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Polydipsia-hyponatremia: Evidence for specific cerebral structural pathology and implications for the pathophysiology of schizophrenia
377
suicidal behavior rather than diagnosis. Serotonin receptors have been subclassified as 5HT1, 5HTla, 5HT2 and 5HT3 receptors. The precise mechanism of serotonin receptor regulation is not known. It is known that 5HT2 receptor density can increase after chemical lesions of the serotonergic system. This has not been seen to date in 5HTl or 5HT3 receptors. 5HT2 receptors are down regulated by some 5Hl2 antagonists and 5HT2 reuptake inhibitors. 5HT2 receptors have been shown to be increased in all cortical layers of the prefrontal cortex in suicide victims. The cause of the increased receptor number is not known. It may represent compensatory 5HT2 receptor up-regulation secondary to reduced serotonergic activity. In this study, we are attempting to assess serotonergic function in CNS tissue from schizophrenic patients who committed suicide. Tissue for this study was collected from ten suicide cases with a DSM-III-R diagnosis of schizophrenia, (7 male, 3 female, 32 years mean age of death). Cases were matched by sex, age of death, postmortem interval and medical illness with 10 non-suicide schizophrenic subjects and 10 non-suicide, controls without a psychiatric diagnosis. 5HT2 and 5HTla receptor density was obtained from homogenates of the prefrontal cortex and caudate nucleus. 5HT and SHIM levels were determined in those regional samples as well as samples from the brain stem, and for CSF in some cases. Data as to the number and affinity of the serotonin receptors in these brain areas will be reported.
Polydipsia-hyponatremia: Evidence for specific cerebral structural pathology and implications for the pathophysiology of schizophrenia D.G. Kirch*, R.L. Suddath, M. Foote, W.V.R. Vieweg, L. Godleski, A.C. Jaeger, D.R. Weinberger, Wyatt
R.J.
Neuropsychiatty, Clinical Brain Disorders, and Schizophrenia Research Branches, National Instihrte of Mental Health, 5600 Fishers Lane, Room IOC-06, Rockville, MD 2085’7, U.S.A.
In recent years there has been increasing recognition that a significant number of schizophrenic patients display excessive fluid intake (polydipsia), which in some cases is so severe as to lead to a dilutional hyponatremia with the accompanying clinical syndrome of water intoxication. The latter is potentially lethal and represents a previously under-recognized cause of morbidity and mortality among schizophrenic patients. The clinical phenomenology of polydipsia-hyponatremia is unusual, insofar as it does not typically appear until several years after the onset of psychosis. Although some have proposed that polydipsia-hyponatremia may relate to chronic neuroleptic exposure and accompanying inappropriate secretion of antidiuretic hormone, there is no conclusive evidence that the syndrome is simply a side effect of neuroleptic treatment. This presentation will review the cumulative evidence that polydipsia-hyponatremia is, in fact, associated with a more significant degree of cerebral structural pathology, as evaluated by brain imaging techniques, than is usually seen in schizophrenic subjects. The data reviewed will include an early computed tomographic (CT) scan series showing marked ventricular enlargement in some cases of the polydipsia-hyponatremia syndrome. Data will also be presented from a study in which a vasopressin analogue was administered as a treatment for schizophrenia, with a subgroup of treated patients developing the complication of hyponatremia. This subgroup of patients had significantly larger lateral ventricles on CT scans compared with patients who maintained normal fluid balance. Finally, the cumulative data will be presented from a magnetic resonance imaging (MRI) study of three groups of subjects: 19 schizophrenic patients with documented polydipsia-hyponatremia; 19 schizophrenic patients with no evidence of this syndrome; and 19 normal control subjects. The schizophrenic patients with polydipsia-hyponatremia had significantly decreased volumes of the amygdala-hippocampal complex compared with both non-hyponatremic schizophrenic patients and normal controls. Similar differences were also seen in ventricular volumes, with the largest ventricles in the polydipsic-hyponatremic group. The implications of these structural findings for the etiopathogenesis of schizophrenia will be presented.
Neuroendocrine schizophrenia
determinants
of disturbed water regulation
W.B. Lawson*, H. Kazumi, T. Inagami, D. Kirch, G. Robertson,
E. Morales, A. Lager
Department of Psychiatry, Vanderbilt Universiy Medical Center, NashviNe, TN 37232, U.S.A.
in
suicidal behavior rather than diagnosis. Serotonin receptors have been subclassified as 5HT1, 5HTla, 5HT2 and 5HT3 receptors. The precise mechanism of serotonin receptor regulation is not known. It is known that 5HT2 receptor density can increase after chemical lesions of the serotonergic system. This has not been seen to date in 5HTl or 5HT3 receptors. 5HT2 receptors are down regulated by some 5Hl2 antagonists and 5HT2 reuptake inhibitors. 5HT2 receptors have been shown to be increased in all cortical layers of the prefrontal cortex in suicide victims. The cause of the increased receptor number is not known. It may represent compensatory 5HT2 receptor up-regulation secondary to reduced serotonergic activity. In this study, we are attempting to assess serotonergic function in CNS tissue from schizophrenic patients who committed suicide. Tissue for this study was collected from ten suicide cases with a DSM-III-R diagnosis of schizophrenia, (7 male, 3 female, 32 years mean age of death). Cases were matched by sex, age of death, postmortem interval and medical illness with 10 non-suicide schizophrenic subjects and 10 non-suicide, controls without a psychiatric diagnosis. 5HT2 and 5HTla receptor density was obtained from homogenates of the prefrontal cortex and caudate nucleus. 5HT and SHIM levels were determined in those regional samples as well as samples from the brain stem, and for CSF in some cases. Data as to the number and affinity of the serotonin receptors in these brain areas will be reported.
Polydipsia-hyponatremia: Evidence for specific cerebral structural pathology and implications for the pathophysiology of schizophrenia D.G. Kirch*, R.L. Suddath, M. Foote, W.V.R. Vieweg, L. Godleski, A.C. Jaeger, D.R. Weinberger, Wyatt
R.J.
Neuropsychiatty, Clinical Brain Disorders, and Schizophrenia Research Branches, National Instihrte of Mental Health, 5600 Fishers Lane, Room IOC-06, Rockville, MD 2085’7, U.S.A.
In recent years there has been increasing recognition that a significant number of schizophrenic patients display excessive fluid intake (polydipsia), which in some cases is so severe as to lead to a dilutional hyponatremia with the accompanying clinical syndrome of water intoxication. The latter is potentially lethal and represents a previously under-recognized cause of morbidity and mortality among schizophrenic patients. The clinical phenomenology of polydipsia-hyponatremia is unusual, insofar as it does not typically appear until several years after the onset of psychosis. Although some have proposed that polydipsia-hyponatremia may relate to chronic neuroleptic exposure and accompanying inappropriate secretion of antidiuretic hormone, there is no conclusive evidence that the syndrome is simply a side effect of neuroleptic treatment. This presentation will review the cumulative evidence that polydipsia-hyponatremia is, in fact, associated with a more significant degree of cerebral structural pathology, as evaluated by brain imaging techniques, than is usually seen in schizophrenic subjects. The data reviewed will include an early computed tomographic (CT) scan series showing marked ventricular enlargement in some cases of the polydipsia-hyponatremia syndrome. Data will also be presented from a study in which a vasopressin analogue was administered as a treatment for schizophrenia, with a subgroup of treated patients developing the complication of hyponatremia. This subgroup of patients had significantly larger lateral ventricles on CT scans compared with patients who maintained normal fluid balance. Finally, the cumulative data will be presented from a magnetic resonance imaging (MRI) study of three groups of subjects: 19 schizophrenic patients with documented polydipsia-hyponatremia; 19 schizophrenic patients with no evidence of this syndrome; and 19 normal control subjects. The schizophrenic patients with polydipsia-hyponatremia had significantly decreased volumes of the amygdala-hippocampal complex compared with both non-hyponatremic schizophrenic patients and normal controls. Similar differences were also seen in ventricular volumes, with the largest ventricles in the polydipsic-hyponatremic group. The implications of these structural findings for the etiopathogenesis of schizophrenia will be presented.
Neuroendocrine schizophrenia
determinants
of disturbed water regulation
W.B. Lawson*, H. Kazumi, T. Inagami, D. Kirch, G. Robertson,
E. Morales, A. Lager
Department of Psychiatry, Vanderbilt Universiy Medical Center, NashviNe, TN 37232, U.S.A.
in