pituitrin and Schizophrenia

Oxytocin and vasopressin share a similar chemical structure but have different functions. Both hormones are produced in different brain areas, are transported through the hypophyseal portal system, pass to the anterior hypophysis, and released to reach their target organs. These hormones also act as neuromodulators, where its receptors are found in the lateral septum, the middle amygdala, the hippocampus, the hypothalamus, and the brain stem. These brain structures regulate socio-sexual behaviors in vertebrates. Moreover, the oxytocinergic and the vasopressin systems are sexually different. The sexual steroids promote oxytocin release and the oxytocin receptor synthesis, as well as promoting or inhibiting vasopressin release and its receptor genetic transcription. Both neuropeptides are involved in social recognition, male-female pair bonding, aggression, and cognition. Furthermore, the disruption or malfunctioning of the oxytocin and vasopressin systems adds to the causes of some psychiatric disorders like depression, schizophrenia, autism, and borderline personality.. La oxitocina y la vasopresina son similares en estructura química, pero difieren en sus funciones. Ambas se producen en diversas áreas del cerebro, se transportan a través del sistema porta hipofisario a la hipófisis anterior y se distribuyen a sus órganos blanco actuando como hormonas. Estas fungen también como neurorreguladores, con receptores dispersos en el septum lateral, la amígdala central, el hipocampo, el hipotálamo y el tronco encefálico, estructuras asociadas a la conducta sociosexual en todos los vertebrados. Los sistemas vasopresinérgico y oxitocinérgico difieren entre los cerebros femenino y masculino. Aunado a esto, los esteroides sexuales intervienen en la expresión de los genes para oxitocina, la síntesis de sus receptores y su liberación. Además, promueven o inhiben la transcripción de los genes para vasopresina. Ambos neuropéptidos participan en el reconocimiento social, el vínculo de pareja, la cognición y la agresión. La disrupción de los sistemas de estos neuromoduladores se suma a las causas de algunos desórdenes psiquiátricos, como la depresión, la esquizofrenia, el autismo y la personalidad limítrofe. Esta revisión está enfocada a describir las diferencias entre géneros, tanto de la síntesis, como la distribución de los receptores y los efectos que generan la oxitocina y la vasopresina en la conducta para comprender la prevalencia, la sintomatología y la respuesta a los tratamientos a dichas patologías.

Topics: Animals; Brain; Female; Humans; Male; Oxytocin; Schizophrenia; Vasopressins

Although the neurohypophyseal hormones vasopressin (VP) and oxytocin (OT) are mostly known for their role respectively in antidiuresis, and in labour, lactation and maternal behavior, both might exert widespread influences either on emotion and cognition in healthy subjects, showing some gender-related differences. They interact with each other facilitating shifts between positive socially- oriented and defensive states. In fact, VP amplifies the reactivity to stressors showing also beneficial effects on attention, verbal learning as well as memory, whereas OT reduces the amplitude of the stress response, improves emotion processing, and can play a negative effect on memory and verbal learning in healthy individuals. Several data indicate the possible involvement of these neuropeptides in the pathophysiology of psychiatric conditions involving social interactions, such as autism, as well as in schizophrenia and depression. The aim of this paper is to review the literature relating to the role played by neurohypophyseal hormones in neuropsychiatric disorders.. We analyzed the best of published literature dealing with the relationships between neurohypophyseal hormones and neuropsychiatric conditions like autism (AD), major depressive disorder (MDD), bipolar disorder (BD) and schozophrenia, identifying keywords and MeSH terms in Pubmed and then searching them. The last search was performed on December 2017.. Several studies indicate a role played by OT and VP in AD, schizophrenia, MDD and BD. Even if conflicting data have been reported, several mechanisms may be involved in these behavioral diseases, such as differences in aminoacid sequence and peptide biological activity, neurotransmission and genetic disorders involving OT and VP receptors.. The involvment of VP and OT in neurpopsychiatric disorders can support a possible beneficial therapy with OT or with VP antagonists. The target may be obtained using effective drug delivery methods as well as the association with other drugs.

Topics: Affect; Animals; Autism Spectrum Disorder; Bipolar Disorder; Depressive Disorder, Major; Humans; Mental Disorders; Oxytocin; Pituitary Gland, Posterior; Schizophrenia; Schizophrenic Psychology; Signal Transduction; Vasopressins

The motivation to engage in social behaviors is influenced by past experience and internal state, but also depends on the behavior of other animals. Across species, the oxytocin (Oxt) and vasopressin (Avp) systems have consistently been linked to the modulation of motivated social behaviors. However, how they interact with other systems, such as the mesolimbic dopamine system, remains understudied. Further, while the neurobiological mechanisms that regulate prosocial/cooperative behaviors have been extensively examined, far less is understood about competitive behaviors, particularly in females. In this chapter, we highlight the specific contributions of Oxt and Avp to several cooperative and competitive behaviors and discuss their relevance to the concept of social motivation across species, including humans. Further, we discuss the implications for neuropsychiatric diseases and suggest future areas of investigation.

Topics: Aggression; Animals; Autism Spectrum Disorder; Behavior, Animal; Brain; Competitive Behavior; Cooperative Behavior; Dopamine; Female; Humans; Mental Disorders; Motivation; Oxytocin; Pair Bond; Personality Disorders; Schizophrenia; Schizophrenic Psychology; Social Behavior; Stress Disorders, Post-Traumatic; Vasopressins

Vasopressin is a neuropeptide with multiple functions. In addition to its predominantly antidiuretic action after peripheral secretion from the posterior pituitary, it seems to fulfill--together with its receptor subtype--all requirements for a neuropeptide system critically involved in higher brain functions, including cognitive abilities and emotionality. Following somatodendritic and axonal release in distinct brain areas, vasopressin acts as a neuromodulator and neurotransmitter in multiple and varying modes of interneuronal communication. Accordingly, changes in vasopressin expression and release patterns may have wide-spread consequences. As shown in mice, rats, voles, and humans, central vasopressin release along a continuum may be beneficial to the individual, serving to adjust physiology and behavior in stressful scenarios, possibly at the potential expense of increasing susceptibility to disease. Indeed, if over-expressed and over-released, it may contribute to hyper-anxiety and depression-like behaviors. A vasopressin deficit, in turn, may cause signs of both diabetes insipidus and total hypo-anxiety. The identification of genetic polymorphisms underlying these phenomena does not only explain individual variation in social memory and emotionality, but also help to characterize potential targets for therapeutic interventions. The capability of both responding to stressful stimuli and mediating genetic polymorphisms makes the vasopressin system a key mediator for converging (i.e., environmentally and genetically driven) behavioral regulation.

Topics: Animals; Autistic Disorder; Brain; Diabetes Insipidus; Emotions; Humans; Mental Disorders; Polymorphism, Genetic; Schizophrenia; Social Behavior; Vasopressins

The amygdala is a complex structure playing primary role in the processing and memorizing of emotional reactions. The amygdalae send impulses to the hypothalamus for activation of the sympathetic nervous system, to the reticular nucleus for increasing reflexes, to the nuclei of the trigeminal nerve and facial nerve for facial expressions of fear, and to the ventral tegmental area, locus coeruleus, and laterodorsal tegmental nucleus for activation of dopamine, norepinephrine and epinephrine release. The amygdala plays a key role in what has been called the "general-purpose defense response control network" and reacts in response to unpleasant sights, sensations, or smells. Anger, avoidance, and defensiveness are emotions activated largely by the amygdale. The amygdala is responsible for activating ancestral signs of distress such as "tense-mouth" and defensive postures such as crouching. Poor functioning of amygdala has also been associated with anxiety, autism, depression, narcolepsy, post-traumatic stress disorder, phobias, frontotemporal dementia, and schizophrenia. Impairment of emotional event memory in patients with Alzheimer's disease also correlates with the intensity of amygdalar damage. All these events speak out for the importance to preserve the normal function of the amygdala which can only be achieved by constant deepening of our knowledge about this unique structure.

Topics: Alzheimer Disease; Amygdala; Anxiety Disorders; Autistic Disorder; Corticotropin-Releasing Hormone; Dementia; Emotions; gamma-Aminobutyric Acid; Humans; Neurotransmitter Agents; Oxytocin; Schizophrenia; Vasopressins

The hippocampal formation (HF) is one of the brain structures most consistently altered in schizophrenia, yet the contribution of HF pathology to severe mental illness is poorly understood. We present evidence that our current ignorance is attributable to the fact that the anterior HF is heavily involved in schizophrenia but has been inadequately examined by schizophrenia investigators. We propose that the anterior HF in humans, and its counterpart in rodents (ventral HF), constrain diverse responses to psychological stimuli and that disruption of this function contributes to schizophrenia. While current data suggest that hallmark symptoms of schizophrenia most likely result from the role of the anterior HF in the integrated neurocircuit that includes the prefrontal cortex, ventral striatum, and ventral tegmental area, better characterized and phylogenetically preserved neurocircuits may be similarly affected by anterior HF pathology and account for associated findings of the disorder. We propose that focusing on the impact of ventral HF pathology on these simpler circuits and functions in rodents may provide insight into the pathophysiology of severe mental illness in humans. We review several associated findings in schizophrenia to assess the likelihood that each could be a product of this putative anterior HF dysfunction and could therefore be productively studied in rodents by probing ventral HF function.

Topics: Galvanic Skin Response; Heart Rate; Hippocampus; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Schizophrenia; Stereotyped Behavior; Stress, Psychological; Vasopressins

The study of psychoneuroendocrinology of schizophrenia has yielded an extensive but inconclusive body of data. Investigations to date have been limited by several factors, including the confounding effects of neuroleptic drugs, methodological limitations, and lack of appreciation for the heterogeneity of the illness. Previously, the focus of research has been on the measurement of anterior pituitary hormones, guided by the assumptions that these hormones are regulated by the central nervous system (CNS) to a significant degree and that the unique anatomic relationship of the pituitary gland to the hypothalamus and the CNS is potentially relevant. Patients with schizophrenia do appear to have distinct endocrinologic profiles. However, although the hormonal differences between patients with schizophrenia and the general population appear to be subtle in magnitude. Nonetheless, investigation, and the exploration of the possible effect of gonadal and posterior pituitary hormones merits particular attention.

Topics: Adrenocorticotropic Hormone; Gonadal Steroid Hormones; Growth Hormone-Releasing Hormone; Human Growth Hormone; Humans; Hydrocortisone; Prolactin; Schizophrenia; Schizophrenic Psychology; Vasopressins

Thirst and drinking are essential components of normal osmoregulation in healthy man. Abnormalities of thirst appreciation, in particular hypodipsia, have profound implications for water homeostasis. The combination of cranial diabetes insipidus and hypodipsia can have particularly serious consequences, with the potential for life-threatening hyponatraemia. Although the tools for measuring thirst are subjective and lack true specificity, their use in clinical research has contributed greatly to our understanding of the physiology of thirst appreciation and the abnormal control of thirst in osmoregulatory disorders. The precise neural control of thirst appreciation remains unknown, and perhaps as a result of this, satisfactory therapies for the treatment of disorders of thirst have not yet been developed; behavioural modification and retraining of drinking habits remain the rather limited cornerstones of management.

Topics: Adult; Aged; Aging; Brain Neoplasms; Diabetes Insipidus; Diabetes Mellitus; Drinking; Humans; Inappropriate ADH Syndrome; Middle Aged; Schizophrenia; Thirst; Vasopressins; Water-Electrolyte Balance

A 31-year-old woman with untreated chronic schizophrenia developed extreme polydipsia which rapidly led to coma and death due to cerebral edema. Hyponatremia (120 mEq/liter) and serum hypo-osmolality (260 mOsm/kg) were associated with marked polyuria (up to 1850 ml/hour) and appropriately low urinary osmolality (90 mOsm/kg) which responded to treatment. This case and few qualifying previous reports which are reviewed support the possibility that pure self-induced water intoxication with no major contribution of inadequate release of antidiuretic hormone may occur, and that extreme polydipsia can sometimes overwhelm normal renal diluting capacity in psychotic patients.

Topics: Adult; Drinking; Female; Humans; Osmolar Concentration; Schizophrenia; Vasopressins; Water Intoxication

Topics: Animals; Anticonvulsants; Antipsychotic Agents; Depressive Disorder; Drug Therapy, Combination; Endorphins; Enkephalins; Humans; Mental Disorders; Naloxone; Naltrexone; Nerve Tissue Proteins; Pituitary Hormones; Psychotropic Drugs; Schizophrenia; Substance-Related Disorders; Vasopressins

Topics: Aged; Alzheimer Disease; Animals; Brain; Cholecystokinin; Depressive Disorder; Endorphins; Female; Humans; Male; Mental Disorders; Middle Aged; Nerve Tissue Proteins; Neurotransmitter Agents; Schizophrenia; Substance P; Vasopressins

Topics: Acupuncture Therapy; Adrenocorticotropic Hormone; Animals; Endorphins; Enkephalins; Gonadotropin-Releasing Hormone; Humans; Hypothalamic Hormones; Melanocyte-Stimulating Hormones; MSH Release-Inhibiting Hormone; Peptides; Pituitary Hormones; Rats; Schizophrenia; Somatostatin; Thyrotropin-Releasing Hormone; Vasopressins

Topics: Adrenocorticotropic Hormone; Aged; Amnesia; Brain; Contingent Negative Variation; Cyclic AMP; Electroencephalography; Humans; Male; Memory; Mental Disorders; Middle Aged; Myelin Sheath; Neurotransmitter Agents; Phosphorylation; Pituitary Hormones; Prostaglandins; Schizophrenia; Vasopressins

Topics: Animals; Hormones; Humans; Memory; Nerve Tissue Proteins; Nervous System Physiological Phenomena; Neurology; Neuropeptides; Psychiatry; Research; Schizophrenia; Stress, Psychological; Vasopressins

Topics: Adrenocorticotropic Hormone; Animals; Cortisone; Electroconvulsive Therapy; Endocrine System Diseases; Hormones; Humans; Learning; Memory; Mental Disorders; MSH Release-Inhibiting Hormone; Nerve Tissue Proteins; Peptides; Psychoses, Substance-Induced; Psychotropic Drugs; Schizophrenia; Somatomedins; Somatostatin; Steroids; Substance P; Thyrotropin; Vasopressins

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.

Topics: Administration, Intranasal; Adolescent; Adult; Blood Pressure; Cross-Over Studies; Double-Blind Method; Eating; Female; Humans; Male; Middle Aged; Neurophysins; Osmolar Concentration; Oxytocin; Protein Precursors; Schizophrenia; Sodium; Vasopressins; Young Adult

A vasopressin derivative or placebo was administered to 21 chronic schizophrenia patients for 3 weeks in a randomized crossover double-blind design. The patients were divided into those above and below the median on baseline memory measured by the Wechsler memory scale. Vasopressin treatment did not improve memory either in those patients with below median baseline memory or in the group as a whole.

Topics: Adult; Chronic Disease; Clinical Trials as Topic; Deamino Arginine Vasopressin; Double-Blind Method; Female; Humans; Male; Memory Disorders; Middle Aged; Random Allocation; Schizophrenia; Vasopressins

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Aged; Clinical Trials as Topic; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Hypothalamus; Insulin; Middle Aged; Pituitary Gland; Schizophrenia; Stimulation, Chemical; Vasopressins

Topics: Altruism; Humans; Schizophrenia; Vasopressins

Due to its various function vasopressin has been associated with many psychiatric disorders, including schizophrenia. Our previous study confirmed that vasopressin-deficient (di/di) Brattleboro rat can be a good genetic model for schizophrenia. Our present aim was to confirm whether the treatment effects of marketed antipsychotics are similar in di/di rats to those seen in human schizophrenic patients. Chronic subcutaneous administration of aripiprazole (5 mg/kg), clozapine (1 mg/kg), haloperidol (0.1 mg/kg), olanzapine (0.3 mg/kg) or risperidone (0.25 mg/kg) was used for 15 days in control (+/+ Brattleboro) and di/di rats. Social discrimination, social avoidance and prepulse inhibition tests were conducted on day 1, 8 and 15 of the treatment. Vasopressin-deficient rats showed social memory- and sensorimotor gating deficit. All used antipsychotics successfully normalized the reduced prepulse inhibition of di/di animals. However, most were effective only after prolonged treatment. Aripiprazole, clozapine, and olanzapine normalized the social memory deficit, while the effects of haloperidol and risperidone were not unequivocal. All drugs reduced social interest to some extent both in control and in di/di animals, aripiprazole being the less implicated in this regard during the social avoidance test. The restoration of schizophrenia-like behavior by antipsychotic treatment further support the utility of the vasopressin-deficient Brattleboro rat as a good preclinical model. Reduced social interest might be a general side-effect of antipsychotics, and aripiprazole has the most favorable profile in this regard.

Topics: Animals; Antipsychotic Agents; Disease Models, Animal; Drug Evaluation, Preclinical; Humans; Injections, Subcutaneous; Male; Rats; Rats, Brattleboro; Rats, Transgenic; Schizophrenia; Social Behavior; Vasopressins

Risky co-operation is when an individual chooses to co-operate in a social situation despite the possibility of the partner refusing to co-operate. Although this is a deviation from rational behavior, it may have helped humans in societal adaptation. Risky co-operation holds significance in social functioning. However, the status of risky cooperative behavior in schizophrenia, a disorder with impaired social cognition, is yet to be investigated. Moreover, the underlying neurobiology is unexplored. 27 individuals with schizophrenia and 30 healthy volunteers performed an iterative stag hunt game, an ecologically valid, neuroeconomics game to measure risky cooperative behavior. The patients and healthy volunteers were matched on age and sex. An independent group of patients (n = 30) later performed the stag hunt game with intranasal vasopressin or saline in a counterbalanced crossover study design. Patients with schizophrenia, compared to healthy controls, switched from high-risk situations to a low-risk situation at lower payoff, suggesting impaired co-operation in a risky situation. Group differences were significant even after controlling for general risk- taking tendency and subjective mood state. In part-II of the study, there was no statistically significant difference in risky co-operative behavior with vasopressin. The results suggest impaired risky co-operative behavior in schizophrenia, which could influence the functional outcome. The study also provides a testable, ecologically valid paradigm for risky co-operative behavior in schizophrenia. Though single dose vasopressin did not influence the risky co-operative behavior, long term study with repeated administration is needed for a definitive conclusion.

Topics: Cooperative Behavior; Cross-Over Studies; Game Theory; Humans; Schizophrenia; Schizophrenic Psychology; Social Behavior; Vasopressins

This study investigates the expression of mRNA encoding vasopressin in the hypothalamus of autopsy brains of individuals diagnosed with schizophrenia.. Ten brains of individuals with schizophrenia and 10 brains from individuals without any disease were examined during autopsy. The hypothalamic block was dissected and immersion fixed in paraformaldehyde, sucrose substituted, frozen, and cut into 20-µm-thick coronal cryostat sections. The sections were hybridized with an S-35-labeled DNA antisense oligo probe and after washing covered by an X-ray film. The hybridization signals on the films were transferred to a computer and densitometrically quantified.. The densitometry signals showed a statistically significant lower mRNA expression (53% decrease; p = 0.014) in the paraventricular nucleus of the individuals with schizophrenia compared to the controls. In the supraoptic nucleus, the decrease in the group with schizophrenia was 39% compared to the controls, but this decrease was not statistically significant (p = 0.194).. Our results show a low expression of mRNA encoding vasopressin in the paraventricular nucleus of the individuals with schizophrenia. We suggest that vasopressin is not directly involved in the pathogenesis of schizophrenia, but might influence schizophrenic symptoms via vasopressin receptors located in the social behavioral neural network in the forebrain.

Topics: Adult; Aged; Animals; Case-Control Studies; Female; Humans; Hypothalamus; Male; Middle Aged; Neurophysins; Paraventricular Hypothalamic Nucleus; Protein Precursors; Radiochemistry; RNA, Messenger; Schizophrenia; Supraoptic Nucleus; Vasopressins; Young Adult

Topics: Adolescent; Adult; Chronic Disease; Cognition Disorders; Female; Humans; Neuropsychological Tests; Oxytocin; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Vasopressins; Young Adult

Many with schizophrenia experiences deficits in social cognition, neurocognition and metacognition. Yet the biological mechanisms which may underpin these cognitive deficits are poorly understood. Two candidate causes of these deficits are disturbances in oxytocin (OT) and vasopressin (VP). To explore this we assessed plasma OT and VP in 34 schizophrenia patients and 31 healthy controls. We also concurrently assessed social cognition using the Reading the Mind from the Eyes test, neurocognition using the Wisconsin Card Sorting Test and metacognition using the Metacognitive Assessment Scale-Abbreviated. Group comparisons revealed lower plasma OT levels in the schizophrenia group. Plasma VP levels did not differ between groups. Correlations revealed that lower levels of OT were associated with poorer levels of metacognitive functioning in the schizophrenia group but not poorer social cognition or neurocognition. In a stepwise multiple regression, plasma OT level, neurocognition and social cognition contributed uniquely to the prediction of metacognition in the schizophrenia group. Results may suggest that disturbance in OT is linked with deficits in metacognition and may interact with other forms of cognitive deficits, interfering with the person's abilities to form a complex and integrated sense of self and others.

Topics: Adult; Case-Control Studies; Cognition; Cognition Disorders; Female; Humans; Male; Metacognition; Neuropsychological Tests; Oxytocin; Schizophrenia; Schizophrenic Psychology; Social Behavior; Social Perception; Vasopressins; Young Adult

Oxytocin (OT) and arginine vasopressin (AVP) exert sexually dimorphic effects on cognition and emotion processing. Abnormalities in these hormones are observed in schizophrenia and may contribute to multiple established sex differences associated with the disorder. Here we examined sex-dependent hormone associations with resting brain activity and their clinical associations in schizophrenia patients.. OT and AVP serum concentrations were assayed in 35 individuals with schizophrenia (23 men) and 60 controls (24 men) from the Chicago BSNIP study site. Regional cerebral function was assessed with resting state fMRI by measuring the amplitude of low-frequency fluctuations (ALFF) which are believed to reflect intrinsic spontaneous neuronal activity.. In female patients, lower OT levels were associated with lower ALFF in frontal and cerebellar cortices (p's < 0.05) and in female controls AVP levels were inversely associated with ALFF in the frontal cortex (p = 0.01). In male patients, lower OT levels were associated with lower ALFF in the posterior cingulate and lower AVP levels were associated with lower ALFF in frontal cortex (p's < 0.05). In male controls, lower OT levels were associated with lower ALFF in frontal cortex and higher ALFF in the thalamus (p's < 0.05). There were some inverse ALFF-behavior associations in patients.. Alterations in peripheral hormone levels are associated with resting brain physiology in a sex-dependent manner in schizophrenia. These effects may contribute to sex differences in psychiatric symptom severity and course of illness in schizophrenia.

Topics: Adult; Brain; Brain Mapping; Cross-Sectional Studies; Female; Humans; Magnetic Resonance Imaging; Male; Neurophysins; Oxytocin; Protein Precursors; Rest; Schizophrenia; Sex Characteristics; Vasopressins

Few studies have addressed likely gene × gene (ie, epistatic) interactions in mediating risk for schizophrenia. Using a preclinical genetic approach, we investigated whether simultaneous disruption of the risk factors Neuregulin-1 (NRG1) and Disrupted-in-schizophrenia 1 (DISC1) would produce a disease-relevant phenotypic profile different from that observed following disruption to either gene alone. NRG1 heterozygotes exhibited hyperactivity and disruption to prepulse inhibition, both reversed by antipsychotic treatment, and accompanied by reduced striatal dopamine D2 receptor protein expression, impaired social cognition, and altered glutamatergic synaptic protein expression in selected brain areas. Single gene DISC1 mutants demonstrated a disruption in social cognition and nest-building, altered brain 5-hydroxytryptamine levels and hippocampal ErbB4 expression, and decreased cortical expression of the schizophrenia-associated microRNA miR-29b. Co-disruption of DISC1 and NRG1, indicative of epistasis, evoked an impairment in sociability and enhanced self-grooming, accompanied by changes in hypothalamic oxytocin/vasopressin gene expression. The findings indicate specific behavioral correlates and underlying cellular pathways downstream of main effects of DNA variation in the schizophrenia-associated genes NRG1 and DISC1.

Topics: Amphetamines; Animals; Behavior, Animal; Brain; Disease Models, Animal; Endophenotypes; Epistasis, Genetic; Female; Grooming; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nerve Tissue Proteins; Nesting Behavior; Neuregulin-1; Oxytocin; Prepulse Inhibition; Psychomotor Agitation; Psychotic Disorders; Schizophrenia; Social Behavior; Vasopressins

The vasopressin- and oxytocin-degrading enzyme insulin-regulated aminopeptidase (IRAP) is expressed in various organs including the brain. However, knowledge about its presence in human hypothalamus is fragmentary. Functionally, for a number of reasons (genetic linkage, hydrolysis of oxytocin and vasopressin, its role as angiotensin IV receptor in learning and memory and others) IRAP might play a role in schizophrenia. We studied the regional and cellular localization of IRAP in normal human brain with special emphasis on the hypothalamus and determined numerical densities of IRAP-expressing cells in the paraventricular, supraoptic and suprachiasmatic nuclei in schizophrenia patients and controls. By using immunohistochemistry and Western blot analysis, IRAP was immunolocalized in postmortem human brains. Cell countings were performed to estimate numbers and numerical densities of IRAP immunoreactive hypothalamic neurons in schizophrenia patients and control cases. Shape, size and regional distribution of IRAP-expressing cells, as well the lack of co-localization with the glia marker glutamine synthetase, show that IRAP is expressed in neurons. IRAP immunoreactive cells were observed in the hippocampal formation, cerebral cortex, thalamus, amygdala and, abundantly, hypothalamus. Double labeling experiments (IRAP and oxytocin/neurophysin 1, IRAP with vasopressin/neurophysin 2) revealed that IRAP is present in oxytocinergic and in vasopressinergic neurons. In schizophrenia patients, the numerical density of IRAP-expressing neurons in the paraventricular and the suprachiasmatic nuclei is significantly reduced, which might be associated with the reduction in neurophysin-containing neurons in these nuclei in schizophrenia. The pathophysiological role of lowered hypothalamic IRAP expression in schizophrenia remains to be established.

Topics: Aged; Autopsy; Chronic Disease; Cystinyl Aminopeptidase; Female; Glutamate-Ammonia Ligase; Humans; Hypothalamus; Male; Middle Aged; Neurons; Neurophysins; Oxytocin; Paraventricular Hypothalamic Nucleus; Pituitary Gland, Posterior; Schizophrenia; Suprachiasmatic Nucleus; Vasopressins

Hemodynamic augmentation is utilized as a treatment in the setting of symptomatic cerebral vasospasm. This approach includes the use of vasopressors to induce hypertension with the aim of improved cerebral blood flow. Agents with potent alpha-1 antagonism properties, including clozapine, can inhibit or blunt the response of several vasopressor agents.. Case report.. A 54-year-old schizophrenic male with an aneurysmal subarachnoid hemorrhage required hemodynamic augmentation in which several vasopressor trials resulted in no or poor response. The addition of epinephrine resulted in a decrease of mean arterial pressure. Vasopressin initiation demonstrated an immediate vasopressor effect.. Vasopressors are an important treatment modality in symptomatic cerebral vasospasm. This case highlights the potential for clozapine to blunt the effects of vasopressors; or in the case of epinephrine, it causes a reversal effect. Vasopressin may be considered an agent of choice in patients who have recently taken clozapine and require hemodynamic augmentation.

Topics: Clozapine; Drug Interactions; Epinephrine; GABA Antagonists; Humans; Hypertension; Intracranial Aneurysm; Male; Middle Aged; Schizophrenia; Subarachnoid Hemorrhage; Vasoconstrictor Agents; Vasopressins; Vasospasm, Intracranial

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.

Topics: Adult; Autistic Disorder; Humans; Male; Oxytocin; Schizophrenia; Schizophrenic Psychology; Vasopressins

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.

Topics: Adult; Arabs; Bipolar Disorder; Brain; Case-Control Studies; Cohort Studies; Family; Female; Gene Expression Regulation; Haplotypes; Humans; Israel; Jews; Male; Membrane Proteins; Neurophysins; Oxytocin; Pedigree; Phosphotransferases (Alcohol Group Acceptor); Polymorphism, Single Nucleotide; Prevalence; Protein Precursors; Schizophrenia; Vasopressins

Topics: Adrenergic alpha-Antagonists; Antipsychotic Agents; Clozapine; Epinephrine; Gastroesophageal Reflux; Hemodynamics; Humans; Hypotension; Intraoperative Complications; Lung Neoplasms; Male; Middle Aged; Schizophrenia; Tobacco Use Disorder; Vasoconstrictor Agents; Vasopressins

Schizophrenia, many believe, reflects an enhanced vulnerability to psychological stress. Controlled exposure to stressors, however, has produced inconclusive results, particularly with regards to neurohormones. Some of the variability may be attributable to the nature and psychological significance of the stimulus and failure to control physiologic confounds. In addition, it is possible that the heterogeneity of schizophrenia is an important factor. In a carefully designed study and in a controlled setting, we measured the neuroendocrine response of eight polydipsic hyponatremic (PHS), seven polydipsic normonatremic (PNS), and nine nonpolydipsic normonatremic (NNS) (ie normal water balance) schizophrenic in-patients as well as 12 healthy controls (HC) to two different stressors: one of which appears to influence neuroendocrine secretion through its psychological (cold pressor) and the other (upright posture) through its systemic actions. Subjects in the three psychiatric groups were stabilized and acclimated to the research setting, and all received saline to normalize plasma osmolality. Following the cold pressor, plasma adrenocorticotropin and cortisol levels showed a more prolonged rise in PHS patients relative to PNS patients. NNS patients, in contrast, exhibited blunted responses relative to both of the polydipsic groups and the HC. Peak vasopressin responses were also greater in PHS and blunted in NNS patients. Responses to the postural stimulus were similar across patient groups. These findings provide a mechanism for life threatening water intoxication in schizophrenia; help to reconcile conflicting findings of stress responsiveness in schizophrenia; and potentially identify a discrete patient subset with enhanced vulnerability to psychological stress.

Topics: Adult; Cold Temperature; Drinking; Endocrine System Diseases; Female; Humans; Hyponatremia; Hypothalamo-Hypophyseal System; Male; Middle Aged; Neurosecretory Systems; Schizophrenia; Stress, Psychological; Thirst; Vasopressins; Water Intoxication; Water-Electrolyte Imbalance

A 27-year-old man with schizophrenia took an overdose of a psychotic agent. He became unconscious and had severe hypotension. Although he was diagnosed as having distributive shock caused by drug overdose and treated by hydration and catecholamine, the shock status was lasting. The use of vasopressin changed the situation dramatically. After the injection of vasopressin at maximum dose, 0.1 U/min, the dose of vasopressin could be tapered. He recovered from shock and was discharged on the third day without sequelae. There are an increasing number of reports that indicate that vasopressin is effective for distributive shock, especially catecholamine-resistant septic shock. It seems that the appropriate dose of vasopressin is under 0.04U/min considering the deterioration of cardiac function although the maximum dose of vasopressin was O.1U/min in this case. For that reason, monitoring by pulmonary artery catheter is recommended. The side effects of vasopressin should be discussed for appropriate use.

Topics: Adult; Antidiuretic Agents; Antipsychotic Agents; Catecholamines; Drug Overdose; Humans; Injections, Intravenous; Male; Schizophrenia; Shock; Treatment Outcome; Vasoconstrictor Agents; Vasopressins

Dysfunction in water intake and metabolism has frequently been reported in schizophrenia. The general population of schizophrenics under neuroleptic treatment secretes lower amounts of vasopressin than controls at comparable values of plasma osmolality. The purpose of the present study was to investigate the synthetic activity of vasopressin neurons of the dorsolateral supraoptic nucleus in schizophrenia on postmortem material using a battery of histochemical activity markers. Our material consisted of formalin-fixed and paraffin-embedded hypothalami from 5 schizophrenic patients under neuroleptic treatment and from 5 matched controls, obtained from The Netherlands' Brain Bank. DSM-III or DSM-IV criteria were used for the clinical diagnosis. The histochemical markers used to study the neuronal activity of the magnocellular vasopressin-synthesizing neurons were: cell size, size of the Golgi apparatus, and expression of vasopressin and tyrosine hydroxylase mRNA by in situ hybridization. Morphometric evaluation and statistical analysis (Mann-Whitney U test) were performed. Our results showed no statistically significant differences in any of the neuronal activity markers between schizophrenic patients and controls. Therefore, the neurosecretory activity of vasopressin neurons of the dorsolateral part of the supraoptic nucleus does not appear to be changed in schizophrenic patients under medication. Since our sample did not include patients with reported polydipsia or hyponatremia, prospective investigation is needed to evaluate the above-mentioned neuronal activity markers in such a particular subgroup of schizophrenic patients.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Female; Golgi Apparatus; Humans; Immunohistochemistry; In Situ Hybridization; Male; Middle Aged; Neurons; Organ Size; RNA, Messenger; Schizophrenia; Supraoptic Nucleus; Tyrosine 3-Monooxygenase; Vasopressins

A patient with a history of schizophrenia was brought to the emergency department with extensive self-inflicted soft tissue injuries. Primary polydipsia was evident on admission, because he had a maximally dilute urine, a urine flow rate of 10 ml/min, and hyponatraemia (100 mmol/l). During an imaginary consultation with Professor McCance in which he applied basic principles of integrative physiology and a deductive analysis in quantitative terms, other reasons for the polyuric state were considered. Moreover, based on the very low value for the concentration of urea in plasma (< 0.7 mmol/l, BUN 1 mg /dl), the goals of therapy to prevent osmotic demyelination became evident. Applying this simple approach, a more comprehensive and accurate differential diagnosis, and a plan for therapy to avoid serious complications was compiled.

Topics: Adult; Diabetes Insipidus; Diagnosis, Differential; Diuresis; Humans; Hyponatremia; Male; Polyuria; Renal Agents; Schizophrenia; Urea; Vasopressins

Although both vasopressin and stress have been implicated in the course of schizophrenia, it is unknown whether schizophrenic patients have altered stress-induced function of the vasopressinergic system. We examined the effects of acute metabolic stress induced by pharmacological doses (40 mg/kg) of 2-deoxyglucose (2DG) on plasma concentrations of vasopressin in 13 patients with schizophrenia (with no history of polydipsia and hyponatremia) and 12 healthy control subjects. Baseline vasopressin levels were lower in the schizophrenic patients and progressively increased in both groups throughout the 60 min following 2DG administration to a similar absolute amount, thus remaining lower in the schizophrenic group. Concomitantly, patients with schizophrenia had significantly higher 2DG-induced plasma homovanillic acid (HVA) and 5-hydroxyindoleacetic acid levels. Vasopressin responses correlated positively and significantly with the HVA responses in schizophrenics and with the pituitary-adrenal axis responses in controls. These results suggest two different patterns of neuroendocrine alterations in schizophrenia, namely a relatively normal vasopressin response to 2DG despite significantly decreased baseline levels and exaggerated responses of the peripheral dopaminegic and serotonergic systems in the face of normal baseline concentrations.

Topics: Adrenocorticotropic Hormone; Adult; Behavior; Female; Homovanillic Acid; Humans; Hydrocortisone; Hydroxyindoleacetic Acid; Male; Schizophrenia; Serotonin; Stress, Physiological; Vasopressins

1. Many polydipsic schizophrenics exhibit enhanced antidiuretic hormone (ADH) activity and thus are hyponatremic and suffer life-threatening water intoxication. Excess cortisol inhibits ADH, while cortisol insufficiency produces impairments in water balance resembling those seen in hyponatremic schizophrenics. Furthermore, hyponatremia normally upregulates cortisol receptors on the neurons which synthesize ADH, which should make them more sensitive to the effects of cortisol. 2. The author treated a hyponatremic schizophrenic, whose water imbalance was unresponsive to standard clinical interventions including clozapine, with a 4-week open trial of 60 mg cortisol daily, followed by a three week taper. 3. Mean serum sodium levels appeared to increase modestly from 114.3 to 118.5 mEq/l while the patient received adjunctive cortisol (P < .06). 4. While a modest effect was seen, the results do not suggest that adjunctive cortisol will reverse hyponatremia, and instead support other data indicating that these patients exhibit a central resistance to glucocorticoid actions.

Topics: Adult; Anti-Inflammatory Agents; Drinking Behavior; Humans; Hydrocortisone; Hyponatremia; Male; Schizophrenia; Sodium; Vasopressins; Water Intoxication; Water-Electrolyte Balance

Chronic schizophrenic patients are reported to develop imbalanced water homeostasis by the pathological secretion of vasopressin and aldosterone. We measured plasma vasopressin, aldosterone and atrial natriuretic peptide in schizophrenic patients to elucidate the role of these hormones during a perioperative period. Eighteen schizophrenic patients with chronic antipsychotic drugs over 10 years and 22 as a control group who underwent elective lower abdominal surgery were the subjects of this study. In the schizophrenic patients, plasma aldosterone secretion was significantly inhibited, while plasma vasopressin and atrial natriuretic peptide were significantly increased during surgery. A good relationship (r = 0.69, p < 0.01) between plasma atrial natriuretic peptide and plasma osmolality was obtained 60 min after skin incision, but not before the induction of anesthesia. The findings suggest that chronic schizophrenic patients may develop an abnormal secretion of vasopressin, aldosterone and atrial natriuretic peptide during anesthesia.

Topics: Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Case-Control Studies; Chronic Disease; Dopamine; Female; Humans; Intraoperative Period; Linear Models; Male; Middle Aged; Osmolar Concentration; Prospective Studies; Schizophrenia; Time Factors; Vasopressins; Water-Electrolyte Imbalance

Polydipsia-hyponatremia is a poorly understood disorder that causes considerable mortality and morbidity. Hyponatremia in polydipsia-hyponatremia has been attributed to disturbances in antidiuretic hormone (ADH) function. Improvements in polydipsia-hyponatremia during clozapine treatment offered the chance to see if levels of ADH and other hormones associated with osmoregulation changed with improvement in biochemical and clinical measures of polydipsia-hyponatremia.. In this preliminary, longitudinal study, we studied 2 male schizophrenic patients (DSM-III-R) who had polydipsia-hyponatremia. Measures were (1) biochemical and clinical: serum sodium and osmolality, urine osmolality and specific gravity, normalized diurnal weight gain, and estimated urine volume and (2) endocrine: ADH, angiotensin II, atrial natriuretic peptide, and prolactin. Measures were collected during 2 months of baseline (typical neuroleptic) and 6 months of clozapine treatment.. Single-case statistical procedures showed significant changes in sodium levels (a.m. and p.m.), estimated urine volume, and a.m. urine specific gravity in both patients and significantly decreased diurnal weight gain in 1 patient. Both serum and urine osmolality showed improvement, but values did not reach statistical significance. Low baseline ADH levels persisted through 6 months of clozapine treatment and showed no changes in the context of improvements in serum sodium and osmolality. No significant changes were seen in levels of angiotensin II and atrial natriuretic peptide.. Given the limitations of this study, there is some evidence to suggest that the improvements in serum sodium and osmolality during clozapine treatment of polydipsia-hyponatremia may not be related to serum levels of ADH, although altered ADH receptor function cannot be ruled out. These data need to be extended in larger samples.

Topics: Adult; Angiotensin II; Atrial Natriuretic Factor; Circadian Rhythm; Clozapine; Humans; Hyponatremia; Longitudinal Studies; Male; Middle Aged; Osmolar Concentration; Prolactin; Schizophrenia; Sodium; Urine; Vasopressins; Water Intoxication

For unclear reasons, life-threatening water intoxication often coincides with acute psychosis in polydipsic schizophrenic patients with chronic hyponatremia. In contrast, most polydipsic schizophrenic patients are normonatremic and never manifest hyponatremia. To explore whether the effect of acute psychosis on water balance differs in these 2 schizophrenic subgroups, we compared their responses to drug-induced psychotic exacerbations.. Matched polydipsic schizophrenic patients with (n = 6) and without (n = 8) hyponatremia were identified based on past and current indexes of fluid intake and hydration. A transient psychotic exacerbation was induced with an infusion of the psychotomimetic methylphenidate hydrochloride (0.5 mg/kg of body weight over a 60-second period). Antidiuretic hormone levels, subjective desire for water, and factors known to influence water balance were measured at 15-minute intervals for 2 hours.. Except for the expected differences in plasma osmolality and sodium, basal measures were similar in the 2 groups. Following methylphenidate administration, antidiuretic hormone levels increased more in the hyponatremic patients (P < .02), despite their consistently lower plasma osmolality (P < .007). No known or putative antidiuretic hormone stimulus could account for this finding. Only basal positive psychotic symptoms (P < .09) and plasma sodium (P < .18) were even marginally associated with the peak antidiuretic hormone responses, but neither factor could explain the difference in the response by the 2 groups.. Psychotic exacerbations are associated with enhanced antidiuretic hormone secretion, for unknown reasons, in schizophrenic patients with hyponatremia and polydipsia, thereby placing them at increased risk of life-threatening water intoxication.

Topics: Acute Disease; Adult; Arginine Vasopressin; Blood Pressure; Drinking; Female; Heart Rate; Humans; Hydrocortisone; Hyponatremia; Inappropriate ADH Syndrome; Male; Methylphenidate; Osmolar Concentration; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Sodium; Thirst; Vasopressins; Water Intoxication

To determine whether polydipsia is responsible for the altered water excretion in the subset of polydipsic schizophrenic patients who develop hyponatremia, the regulation of antidiuretic function was assessed in polydipsic schizophrenic patients with hyponatremia (n = 5), polydipsic schizophrenic patients without hyponatremia (n = 5), nonpolydipsic schizophrenic patients (n = 6), and normal controls (n = 8). The severity and duration of polyuria were similar in the two polydipsic groups. After oral water loading, maximal free water clearance was similar across all four groups. Free water clearance diminished, however, at lower plasma osmolalities in the hyponatremic polydipsics (P < 0.02) and at higher plasma osmolalities in the normonatremic polydipsics (P < 0.05) relative to that in the nonpolydipsic schizophrenics and normal subjects. The increase in plasma vasopressin after osmotic stimulation with hypertonic saline was slightly, but significantly (P < 0.02), blunted in both polydipsic groups. Hyponatremia occurs in some polydipsic schizophrenics because the relationship between free water clearance to plasma osmolality/sodium is shifted to the left. Polydipsia per se is not responsible for this still unexplained shift.

Topics: Adult; Blood Glucose; Blood Pressure; Creatinine; Female; Humans; Hyponatremia; Male; Middle Aged; Polyuria; Schizophrenia; Schizophrenic Psychology; Sodium; Thirst; Urea; Urine; Vasopressins

Topics: Drinking; Hippocampus; Humans; Neurocognitive Disorders; Schizophrenia; Schizophrenic Psychology; Stereotyped Behavior; Vasopressins; Water Intoxication

Topics: Antipsychotic Agents; Combined Modality Therapy; Electroconvulsive Therapy; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Middle Aged; Schizophrenia; Schizophrenic Psychology; Vasopressins

The authors studied antidiuretic hormone (ADH) secretion in schizophrenics on antipsychotic drugs. The mean plasma level of ADH is lower among schizophrenics than among controls at comparable values of plasma osmolality. In regression analysis of the relationship between plasma ADH and plasma osmolality, the slope of the regression line is gentler and the threshold of ADH secretion is lower in schizophrenics than that in control subjects. The authors suggest that the relationship between plasma ADH and plasma osmolality may be different in schizophrenics receiving antipsychotic drugs than in controls.

Topics: Adult; Antipsychotic Agents; Chlorpromazine; Drinking; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Risk Factors; Schizophrenia; Vasopressins; Water-Electrolyte Balance

Basal plasma vasopressin-neurophysin (hNpI) was estimated in 50 drug-free neuropsychiatric patients classified according to the Research Diagnostic Criteria. The hNpI concentration was higher in the 5 manics (0.76 +/- 0.15 ng/ml) than in the 16 schizophrenics (0.53 +/- 0.08), 12 minor depressed (0.54 +/- 0.06) and 17 major depressed (0.48 +/- 0.10; p less than 0.05). Thus, those results confirm our initial observation of an increased vasopressinergic function in the manic compared to the depressed phase in one bipolar patient. Whether this increase in the vasopressin release is a consequence of the neuropsychiatric disorders or initiates and/or participates in their pathophysiology remains to be elucidated. The hypothetic consequence on water metabolism of such an increase remains also to be defined.

Topics: Adolescent; Adult; Bipolar Disorder; Depression; Depressive Disorder; Humans; Middle Aged; Neurophysins; Psychotic Disorders; Schizophrenia; Vasopressins

Elevated plasma vasopressin concentrations have been documented in antipsychotic drug-treated patients as well as a drug-free acutely psychotic patients. To evaluate the effects of antipsychotic drugs on plasma vasopressin, we measured vasopressin response to a single dose of intramuscular chlorpromazine or intravenous haloperidol in normal individuals and to 2 weeks of oral antipsychotics in patients with acute schizophrenia. Neither intramuscular chlorpromazine nor intravenous haloperidol affected plasma vasopressin in normals, except in one subject who developed high plasma vasopressin concentrations coincident with marked hypotension following chlorpromazine. Prior to antipsychotics, two acute schizophrenia patients had elevated plasma vasopressin concentrations, which normalized during antipsychotic drug treatment. We conclude that antipsychotics do not directly stimulate vasopressin release, but may indirectly stimulate vasopressin release by well-described baroreceptor reflex mechanisms if hypotension occurs. Also, acute schizophrenia may be associated with increased plasma vasopressin levels in some patients.

Topics: Adult; Chlorpromazine; Female; Haloperidol; Humans; Male; Schizophrenia; Vasopressins

A 17-year-old schizophrenic developed severe hypernatremia during a period of psychosis. The thirst-deficient abnormality that caused this hypernatremia resolved when his psychosis improved. The primary disorders causing a thirst deficiency leading to hypernatremia fall into three categories: lesions of the central nervous system, mineralocorticoid excess, and drug side effects. None of these disorders was found in our patient. We conclude that psychosis can severely impair the thirst mechanism directly.

Topics: Adolescent; Dehydration; Humans; Hypernatremia; Male; Osmolar Concentration; Schizophrenia; Thirst; Vasopressins

Topics: Humans; Mental Disorders; Schizophrenia; Vasopressins; Water Intoxication

Topics: Humans; Inappropriate ADH Syndrome; Male; Schizophrenia; Thirst; Vasopressins

Topics: Haloperidol; Humans; Schizophrenia; Syndrome; Thioridazine; Vasopressins

Topics: Body Weight; Chemical Phenomena; Chemistry; Humans; Hyponatremia; Male; Middle Aged; Natriuresis; Osmolar Concentration; Schizophrenia; Syndrome; Thiothixene; Vasopressins; Water

Topics: Acute Disease; Adrenocorticotropic Hormone; Adult; Humans; Male; Middle Aged; Phenothiazines; Pigments, Biological; Psychoses, Alcoholic; Schizophrenia; Suicide; Vasopressins

Topics: Adult; Female; Humans; Pituitary Gland, Posterior; Schizophrenia; Vasopressins; Water Intoxication; Water-Electrolyte Balance

Topics: Adolescent; Adult; Animals; Biological Assay; Body Weight; Electroconvulsive Therapy; Humans; Male; Rats; Schizophrenia; Vasopressins

Topics: Adolescent; Adult; Anxiety Disorders; Body Weight; Chlorpromazine; Electroconvulsive Therapy; Humans; Male; Schizophrenia; Stimulation, Chemical; Vasopressins

Topics: Age Factors; Aged; Blood Pressure; Electrocardiography; Female; Humans; Hydrocortisone; Injections, Intravenous; Middle Aged; Nausea; Psychiatric Status Rating Scales; Schizophrenia; Vasopressins; Vomiting

Topics: Adult; Chlorpromazine; Electroshock; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Insulin Coma; Male; Middle Aged; Pituitary-Adrenal System; Schizophrenia; Vasopressins

Topics: Heart Failure; Humans; Patient Discharge; Schizophrenia; Vasopressins; Water; Water Intoxication

Topics: Bipolar Disorder; Depression; Epilepsy; Estrogens; Female; Humans; Hydantoins; Intellectual Disability; Mental Disorders; Mentally Ill Persons; Nitrates; Potassium; Premenstrual Syndrome; Progesterone; Schizophrenia; Thyroid Hormones; Tranquilizing Agents; Vasopressins

Topics: Arginine Vasopressin; Humans; Pituitary Gland, Posterior; Schizophrenia; Vasopressins

Topics: Arginine Vasopressin; Convulsive Therapy; Electroconvulsive Therapy; Humans; Schizophrenia; Vasopressins

Topics: Arginine Vasopressin; Humans; Schizophrenia; Vasopressins

Topics: Arginine Vasopressin; Humans; Mentally Ill Persons; Pituitary Gland, Posterior; Schizophrenia; Vasopressins

Topics: Humans; North Carolina; Schizophrenia; Vasopressins