The calcium mobilization properties and the protein localization of mutant HCRTR1 seem to be unaltered. Our preliminary data suggest that mutation carriers might have an increased susceptibility to polydipsia through an undetermined mechanism. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Biol. Psychiatry 2005 Sep 58: 401-7 |
| PMID | 15978554 |
| Title | Association of an orexin 1 receptor 408Val variant with polydipsia-hyponatremia in schizophrenic subjects. |
| Abstract | Primary polydipsia is a common complication in patients with chronic psychoses, particularly schizophrenia. Disease pathogenesis is poorly understood, but one contributory factor is thought to be dopamine dysregulation caused by prolonged treatment with neuroleptics. Both angiotensin-converting enzyme (ACE) and orexin (hypocretin) signaling can modulate drinking behavior through interactions with the dopaminergic system. We performed association studies on the insertion/deletion (I/D) sequence polymorphism of ACE and single nucleotide polymorphisms within the prepro-orexin (HCRT), orexin receptor 1 (HCRTR1), and orexin receptor 2 (HCRTR2) genes. Genotypes were determined by polymerase chain reaction amplification, followed by either electrophoretic separation or direct sequencing. The ACE I/D polymorphism showed no association with polydipsic schizophrenia. Screening of the orexin signaling system detected a 408 isoleucine to valine mutation in HCRTR1 that showed significant genotypic association with polydipsic-hyponatremic schizophrenia (p = .012). The accumulation of this mutation was most pronounced in polydipsic versus nonpolydipsic schizophrenia (p = .0002 and p = .008, for the respective genotypic and allelic associations). The calcium mobilization properties and the protein localization of mutant HCRTR1 seem to be unaltered. Our preliminary data suggest that mutation carriers might have an increased susceptibility to polydipsia through an undetermined mechanism. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Psychopharmacology (Berl.) 2009 May 203: 693-702 |
| PMID | 19052729 |
| Title | Hyperphagia and increased meal size are responsible for weight gain in rats treated sub-chronically with olanzapine. |
| Abstract | Atypical antipsychotic-induced weight gain is a significant impediment in the treatment of schizophrenia. In a putative model of antipsychotic drug-induced weight gain, we investigated the effects of sub-chronic olanzapine on body weight, meal patterns, the expression of genes encoding for hypothalamic feeding-related neuropeptides and the contribution of hyperphagia to olanzapine-induced weight gain in rats. In experiment 1, female rats received either olanzapine (1 mg/kg, p.o.) or vehicle, twice daily for 7 days, while meal patterns were recorded. At the end of the treatment regimen, we measured the levels of hypothalamic messenger RNAs (mRNAs) encoding neuropeptide-Y (NPY), hypocretin/orexin (HCRT), melanin concentrating hormone and pro-opiomelanocortin. NPY and HCRT mRNA levels were also assessed in a separate cohort of female rats treated acutely with olanzapine (1 mg/kg, p.o.). In experiment 2, we investigated the effect of a pair-feeding paradigm on sub-chronic (1 mg/kg, p.o.) olanzapine-induced weight gain. In experiment 1, sub-chronic olanzapine increased body weight, food intake and meal size. Hypothalamic neuropeptide mRNA levels were unchanged after both acute and sub-chronic olanzapine treatment. In experiment 2, the restriction of food intake to the level of vehicle-treated controls abolished the sub-chronic olanzapine-induced increase in body weight. Hyperphagia mediated by drug-induced impairments in satiety (as evidenced by increased meal size) is a key requirement for olanzapine-induced weight gain in this paradigm. However, olanzapine-induced hyperphagia and weight gain may not be mediated via alterations in the expression of the feeding-related hypothalamic neuropeptides examined in this study. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | BMJ Qual Improv Rep 2012 -1 1: -1 |
| PMID | 26734152 |
| Title | A medication workshop for patients with schizophrenia living in community care homes. |
| Abstract | Psychoeducation for patients with schizophrenia can improve a range of outcomes. Our aim was to test a workshop intervention enabling service users to learn more about mental illness and their medication. A Quality Improvement Project was undertaken to create a workshop for patients with a diagnosis of schizophrenia within the Haringey Community Rehabilitation Team (HCRT) . The response was tested using anonymous questionnaires after each workshop. We held ten workshops (total of 47 participants), after which 83% of patients felt that the workshop had helped them to understand more about their mental health, 77% felt they were able to understand the purpose of their medication, 79% felt they were able to understand the side effects, and 70% felt they could have a say in prescribing. Objectives for the Quality Improvement Project were met. This workshop will be used for other patients within the HCRT and is transferable to other community mental health teams. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Folia Biol. (Praha) 2015 -1 61: 110-5 |
| PMID | 26213855 |
| Title | Effect of Asenapine on the Activity of Hypocretin Neurons in Normal and Unpredictable Mild Stress Preconditioned Rats. |
| Abstract | Asenapine (ASE) is a novel atypical antipsychotic used in schizophrenia treatment. Here, the effect of ASE on Fos expression in hypocretin (HCRT) neurons in medial and lateral portions of the lateral hypothalamus (LH) and the effect of chronic unpredictable variable mild stress (CMS) preconditioning were studied. CMS consisted of restraint, social isolation, crowding, swimming, and cold and lasted 21 days. The rats were sacrificed on day 22, 90 min after a single injection of vehicle (saline 300 ?l/rat subcutaneously--s.c.) or ASE (0.3 mg/kg s.c.). Control (CON), ASE, CMS, and CMS+ASE groups were used. Fos protein was visualized by the avidin biotin peroxidase technique, while HCRT perikarya by fluorescent dye. Fos/HCRT co-localizations were evaluated under parallel light and fluorescent illuminations. In the single Fos expression assessment, the Fos number was significantly higher in the medial in comparison with the lateral LH portion in each group. No differences in Fos amount were observed between the individual groups within the medial and lateral LH portions. In the Fos/HCRT co-localization assessments, ASE significantly reduced the number of Fos/HCRT neurons in the medial, but not lateral, LH portion in ASE and CMS+ASE groups. CMS only slightly contributed to the inhibitory effect of ASE in the CMS+ASE groups. The present data show as the first that ASE may reduce the activity of HCRT cells in the medial LH portion, which might correspond with the relatively low weight gain liability of ASE. CMS preconditioning did not significantly interfere with this impact of ASE. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | Neurol. Res. 2016 Jan 38: 32-9 |
| PMID | 26883904 |
| Title | Stress alters asenapine-induced Fos expression in the Meynert's nucleus: response of adjacent hypocretin and melanin-concentrating hormone neurons in rat. |
| Abstract | Asenapine (ASE), an atypical antipsychotic drug used in the treatment of schizophrenia, induces Fos expression in forebrain. Effect of ASE on activity of basal nucleus of Meynert (NBM) cells, a part of the striatal-cortical circuits, was studied. We were also interested to reveal whether a chronic unpredictable variable mild stress (CMS) preconditioning might affect the ASE impact. Rats were divided into as follows: controls-vehicle, controls-ASE, stressed-vehicle and stressed-ASE groups. CMS included restrain, social isolation, crowding, swimming and cold applied for 21 days. On the 22nd day, rats were subcutaneously injected with ASE (0.3 mg/kg) or vehicle (saline 300 ?l/rat), 90 min prior euthanizing. After transcardial fixation, brains were cut into 30 ?m thick coronal sections. Fos protein presence, as indicator of cell activity, was detected by ABC immunohistochemistry. Hypocretin (HCRT) and melanin-concentrating hormone (MCH) containing cells were visualized with fluorescent dyes. ASE induced significant increase in Fos expression in NBM in both controls and CMS preconditioned rats in comparison with the related vehicle-treated controls. CMS preconditioning, however, significantly lowered the Fos response to ASE in NBM. From Hrct and MCH cells, only HCRT ones displayed Fos presence in response to ASE. This study demonstrates for the first time that ASE may target a special group of cells occupying NBM, which effect can be modulated by CMS preconditioning. This finding extends a view that ASE impact may extend beyond the classical forebrain target areas common for the action of all antipsychotics and might be helpful in the identification of sites and side effects of its therapeutic actions. |
| SCZ Keywords | schizophrenia, schizophrenic |