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)

Auditory brainstem-evoked responses (ABRs) were recorded and the CSF concentration of the amine metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were measured in 39 drug-free schizophrenic patients. Twenty-four of the patients were first admissions and had never received antipsychotic medication. The ABRs were judged according to our normative data and the CSF concentrations of the amine metabolites were compared with those of 47 healthy volunteers. Clear-cut abnormal ABRs, identified as a lack of one or more peaks or abnormal peak latencies, were found in 15 patients. In controls and patients with normal ABRs, there was a significant positive correlation between the cerebrospinal fluid (CSF) levels of HVA and 5-HIAA; no such correlation was found in patients with abnormal ABRs. Schizophrenics with abnormal ABRs had significantly lower levels of HVA, but not 5-HIAA, in the CSF when compared with controls. Schizophrenic patients with normal ABRs (n = 24) did not differ from the controls with regard to the amine metabolites in CSF. A comparison of the CSF levels of HVA and 5-HIAA yielded no significant difference between patients with normal and those with abnormal ABRs. In contrast, when only first-episode, never-treated schizophrenics were considered, patients with abnormal ABRs (n = 10) had significantly lower levels of both HVA and 5-HIAA when compared with those having normal ABRs (n = 14). The results indicate an association between brainstem dysfunction and reduced central nervous dopaminergic and possibly also serotoninergic activity in schizophrenia.
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PMID:Relationship between abnormal brainstem auditory-evoked potentials and subnormal CSF levels of HVA and 5-HIAA in first-episode schizophrenic patients. 169 68

Cerebrospinal fluid (CSF) levels of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) were determined in 40 drug-free schizophrenic patients and 21 healthy volunteers by a mass fragmentographic method. Twenty-one of the schizophrenic patients were first admissions who had never received neuroleptics. Significantly, lower levels of HVA but not 5HIAA were found in the patient group, and no difference was found between chronic, previously neuroleptic-treated and never-medicated patients. HVA levels correlated positively with social interest and total positive scores on the Nurses Observation Scale for Inpatient Evaluation (NOSIE-30) and negatively with lassitude and slowness of movements on the Comprehensive Psychopathological Rating Scale (CPRS). Low levels of 5HIAA were correlated to the CPRS items delusions and apparent sadness. There were slightly higher CSF levels of 5HIAA in patients with a family history of schizophrenia, but no such difference was seen for HVA. In both schizophrenic and control subjects CSF levels of HVA and 5HIAA showed a strong intraindividual correlation. The results indicate decreased central nervous system dopaminergic turnover in schizophrenia which seems to be associated with "negative" symptomatology.
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PMID:Low HVA and normal 5HIAA CSF levels in drug-free schizophrenic patients compared to healthy volunteers: correlations to symptomatology and family history. 241 Sep 40

The cerebrospinal fluid monoamine metabolites, homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA), were compared with ventricle-brain ratios (VBRs) in a group of adolescent inpatients who were divided into psychotic and nonpsychotic groups. HVA, 5HIAA, and VBR did not differ significantly between the two groups. There were no significant relationships between these variables in the nonpsychotic group. Psychotic adolescents, however, displayed significant negative correlations between VBR and HVA, and between VBR and 5HIAA. The relationship between VBR and monoamine metabolites appears to occur in psychoses other than schizophrenia, is present early in the course of illness, and probably does not represent a dilutional effect.
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PMID:Brain ventricular size and CSF monoamine metabolites in an adolescent inpatient population. 241 97

Cerebrospinal fluid (CSF) levels of an opioid receptor-active, chromatographically separated endorphin fraction (Fraction I) were measured in 45 schizophrenic patients and 18 healthy volunteers. Significantly increased levels of Fraction I differentiated the patient group from controls, with no difference being found between newly admitted untreated and chronic previously neuroleptic-treated subjects. Fraction I levels did not correlate with age, weight, height, duration of illness, total time hospitalized, or age when symptoms first appeared. No differences were found between patients with or without a family history of schizophrenia. Fraction I levels were negatively correlated with "hallucinations" and "indecision" on the Comprehensive Psychopathological Rating Scale. Increased levels of Fraction I were associated with low levels of the dopamine metabolite homovanillic acid in drug-free schizophrenics. This relationship was not present after neuroleptic treatment or in healthy controls. No relationship was found between Fraction I and the serotonin metabolite 5-hydroxyindoleacetic acid. Neuroleptic treatment did not significantly change Fraction I levels; when only patients above the control range were considered, however, a significant decrease was observed. The data support our previous hypothesis of an increased opioid activity in schizophrenia and further indicate a concomitant dysfunction of brain endorphin and dopamine activity in schizophrenic patients.
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PMID:CSF levels of receptor-active endorphins in schizophrenic patients: correlations with symptomatology and monoamine metabolites. 243 27

The mean combined total body excretion of dopamine (DA) and its metabolites, measured by summing the molar excretion of DA and its metabolites in 24-hour urine samples (Sum DA), was reduced in 20 patients with schizophrenia who had not been receiving medication for at least two weeks. These patients were relatively resistant to treatment, as they were unable to live independently outside institutional settings despite conventional neuroleptic therapy. In contrast, sum norepinephrine (Sum NE), measured by summing the molar excretion of NE and its metabolites, was not reduced. These results are highlighted by expressing the data in terms of the ratio of Sum DA/Sum NE. Patients with schizophrenia had a significantly lower ratio. Treatment with haloperidol normalized the low ratio. Urinary excretion of 5-hydroxyindoleacetic acid was normal in the schizophrenic patients. These results suggest that chronic schizophrenia is more likely to be associated with a low rather than a high state of DA activity.
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PMID:Preliminary evidence of reduced combined output of dopamine and its metabolites in chronic schizophrenia. 244 Apr 12

Twenty-three inpatients who met DSM-III criteria for schizophrenia were selected for cerebrospinal fluid (CSF) neurochemical study of tardive dyskinesia (TD). Ten inpatients had tardive dyskinesia, and the remaining 13 patients without TD served as controls. There were no intergroup differences in sex, age, duration of neuroleptic treatment, or in total amount of neuroleptics received between the TD and the control groups. Cerebrospinal fluid was collected by lumbar puncture, and concentrations of homovanillic acid (HVA), MHPG, 5-hydroxyindoleacetic acid (5-HIAA), and acetylcholinesterase (AChE) activity were measured. The concentrations of MHPG (TD 11.56 +/- 3.48 ng/ml versus control 14.20 +/- 3.86 ng/ml), 5-HIAA (45.27 +/- 9.77 ng/ml versus 40.34 +/- 13.77 ng/ml), and HVA (38.26 +/- 18.31 ng/ml versus 31.40 +/- 7.83 ng/ml), and the activity of AChE (TD 7.95 +/- 5.21 mmol/g.hr versus control 12.89 +/- 8.04 mmol/g.hr) showed no significant differences between the two groups, but the ratios of HVA/AChE (t = 2.21, p = 0.05), 5-HIAA/AChE (t = 2.62, p = 0.02), MHPG/HVA (t = -2.16, p = 0.04), and MHPG/5-HIAA (t = -2.48, p = 0.02) were statistically different. The results indicated that TD might involve an imbalance of dopamine-acetylcholine, noradrenalin-dopamine, noradrenalin-serotonin, and serotonin-acetylcholine.
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PMID:CSF neurochemical study of tardive dyskinesia. 246 90

Magnesium and calcium concentrations were measured in the cerebrospinal fluid (CSF) of 15 neurological controls and 41 psychiatric patients suffering from major depression (n = 16), schizophrenic disorder (n = 15), or adjustment disorder (n = 10). All subjects were women 19-67 years of age and free from drugs at the time of the study. CSF was evaluated for 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and cortisol (CS) levels, and all patients received a dexamethasone suppression test (DST) following lumbar puncture. CSF calcium levels did not differ among groups, although we found a trend toward higher mean levels in both depression and schizophrenia. By contrast, CSF magnesium was found to be significantly lower in both depression and adjustment disorder; if, however, patients who had made suicide attempts were excluded, the difference became insignificant. Patients who had made suicide attempts (by using either violent or nonviolent means) had significantly lower mean CSF magnesium level irrespective of the diagnosis. CSF calcium did not correlate with magnesium, 5-HIAA, HVA, CS, global severity, therapeutic response, or DST, but CSF magnesium correlated significantly with CSF 5-HIAA, especially after correcting for age and body height. Both variables seemed to be primarily related to recorded suicide attempts, but decreased magnesium was not limited to violent cases.
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PMID:Cerebrospinal fluid magnesium and calcium related to amine metabolites, diagnosis, and suicide attempts. 257 29

Studies examining serotonin (5-hydroxytryptamine; 5HT) in schizophrenia show variable and inconsistent findings, which might reflect the heterogeneity of the disease. When these studies are reviewed in the light of Crow's "two-syndrome" paradigm of schizophrenia, a new trend emerges. It appears that 5HT findings may be related to certain features of Type II schizophrenia such as negative symptoms, degenerative brain changes, and chronicity in the following manner: (1) 5HT2 antagonists, which have recently become available, have been shown to have an antipsychotic effect, particularly on the negative symptom cluster. (2) Decreased levels of 5-hydroxyindoleacetic acid in cerebrospinal fluid have been found to be correlated with cortical atrophy or ventricular enlargement in schizophrenic patients. (3) A subgroup of chronic schizophrenic patients has been shown to have elevated levels of platelet or whole blood 5HT. We propose, then, that 5HT dysfunction might be related to Type II, or negative syndrome, schizophrenia, and that the nature of this dysfunction might involve 5HT postsynaptic receptor hypersensitivity. We further suggest that the pharmacotherapy of schizophrenia should include a 5HT-blocking component, as well as a dopamine-blocking component, and we propose that future research should address the role of selective 5HT receptor hypersensitivity in schizophrenia.
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PMID:The role of serotonin in schizophrenia. 305 73

Suicide is a significant cause of mortality in patients suffering from major affective disorders, schizophrenia, and alcoholism. Generally, several clinical and psychosocial factors combine to result in suicide. These risk factors have high sensitivity but low specificity; only a small minority of patients who meet risk criteria actually complete suicide. Therefore, clinicians have had great difficulty in assessing suicide risk; more clinically useful risk indicators are crucially needed. Biologic markers such as low cerebrospinal fluid levels of the serotonin metabolite 5-hydroxyindoleacetic acid and related indices of serotonergic function appear to correlate with violent and impulsive suicidal behavior. These and other biologic changes may have predictive value in determining suicide risk, as well as contributing to the formulation of a more complete model to explain suicidal behavior that combines genetic, biologic, psychologic, and social factors.
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PMID:Psychobiologic predictors of suicide. 332 36

We previously reported that compared with normals, patients with chronic schizophrenia have reduced regional cerebral blood flow (rCBF) in dorsolateral prefrontal cortex (DLPFC) during performance of the Wisconsin Card Sort Test (WCS), a DLPFC-related cognitive task, but not during nonprefrontal tasks, such as a simple number-matching (NM) test. We also found that unlike normals, patients failed to activate DLPFC during the WCS over their own baseline (NM) level. To explore the reproducibility of these findings, a new cohort of 16 medication-free patients underwent a series of xenon 133 inhalation rCBF studies under the following conditions: at rest, while performing the WCS, and while performing NM. The results confirmed our earlier findings. In addition, the concentrations in cerebrospinal fluid of homovanillic acid and 5-hydroxyindoleacetic acid correlated with prefrontal rCBF during the WCS but not during the NM test or at rest. The results show that behavior-specific hypofunction of DLPFC in schizophrenia is reproducible, and they implicate a monoaminergic mechanism.
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PMID:Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia. III. A new cohort and evidence for a monoaminergic mechanism. 199 24


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