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)

In 36 drug-free schizophrenic patients, lumbar CSF was analyzed by mass fragmentography for the major monoaminergic transmitter metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG). High or deviant concentrations of 5-HIAA were significantly related to a family history of schizophrenia. For patients with deviant 5-HIAA levels, the probability for a family history of schizophrenia was eight times higher than in subjects with normal values. High concentrations of HVA also tended to be significantly related to a family history of schizoprenia. The majority of schizophrenic patients, who lacked family history for the disorder, had normal monoamine metabolite concentrations in CSF. The results suggest a coupling between biochemical variables related to central serotonin and dopamine metabolism and forms of schizophrenia that have a familial disposition.
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PMID:Aberrant monoamine metabolite levels in CSF and family history of schizophrenia. Their relationships in schizophrenic patients. 615 28

The symptom scores on the Schedule for Affective Disorders and Schizophrenia (SADS) of 21 unipolar and 12 bipolar depressive patients diagnosed with Research Diagnostic Criteria (RDC) were correlated with the monoamine metabolites homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5HIAA) in the cerebrospinal fluid (CSF). For the unipolar group, multiple regression analyses revealed strong multiple correlations (from r = 0.92 to 0.97) to the effect that high- and low-HVA, high- and low-MHPG, and high- and low-5HIAA syndromes, respectively, could be isolated. The bipolars were too few for the same analyses to work well, but there is evidence for the high- and low-monoamine syndromes to be characterized by differential symptomatology in bipolar and unipolar patients. Through the comparison of monoamine metabolite values predicted from a total of 18 SADS symptom items with the true CSF values, a computer program was able to classify 20 of the 21 unipolar and all the 12 bipolars correctly. The results are consistent with a hypothesis of the pathoplastic role of individually set (genetically determined?) brain monoamine homeostases in shaping the profile of an affective episode.
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PMID:Symptom patterns in unipolar and bipolar depression correlating with monoamine metabolites in the cerebrospinal fluid: I. General patterns. 617 40

Suicidality scores from the Schedule for Affective Disorders and Schizophrenia on 21 unipolar and 12 bipolar depressives were correlated with monoamine metabolites in the cerebrospinal fluid using multiple regression analyses. The single item of Suicidal Tendencies Worst Week correlated highly significantly and negatively with 3-methoxy-4-hydroxyphenylglycol (MHPG) and only to a very slight degree with 5-hydroxyindoleacetic acid (5HIAA). Seriousness of Intent of Worst Suicide Attempt earlier in life correlated significantly and negatively with both MHPG and 5HIAA. Subjective Anger was positively and Overt Anger negatively associated with thoughts of suicide. The results support earlier reports that depressives with low 5HIAA are prone to violent suicides, but also point to the equal, if not even greater involvement of MHPG and noradrenergic neuronal systems in carrying out a wish for death.
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PMID:Symptom patterns in unipolar and bipolar depression correlating with monoamine metabolites in the cerebrospinal fluid: II. Suicide. 617 41

The effect of 1 mg dexamethasone on CSF levels of 5-hydroxyindoleacetic acid (5 HIAA), homovanillic acid (HVA) and cortisol (CS) was investigated in 100 psychiatric inpatients: 45 subjects had their lumbar punctures 1-4 days following dexamethasone administration, and the results were compared with those from 55 other patients investigated before drug ingestion. All patients were women, and none had received psychotropic medication for at least two weeks before the study. Seven subjects consented to two LPs both before and after dexamethasone. As expected, cortisol in the CSF significantly decreased after dexamethasone: the decrease was greatest 10 hours following the drug. HVA showed a weak and transient elevation after 10 hours only. CSF 5 HIAA was found to be significantly increased in postdexamethasone samples and high levels were still found even after 82 hours. Diagnostic differences (major or minor depression, schizophrenia, alcohol abuse or dependence) did not account for the observed differences. Repeated CSF examinations in seven subjects corroborated these findings: all cortisol values were decreased and all 5 HIAA values were increased after dexamethasone while HVA values showed random changes. The data may suggest that serotonergic mechanisms may be involved in dexamethasone action in the CNS. In addition, dexamethasone administration can alter CSF 5 HIAA level, a possible factor which should be taken into consideration in CSF studies.
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PMID:The effect of dexamethasone on cerebrospinal fluid monoamine metabolites and cortisol in psychiatric patients. 619 44

Des-tyr1-gamma-endorphin (DT gamma E) was administered intramuscularly in a dose of 1 mg/day for 10 days to 18 neuroleptic-free schizophrenic patients in a double-blind crossover design. Six patients showed either a slight or no antipsychotic response; seven patients showed a moderate antipsychotic response; and the remaining five patients showed a marked antipsychotic response. DT gamma E led to a decrease of plasma prolactin levels in patients treated with DT gamma E in the first period of experimental treatment as compared to those treated with placebo. Neither plasma levels of growth hormone and cortisol nor cerebrospinal fluid concentrations of homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylglycol were affected by DT gamma E. Patients suffering from a hebephrenic or paranoid type of schizophrenia and those presenting relatively fewer negative symptoms were most susceptible to treatment with DT gamma E. These data confirm and extend previous findings that DT gamma E has antipsychotic properties in a number of schizophrenic patients.
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PMID:Clinical, biochemical, and hormonal aspects of treatment with Des-tyr1-gamma-endorphin in schizophrenia. 620 51

141 female psychiatric patients, suffering from major depression, schizophrenia, alcohol dependence or adjustment disorder, were investigated for their 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and cortisol level in the cerebrospinal fluid (CSF). Dexamethasone suppression tests were also performed in 111 cases, and TRH/TSH tests in 40 subjects. Fifty-two patients were hospitalized following a recent suicide attempt, 18 of which were made using a violent method. The other 34 attempters took tranquilizer or sedative overdoses. CSF 5-HIAA was significantly lower in violent attempters in all 4 diagnostic categories. CSF HVA was higher in those taking drug overdoses, but only in depression (and less markedly in schizophrenia). CSF cortisol did not differ among either diagnostic or suicidal subgroups. Dexamethasone suppression was more frequently abnormal in suicidal patients than in nonattempters, and this difference was more important where the overall nonsuppression rate was lower. Maximal TSH response to TRH showed an inverse correlation with CSF 5-HIAA, and it was lowest in the nonattempter group. The difference between violent suicide attempters and nonattempters in their TSH response was significant. Since these biochemical changes were more or less independent of clinical diagnoses, it seems relevant to explore further the biological background of human aggression and suicide as a separate research direction.
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PMID:Biochemical markers in suicidal patients. Investigations with cerebrospinal fluid amine metabolites and neuroendocrine tests. 620 31

While circadian rhythms of many biological processes have been well characterized in humans, variations throughout the year have been little studied. Lumbar cerebrospinal fluid (CSF) neurotransmitter metabolite levels for homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenyl glycol (MHPG) were determined in patients with schizophrenia and Alzheimer's disease. Samples from both groups taken during October through March had significantly higher levels of HVA and 5-HIAA, but not MHPG, than samples from April through September.
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PMID:Seasonal variations of human lumbar CSF neurotransmitter metabolite concentrations. 620 14

Considerable evidence has accrued in the last two decades to support the hypothesis that alterations in serotonergic neuronal function in the central nervous system occur in patients with major depression. These findings include the following: (a) reduced cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite of serotonin (5-HT) in drug-free depressed patients; (b) reduced concentrations of 5-HT and 5-HIAA in postmortem brain tissue of depressed and (or) suicidal patients; (c) decreased plasma tryptophan concentrations in depressed patients and a profound relapse in remitted depressed patients who have responded to a serotonergic antidepressant when brain tryptophan availability is reduced; (d) in general, all clinically efficacious antidepressants augment 5-HT neurotransmission following chronic treatment; (e) clinically efficacious antidepressant action by all inhibitors of 5-HT uptake; (f) increases in the density of 5-HT2 binding sites in postmortem brain tissue of depressed patients and suicide victims, as well as in platelets of drug-free depressed patients; (g) decreased number of 5-HT transporter (determined with [3H]imipramine or [3H]paroxetine) binding sites in postmortem brain tissue of suicide victims and depressed patients and in platelets of drug-free depressed patients. In our studies, this reduction in platelet 5-HT transporter binding is not due to prior antidepressant treatment of hypercortisolemia and is not observed in mania, Alzheimer disease, schizophrenia, panic disorder, fibromyalgia, or atypical depression. In a pilot study, this deficit predicted treatment response to an experimental antidepressant. These findings support the hypothesis that alterations in 5-HT neurons play a role in the pathophysiology of depression.
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PMID:Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. 1949 50

The effects of clozapine on the dopamine and serotonin systems may underlie its atypical pharmacologic and clinical profile. To examine this hypothesis, we measured dopamine and serotonin plasma and cerebrospinal (CSF) metabolites and the relationship of these values to treatment response in 19 neuroleptic refractory and intolerant schizophrenic patients. Only a small change in the CSF and plasma homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) levels was found. However, the pretreatment CSF HVA/5HIAA ratio and, to a lesser extent, the CSF HVA level predicted treatment response. These results suggest that the modest relationship between HVA and 5-HIAA and treatment response supports the involvement of both neurotransmitters in the pathophysiology of schizophrenia.
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PMID:The dopamine-serotonin relationship in clozapine response. 753 Mar 78

Concentrations of cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) were similar in patients with major depressive disorder and in those with non-depressive psychiatric problems, although concentrations were significantly lower in suicidal patients (particularly in those attempters who used violent methods) than in non-suicidal patients. In contrast, post mortem CSF 5-HIAA concentrations in suicide victims were significantly higher than in controls. In addition, there appear to be fewer imipramine binding sites in the left frontal cortex of the brain than the right in suicide victims, the converse being true for controls. The serotonergic dysfunction associated with suicidal behaviour is likely to be involved in other conditions such as depression, schizophrenia and anxiety disorder. Thus selective serotonin reuptake inhibitors may be useful in the treatment of various types of psychiatric disease. Fluvoxamine, in particular, is associated with a very low incidence of suicidality compared with other antidepressants.
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PMID:Prophylactic potential of selective reuptake inhibitors in suicidal patients. 754 77


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