Psychopathological characteristics in patients with arginine vasopressin deficiency (central diabetes insipidus) and primary polydipsia compared to healthy controls.

OBJECTIVE: Distinguishing arginine vasopressin deficiency (AVP-D; central diabetes insipidus) from primary polydipsia (PP), commonly referred to as psychogenic polydipsia, is challenging. Psychopathologic findings, commonly used for PP diagnosis in clinical practice, are rarely evaluated in AVP-D patients, and no comparative data between the two conditions currently exist. DESIGN: Data from two studies involving 82 participants [39 AVP-D, 28 PP, and 15 healthy controls (HC)]. METHODS: Psychological evaluations were conducted using standardized questionnaires measuring anxiety [State-Trait Anxiety Inventory (STAI)], alexithymia [Toronto Alexithymia Scale (TAS-20)], depressive symptoms (Beck's Depression Inventory-II (BDI-II), and overall mental health [Short Form-36 Health Survey (SF-36)]. Higher STAI, TAS-20, and BDI-II scores suggest elevated anxiety, alexithymia, and depression, while higher SF-36 scores signify better overall mental health. RESULTS: Compared to HC, patients with AVP-D and PP showed higher levels of anxiety (HC 28 points [24-31] vs AVP-D 36 points [31-45]; vs PP 38 points [33-46], P < .01), alexithymia (HC 30 points [29-37] vs AVP-D 43 points [35-54]; vs PP 46 points [37-55], P < .01), and depression (HC 1 point [0-2] vs AVP-D 7 points [4-14]; vs PP 7 points [3-13], P < .01). Levels of anxiety, alexithymia, and depression showed no difference between both patient groups (P = .58, P = .90, P = .50, respectively). Compared to HC, patients with AVP-D and PP reported similarly reduced self-reported overall mental health scores (HC 84 [68-88] vs AVP-D 60 [52-80], P = .05; vs PP 60 [47-74], P < .01). CONCLUSION: This study reveals heightened anxiety, alexithymia, depression, and diminished overall mental health in patients with AVP-D and PP. The results emphasize the need for careful interpretation of psychopathological characteristics to differentiate between AVP-D and PP.

A randomized controlled trial of the GLP-1 receptor agonist dulaglutide in primary polydipsia.

BackgroundPrimary 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, GLP-1 has also been shown to play a role in thirst and drinking behavior. The aim of this trial was to investigate whether GLP-1 receptor agonists reduce fluid intake in patients with primary polydipsia.MethodsIn this randomized, double-blind, placebo-controlled, 3-week crossover trial, 34 patients with primary polydipsia received weekly dulaglutide (1.5 mg, Trulicity) in one treatment segment and placebo (0.9% sodium chloride) in the other. During the last treatment week, patients attended an 8-hour evaluation visit with free access to water. The primary endpoint was total fluid intake during the evaluation visits. Treatment effects were estimated using linear mixed-effects models. In a subset of 15 patients and an additional 15 matched controls, thirst perception and neuronal activity in response to beverage pictures were assessed by functional MRI.RESULTsPatients on dulaglutide reduced their fluid intake by 490 mL (95% CI: -780, -199; P = 0.002), from 2950 mL (95% CI: 2435, 3465) on placebo to 2460 mL (95% CI: 1946, 2475) on dulaglutide (model estimates), corresponding to a relative reduction of 17%. Twenty-four-hour urinary output was reduced by -943 mL (95% CI: -1473, -413; P = 0.001). Thirst perception in response to beverage pictures was higher for patients with primary polydipsia than for controls, and lower for patients on dulaglutide versus placebo, but functional activity was similar among groups and treatments.CONCLUSIONSGLP-1 receptor agonists reduce fluid intake and thirst perception in patients with primary polydipsia and could therefore be a treatment option for these patients.Trial registrationClinicaltrials.gov NCT02770885.FundingSwiss National Science Foundation (grant 32473B_162608); University Hospital and University of Basel; Young Talents in Clinical Research grant from the Swiss Academy of Medical Sciences and the Gottfried & Julia Bangerter-Rhyner Foundation; Top-up Grant from the PhD Programme in Health Sciences, University of Basel.

Do psychoactive drugs have a therapeutic role in compulsivity? Studies on schedule-induced polydipsia.

RATIONALE: Clinical studies have shown that some psychoactive recreational drugs have therapeutic applications in anxiety, depression, and schizophrenia. However, to date, there are few studies on the therapeutic potential efficacy of recreational drugs in compulsive neuropsychiatric disorders. OBJECTIVES: We explored the therapeutic potential of different psychoactive and psychedelic drugs in a preclinical model of compulsive behavior. METHODS: Outbred male Wistar rats were selected as either high (HD) or low (LD) drinkers according to their behavior in schedule-induced polydipsia (SIP). Subsequently, we assessed the effects of acute administration of scopolamine (0.125, 0.25, and 0.5 mg/kg), methamphetamine (0.25, 0.5, 1.25, and 2.5 mg/kg), ketamine (1.25, 2.5, 5, and 10 mg/kg), cannabidiol (1 and 3 mg/kg), WIN21255-2 (0.5, 075, and 1 mg/kg), and AM404 (0.25 and 0.5 mg/kg) on compulsive drinking in SIP. RESULTS: Scopolamine reduced dose-dependent compulsive drinking in HD compared with LD rats in SIP. Methamphetamine induced a dose-dependent inverted U-curve effect in both groups, in which lower doses increased and higher doses reduced compulsive drinking in SIP. Ketamine, cannabidiol, WIN21255-2, and AM404 did not have any relevant effects in SIP. CONCLUSIONS: These data provide new evidence that low doses of scopolamine and intermediate doses of methamphetamine might therapeutically reduce compulsive behaviors and suggest that there is not a direct participation of the endocannabinoid system in compulsive behavior on SIP. The research in the underlying neurochemical mechanisms of these psychoactive drugs might provide an additional insight on new therapeutic targets in compulsive neuropsychiatric disorders.

Managing hyponatraemia secondary to primary polydipsia: beware too rapid correction of hyponatraemia.

We describe three cases of severe hyponatraemia in the setting of primary polydipsia that were managed in our centre in 2016. Despite receiving different solute loads, large volume diuresis and rapid correction of serum sodium occurred in all cases. Given the potentially catastrophic consequence of osmotic demyelination, we highlight the judicious use of desmopressin and hypotonic fluid infusion to mitigate sodium overcorrection in this setting.

Effects of diet quality on vulnerability to mild subchronic social defeat stress in mice.

OBJECTIVES: The chronic social defeat stress (CSDS) mouse model is a potentially useful system for understanding stress responses to social environments. We previously developed a mouse model of subchronic and mild social defeat stress (sCSDS) that exhibits increased body weight gain and food intake following polydipsia-like features. sCSDS mice also show avoidance behavior in a social interaction test. In this study, we examined the effects of diet quality on susceptibility to sCSDS by feeding these mice semi- and non-purified diets. METHODS: Male C57BL/6J (B6; n = 82) mice were exposed to sCSDS using male ICR mice. The B6 mice were divided into four test groups: semi-purified pellet diet + sCSDS, non-purified pellet diet + sCSDS, semi-purified diet + control (no sCSDS), and non-purified diet + control. RESULTS: Although increased body weight, and food and water intake following sCSDS exposure were consistently observed in the groups that were fed semi- and non-purified diets, social avoidance behavior was influenced by food type (i.e., sCSDS mice fed semi-purified diet showed the greatest social avoidance behavior). In addition, the rates of stress susceptibility were estimated at 73.9 and 34.8% in sCSDS mice fed semi-purified and non-purified diets, respectively (P < 0.05). For comparison, the susceptible-like phenotype rates were estimated at 12.5 and 8.3% in healthy control mice fed semi-purified and non-purified diets, respectively. DISCUSSION: These results suggest that diet quality affects the vulnerability of mice to social defeat stress.

Psychogenic polydipsia, hyponatremia and osmotic myelinolysis.

OBJECTIVE: Description of a case of osmotic myelinolysis associated with hyponatremia produced as a consequence of compulsive water drinking. METHOD: Case report and review of relevant literature. RESULTS: Compulsive water drinking or psychogenic polydipsia is a common cause of hyponatremia among individuals with chronic mental illness. Central pontine myelinolysis and extrapontine myelinolysis are serious neurological complications resulting from rapid correction of serum sodium and associated changes in serum osmolality. A case of extrapontine myelinolysis confirmed by characteristic MRI findings following an episode of extreme hyponatremia caused by psychogenic polydipsia is described involving a patient with an adult lifelong history of chronic mental illness diagnosed as schizoaffective disorder. With supportive care the related cognitive deficits and balance difficulties resolved completely. CONCLUSIONS: Clinicians should be aware of the potential for hyponatremia resulting from compulsive water drinking to cause myelinolysis with delayed development of cognitive and gait symptoms that responds to supportive care if identified early.

[Fatal aspiration following polydipsia in schizophrenia]. / Polydipsie bei paranoider schizophrenie mit tödlichem ausgang.

OBJECTIVE AND METHODS: Polydipsia with hyponatraemia commonly occurs with chronic psychosis and is associated with a reduced life expectancy for individuals diagnosed with schizophrenia. We describe a 51 years old man who presented with polydipsia during a relapse of paranoid schizophrenia. While treated with Clozapine, and despite regular observation and daily control of creatinine and electrolytes, the man suddenly collapsed and died after drinking huge amounts of water. No sedation from psychotropic medication or drugs and alcohol was present in this case. Sodium levels on the day of death and the day before were within normal range. A post-mortem revealed aspiration of water and gastric content as the cause of asphyxiation and death. A literature search in Medline and Embase did not yield a description of a similar case. RESULTS AND CONCLUSIONS: This case highlights the risk of aspiration associated with polydipsia in chronic schizophrenia. Daily control of electrolytes to identify hyponatremia and regular observation are recommended but may not be sufficient to prevent sudden death from drinking huge amounts of water.