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Mirjam Christcrain - One of the best experts on this subject based on the ideXlab platform.
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glp1 receptor agonists reduce fluid intake in Primary Polydipsia
Journal of the Endocrine Society, 2021Co-Authors: Bettina Winzeler, Julie Refardt, Clara O Sailer, David Coynel, Vogt Deborah, Zanchi Davide, Sandrine Andrea Urwyler, Mirjam ChristcrainAbstract:Background Primary Polydipsia, characterized by excessive fluid intake, carries the risk of water intoxication and hyponatremia, but treatment options are scarce. Glucagon-like peptide-1 (GLP-1) reduces appetite and food intake. In experimental models, they also play a role in thirst and drinking behavior in. The aim of this trial was to investigate whether GLP-1 receptor agonists reduce fluid intake in patients with Primary Polydipsia. Methods: In this randomized, double-blind, placebo-controlled, 3-week crossover-trial, 34 patients with Primary Polydipsia received weekly dulaglutide (Trulicity®) 1.5mg and placebo (0.9% sodium chloride). During the last treatment week, patients attended an 8-hour evaluation visit with free water access. The Primary endpoint was total fluid intake during the evaluation visits. The treatment effect was estimated using a linear mixed-effects model. In a subset of 15 patients and matched controls, thirst perception and neuronal activity in response to beverage pictures were assessed by functional MRI. Results Median [IQR] total fluid intake was 2250ml [1600-2600] on dulaglutide versus 2400ml [1850-3400] on placebo. Patients on dulaglutide reduced fluid intake by 490ml [95%-CI -780, -199], p=0.002, corresponding to a relative reduction of 17%. 24-hour urinary output was reduced by -943ml [95%-CI -1473, -413]. Thirst perception in response to beverage pictures was higher in patients with Primary Polydipsia versus controls and lower on dulaglutide versus placebo, but functional neuronal activity was similar between groups and treatments. Conclusion: GLP-1 receptor agonists reduce fluid intake and thirst perception in patients with Primary Polydipsia and could therefore be a novel treatment option for these patients.
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eje award 2019 new diagnostic approaches for patients with polyuria Polydipsia syndrome
European Journal of Endocrinology, 2019Co-Authors: Mirjam ChristcrainAbstract:: Diabetes insipidus (DI), be it from central or nephrogenic origin, must be differentiated from secondary forms of hypotonic polyuria such as Primary Polydipsia. Differentiation is crucial since wrong treatment can have deleterious consequences. Since decades, the gold standard for differentiation has been the water deprivation test, which has limitations leading to an overall unsatisfying diagnostic accuracy. Furthermore, it is cumbersome for patients with a long test duration. Clinical signs and symptoms and MRI characteristics overlap between patients with DI and Primary Polydipsia. The direct test including vasopressin (AVP) measurement upon osmotic stimulation was meant to overcome these limitations, but failed to enter clinical practice mainly due to technical constraints of the AVP assay. Copeptin is secreted in equimolar amount to AVP but can easily be measured with a sandwich immunoassay. A high correlation between copeptin and AVP has been shown. Accordingly, copeptin mirrors the amount of AVP in the circulation and has led to a 'revival' of the direct test in the differential diagnosis of DI. We have shown that a baseline copeptin, without prior thirsting, unequivocally identifies patients with nephrogenic DI. In contrast, for the differentiation between central DI and Primary Polydipsia, a stimulated copeptin level of 4.9 pmol/L upon hypertonic saline infusion differentiates these two entities with a high diagnostic accuracy and is superior to the water deprivation test. Close sodium monitoring during the test is a prerequisite. Further new test methods are currently evaluated and might provide an even simpler way of differential diagnosis in the future.
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Primary Polydipsia in the medical and psychiatric patient characteristics complications and therapy
Swiss Medical Weekly, 2017Co-Authors: Clara O Sailer, Bettina Winzeler, Mirjam ChristcrainAbstract:With the increasing popularity of lifestyle programmes and the common perception that consuming several litres of fluid per day is healthy, the prevalence of Primary Polydipsia is increasing, particularly outside of the psychiatric setting.
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Primary Polydipsia in the medical and psychiatric patient characteristics complications and therapy
Swiss Medical Weekly, 2017Co-Authors: Clara O Sailer, Bettina Winzeler, Mirjam ChristcrainAbstract:Primary Polydipsia (PP) has been defined as excessive intake of fluids. However, the pathogenesis of PP remains unexplored. Different theories include a dysfunction in the thirst mechanism, involvement of the hippocampus, stress-reducing behaviour and lesion occurrences in specific areas of the brain. Most studies have been performed in the psychiatric setting, indicating that PP coincides with schizophrenia, anxiety disorder and depression. However, an increasing number of case reports emphasise the incidence of PP in non-psychiatric patients. As often recommended by healthcare professions and in life-style programmes, the phenomenon of excessive fluid intake appears to be growing, especially in health-conscious and active people. PP is part of the polyuria-Polydipsia syndrome, so the differential diagnosis diabetes insipidus (central or nephrogenic) must be excluded. The gold standard when differentiating between these disorders has been the water deprivation test. However, new options for distinguishing between these entities have been proposed e.g., measurement of copeptin, a reliable surrogate marker of the hormone arginine vasopressin (AVP). The major risk of excessive drinking is the development of hyponatraemia and the ensuing complications. In patients with PP, factors reducing the renal excretory capacity of the kidney such as acute illness, medications or low solute intake may accumulate in hyponatraemia. Treatment options for PP remain scarce. Different medication and behavioural therapy have been investigated, but never on a large scale and rarely in non-psychiatric patients. This review provides an overview of the pathophysiology, characteristics, complications, and outcomes of patients with PP in the medical and psychiatric patient.
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characteristics and outcomes of patients with profound hyponatraemia due to Primary Polydipsia
Clinical Endocrinology, 2017Co-Authors: Clara O Sailer, Birsen Arici, Bettina Winzeler, Nicole Nigro, Isabelle Suterwidmer, Martina Bally, Philipp Schuetz, Beat Mueller, Mirjam ChristcrainAbstract:Objective Hyponatremia due to excessive fluid intake (i.e. Primary Polydipsia (PP)) is common. It may culminate in profound hyponatremia—carrying considerable risk of morbidity. However, data on patients with PP leading to hyponatremia is lacking. Herein, we describe the characteristics of polydiptic patients hospitalised with profound hyponatremia, and assess one-year outcomes. Design Substudy of the prospective observational Co-MED Study. Patients Patients with an episode of profound hyponatremia (≤125mmol/l) due to PP in the medical emergency were eligible and classified into psychogenic Polydipsia (PsyP), dipsogenic Polydipsia (DiP), and beer potomania (BP). Measurements Symptoms, laboratory findings, and factors contributing to hyponatremia (comorbidities, medication, and liquid intake) were assessed. A one-year follow-up was performed to evaluate recurrence of hyponatremia, re-admission rate, and mortality. Results 23 patients were included (median age 56 years [IQR 50-65], 74% female), 7 had PsyP, 8 DiP, and 8 BP. Median serum sodium of all patients was 121mmol/l (IQR 114-123), median urine osmolality 167mmol/l (IQR 105-184), and median copeptin 3.6mmol/l (IQR 1.9-5.5). Psychiatric diagnosis, particularly dependency disorder (43%) and depression (35%), were highly prevalent. Factors provoking hyponatremia were found in all patients (e.g. acute water load, medication, stress). During the follow-up period, 67% of patients were readmitted, 52% of these with re-hyponatremia, and 3 patients (38%) with BP died. Conclusion Patients with PP are more likely to be female, and have addictive and affective disorders. Given the high recurrence, re-hospitalisation, and mortality rate, careful monitoring and long-term follow-up including controls of serum sodium, education and behavioural therapy is needed. This article is protected by copyright. All rights reserved.
Nicholas J Delva - One of the best experts on this subject based on the ideXlab platform.
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increased drinking following social isolation rearing implications for Polydipsia associated with schizophrenia
PLOS ONE, 2013Co-Authors: Emily R Hawken, Nicholas J Delva, Richard J BeningerAbstract:Primary Polydipsia, excessive drinking without known medical cause, is especially associated with a diagnosis of schizophrenia. We used animal models of schizophrenia-like symptoms to examine the effects on schedule-induced Polydipsia: post-weaning social isolation rearing, subchronic MK-801 treatment (an NMDA-receptor antagonist) or the two combined. Male, Sprague-Dawley rats reared in groups or in isolation beginning at postnatal day 21 were further divided to receive subchronic MK-801 (0.5 mg/kg twice daily) or saline for 7 days beginning on postnatal day 62. Following a 4-day withdrawal period, all groups were trained on a schedule-induced Polydipsia paradigm. Under food-restriction, animals reared in isolation and receiving food pellets at 1-min intervals developed significantly more drinking behavior than those reared with others. The addition of subchronic MK-801 treatment did not significantly augment the amount of water consumed. These findings suggest a predisposition to Polydipsia is a schizophrenia-like behavioral effect of post-weaning social isolation.
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increased schedule induced Polydipsia in the rat following subchronic treatment with mk 801
Schizophrenia Research, 2011Co-Authors: Emily R Hawken, Nicholas J Delva, James N Reynolds, Richard J BeningerAbstract:Primary Polydipsia, defined as excessive fluid intake not explained by medical causes, has been reported to occur in over 20% of chronically ill psychiatric inpatients and is especially common in schizophrenic populations. We tested the hypothesis that in an animal model of schizophrenia-like symptoms (subchronic injections of MK-801, 0.5 mg/kg twice daily for 7 days) an increase in the acquisition of schedule-induced Polydipsia (SIP) will occur. Young adult, male rats acquired SIP when food-restricted and placed on a non-contingent fixed-time 1-min food schedule. In comparison with saline-treated control animals, subchronic MK-801 treatment significantly increased SIP. These findings suggest an animal model of Polydipsia associated with schizophrenia in humans.
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mortality over a 20 year period in patients with Primary Polydipsia associated with schizophrenia a retrospective study
Schizophrenia Research, 2009Co-Authors: Emily R Hawken, Jake M Crookall, Deirdre Reddick, Richard Millson, Roumen Milev, Nicholas J DelvaAbstract:Abstract Primary Polydipsia, excessive fluid intake without medical cause, is present in over 20% of seriously and persistently ill psychiatric inpatients. The long-term effects of Primary Polydipsia on longevity have not previously been examined. Inpatients in a psychiatric hospital were screened for Polydipsia in 1985. Those identified to be polydipsic, the majority of whom suffered from schizophrenia, were re-evaluated in 2005 and compared with a control group of non-polydipsic patients. Chart reviews were conducted and follow-up data were obtained. Of 172 patients at the time of screening, 48 suffering from schizophrenia either had or went on to develop Polydipsia; 42 non-polydipsic patients with schizophrenia from the original survey were randomly selected as controls. Primary Polydipsia had a significant negative effect on longevity. The median age at death (age at which 50% of cases have died) was 59 years for polydipsic patients and 68 for non-polydipsic control patients. Adjusting for duration of schizophrenia, smoking, and diagnosis, a patient with Polydipsia had a 74% greater chance of dying before a non-polydipsic patient (a hazard ratio of 2.84 [95% Confidence Interval (CI): 1.22–6.64]). Outcome was worst in patients with severe Polydipsia: the median age at death was 57 years and a patient with severe Polydipsia had a 75% greater chance of dying before a non-polydipsic patient (hazard ratio of 3.36 [95% CI: 1.31–8.60]). When Polydipsia is associated with schizophrenia, mortality is increased in comparison to that in patients with schizophrenia who do not drink water to excess.
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effects of clonidine in schizophrenic patients with Primary Polydipsia three single case studies
Progress in Neuro-psychopharmacology & Biological Psychiatry, 2002Co-Authors: Nicholas J Delva, Emily R Hawken, Anna Chang, Stuart J Lawson, James A OwenAbstract:A pilot study was conducted in schizophrenic patients with Primary Polydipsia to determine the tolerability of adding clonidine to an existing antipsychotic drug regimen and to seek evidence of an antidipsic effect. Three patients with chronic schizophrenia and Primary Polydipsia underwent open controlled prospective trials of treatment with clonidine in doses of up to 800 μg/day. The trials lasted from 2 to 5 months each, and analysis of variance was used to test for changes in dependent variables on a case-by-case basis. Blood pressure and pulse declined significantly in a dose-dependent manner, but fluid intake, as assessed by measurements of weight and 24-h urine volume, was not affected. Hypotension and bradycardia limited the extent to which the dose of clonidine could be increased. The lack of evident effect of clonidine on Polydipsia in this small sample and the inconsistent results of two other recent studies of clonidine in patients with schizophrenia and Primary Polydipsia provide little overall support for the effectiveness of clonidine treatment in Primary Polydipsia associated with schizophrenia.
Emily R Hawken - One of the best experts on this subject based on the ideXlab platform.
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the amphetamine sensitization model of schizophrenia symptoms and its effect on schedule induced Polydipsia in the rat
Psychopharmacology, 2014Co-Authors: Emily R Hawken, Richard J BeningerAbstract:Rationale Amphetamine enhances dopamine (DA) transmission and induces psychotic states or exacerbates psychosis in at-risk individuals. Amphetamine sensitization of the DA system has been proposed as a rodent model of schizophrenia-like symptoms. In humans, excessive nonphysiologic drinking or Primary Polydipsia is significantly associated with a diagnosis of schizophrenia. In rodents, nonphysiologic drinking can be induced by intermittent presentation of food in the presence of a drinking spout to a hungry animal; this phenomenon is termed, “schedule-induced Polydipsia” (SIP).
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identification of Primary Polydipsia in a severe and persistent mental illness outpatient population a prospective observational study
Psychiatry Research-neuroimaging, 2013Co-Authors: Felicia Iftene, Emily R Hawken, Roumen Milev, Christopher Bowie, Ewa Talikowskaszymczak, Desmond Potopsingh, Samia Hanna, Jillian Mulroy, Dianne Groll, Richard MillsonAbstract:Studies to date have only investigated Primary Polydipsia in hospitalized psychiatric patient populations, where rates range from 3% to 25%. The objective of the present study was to determine the occurrence of Primary Polydipsia in a psychiatric outpatient population, and to determine the perceptions of outpatients with self-induced water intoxication regarding reasons for drinking excess fluids, health risks, and insight into their behavior. All 115 psychiatric outpatients from a Community Outreach Program in Kingston, Ontario, were invited to participate in this study. Of these, 89 (77.4%) were enrolled. Data collection included chart reviews, structured interviews, weight measurements, and urine collection. The incidence of Primary Polydipsia was found to be 15.7%. One-half of the polydipsic people presenting with medical complications suggestive for water intoxication had cigarette smoking as a strong correlate. There were interesting answers to the self-induced water intoxication questionnaire. These showed a lack of knowledge related to the normal quantity of fluids necessary daily and about healthy behaviors. Excessive drinking occurs in psychiatric patient populations outside of institutional/ hospital settings. Patients have limited awareness of the severity and possible complications from their problem. Given the prevalence of Polydipsia, more effort should be put into identifying and treating this problem.
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increased drinking following social isolation rearing implications for Polydipsia associated with schizophrenia
PLOS ONE, 2013Co-Authors: Emily R Hawken, Nicholas J Delva, Richard J BeningerAbstract:Primary Polydipsia, excessive drinking without known medical cause, is especially associated with a diagnosis of schizophrenia. We used animal models of schizophrenia-like symptoms to examine the effects on schedule-induced Polydipsia: post-weaning social isolation rearing, subchronic MK-801 treatment (an NMDA-receptor antagonist) or the two combined. Male, Sprague-Dawley rats reared in groups or in isolation beginning at postnatal day 21 were further divided to receive subchronic MK-801 (0.5 mg/kg twice daily) or saline for 7 days beginning on postnatal day 62. Following a 4-day withdrawal period, all groups were trained on a schedule-induced Polydipsia paradigm. Under food-restriction, animals reared in isolation and receiving food pellets at 1-min intervals developed significantly more drinking behavior than those reared with others. The addition of subchronic MK-801 treatment did not significantly augment the amount of water consumed. These findings suggest a predisposition to Polydipsia is a schizophrenia-like behavioral effect of post-weaning social isolation.
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increased schedule induced Polydipsia in the rat following subchronic treatment with mk 801
Schizophrenia Research, 2011Co-Authors: Emily R Hawken, Nicholas J Delva, James N Reynolds, Richard J BeningerAbstract:Primary Polydipsia, defined as excessive fluid intake not explained by medical causes, has been reported to occur in over 20% of chronically ill psychiatric inpatients and is especially common in schizophrenic populations. We tested the hypothesis that in an animal model of schizophrenia-like symptoms (subchronic injections of MK-801, 0.5 mg/kg twice daily for 7 days) an increase in the acquisition of schedule-induced Polydipsia (SIP) will occur. Young adult, male rats acquired SIP when food-restricted and placed on a non-contingent fixed-time 1-min food schedule. In comparison with saline-treated control animals, subchronic MK-801 treatment significantly increased SIP. These findings suggest an animal model of Polydipsia associated with schizophrenia in humans.
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mortality over a 20 year period in patients with Primary Polydipsia associated with schizophrenia a retrospective study
Schizophrenia Research, 2009Co-Authors: Emily R Hawken, Jake M Crookall, Deirdre Reddick, Richard Millson, Roumen Milev, Nicholas J DelvaAbstract:Abstract Primary Polydipsia, excessive fluid intake without medical cause, is present in over 20% of seriously and persistently ill psychiatric inpatients. The long-term effects of Primary Polydipsia on longevity have not previously been examined. Inpatients in a psychiatric hospital were screened for Polydipsia in 1985. Those identified to be polydipsic, the majority of whom suffered from schizophrenia, were re-evaluated in 2005 and compared with a control group of non-polydipsic patients. Chart reviews were conducted and follow-up data were obtained. Of 172 patients at the time of screening, 48 suffering from schizophrenia either had or went on to develop Polydipsia; 42 non-polydipsic patients with schizophrenia from the original survey were randomly selected as controls. Primary Polydipsia had a significant negative effect on longevity. The median age at death (age at which 50% of cases have died) was 59 years for polydipsic patients and 68 for non-polydipsic control patients. Adjusting for duration of schizophrenia, smoking, and diagnosis, a patient with Polydipsia had a 74% greater chance of dying before a non-polydipsic patient (a hazard ratio of 2.84 [95% Confidence Interval (CI): 1.22–6.64]). Outcome was worst in patients with severe Polydipsia: the median age at death was 57 years and a patient with severe Polydipsia had a 75% greater chance of dying before a non-polydipsic patient (hazard ratio of 3.36 [95% CI: 1.31–8.60]). When Polydipsia is associated with schizophrenia, mortality is increased in comparison to that in patients with schizophrenia who do not drink water to excess.
Bettina Winzeler - One of the best experts on this subject based on the ideXlab platform.
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glp1 receptor agonists reduce fluid intake in Primary Polydipsia
Journal of the Endocrine Society, 2021Co-Authors: Bettina Winzeler, Julie Refardt, Clara O Sailer, David Coynel, Vogt Deborah, Zanchi Davide, Sandrine Andrea Urwyler, Mirjam ChristcrainAbstract:Background Primary Polydipsia, characterized by excessive fluid intake, carries the risk of water intoxication and hyponatremia, but treatment options are scarce. Glucagon-like peptide-1 (GLP-1) reduces appetite and food intake. In experimental models, they also play a role in thirst and drinking behavior in. The aim of this trial was to investigate whether GLP-1 receptor agonists reduce fluid intake in patients with Primary Polydipsia. Methods: In this randomized, double-blind, placebo-controlled, 3-week crossover-trial, 34 patients with Primary Polydipsia received weekly dulaglutide (Trulicity®) 1.5mg and placebo (0.9% sodium chloride). During the last treatment week, patients attended an 8-hour evaluation visit with free water access. The Primary endpoint was total fluid intake during the evaluation visits. The treatment effect was estimated using a linear mixed-effects model. In a subset of 15 patients and matched controls, thirst perception and neuronal activity in response to beverage pictures were assessed by functional MRI. Results Median [IQR] total fluid intake was 2250ml [1600-2600] on dulaglutide versus 2400ml [1850-3400] on placebo. Patients on dulaglutide reduced fluid intake by 490ml [95%-CI -780, -199], p=0.002, corresponding to a relative reduction of 17%. 24-hour urinary output was reduced by -943ml [95%-CI -1473, -413]. Thirst perception in response to beverage pictures was higher in patients with Primary Polydipsia versus controls and lower on dulaglutide versus placebo, but functional neuronal activity was similar between groups and treatments. Conclusion: GLP-1 receptor agonists reduce fluid intake and thirst perception in patients with Primary Polydipsia and could therefore be a novel treatment option for these patients.
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arginine stimulated copeptin measurements in the differential diagnosis of diabetes insipidus a prospective diagnostic study
The Lancet, 2019Co-Authors: Bettina Winzeler, Julie Refardt, Clara O Sailer, Nicole Cesananigro, Deborah R Vogt, Cornelia Imber, Benedict Morin, Milica Popovic, Michelle Steinmetz, Gabor SzinnaiAbstract:Summary Background Differential diagnosis of diabetes insipidus is challenging. The most reliable approach is hypertonic saline-stimulated copeptin measurements. However, this test is based on the induction of hypernatraemia and requires close monitoring of plasma sodium concentrations. Arginine-stimulated copeptin measurements might provide an alternative, simple, and safe test. Methods In this prospective diagnostic study, we recruited a development cohort from University Hospital Basel, Basel, Switzerland, and a validation cohort from five centres in Basel, Aarau, Luzern, Bern, and St Gallen, Switzerland, and the University Hospital Wurzburg, Wurzburg, Germany. For both cohorts, patients were eligible for inclusion if they were aged 18 years or older, were newly referred with polyuria (>50 mL/kg bodyweight per day) or had a known diagnosis of central diabetes insipidus or Primary Polydipsia. We also recruited a comparator cohort of healthy controls in parallel to each cohort, comprising adults (aged 18 years and older, with normal drinking habits, and no history of polyuria) and children who underwent arginine stimulation to diagnose growth hormone deficiency (children were only included in the comparator cohort to the development cohort as proof of concept). Patients and healthy controls underwent arginine stimulation with measurement of plasma copeptin at baseline and 30, 45, 60, 90, and 120 min. The Primary objective in the development cohort was to determine the diagnostic accuracy of plasma copeptin concentrations to discriminate between diabetes insipidus and Primary Polydipsia, and in the validation cohort was to confirm those results. Adverse effects of the test were monitored in all participants, with tolerability of the test rated using a visual analogue scale (VAS) that ranged from no (0) to maximum (10) discomfort. This trial is registered with ClinicalTrials.gov, number NCT00757276. Findings Between May 24, 2013, and Jan 11, 2017, 52 patients were enrolled in the development cohort (12 [23%] with complete diabetes insipidus, nine [17%] with partial diabetes insipidus, and 31 [60%] with Primary Polydipsia) alongside 20 healthy adults and 42 child controls. Between Oct 24, 2017, and June 27, 2018, 46 patients were enrolled in the validation cohort (12 [26%] with complete diabetes insipidus, seven [15%] with partial diabetes insipidus, and 27 [59%] with Primary Polydipsia) alongside 30 healthy adult controls (two patients in this cohort were excluded from the main analysis because of early vomiting during the test). In the pooled patient and control datasets, median arginine-stimulated copeptin concentrations increased in healthy adult controls (from 5·2 pM [IQR 3·3–10·9] to a maximum of 9·8 pM [6·4–19·6]) and in participants with Primary Polydipsia (from 3·6 pM [IQR 2·4–5·7] to a maximum of 7·9 pM [5·1–11·8]), but only minimally in those with diabetes insipidus (2·1 pM [IQR 1·9–2·7] to a maximum of 2·5 pM [1·9–3·1]). In the development cohort, a cutoff of 3·5 pM at 60 min provided the highest diagnostic accuracy of 94% (95% CI 84–98). The accuracy of this cutoff in the validation cohort was 86% (95% CI 73–94). By pooling the data from both cohorts, an optimal accuracy of 93% (95% CI 86–97) was reached at a cutoff of 3·8 pM copeptin at 60 min (sensitivity 93%, 95% CI 86–98; specificity 92%, 95% CI 84–100). The test was safe and well tolerated, with median VAS scores of 3·5 (IQR 2–4) in patients with diabetes insipidus, 3 (2–4) in those with Primary Polydipsia, 1 (1–3) in healthy adults, and 1 (0–5) in healthy children in the pooled participant dataset. Interpretation Arginine-stimulated copeptin measurements are an innovative test for diabetes insipidus with high diagnostic accuracy, and could be a simplified, novel, and safe diagnostic approach to diabetes insipidus in clinical practice. Funding Swiss National Science Foundation and University Hospital Basel.
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Copeptin and its role in the diagnosis of diabetes insipidus and the syndrome of inappropriate antidiuresis.
Clinical Endocrinology, 2019Co-Authors: Julie Refardt, Bettina Winzeler, Mirjam Christ-crainAbstract:Copeptin is secreted in an equimolar amount to arginine vasopressin (AVP) but can easily be measured in plasma or serum with a sandwich immunoassay. The main stimuli for copeptin are similar to AVP, that is an increase in osmolality and a decrease in arterial blood volume and pressure. A high correlation between copeptin and AVP has been shown. Accordingly, copeptin mirrors the amount of AVP in the circulation. Copeptin has, therefore, been evaluated as diagnostic biomarker in vasopressin-dependent disorders of body fluid homeostasis. Disorders of body fluid homeostasis are common and can be divided into hyper- and hypoosmolar circumstances: the classical hyperosmolar disorder is diabetes insipidus, while the most common hypoosmolar disorder is the syndrome of inappropriate antidiuresis (SIAD). Copeptin measurement has led to a "revival" of the direct test in the differential diagnosis of diabetes insipidus. Baseline copeptin levels, without prior thirsting, unequivocally identify patients with nephrogenic diabetes insipidus. In contrast, for the difficult differentiation between central diabetes insipidus and Primary Polydipsia, a stimulated copeptin level of 4.9 pmol/L upon hypertonic saline infusion differentiates these two entities with a high diagnostic accuracy and is clearly superior to the classical water deprivation test. On the contrary, in the SIAD, copeptin measurement is of only little diagnostic value. Copeptin levels widely overlap in patients with hyponatraemia and emphasize the heterogeneity of the disease. Additionally, a variety of factors lead to unspecific copeptin elevations in the acute setting further complicating its interpretation. The broad use of copeptin as diagnostic marker in hyponatraemia and specifically to detect cancer-related disease in SIADH patients can, therefore, not be recommended.
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Primary Polydipsia in the medical and psychiatric patient characteristics complications and therapy
Swiss Medical Weekly, 2017Co-Authors: Clara O Sailer, Bettina Winzeler, Mirjam ChristcrainAbstract:With the increasing popularity of lifestyle programmes and the common perception that consuming several litres of fluid per day is healthy, the prevalence of Primary Polydipsia is increasing, particularly outside of the psychiatric setting.
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Primary Polydipsia in the medical and psychiatric patient characteristics complications and therapy
Swiss Medical Weekly, 2017Co-Authors: Clara O Sailer, Bettina Winzeler, Mirjam ChristcrainAbstract:Primary Polydipsia (PP) has been defined as excessive intake of fluids. However, the pathogenesis of PP remains unexplored. Different theories include a dysfunction in the thirst mechanism, involvement of the hippocampus, stress-reducing behaviour and lesion occurrences in specific areas of the brain. Most studies have been performed in the psychiatric setting, indicating that PP coincides with schizophrenia, anxiety disorder and depression. However, an increasing number of case reports emphasise the incidence of PP in non-psychiatric patients. As often recommended by healthcare professions and in life-style programmes, the phenomenon of excessive fluid intake appears to be growing, especially in health-conscious and active people. PP is part of the polyuria-Polydipsia syndrome, so the differential diagnosis diabetes insipidus (central or nephrogenic) must be excluded. The gold standard when differentiating between these disorders has been the water deprivation test. However, new options for distinguishing between these entities have been proposed e.g., measurement of copeptin, a reliable surrogate marker of the hormone arginine vasopressin (AVP). The major risk of excessive drinking is the development of hyponatraemia and the ensuing complications. In patients with PP, factors reducing the renal excretory capacity of the kidney such as acute illness, medications or low solute intake may accumulate in hyponatraemia. Treatment options for PP remain scarce. Different medication and behavioural therapy have been investigated, but never on a large scale and rarely in non-psychiatric patients. This review provides an overview of the pathophysiology, characteristics, complications, and outcomes of patients with PP in the medical and psychiatric patient.
Richard J Beninger - One of the best experts on this subject based on the ideXlab platform.
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the amphetamine sensitization model of schizophrenia symptoms and its effect on schedule induced Polydipsia in the rat
Psychopharmacology, 2014Co-Authors: Emily R Hawken, Richard J BeningerAbstract:Rationale Amphetamine enhances dopamine (DA) transmission and induces psychotic states or exacerbates psychosis in at-risk individuals. Amphetamine sensitization of the DA system has been proposed as a rodent model of schizophrenia-like symptoms. In humans, excessive nonphysiologic drinking or Primary Polydipsia is significantly associated with a diagnosis of schizophrenia. In rodents, nonphysiologic drinking can be induced by intermittent presentation of food in the presence of a drinking spout to a hungry animal; this phenomenon is termed, “schedule-induced Polydipsia” (SIP).
-
increased drinking following social isolation rearing implications for Polydipsia associated with schizophrenia
PLOS ONE, 2013Co-Authors: Emily R Hawken, Nicholas J Delva, Richard J BeningerAbstract:Primary Polydipsia, excessive drinking without known medical cause, is especially associated with a diagnosis of schizophrenia. We used animal models of schizophrenia-like symptoms to examine the effects on schedule-induced Polydipsia: post-weaning social isolation rearing, subchronic MK-801 treatment (an NMDA-receptor antagonist) or the two combined. Male, Sprague-Dawley rats reared in groups or in isolation beginning at postnatal day 21 were further divided to receive subchronic MK-801 (0.5 mg/kg twice daily) or saline for 7 days beginning on postnatal day 62. Following a 4-day withdrawal period, all groups were trained on a schedule-induced Polydipsia paradigm. Under food-restriction, animals reared in isolation and receiving food pellets at 1-min intervals developed significantly more drinking behavior than those reared with others. The addition of subchronic MK-801 treatment did not significantly augment the amount of water consumed. These findings suggest a predisposition to Polydipsia is a schizophrenia-like behavioral effect of post-weaning social isolation.
-
increased schedule induced Polydipsia in the rat following subchronic treatment with mk 801
Schizophrenia Research, 2011Co-Authors: Emily R Hawken, Nicholas J Delva, James N Reynolds, Richard J BeningerAbstract:Primary Polydipsia, defined as excessive fluid intake not explained by medical causes, has been reported to occur in over 20% of chronically ill psychiatric inpatients and is especially common in schizophrenic populations. We tested the hypothesis that in an animal model of schizophrenia-like symptoms (subchronic injections of MK-801, 0.5 mg/kg twice daily for 7 days) an increase in the acquisition of schedule-induced Polydipsia (SIP) will occur. Young adult, male rats acquired SIP when food-restricted and placed on a non-contingent fixed-time 1-min food schedule. In comparison with saline-treated control animals, subchronic MK-801 treatment significantly increased SIP. These findings suggest an animal model of Polydipsia associated with schizophrenia in humans.