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      Absence of a Difference in the Neurosecretory Activity of Supraoptic Nucleus Vasopressin Neurons of Neuroleptic-Treated Schizophrenic Patients

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          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.

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          Most cited references 40

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          Polydipsia and water intoxication in psychiatric patients: a review of the epidemiological literature.

          Polydipsia among chronic psychiatric patients is poorly understood and underdiagnosed. It may have three stages: simple polydipsia, polydipsia with water intoxication, and physical complications. Epidemiological surveys have used staff reports and polyuria measures to identify polydipsic patients. Water intoxication has been screened by chart review, weight, or serum sodium data. According to these surveys, polydipsia, not explained by medically induced polyuria, may be present in more than 20% of chronic inpatients. Up to 5% of chronic inpatients had episodes of water intoxication although mild cases may have been missed. Single time point surveys show that 29% of polydipsic patients had presented water intoxication. Methodologically limited clinical studies suggest that polydipsia with water intoxication rather than simple polydipsia may be associated with poor prognosis in schizophrenia. Epidemiological surveys found polydipsia with water intoxication to be associated with chronicity, schizophrenia, smoking, some medications, male gender, and white race. New pathophysiological models need to elucidate these findings.
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            Nitric oxide synthase-containing neurons in the human hypothalamus: reduced number of immunoreactive cells in the paraventricular nucleus of depressive patients and schizophrenics.

            The neuroanatomical distribution of nitric oxide synthase-immunoreactive neurons was investigated in post mortem hypothalami of 10 patients suffering from schizophrenia, eight patients with depression and 13 matched control cases. Neuronal nitric oxide synthase containing nerve cells were detected in several hypothalamic nuclei including the medial preoptic region, the ventromedial, infundibular and suprachiasmatic nuclei and the lateral hypothalamus. The vast majority of hypothalamic nitric oxide synthase-immunoreactive neurons was found to be located in the paraventricular nucleus. Both magno and parvocellular paraventricular neurons contained the enzyme. A small subset of immunoreactive parvocellular paraventricular neurons co-expresses corticotropin-releasing hormone. The supraoptic nucleus did not contain nitric oxide synthase-immunoreactive neurons. Cell counts of paraventricular nitric oxide synthase-positive neurons in controls, schizophrenics and depressed patients revealed a statistically significant reduction of cell density in the right paraventricular nucleus of depressed patients and schizophrenics as compared to controls. The total amount of nitric oxide synthase-immunoreactive paraventricular neurons was smaller in depressive and schizophrenic patients than in normal cases. The putative pathophysiologic significance of the reduced expression of paraventricular nitric oxide synthase in depressive patients might be related to the supposed regulatory function of nitric oxide in the release of corticotropin-releasing hormone and arginine-vasopressin and/or oxytocin, which have been reported to be over-expressed in the so-called endogenous psychoses, especially in depression.
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              Mechanisms of altered water metabolism in psychotic patients with polydipsia and hyponatremia.

              Water intoxication is a serious problem in many patients with chronic psychiatric illness. In an effort to determine the mechanism of this disorder, we investigated the osmoregulation of water intake and antidiuretic function in psychiatric patients with polydipsia and hyponatremia and in matched controls with psychiatric illness but neither polydipsia nor hyponatremia. We found that a water load suppressed plasma osmolality and vasopressin and urine osmolality in both groups, but that urinary dilution and free water clearance were impaired in the patients with hyponatremia, even though plasma levels of vasopressin and solute clearance were similar in the two groups. Moreover, during water loading and infusion of hypertonic saline, the plasma level of vasopressin was higher at any given plasma osmolality in the test patients than in the controls, indicating a downward resetting of the osmostat. Patients' estimates of the amount of water they desired were shown to correlate significantly with the amount of water consumed and, at any given level of plasma osmolality, appeared to be higher in the test patients than in the controls. We conclude that psychiatric patients with polydipsia and hyponatremia have unexplained defects in urinary dilution, the osmoregulation of water intake, and the secretion of vasopressin.

                Author and article information

                S. Karger AG
                February 2006
                22 February 2006
                : 82
                : 2
                : 63-69
                aDepartment of Psychiatry, University of Athens, and bUniversity Mental Health Research Institute, Athens, Greece; cNetherlands’ Institute for Brain Research, Amsterdam, The Netherlands
                90981 Neuroendocrinology 2005;82:63–69
                © 2005 S. Karger AG, Basel

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                Page count
                Tables: 3, References: 60, Pages: 7
                Original Paper


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