| 1 | Psychopharmacology (Berl.) 2000 Apr 149: 319-25 |
|---|---|
| PMID | 10823414 |
| Title | Selective impairments in the stress response in schizophrenic patients. |
| Abstract | In the vulnerability-stress concept of schizophrenia, schizophrenic patients are thought to display increased sensitivity to stress. Little is known about the biological mechanisms that are involved in stress processing in schizophrenic patients. In this study, hypothalarnic-pituitary-adrenal (HPA) function in schizophrenic patients was studied for its essential role in stress processing and adaptation to the environment. Eighteen schizophrenic patients were compared to 21 healthy controls in their salivary cortisol response to a physical (bicycle ergometry) and a psychosocial (public speaking) stressor. Coping questionnaires were included as a measure of stress processing at the psychological level. Basal HPA function was assessed by measuring cortisol day profiles and feedback activity by using dexamethasone and hydrocortisone. schizophrenic patients showed blunted cortisol responses to the psychosocial stressor, but not to the physical stressor, in spite of similar increases in heart rate. The cortisol response to the psychosocial stressor tended to be negatively correlated to the use of passive and avoidant coping strategies. Basal HPA function appeared intact in the schizophrenic patients. The findings show a selective impairment in the response to psychosocial stress in schizophrenic patients. This suggests the involvement of brain systems that play a role in the activation of the HPA system to psycho-social stress, like arginin-vasopressin (AVP), and cognitive processes, like coping. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 2 | Psychopharmacology (Berl.) 2000 Apr 149: 319-25 |
| PMID | 10823414 |
| Title | Selective impairments in the stress response in schizophrenic patients. |
| Abstract | In the vulnerability-stress concept of schizophrenia, schizophrenic patients are thought to display increased sensitivity to stress. Little is known about the biological mechanisms that are involved in stress processing in schizophrenic patients. In this study, hypothalarnic-pituitary-adrenal (HPA) function in schizophrenic patients was studied for its essential role in stress processing and adaptation to the environment. Eighteen schizophrenic patients were compared to 21 healthy controls in their salivary cortisol response to a physical (bicycle ergometry) and a psychosocial (public speaking) stressor. Coping questionnaires were included as a measure of stress processing at the psychological level. Basal HPA function was assessed by measuring cortisol day profiles and feedback activity by using dexamethasone and hydrocortisone. schizophrenic patients showed blunted cortisol responses to the psychosocial stressor, but not to the physical stressor, in spite of similar increases in heart rate. The cortisol response to the psychosocial stressor tended to be negatively correlated to the use of passive and avoidant coping strategies. Basal HPA function appeared intact in the schizophrenic patients. The findings show a selective impairment in the response to psychosocial stress in schizophrenic patients. This suggests the involvement of brain systems that play a role in the activation of the HPA system to psycho-social stress, like arginin-vasopressin (AVP), and cognitive processes, like coping. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 3 | Peptides 2001 Jan 22: 67-72 |
| PMID | 11179599 |
| Title | Arginine vasopressin in the cytoplasm and nuclear fraction of lymphocytes from healthy donors and patients with depression or schizophrenia. |
| Abstract | We investigated whether cytoplasmic or nuclear extracts of human peripheral blood lymphocytes contain AVP in samples from healthy controls and patients diagnosed as depressed or schizophrenic. Both the cytoplasmic and nuclear extracts contained AVP as determined by radioimmunoassay. AVP and other peptides were detected in the purified samples by matrix-assisted laser desorption/ionization time of flight mass spectrometry. It is the first time that AVP has been characterized in human lymphocytes of patients with depression or schizophrenia. This finding demonstrates the presence of another important component within the potential regulatory loop between immune and neuro-endocrine tissues. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 4 | Peptides 2001 Jan 22: 67-72 |
| PMID | 11179599 |
| Title | Arginine vasopressin in the cytoplasm and nuclear fraction of lymphocytes from healthy donors and patients with depression or schizophrenia. |
| Abstract | We investigated whether cytoplasmic or nuclear extracts of human peripheral blood lymphocytes contain AVP in samples from healthy controls and patients diagnosed as depressed or schizophrenic. Both the cytoplasmic and nuclear extracts contained AVP as determined by radioimmunoassay. AVP and other peptides were detected in the purified samples by matrix-assisted laser desorption/ionization time of flight mass spectrometry. It is the first time that AVP has been characterized in human lymphocytes of patients with depression or schizophrenia. This finding demonstrates the presence of another important component within the potential regulatory loop between immune and neuro-endocrine tissues. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 5 | Life Sci. 2001 Sep 69: 2147-56 |
| PMID | 11669458 |
| Title | Effect of chronic treatment with haloperidol on vasopressin release and behavioral changes by osmotic stimulation of the supraoptic nucleus. |
| Abstract | Chronic treatment with dopamine D2 blockers in schizophrenic patients has been proposed as one of the causes of polydipsia and water intoxication, but this conclusion is still controversial. To investigate the relationship between dopamine D2 blockers and these syndromes, we designed a behavioral and neurochemical study using hyperosmotic stimulation in the supraoptic nucleus (SON) by microdialysis after chronic treatment with haloperidol in rats. Animals were injected with haloperidol decanoate (20 mg/kg, i.m.) or sesame oil at 2-week intervals for 8 successive weeks. During the 7th week, water-intake was increased 30-60 min after the hyperosmotic stimulation in both groups, but more so in haloperidol-treated animals compared to that in the control group. Moreover, arginine vasopressin (AVP) was released by the hyperosmotic stimulation in SON, but was not significantly different between groups. In addition, striatal dopamine levels 3-4 days after the microdialysis study showed a significant decrease in the haloperidol-treated animals. These results suggest that chronic treatment with haloperidol enhances water-intake produced by hyperosmotic stimulation in the SON but does not increase AVP levels in dialysates following hyperosmotic stimulation. Thus, these symptoms may be mediated by dopaminergic systems in brain. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 6 | Psychiatry Res 2001 Feb 101: 39-45 |
| PMID | 11223118 |
| Title | Roles of arginine vasopressin and atrial natriuretic peptide in polydipsia-hyponatremia of schizophrenic patients. |
| Abstract | Respective contributions of arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) to the urinary sodium concentration were evaluated in 23 naturalistic incidents of polydipsia-hyponatremia observed in 11 hospitalized schizophrenics (10 males and 1 female). The sodium concentration of the spontaneously excreted urine was examined before and after the forced water restriction. Before the water restriction, mean (+/-S.D.) plasma ANP was 52.8 +/- 33.9 pg/ml (range = 6.9-137). Plasma AVP levels were below 0.3 pg/ml in 15 episodes; relatively high levels (> or = 0.3) were noted in eight episodes. Means of urinary sodium concentration (mEq/l) were significantly higher in episodes with high AVP (> or = 0.3) alone (25.0 +/- 8.2, n=4), with high ANP (> 43) alone (21.3+/-7.4, n = 9), and with high AVP and ANP (26.8 +/- 6.4, n = 4) as compared to that of the low AVP (< 0.3) and ANP (< or = 43) group (13.5 +/- 3.7, n = 6). The data indicate that the elevated urinary sodium in polydipsic patients is possibly due to the AVP-induced antidiuresis and/or the ANP-induced natriuresis. In addition, we observed a close relationship between elevated plasma AVP and vomiting, suggesting that vomiting is one of the causal factors responsible for AVP elevations in this syndrome. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 7 | Psychiatry Res 2001 Feb 101: 39-45 |
| PMID | 11223118 |
| Title | Roles of arginine vasopressin and atrial natriuretic peptide in polydipsia-hyponatremia of schizophrenic patients. |
| Abstract | Respective contributions of arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) to the urinary sodium concentration were evaluated in 23 naturalistic incidents of polydipsia-hyponatremia observed in 11 hospitalized schizophrenics (10 males and 1 female). The sodium concentration of the spontaneously excreted urine was examined before and after the forced water restriction. Before the water restriction, mean (+/-S.D.) plasma ANP was 52.8 +/- 33.9 pg/ml (range = 6.9-137). Plasma AVP levels were below 0.3 pg/ml in 15 episodes; relatively high levels (> or = 0.3) were noted in eight episodes. Means of urinary sodium concentration (mEq/l) were significantly higher in episodes with high AVP (> or = 0.3) alone (25.0 +/- 8.2, n=4), with high ANP (> 43) alone (21.3+/-7.4, n = 9), and with high AVP and ANP (26.8 +/- 6.4, n = 4) as compared to that of the low AVP (< 0.3) and ANP (< or = 43) group (13.5 +/- 3.7, n = 6). The data indicate that the elevated urinary sodium in polydipsic patients is possibly due to the AVP-induced antidiuresis and/or the ANP-induced natriuresis. In addition, we observed a close relationship between elevated plasma AVP and vomiting, suggesting that vomiting is one of the causal factors responsible for AVP elevations in this syndrome. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 8 | World J. Biol. Psychiatry 2001 Jan 2: 27-33 |
| PMID | 12587182 |
| Title | Neuroendocrine effects of a short-term osmotic stimulus in patients with chronic schizophrenia. |
| Abstract | We studied the effects of a short-term hypertonic stimulus on plasma levels of the stress hormones adrenocorticotropin (ACTH), cortisol, prolactin, and the blood volume- and electrolyte-controlling hormones arginine vasopressin (AVP) and atrial natriuretic peptide (ANP). Seven patients suffering from chronic schizophrenia with negative symptoms and ten healthy control subjects were investigated by a 20-minute infusion of 10 ml/kg body weight of hypertonic (2.5%) versus isotonic (0.9%) saline. All patients, who were medication-free for at least one week prior to the study, and all control subjects participated in two investigations in randomized order according to a single-blind cross-over design. During hypertonic infusion, plasma osmolarity and sodium levels were increased similarly in both groups and significantly more than during isotonic saline. Hypertonic saline caused a significant increase of plasma ACTH, cortisol and prolactin in patients in contrast to controls. AVP and ANP plasma concentrations were elevated after infusion of hypertonic saline, however, only patients showed a significant rise in plasma ANP. These results show that a dysregulation of the hypothalamic-pituitary-adrenal (HPA) system in a subset of patients with chronic schizophrenia may become overt during an osmotic stimulation, indicating an increased sensitivity of patients with schizophrenia to osmotic stress. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 9 | J. Neural Transm. Suppl. 2003 -1 -1: 17-34 |
| PMID | 12830927 |
| Title | The role of peptides in treatment of psychiatric disorders. |
| Abstract | About 25 years ago the observation that neuropeptides serve as signalling molecules in the nervous system generated great expectations for drug industry. In this article the progress made since then in exploiting neuropeptide systems pharmacologically in psychiatry is highlighted. In affective disorders a number of neuropeptides seem to be causally involved in development and course of illness, especially corticotropin releasing hormone (CRH), vasopressin (AVP) and substance P, whose receptors are now targeted with small molecules designed to reduce depressive and anxiety symptoms. Although not exactly neuropeptides, also neurotrophins, may have a distinct role in antidepressant action and possibly also in causation of depression. schizophrenia-like symptoms are caused by neurotensin (NT), supporting the notion that drugs interfering with NT systems are potential antipsychotics. Finally, sleep disorders, currently treated with hypnotics, that have serious adverse effects can be targeted with neuropeptides. According to the work by Axel Steiger several neuropeptides even if peripherally administered produce improvements of quality of sleep. All these observations call for intensified application of novel research tools necessary to exploit the potential of neuropeptide systems as psychopharmaceutical targets. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 10 | Psychoneuroendocrinology 2004 Nov 29: 1317-25 |
| PMID | 15288711 |
| Title | Neonatal lesions of the ventral hippocampal formation disrupt neuroendocrine responses to auditory stress in the adult rat. |
| Abstract | Lesioning the ventral hippocampal formation (vHF) in the neonatal rat with an excitotoxin replicates several features of schizophrenia. Similar lesions in the adult rat disrupt the normal constraint of neuroendocrine responses to environmental stressors, which is of potential interest because the enhanced HPA axis and antidiuretic hormone activity in schizophrenia is linked to acute stress and hippocampal formation (HF) pathology. In the current study, we investigated the effects of neonatal ventral hippocampal formation lesions (NVHFL) on plasma adrenocorticotropin hormone (ACTH) and arginine vasopressin (AVP) responses following a 2-min acoustic stressor in the adult rat. Levels of the two hormones did not differ between SHAM-operated and NVHFL animals in their home cages. ACTH levels doubled in SHAM-operated animals immediately following stress, but increased more than six-fold in the NVHFL group. AVP levels were halved immediately following stress in SHAM-operated animals, but did not change significantly in NVHFL. Findings could not be attributed to intervening factors known to influence neuroendocrine activity. Thus, NVHFL appear to disrupt the HF-mediated constraint of neuroendocrine responses to stress, and model the neuroendocrine dysfunction seen in schizophrenia. We posit that clarification of how NVHFL alters relatively "simple", well characterized, and phylogenetically preserved systems, such as the neuroendocrine system, may provide insight into the mechanism of hippocampal pathology in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 11 | Psychoneuroendocrinology 2004 Sep 29: 1065-70 |
| PMID | 15219658 |
| Title | Evidence of basal pituitary-adrenal overactivity in first episode, drug naļve patients with schizophrenia. |
| Abstract | Evidence for basal hypothalamic-pituitary-adrenal (HPA) axis dysfunction in schizophrenia is less consistent than that seen in major depression. Potential reasons include sampling procedures and the use of patients on antipsychotic medications which may suppress the HPA axis. Therefore, the objective of this study was to determine whether first episode, drug naļve patients with schizophrenia have evidence of basal HPA axis dysfunction by measuring plasma levels of AVP, ACTH and cortisol from 13:00 to 16:00 h, a time frame which is believed to reflect 24 h concentrations of HPA axis activity. In this cross-sectional study, plasma levels of AVP, ACTH and cortisol were measured in 12 (7 males and 5 females) (mean age +/-SD=33.6+/-12.6 years) patients with DSM-IV schizophrenia and compared with those found in age- and sex-matched healthy controls. Patients and controls did not differ in terms of their 13:00 h cortisol and AVP. However, patients with schizophrenia had higher levels of ACTH as compared to control subjects at 13:00 h (41.3+/-14.6 vs. 12.4+/-1.1 pg/ml respectively; t=1.99, df=11, p <0.05). In comparison to controls subjects, patients with schizophrenia, had higher mean (+/-SE) AUC of ACTH (26.3+/-6.2 vs. 13.9 nmol/l, respectively; t=2.86, df=11, p <0.02) and cortisol (279.4+/-26.0 vs. 213.1+/-18.4 nmol/l, respectively; t=3.72, df=11, p <0.01). Though, patients with schizophrenia, in comparison to control subjects, had lower mean (+/-SE) AUC of AVP (0.87+/-0.24 vs. 1.42+/-0.34 pmol/l, respectively; t=2.29, df=11, p <0.02). First episode, drug naļve patients with schizophrenia show evidence of basal overactivity of the pituitary-adrenal axis. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 12 | Brain Res. 2005 Aug 1053: 131-6 |
| PMID | 16051205 |
| Title | NC-1900, an arginine-vasopressin analogue, ameliorates social behavior deficits and hyperlocomotion in MK-801-treated rats: therapeutic implications for schizophrenia. |
| Abstract | We previously reported that chronic administration of N-methyl-D-aspartate (NMDA) antagonists reduced the density of vasopressin V1a receptors in several brain regions in rats that demonstrated social interaction deficits and increased locomotor activity. These observations indicate the ability of arginine-vasopressin (AVP), or its analogues, to modulate behavioral abnormalities associated with blockade of NMDA receptors. The present study was performed to investigate the effect of NC-1900, an AVP analogue, on social behavior and locomotor activity in rats treated with MK-801, a non-competitive NMDA receptor antagonist. Male Wistar rats were administered MK-801 (0.13 mg/kg/day ip) or saline for 14 days. Social behavior and locomotor activity were measured 45 min after the injection of NC-1900 (10 ng/kg sc) or saline together with the last MK-801 or vehicle administration. Social interaction was quantified by an automated video-tracking system, and stereotyped behavior and ataxia were manually measured. Acute administration of NC-1900 partially reversed MK-801-induced hyperlocomotion and deficits in social interaction, while NC-1900 itself did not affect these behavioral measures in animals chronically treated with vehicle saline. These results suggest that the central AVP system may interact with glutamatergic and dopaminergic transmissions, and indicate potential therapeutic effects of AVP analogues on positive and negative symptoms of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 13 | Psychoneuroendocrinology 2005 Jun 30: 431-7 |
| PMID | 15721055 |
| Title | Male patients with paranoid schizophrenia have greater ACTH and cortisol secretion in response to metoclopramide-induced AVP release. |
| Abstract | Dynamic testing of the hypothalamic-pituitary-adrenal axis in schizophrenia has yielded conflicting results, which may be related to patient selection and previous exposure to psychotropic medication. The objective of this study was to determine the pattern of corticotropin (ACTH) and cortisol release in response to metoclopramide (a dopamine antagonist), which appears to be unique in its ability to release vasopressin (AVP), in drug naive patients with schizophrenia experiencing their first episode of psychosis. In this study, we examined AVP, ACTH and cortisol release in response to metoclopramide in 10 drug-naive, first-episode male patients with a DSM IV diagnosis of paranoid schizophrenia and compared them to healthy control subjects matched for age, sex and smoking status. Patients, as compared to controls had higher levels of baseline plasma cortisol (375.5+/-47.4/l vs. 273.8+/-42.2 nmol/l, respectively; t=2.48, df=9, p< 0.02) and plasma ACTH (14.9+/-0.85 vs. 11.3+/-0.57 pg/ml, respectively; t=4.29, df=9, p<0.001). AVP levels were lower in patients though this did not reach statistical significance (0.89+/-0.09 vs. 1.3+/-0.08 pmol/l, respectively; t=1.97, df=9, p<0.07). A repeated measures 2-way ANOVA to compare responses to metoclopramide over time between the two groups yielded a significant group by time interaction for cortisol (F=11.3, df=6, 108, p<0.001) and ACTH (F=15.65, df=6, 108, p<0.002). Post hoc Tukey's test revealed significant differences between the two groups at +30, +45, +60, +90 and +120 min for cortisol (p<0.01) and at +30, +45, +60 and +90 min for ACTH (p<0.01). The group by time interactions continued to remain significant when cortisol (F=10.9, df=6, 107, p<0.001) and ACTH (F=13.04, df=6, 108, p<0.002) were entered as co-variates. There was a significant positive correlation between AVP and cortisol responses in patients (r=0.65, df=8, p<0.01). Male patients with paranoid schizophrenia release greater amounts of ACTH and cortisol in responses to metoclopramide-induced AVP secretion than control subjects. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 14 | Neuropsychopharmacology 2005 Nov 30: 1996-2005 |
| PMID | 15956991 |
| Title | Disruption of the prepulse inhibition of the startle reflex in vasopressin V1b receptor knockout mice: reversal by antipsychotic drugs. |
| Abstract | In the present study, we investigated whether mice lacking the arginine vasopressin (AVP) V1b receptor (V1bR) exhibit deficits of prepulse inhibition (PPI) of the startle reflex, reminiscent of the sensorimotor gating deficits observed in a large majority of schizophrenic patients. V1bR knockout (KO) mice displayed significantly reduced levels of PPI of the startle reflex. In addition to PPI deficits, V1bR KO mice showed increased acoustic startle response. However, acoustic startle response was not significantly correlated to the PPI of the startle reflex in V1bR KO mice. V1bR KO mice also showed a decrease in basal levels of extracellular dopamine (DA) in the medial prefrontal cortex, which is thought to be an important brain region for PPI. Moreover, PPI deficits observed in the V1bR KO mice are significantly reversed by atypical antipsychotics such as risperidone and clozapine but not by a typical neuroleptic haloperidol, like in schizophrenic patients. By contrast, we did not observe any significant differences between V1bR KO mice and wild-type mice in the open-field, light/dark, elevated plus maze, and forced swimming tests. The results of the present study indicate that V1bR may be involved in the regulation of PPI of the startle reflex. The V1bR has been considered an important molecular target for the development of antipsychotic drugs. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 15 | Nihon Shinkei Seishin Yakurigaku Zasshi 2006 Apr 26: 101-5 |
| PMID | 16722468 |
| Title | [Vasopressin receptor knockout mice as an animal model of psychiatric disorders]. |
| Abstract | Arginine vasopressin (AVP) is a neurohypophyseal peptide best known as an antidiuretic hormone. AVP receptors have been classified into three subtypes: V1a, V1b, and V2 receptors. The V1a receptor (V1aR) and V1b receptor (V1bR) are widely distributed in the central nervous system, including the cortex and hippocampus. In the present study, we examined the performance of V1aR or V1bR knockout (KO) mice compared to wild-type (WT) mice in behavioral tests. V1aR KO mice exhibited impairments of spatial learning (eight-arm radial maze), prepulse inhibition (PPI) and social behavior in comparison to WT mice. On the other hand, V1bR KO mice also displayed impairments of PPI and social behavior. These results suggest that V1aR and V1bR may be involved in psychiatric disorders associated with impairments of sensorimotor gating and social behavior such as schizophrenia and autism. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 16 | Magn Reson Med Sci 2006 Dec 5: 211-5 |
| PMID | 17332713 |
| Title | Transient splenial lesion of the corpus callosum after acute withdrawal of antiepileptic drug: a case report. |
| Abstract | Transient lesions at the splenium of the corpus callosum (SCC) have been reported after withdrawal of specific antiepileptic drugs (AED), though the pathophysiology of the lesions remains unclear. We examined and treated a schizophrenic patient who developed a transient SCC lesion after withdrawal of the AED, carbamazepine. Interestingly, the SCC lesion was accompanied by the onset of diabetes insipidus, a state of arginine-vasopressin (AVP) insufficiency. Because carbamazepine is shown to potentiate the effect of AVP, our case suggests that an insufficiency of AVP followed by withdrawal of AED could contribute to the pathogenesis of a transient SCC lesion. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 17 | Behav. Brain Res. 2007 Mar 178: 123-7 |
| PMID | 17227684 |
| Title | Impaired social interaction and reduced anxiety-related behavior in vasopressin V1a receptor knockout mice. |
| Abstract | The arginine vasopressin (AVP) system plays an important role in social behavior. Autism, with its hallmark disturbances in social behavior, has been associated with the V1a receptor (V1aR) gene. Furthermore, impairments of social function are often observed in symptoms of schizophrenia. Subchronic phencyclidine (PCP) produces behaviors relating to certain aspects of schizophrenic symptoms such as impairing social interaction in animals and it reduces the density of V1aR binding sites in several brain regions. Here, we report that V1aR knockout (KO) mice exhibited impairment of social behavior in a social interaction test, and showed reduced anxiety-related behavior in elevated plus-maze and marble-burying behavior tests. Given the current findings, the V1aR may be involved in the regulation of social interaction, and V1aR KO mice could be used as an animal model of psychiatric disorders associated with social behavior deficits, such as autism and schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 18 | Behav. Brain Res. 2007 Mar 178: 123-7 |
| PMID | 17227684 |
| Title | Impaired social interaction and reduced anxiety-related behavior in vasopressin V1a receptor knockout mice. |
| Abstract | The arginine vasopressin (AVP) system plays an important role in social behavior. Autism, with its hallmark disturbances in social behavior, has been associated with the V1a receptor (V1aR) gene. Furthermore, impairments of social function are often observed in symptoms of schizophrenia. Subchronic phencyclidine (PCP) produces behaviors relating to certain aspects of schizophrenic symptoms such as impairing social interaction in animals and it reduces the density of V1aR binding sites in several brain regions. Here, we report that V1aR knockout (KO) mice exhibited impairment of social behavior in a social interaction test, and showed reduced anxiety-related behavior in elevated plus-maze and marble-burying behavior tests. Given the current findings, the V1aR may be involved in the regulation of social interaction, and V1aR KO mice could be used as an animal model of psychiatric disorders associated with social behavior deficits, such as autism and schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 19 | Harv Rev Psychiatry 2008 -1 16: 13-24 |
| PMID | 18306096 |
| Title | Hyponatremia in psychiatric patients: update on evaluation and management. |
| Abstract | Hyponatremia (serum sodium concentration < 136 mEq/L) is a prevalent and potentially dangerous medical comorbidity in psychiatric patients. MEDLINE was used to identify peer-reviewed publications that described the role of arginine vasopressin (AVP) in the pathogenesis of hyponatremia, the presentation and treatment of hyponatremia in psychiatric patients, and promising new treatment options. Polydipsia may lead to hyponatremia in patients with schizophrenia, which is mediated, in part, by a reduced osmotic threshold for the release of AVP and by a defect in the osmoregulation of thirst. Acute-onset hyponatremia may require emergent treatment with hypertonic (3%) saline, whereas chronic cases mandate gradual correction to minimize the risk of osmotic demyelination. The AVP-receptor antagonists, including conivaptan, tolvaptan, lixivaptan, and satavaptan, represent a therapeutic advance in the treatment of dilutional hyponatremia. Based on the role of AVP in the development of hyponatremia, further studies are warranted to determine the efficacy of the AVP-receptor antagonists in psychiatric patients with hyponatremia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 20 | Synapse 2008 Jan 62: 1-7 |
| PMID | 17948890 |
| Title | Effect of MK-801 on gene expressions in the amygdala of rats. |
| Abstract | Rodents treated with N-methyl-D-aspartate (NMDA) antagonists have been thought to be an animal model of schizophrenia. In this study, we examined gene expression in the amygdala of rats chronically treated with MK-801, as well as behavioral changes, such as social behavior, in these animals. The social interaction test, a measure of social behavior, and locomotor activity was performed in male Wistar rats injected with MK-801 (0.13 mg/kg i.p.) or saline for 14 days. Changes in mRNA levels were analyzed using a GeneChip microarray system. Real-time quantitative PCR (RT-qPCR) assay was subsequently conducted to confirm the results of the microarray analysis. MK-801 decreased social interaction and increased locomotor activity in rats, consistent with previous reports. We found 23 downregulated genes and 16 upregulated genes, with the gene encoding arginine-vasopressin (AVP) being most downregulated, and that for transthyretin (Ttr) most upregulated. mRNA levels, quantified by RT-qPCR assay, were altered for genes related to neuropeptides (AVP, Sstr2), the arachidonic cascade (Ptgds), myelination (Mobp, Enpp2), neurotrophic factors (Igfbp2), and hormonal milieu (Ttr). Downregulation of the AVP gene in the amygdala of MK-801-treated rats may provide a basis for the ability of AVP-analogues to ameliorate the behavioral disturbances caused by blockade of the NMDA receptor. The results of this study provide an insight into the neural substrates responsible for the generation of psychotic symptoms. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 21 | Brain Res Rev 2009 Oct 61: 210-20 |
| PMID | 19595703 |
| Title | The mechanism of life-threatening water imbalance in schizophrenia and its relationship to the underlying psychiatric illness. |
| Abstract | Impaired water excretion was noted to coincide with psychotic exacerbations in the first decades of the past century. In the ensuing decades, life-threatening water intoxication and elevated plasma levels of the antidiuretic hormone, arginine vasopressin (AVP) were reported in a subset of persons with schizophrenia. Subsequent studies demonstrated that the osmotic set point for AVP secretion was transiently reset in these patients by an unknown process and that this was further exacerbated by acute psychosis. More recent studies indicate that the AVP dysfunction is a manifestation of a hippocampal-mediated impairment in the regulation of both AVP and HPA axis responses to psychological, but not other types of, stimuli. Of potential significance, is that schizophrenic patients without water imbalance exhibit the opposite pattern of responses. Preliminary data indicate those with water imbalance also demonstrate a closely linked deficit in central oxytocin activity which may account for their diminished social function. These latter behavioral deficits are perhaps the most disabling and treatment resistant features of schizophrenia, which recent studies suggest, may respond to oxytocin agonists. Together these findings support the view that schizophrenia is a heterogeneous disorder, and provide novel biomarkers and approaches for exploring the pathophysiology and treatment of severe mental illness. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 22 | Brain Res Rev 2009 Oct 61: 210-20 |
| PMID | 19595703 |
| Title | The mechanism of life-threatening water imbalance in schizophrenia and its relationship to the underlying psychiatric illness. |
| Abstract | Impaired water excretion was noted to coincide with psychotic exacerbations in the first decades of the past century. In the ensuing decades, life-threatening water intoxication and elevated plasma levels of the antidiuretic hormone, arginine vasopressin (AVP) were reported in a subset of persons with schizophrenia. Subsequent studies demonstrated that the osmotic set point for AVP secretion was transiently reset in these patients by an unknown process and that this was further exacerbated by acute psychosis. More recent studies indicate that the AVP dysfunction is a manifestation of a hippocampal-mediated impairment in the regulation of both AVP and HPA axis responses to psychological, but not other types of, stimuli. Of potential significance, is that schizophrenic patients without water imbalance exhibit the opposite pattern of responses. Preliminary data indicate those with water imbalance also demonstrate a closely linked deficit in central oxytocin activity which may account for their diminished social function. These latter behavioral deficits are perhaps the most disabling and treatment resistant features of schizophrenia, which recent studies suggest, may respond to oxytocin agonists. Together these findings support the view that schizophrenia is a heterogeneous disorder, and provide novel biomarkers and approaches for exploring the pathophysiology and treatment of severe mental illness. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 23 | Curr Opin Drug Discov Devel 2010 Sep 13: 538-47 |
| PMID | 20812145 |
| Title | Modulation of the vasopressin system for the treatment of CNS diseases. |
| Abstract | Vasopressin (also known as arginine vasopressin [AVP]) is a small cyclic peptide that acts at the V1a, V1b and V2 GPCRs to regulate a wide range of physiological functions, including vasoconstriction, smooth muscle contractility, response to stress, and excretion of water and sodium via the kidney. The potential therapeutic applications of AVP receptor ligands have prompted significant interest in this target within the pharmaceutical research community, and several small-molecule drugs targeting the AVP receptor have reached the market, mainly for cardiovascular indications. The development of AVP receptor modulators for the treatment of CNS indications has proven more challenging, and is the focus of this review. The regulatory role of AVP on the hypothalamic-pituitary-adrenal (HPA) axis suggests potential uses for AVP receptor modulators in various CNS indications, including depression, anxiety and post-traumatic stress disorder. Several clinical trials of V1a and V1b receptor antagonists in CNS indications have been conducted, but none of these drugs have reached the market. In recent years, the discovery of the key role of AVP in modulating complex social behaviors has provided a unique opportunity to understand the physiological mechanisms of social interactions. Ultimately, the ongoing research in this field may enable the development of treatments to alleviate the social deficits associated with conditions such as autism and schizophrenia. Given the large unmet medical need in these areas, a renewed interest in the field of CNS-penetrant AVP receptors modulators is expected. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 24 | Nat. Rev. Neurosci. 2011 Sep 12: 524-38 |
| PMID | 21852800 |
| Title | Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine. |
| Abstract | The neuropeptides oxytocin (OXT) and arginine vasopressin (AVP) are evolutionarily highly conserved mediators in the regulation of complex social cognition and behaviour. Recent studies have investigated the effects of OXT and AVP on human social interaction, the genetic mechanisms of inter-individual variation in social neuropeptide signalling and the actions of OXT and AVP in the human brain as revealed by neuroimaging. These data have advanced our understanding of the mechanisms by which these neuropeptides contribute to human social behaviour. OXT and AVP are emerging as targets for novel treatment approaches--particularly in synergistic combination with psychotherapy--for mental disorders characterized by social dysfunction, such as autism, social anxiety disorder, borderline personality disorder and schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 25 | Eur. J. Neurosci. 2011 Aug 34: 469-77 |
| PMID | 21749489 |
| Title | Relationships among estrogen receptor, oxytocin and vasopressin gene expression and social interaction in male mice. |
| Abstract | The incidence of social disorders such as autism and schizophrenia is significantly higher in males, and the presentation more severe, than in females. This suggests the possible contribution of sex hormones to the development of these psychiatric disorders. There is also evidence that these disorders are highly heritable. To contribute toward our understanding of the mechanisms underlying social behaviors, particularly social interaction, we assessed the relationship of social interaction with gene expression for two neuropeptides, oxytocin (OT) and arginine vasopressin (AVP), using adult male mice. Social interaction was positively correlated with: oxytocin receptor (OTR) and vasopressin receptor (V1aR) mRNA expression in the medial amygdala; and OT and AVP mRNA expression in the paraventricular nucleus of the hypothalamus (PVN). When mice representing extremes of social interaction were compared, all of these mRNAs were more highly expressed in high social interaction mice than in low social interaction mice. OTR and V1aR mRNAs were highly correlated with estrogen receptor ? (ER?) mRNA in the medial amygdala, and OT and AVP mRNAs with estrogen receptor ? (ER?) mRNA in the PVN, indicating that OT and AVP systems are tightly regulated by estrogen receptors. A significant difference in the level of ER? mRNA in the medial amygdala between high and low social interaction mice was also observed. These results support the hypothesis that variations of estrogen receptor levels are associated with differences in social interaction through the OT and AVP systems, by upregulating gene expression for those peptides and their receptors. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 26 | Int. J. Neuropsychopharmacol. 2012 Apr 15: 309-19 |
| PMID | 21899794 |
| Title | Oxytocin and vasopressin genes are significantly associated with schizophrenia in a large Arab-Israeli pedigree. |
| Abstract | We have previously studied the genetics of schizophrenia in a large inbred Arab-Israeli pedigree and found evidence for linkage on chromosome 20p13. This locus harbours four strong candidate genes for schizophrenia: atractin (ATRN), pantonate-kinase2 (PANK2), oxytocin (OXT) and arginine-vasopressin (AVP). In this study we further explored the association of these genes with schizophrenia in the pedigree and searched for the disease-causing variants. A mutation screening of affected individuals from the pedigree was performed by using intensive sequencing in these four genes of interest. Then, we studied the prevalence of the identified variants in all family members (n=56) as well as in Arab-Israeli nuclear families (n=276) and a Jewish case-control sample (n=545). We also studied the possible functional role of these variants by examining their association with gene expression in the brain (n=104). We identified seven genetic variants in the OXT-AVP cluster in affected individuals from the pedigree. Three of these variants were significantly associated with schizophrenia in this pedigree. A 7-SNP haplotype was also significantly associated with disease. We found significant association of some of these variants in the two samples from the general population. Expression data analysis showed a possible functional role of two of these variants in regulation of gene expression. Involvement of OXT and AVP in the aetiology of schizophrenia has been suggested in the past. This study demonstrates, for the first time, a significant genetic association of these neuropeptides with schizophrenia and strongly supports this hypothesis. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 27 | Schizophr. Res. 2013 May 146: 138-43 |
| PMID | 23465965 |
| Title | Peripheral vasopressin but not oxytocin relates to severity of acute psychosis in women with acutely-ill untreated first-episode psychosis. |
| Abstract | In women with chronic schizophrenia, higher levels of peripheral oxytocin have been associated with lower levels of positive but not negative symptoms. Sex-specific associations between endogenous levels of oxytocin (OT) and arginine vasopressin (AVP) with clinical symptoms and cognition in untreated early course patients have not been examined. Clinical ratings and neuropsychological testing were performed in thirty-eight acutely ill, unmedicated first-episode schizophrenia patients (14 women, 24 men). Serum hormone assays were obtained in patients and thirty-eight demographically similar healthy controls. Patients demonstrated increased AVP levels compared to controls (p = 0.01). Higher AVP levels were associated with greater positive symptoms (r = 0.58, p = 0.03) and worse verbal learning (r = -0.63, p = 0.02) in female, but not male, patients. OT levels did not statistically differ between patients and controls, and were unrelated to clinical symptoms or cognition in patients. Results suggest an association of endogenous AVP with increased positive symptom severity and worse cognition in untreated female, but not male, schizophrenia patients. Findings support the role of neuroendocrine alterations in acute psychosis and the importance of examining sex-specific neuroendocrine alterations early in the course of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 28 | Afr J Med Med Sci 2014 Sep 43: 259-64 |
| PMID | 26223145 |
| Title | Serum copeptin and its diagnostic performance in schizophrenia. |
| Abstract | Inappropriate arginine vasopressin (AVP) secretion has been reported in schizophrenic patients. However, there is lack of information on serum level of copeptin and its diagnostic performance in schizophrenia. This study therefore, evaluated serum copeptin and its diagnostic performance in schizophrenic patients. Sixty subjects (30.02 ± 7.17 years) with schizophrenia (19 drug naļve [DNS] and 41 schizophrenics on treatment [SOT]) and 30 healthy individuals (33.62 ± 9.05 years) with no history of schizophrenia were enrolled into this study. schizophrenia was diagnosed using the Tenth edition of the International Classification of Diseases and Related Health Problems (ICD-10). Estimation of serum copeptin, plasma electrolytes (potassium, sodium and chloride) and uric acid was done using ELISA, Ion-Selective electrode (ISE) and enzymatic method respectively. Copeptin was significantly higher while uric acid, potassium and sodium levels were significantly lower in patients with schizophrenia compared with controls. Similarly, copeptin was significantly higher while sodium, potassium and uric acid levels were significantly lower in DNS and SOT compared with controls. However, insignificant elevation in copeptin level and insignificant reduction in sodium, potassium, chloride and uric acid levels were observed in DNS compared with SOT. The Area under the curve (AUROC) for copeptin was 0.686 (P = 0.004). There is elevated copeptin level in patients with schizophrenia and that copeptin levels might be a valuable tool in the diagnosis of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 29 | Afr J Med Med Sci 2014 Sep 43: 259-64 |
| PMID | 26223145 |
| Title | Serum copeptin and its diagnostic performance in schizophrenia. |
| Abstract | Inappropriate arginine vasopressin (AVP) secretion has been reported in schizophrenic patients. However, there is lack of information on serum level of copeptin and its diagnostic performance in schizophrenia. This study therefore, evaluated serum copeptin and its diagnostic performance in schizophrenic patients. Sixty subjects (30.02 ± 7.17 years) with schizophrenia (19 drug naļve [DNS] and 41 schizophrenics on treatment [SOT]) and 30 healthy individuals (33.62 ± 9.05 years) with no history of schizophrenia were enrolled into this study. schizophrenia was diagnosed using the Tenth edition of the International Classification of Diseases and Related Health Problems (ICD-10). Estimation of serum copeptin, plasma electrolytes (potassium, sodium and chloride) and uric acid was done using ELISA, Ion-Selective electrode (ISE) and enzymatic method respectively. Copeptin was significantly higher while uric acid, potassium and sodium levels were significantly lower in patients with schizophrenia compared with controls. Similarly, copeptin was significantly higher while sodium, potassium and uric acid levels were significantly lower in DNS and SOT compared with controls. However, insignificant elevation in copeptin level and insignificant reduction in sodium, potassium, chloride and uric acid levels were observed in DNS compared with SOT. The Area under the curve (AUROC) for copeptin was 0.686 (P = 0.004). There is elevated copeptin level in patients with schizophrenia and that copeptin levels might be a valuable tool in the diagnosis of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 30 | Afr J Med Med Sci 2014 Sep 43: 259-64 |
| PMID | 26223145 |
| Title | Serum copeptin and its diagnostic performance in schizophrenia. |
| Abstract | Inappropriate arginine vasopressin (AVP) secretion has been reported in schizophrenic patients. However, there is lack of information on serum level of copeptin and its diagnostic performance in schizophrenia. This study therefore, evaluated serum copeptin and its diagnostic performance in schizophrenic patients. Sixty subjects (30.02 ± 7.17 years) with schizophrenia (19 drug naļve [DNS] and 41 schizophrenics on treatment [SOT]) and 30 healthy individuals (33.62 ± 9.05 years) with no history of schizophrenia were enrolled into this study. schizophrenia was diagnosed using the Tenth edition of the International Classification of Diseases and Related Health Problems (ICD-10). Estimation of serum copeptin, plasma electrolytes (potassium, sodium and chloride) and uric acid was done using ELISA, Ion-Selective electrode (ISE) and enzymatic method respectively. Copeptin was significantly higher while uric acid, potassium and sodium levels were significantly lower in patients with schizophrenia compared with controls. Similarly, copeptin was significantly higher while sodium, potassium and uric acid levels were significantly lower in DNS and SOT compared with controls. However, insignificant elevation in copeptin level and insignificant reduction in sodium, potassium, chloride and uric acid levels were observed in DNS compared with SOT. The Area under the curve (AUROC) for copeptin was 0.686 (P = 0.004). There is elevated copeptin level in patients with schizophrenia and that copeptin levels might be a valuable tool in the diagnosis of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 31 | Acta Neuropsychiatr 2014 Dec 26: 347-55 |
| PMID | 25288094 |
| Title | Oxytocin and vasopressin levels are decreased in the plasma of male schizophrenia patients. |
| Abstract | Impaired social functioning and autistic symptoms are characteristics of schizophrenia. The social hormones oxytocin (OT) and arginine-vasopressin (AVP) both modulate social interaction and therefore may be involved in the pathogenesis of schizophrenia. We investigated whether men with schizophrenia show altered OT and AVP levels compared with healthy controls (HC) and whether autism symptoms are associated with OT levels. Forty-one men with non-acute schizophrenia and 45 matched HC were enrolled. schizophrenia was assessed with the Positive and Negative Syndrome Scale (PANSS). Blood samples were collected on 2 days, and plasma OT and AVP levels were measured by ELISA immunoassay. The schizophrenia patients had significantly lower plasma OT levels than the HC; a similar trend was found for AVP. Plasma OT levels were associated with severe life events, fewer important attached persons, and a higher score on the PANSS negative scale; the most dominant PANSS items were 'preoccupation', 'emotional withdrawal', and 'passive/apathetic social withdrawal'. These findings support an association between the social hormones OT and AVP and schizophrenia. We suggest that OT metabolism may be altered in schizophrenia, but other possible causes for decreased plasma OT levels in schizophrenia patients include decreased OT synthesis, mRNA expression, and translation. Especially the 'autistic' symptoms of schizophrenia seem to be closely linked to an altered metabolism of OT, the 'attachment' hormone. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 32 | Schizophr Bull 2014 Nov 40: 1374-84 |
| PMID | 24619535 |
| Title | Reduced levels of vasopressin and reduced behavioral modulation of oxytocin in psychotic disorders. |
| Abstract | Oxytocin (OT) and arginine vasopressin (AVP) exert robust influence on social affiliation and specific cognitive processes in healthy individuals. Abnormalities in these neuroendocrine systems have been observed in psychotic disorders, but their relation to impairments in behavioral domains that these endocrines modulate is not well understood. We compared abnormalities of OT and AVP serum concentrations in probands with schizophrenia (n = 57), schizoaffective disorder (n = 34), and psychotic bipolar disorder (n = 75); their first-degree relatives without a history of psychosis (n = 61, 43, 91, respectively); and healthy controls (n = 66) and examined their association with emotion processing and cognition. AVP levels were lower in schizophrenia (P = .002) and bipolar probands (P = .03) and in relatives of schizophrenia probands (P = .002) compared with controls. OT levels did not differ between groups. Familiality estimates were robust for OT (h(2) = 0.79, P = 3.97e-15) and AVP (h(2) = 0.78, P = 3.93e-11). Higher levels of OT were associated with better emotion recognition (? = 0.40, P < .001) and general neuropsychological function (? = 0.26, P = .04) in healthy controls as expected but not in any proband or relative group. In schizophrenia, higher OT levels were related to greater positive symptom severity. The dissociation of OT levels and behavioral function in all proband and relative groups suggests that risk and illness factors associated with psychotic disorders are not related to reduced OT levels but to a disruption in the ability of physiological levels of OT to modulate social cognition and neuropsychological function. Decreased AVP levels may be a marker of biological vulnerability in schizophrenia because alterations were seen in probands and relatives, and familiality was high. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 33 | Front Endocrinol (Lausanne) 2015 -1 6: 5 |
| PMID | 25705203 |
| Title | Vasopressin Proves Es-sense-tial: Vasopressin and the Modulation of Sensory Processing in Mammals. |
| Abstract | As mammals develop, they encounter increasing social complexity in the surrounding world. In order to survive, mammals must show appropriate behaviors toward their mates, offspring, and same-sex conspecifics. Although the behavioral effects of the neuropeptide arginine vasopressin (AVP) have been studied in a variety of social contexts, the effects of this neuropeptide on multimodal sensory processing have received less attention. AVP is widely distributed through sensory regions of the brain and has been demonstrated to modulate olfactory, auditory, gustatory, and visual processing. Here, we review the evidence linking AVP to the processing of social stimuli in sensory regions of the brain and explore how sensory processing can shape behavioral responses to these stimuli. In addition, we address the interplay between hormonal and neural AVP in regulating sensory processing of social cues. Because AVP pathways show plasticity during development, early life experiences may shape life-long processing of sensory information. Furthermore, disorders of social behavior such as autism and schizophrenia that have been linked with AVP also have been linked with dysfunctions in sensory processing. Together, these studies suggest that AVP's diversity of effects on social behavior across a variety of mammalian species may result from the effects of this neuropeptide on sensory processing. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 34 | Front Hum Neurosci 2015 -1 9: 9 |
| PMID | 25667571 |
| Title | Association between Genetic Variation in the Oxytocin Receptor Gene and Emotional Withdrawal, but not between Oxytocin Pathway Genes and Diagnosis in Psychotic Disorders. |
| Abstract | Social dysfunction is common in patients with psychotic disorders. Oxytocin is a neuropeptide with a central role in social behavior. This study aims to explore the relationship between oxytocin pathway genes and symptoms related to social dysfunction in patients with psychotic disorders. We performed association analyses between four oxytocin pathway genes (OXT, OXTR, AVP, and CD38) and four areas of social behavior-related psychopathology as measured by Positive and Negative Syndrome Scale. For this purpose, we used both a polygenic risk score (PGRS) and single OXTR candidate single nucleotide polymorphism previously reported in the literature (rs53576, rs237902, and rs2254298). A total of 734 subjects with DSM-IV psychotic spectrum disorders and 420 healthy controls were included. Oxytocin pathway PGRSs were calculated based on the independent Psychiatric Genomics Consortium study sample. There was a significant association between symptom of Emotional Withdrawal and the previously reported OXTR risk allele A in rs53576. No significant associations between oxytocin pathway gene variants and a diagnosis of psychotic disorder were found. Our findings indicate that while oxytocin pathway genes do not appear to contribute to the susceptibility to psychotic disorders, variations in the OXTR gene might play a role in the development of impaired social behavior. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 35 | J. Neuroendocrinol. 2016 Apr 28: -1 |
| PMID | 26715485 |
| Title | Unaltered Oxytocin and Vasopressin Plasma Levels in Patients with Schizophrenia After 4 Months of Daily Treatment with Intranasal Oxytocin. |
| Abstract | The neuropeptide oxytocin (OXT) has been proposed as a treatment for a number of neuropsychiatric disorders characterised by impaired social behaviour, including schizophrenia. Although several studies have reported the chronic administration of OXT to be safe and tolerable, its effects on circulating levels of OXT, as well as the related neuropeptide arginine vasopressin (AVP), have not been assessed. In the present study, in a within-subjects cross-over, double-blind, randomised controlled trial, we assayed the plasma levels of OXT and AVP in 31 patients with schizophrenia who were treated daily for 4 months with 40 IU of intranasal OXT or placebo. Our data indicate a mean ± SD baseline OXT concentration of 1.62 ± 0.68 pg/ml, as determined by radioimmunoassay, which did not display any significant variation after chronic treatment with OXT or placebo. Similarly, the mean ± SD baseline AVP value of 2.40 ± 1.26 pg/ml remained unchanged. The present study also assessed cardiovascular and body fluid indicators (osmolality, plasma sodium concentration and systolic blood pressure), as well as a parameter for food intake (body mass index), with all observed to remain stable. By reporting that daily treatment with 40 IU of intranasal OXT or placebo for 4 months does not impact on OXT and AVP plasma levels, nor on cardiovascular, body fluids and food intake parameters, the present study represents an important step towards developing OXT as a safe treatment. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |