Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten patients [9 men and 1 woman; mean age 42.4 +/- 8.5 (+/- SD) years] who were smokers and who suffered the complications of self-induced water intoxication and psychosis (SIWIP) (8 patients with schizophrenic disorders, 1 patient with manic-depressive illness, 1 patient with dementia) are reported. Each patient underwent serial determinations of parameters of water metabolism including plasma and urine osmolality and plasma arginine vasopressin (AVP). The syndrome of inappropriate antidiuresis (SIAD) was found in each patient. Because of the reported effect that cigarette smoking has on antidiuresis, we correlated serum nicotine (NIC) levels with plasma and urine osmolality, AVP, and 24-hour urine volume (24 degrees-UV). We found no relationship between NIC and plasma or urine osmolality, AVP, or 24 degrees-UV. In the presence of SIWIP and SIAD, we infer the limbic-hypothalamic neurotransmitters in these psychotic patients are sufficiently powerful in stimulating both compulsive water drinking and inappropriate release of AVP so as to overshadow any effects that NIC may have on water metabolism.
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PMID:Correlation of cigarette-induced increase in serum nicotine levels with arginine vasopressin concentrations in the syndrome of self-induced water intoxication and psychosis (SIWIP). 369

Disturbances of water homeostasis have frequently been reported in schizophrenia. Water homeostasis is regulated by arginine vasopressin (AVP), the renin-angiotensin system and natriuretic hormones. The aim of this study was to determine the activity of the central renin-angiotensin system in schizophrenia by measuring levels of angiotensin-converting enzyme (ACE) in the cerebrospinal fluid (CSF) and blood in 14 in-patients with schizophrenia on neuroleptic medication and in 9 healthy volunteers. The levels of CSF ACE were significantly higher in the schizophrenia group. There were no correlations between CSF ACE and gender, age, age at first episode, duration of illness, term of hospitalization or neuroleptic dosage. No correlations between CSF ACE and serum ACE were found in either group. The authors suggest an activated central renin-angiotensin system in schizophrenia at least during antipsychotic drug treatment, which may cause 'psychogenic' polydipsia in some patients. ACE and the brain renin-angiotensin system may also play a role in the regulation of neuron growth and differentiation in schizophrenia.
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PMID:Elevated angiotensin-converting enzyme (kininase II) in the cerebrospinal fluid of neuroleptic-treated schizophrenic patients. 809 92

1. Estrogen exerts profound effects on mood, mental state and memory by acting on both "classical" monoamine and neuropeptide transmitter mechanisms in brain. Here we review an example of each type of action. 2. With respect to the effect of estrogen on central monoamine neurotransmission, low levels of estrogen in women are associated with the premenstrual syndrome, postnatal depression and post-menopausal depression. Sex differences in schizophrenia have also been attributed to estrogen. Previous studies have shown that estrogen stimulates a significant increase in dopamine2 (D2) receptors in the striatum. Here we show for the first time that estrogen also stimulates a significant increase in the density of 5-hydroxytryptamine2A (5-HT2A) binding sites in anterior frontal, cingulate and primary olfactory cortex and in the nucleus accumbens, areas of the brain concerned with the control of mood, mental state, cognition, emotion and behavior. These findings explain, for example, the efficacy of estrogen therapy or 5-HT uptake blockers such as fluoxetine in treating the depressive symptoms of the premenstrual syndrome. and suggest that the sex differences in schizophrenia may also be due to an action of estrogen mediated by way of 5-HT2A receptors. 3. With respect to the effect of estrogen on central neuropeptide transmission, estrogen stimulates the expression of the arginine vasopressin (AVP) gene in the bed nucleus of the stria terminalis (BNST) in rodents. This results in a 100-fold increase in AVP mRNA in the BNST and a massive increase in AVP peptide in the BNST and its projections to the lateral septum and lateral habenula. The BNST-AVP system enhances and/or maintains "social" or "olfactory" memory, and thus provides a powerful model for correlating transcriptional control of neuropeptide gene expression with behavior. Whether similar mechanisms operate in the human remain to be determined. 4. These two examples of the action of estrogen on central neurotransmission are discussed in terms of their immediate clinical importance for the treatment of depressive symptoms, their use as powerful models for investigations on the steroid control of central neurotransmitter mechanisms, and the role of estrogen as "Nature's" psychoprotectant.
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PMID:Estrogen control of central neurotransmission: effect on mood, mental state, and memory. 881

The aim of this study was to replicate our earlier finding of elevated angiotensin-converting enzyme (ACE) in cerebrospinal fluid (CSF) in schizophrenia and to elucidate the role of neuroleptic treatment in this phenomenon. Drug-free and medicated patients with acute schizophrenic psychoses, as well as healthy controls were recruited. Levels of ACE were measured in CSF and serum from 7 drug-free patients, 36 neuroleptic-treated patients, and 19 healthy control subjects. Although ACE levels in CSF did not differ between patients and controls, the drug-free patients showed significantly lower levels than the neuroleptic-treated patients. Serum ACE did not differ between groups. The elevation of CSF ACE may be more prominent in patients with deficit symptoms than in those with mainly psychotic symptoms. The possible enhancement of CSF ACE production or solubility by neuroleptic treatment is discussed. Elevated ACE levels in CSF may, together with other possible factors, cause polydipsia, stimulate secretion of arginine vasopressin, and even affect neuron growth and differentiation in schizophrenic psychoses.
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PMID:Higher cerebrospinal fluid angiotensin-converting enzyme levels in neuroleptic-treated than in drug-free patients with schizophrenia. 971 31

1. Sex steroid hormones exert profound effects on mood and mental state. Thus, in women, oestrogen is thought to protect against depression and delay the onset of schizophrenia and Alzheimer's disease. 2. Our studies in the female rat show that oestradiol, in its positive feedback mode for gonadotrophin release, increases the expression of genes for the 5-hydroxytryptamine 5-HT2A receptor and the serotonin transporter (SERT) in the dorsal raphe nucleus and the density of 5-HT2A receptor and SERT sites in regions of the forebrain that, in the human, are concerned with cognition, mental state, emotion and memory. 3. In the male rat, castration decreases while oestrogen and testosterone, but not 5 alpha-dihydrotestosterone (5 alpha-DHT), increase the density of 5-HT2A receptors in forebrain. The fact that 5 alpha-DHT has no effect suggests that the action of testosterone depends on its conversion to oestradiol by aromatase. 4. In intact rats, the density of 5-HT2A receptors in cerebral cortex is significantly higher in pro-oestrous female than in male and dioestrous female rats, showing that the spontaneous, preovulatory surge of oestradiol that reaches a peak at 12.00 h of pro-oestrus also increases the density of 5-HT2A receptors in cortex. 5. Oestrogen and testosterone (by way of its conversion to oestrogen) also stimulate the expression of the arginine vasopressin gene in the bed nucleus of the stria terminalis of the rodent, a mechanism that plays a key role in olfactory memory. 6. These actions of sex steroid hormones are discussed in the context of genomic versus non-genomic mechanisms, the recent discovery that there are two oestradiol receptors with different distributions in brain, the significance of our findings for our understanding of the control of mood, mental state and memory and the mechanism by which oestrogen stimulation of the 5-HT2A receptor could delay the onset of Alzheimer's disease.
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PMID:Sex steroid control of mood, mental state and memory. 978 14

We studied the effects of a short-term hypertonic stimulus on plasma levels of the stress hormones adrenocorticotropin (ACTH), cortisol, prolactin, and the blood volume- and electrolyte-controlling hormones arginine vasopressin (AVP) and atrial natriuretic peptide (ANP). Seven patients suffering from chronic schizophrenia with negative symptoms and ten healthy control subjects were investigated by a 20-minute infusion of 10 ml/kg body weight of hypertonic (2.5%) versus isotonic (0.9%) saline. All patients, who were medication-free for at least one week prior to the study, and all control subjects participated in two investigations in randomized order according to a single-blind cross-over design. During hypertonic infusion, plasma osmolarity and sodium levels were increased similarly in both groups and significantly more than during isotonic saline. Hypertonic saline caused a significant increase of plasma ACTH, cortisol and prolactin in patients in contrast to controls. AVP and ANP plasma concentrations were elevated after infusion of hypertonic saline, however, only patients showed a significant rise in plasma ANP. These results show that a dysregulation of the hypothalamic-pituitary-adrenal (HPA) system in a subset of patients with chronic schizophrenia may become overt during an osmotic stimulation, indicating an increased sensitivity of patients with schizophrenia to osmotic stress.
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PMID:Neuroendocrine effects of a short-term osmotic stimulus in patients with chronic schizophrenia. 1258 82

Lesioning the ventral hippocampal formation (vHF) in the neonatal rat with an excitotoxin replicates several features of schizophrenia. Similar lesions in the adult rat disrupt the normal constraint of neuroendocrine responses to environmental stressors, which is of potential interest because the enhanced HPA axis and antidiuretic hormone activity in schizophrenia is linked to acute stress and hippocampal formation (HF) pathology. In the current study, we investigated the effects of neonatal ventral hippocampal formation lesions (NVHFL) on plasma adrenocorticotropin hormone (ACTH) and arginine vasopressin (AVP) responses following a 2-min acoustic stressor in the adult rat. Levels of the two hormones did not differ between SHAM-operated and NVHFL animals in their home cages. ACTH levels doubled in SHAM-operated animals immediately following stress, but increased more than six-fold in the NVHFL group. AVP levels were halved immediately following stress in SHAM-operated animals, but did not change significantly in NVHFL. Findings could not be attributed to intervening factors known to influence neuroendocrine activity. Thus, NVHFL appear to disrupt the HF-mediated constraint of neuroendocrine responses to stress, and model the neuroendocrine dysfunction seen in schizophrenia. We posit that clarification of how NVHFL alters relatively "simple", well characterized, and phylogenetically preserved systems, such as the neuroendocrine system, may provide insight into the mechanism of hippocampal pathology in schizophrenia.
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PMID:Neonatal lesions of the ventral hippocampal formation disrupt neuroendocrine responses to auditory stress in the adult rat. 1528 11

The arginine vasopressin (AVP) system plays an important role in social behavior. Autism, with its hallmark disturbances in social behavior, has been associated with the V1a receptor (V1aR) gene. Furthermore, impairments of social function are often observed in symptoms of schizophrenia. Subchronic phencyclidine (PCP) produces behaviors relating to certain aspects of schizophrenic symptoms such as impairing social interaction in animals and it reduces the density of V1aR binding sites in several brain regions. Here, we report that V1aR knockout (KO) mice exhibited impairment of social behavior in a social interaction test, and showed reduced anxiety-related behavior in elevated plus-maze and marble-burying behavior tests. Given the current findings, the V1aR may be involved in the regulation of social interaction, and V1aR KO mice could be used as an animal model of psychiatric disorders associated with social behavior deficits, such as autism and schizophrenia.
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PMID:Impaired social interaction and reduced anxiety-related behavior in vasopressin V1a receptor knockout mice. 1722 84

We previously reported that vasopressin deficient Brattleboro (BRAT) rats exhibit deficits in prepulse inhibition (PPI) of the startle reflex that are consistent with PPI deficits exhibited by patients with schizophrenia and other neuropsychiatric disorders. Preliminary evidence indicates that this may be the basis of a predictive model for antipsychotic drug efficacy. Here we report the effects of acute and chronic administration of established and putative antipsychotics on these PPI deficits. BRAT rats, compared to their derivative strain, Long Evans rats, exhibited significantly decreased PPI and startle habituation consistent with patients with schizophrenia and other neuropsychiatric disorders. The second generation antipsychotics, risperidone and clozapine as well as a neurotensin agonist (PD149163) increased BRAT rat PPI, whereas saline, the typical antipsychotic, haloperidol, and a vasopressin analog (1-desamino-D-arginine vasopressin) did not. Similar to their effects in humans, chronic administration of antipsychotic drugs produced stronger effects than acute administration. These results further support the BRAT rat as a model of sensorimotor gating deficits with predictive validity for antipsychotics. The model appears to be able to differentiate first generation from second generation antipsychotics, identify putative antipsychotics with novel mechanisms (i.e., peptides) and reasonably model the therapeutic time course of antipsychotic drugs in humans.
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PMID:The effects of chronic administration of established and putative antipsychotics on natural prepulse inhibition deficits in Brattleboro rats. 1755 53

Polydipsic hyponatremic schizophrenic patients (PHS) exhibit enhanced plasma arginine vasopressin (pAVP) and hypothalamic pituitary adrenal (HPA) axis responses to stress that appear attributable to anterior hippocampal dysfunction. Neuroanatomic and electrophysiologic studies indicate oxytocin activity in PHS patients should also be affected. Furthermore, oxytocin normally diminishes HPA responses to stress and facilitates cognitive and behavioral functions impaired in schizophrenia, suggesting that diminished oxytocin activity could contribute to this subsets' neuropsychiatric disorder. In the present study, we measured plasma oxytocin levels at intervals before and after stress induction in six polydipsic hyponatremic (PHS), four polydipsic normonatremic (PNS), five nonpolydipsic normonatremic schizophrenic (NNS) patients and seven healthy controls. Most of these subjects also completed studies measuring their medial temporal lobe volumes, their hippocampal-mediated HPA feedback and their ability to discriminate different facial emotions (an oxytocin-sensitive measure which is markedly impaired in schizophrenia). Results demonstrated that 1) plasma oxytocin levels were lower (p=.006) in hyponatremic patients relative to the other three groups, whose levels were similar and did not change. Oxytocin levels across all subjects were 2) inversely correlated with anterior hippocampal (p=.004) (but not posterior hippocampal or amygdala volumes), and 3) directly correlated with the integrity of hippocampal-mediated HPA feedback (p=.039). Finally, 4) oxytocin levels predicted schizophrenic patients' ability to correctly identify facial emotions (p=.004). These preliminary data provide further evidence that neuroendocrine dysfunction in PHS reflects anterior hippocampal pathology and contributes to a characteristic neuropsychiatric syndrome.
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PMID:Diminished plasma oxytocin in schizophrenic patients with neuroendocrine dysfunction and emotional deficits. 1796 88


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