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)

Blood platelets accumulate, store and release a variety of biogenic amines including norepinephrine, serotonin and dopamine (DA) which are known to act as neurotransmitter substances. Platelet monoamine oxidase (MAO) shares many biochemical properties with the mitochondrial MAO present in brain tissue. For these reasons it has been suggested that platelets might serve as a diagnostic and research model for nerve cells in a variety of neuropsychiatric diseases. In some patients with schizophrenia and manic depressive phychoses, platelet MAO activity is significantly decreased. Central nervous system inhibition of MAO could lead to excess accumulation of monoamines in the brain; this would be consistent with the DA hypothesis of schizophrenia. Disturbances of monoamines and enzyme kinetics in the hereditary ataxias and in Huntington disease have been described, but these findings are unproven and controversal. If platelet models for human neuropsychiatric disease can be established, they will be immensely important in preclinical diagnosis, therapy and genetic counseling.
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PMID:Platelet enzyme abnormalities in neuropsychiatric disease. 610 42

We studied 93 chronic schizophrenic inpatients, who met the Research Diagnostic Criteria for schizophrenia. Data on a number of historical, epidemiologic, phenomenologic, biochemical, neuropathological, and treatment-response variables were analyzed, using univariate and multivariate statistical analyses. Patients were classified into pairs of subgroups, according to each of the following seven dimensions: (1) ventricle/brain ratio (VBR) assessed on computed tomography scans (normal vs. abnormal); (2) premorbid adjustment (good vs. poor); (3) therapeutic response to neuroleptics (good vs. poor); (4) platelet monoamine oxidase (MAO) activity (low vs. high); (5) paranoid features (present vs. absent); (6) tardive dyskinesia (present vs. absence); and (7) hemispheric asymmetry on computed tomography scans (normal vs. abnormal). These seven dimensions were chosen because earlier studies had shown that the variables involved were operationally definable and were of potential relevance to the subgrouping of schizophrenic patients. Our results suggested that two biological variables, viz., VBR and platelet MAO activity, might be useful in identifying two rather distinct subgroups among chronic schizophrenic patients. A subgroup with large VBR was associated with poor premorbid adjustment, neurological impairment, and poor therapeutic response to neuroleptics, while the subgroup with low platelet MAO activity was characterized by the presence of paranoid features and tardive dyskinesia. Possible explanations, implications, and limitations of our findings are discussed.
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PMID:Ex uno multi: subtyping the schizophrenic syndrome. 612 74

New uses are still being discovered for a number of psychotropic agents that have been available for some time. Among the more important recent discoveries are the efficacy of the tricyclic antidepressants for panic disorder and agoraphobia with panic attacks; the use of the monoamine oxidase inhibitors for the above disorders and for atypical depression and hysteroid dysphoria; the use of propranolol for anxiety disorders and for uncontrollable violent outbursts; the antianxiety and antipanic effects of clonidine; and the usefulness of lithium in treating schizophrenia and schizoaffective disorder and for emotionally unstable character disorders. In addition to strengthening the therapeutic armamentarium, the author says, the discovery of new drug response patterns helps generate or strengthen hypotheses about the pathophysiology of various psychiatric disorders.
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PMID:Newer uses for older psychotropic medications. 612 38

Activity levels of platelet monoamine oxidase (MAO) and plasma amine oxidase (PAO) were determined in eight chronic schizophrenic patients who had been treated with neuroleptic drugs for 3 months. The mean reduction in platelet MAO activity was 18.6%. The extent of decrease was statistically significant. The reduction in enzyme activity was unrelated to serum iron levels. PAO activity was unaltered. The implications for schizophrenia research are discussed.
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PMID:Neuroleptic drug effect on platelet monoamine oxidase and plasma amine oxidase in schizophrenia. 612 54

Among the biochemical theories proposed for schizophrenia the best-founded appears to be the dopaminergic theory. Dopaminergic agonists exacerbate schizophrenic symptoms. Neuroleptics, which are the most effective drugs in schizophrenia, are dopaminergic-blocking agents. Other biochemical disorders have been demonstrated in some cases of schizophrenia but results are not always consonant. The presence of abnormal compounds, i.e. methylated derivatives or phenylethylamine, has often been mentioned. Several disorders of enzymes have also been reported, such as a defect in beta-dopamine hydroxylase or an abnormal activity of the MAO which metabolizes the indolamines and catecholamines. Disorders of the metabolism of noradrenaline and serotonin have also been suggested, mainly on experimental evidence. Other compounds have been incriminated, such as endorphins, gamma-aminobutyric acid, lysine-8 vasopressin or prostaglandins. The action of neuroleptics can be ascribed to dopaminergic respector blockade, as a safe approximation. However, the demonstration of several dopaminergic pathways and of several types of receptors makes the understanding of their mode of action all the more difficult that they interplay with many other neurotransmittors.
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PMID:[Biochemistry of schizophrenia and mechanism of action of neuroleptics]. 613 Jun 4

Reported here are the results of a study of symptom state, platelet monoamine oxidase (MAO) activity, and demographic variables in a group of elderly neuroleptic-free schizophrenics. Analyzed by both bivariate and multivariate techniques, the data from this sample indicate that after the effects of demographic variables upon the variance of enzyme activity have been controlled for, the patients most likely to continue to manifest schizophrenic symptomatology in the senium are those with low platelet MAO activity. The results are discussed with respect to other studies of platelet MAO and prognosis in schizophrenia and with respect to future studies.
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PMID:Schizophrenic outcome in late life: symptom state and platelet monoamine oxidase activity. 614 37

Somatostatin-like immunoreactivity was measured in the cerebrospinal fluid (CSF) of 85 inpatients with current or recent episodes of major depressive disorders, diagnosed according to Research Diagnostic Criteria (RDC) as assessed with the Schedule for Affective Disorders and Schizophrenia (SADS). Several biopsychiatric tests were run during the same week of investigation. Results indicate low levels of CSF somatostatin to be a state marker for episodes of depression characterized by sad appearance, feelings of tiredness, insomnia, and subjective inability to acknowledge any external precipitants for the depression. CSF somatostatin was negatively related to platelet monoamine oxidase (MAO) activity; MAO activity appeared to account better for the degree of melancholic features than did somatostatin. The ratio between 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) in CSF also correlated negatively with somatostatin. A positive relationship was noted between CSF xanthine and somatostatin. There was a highly significant curvilinear correlation between CSF somatostatin and serum TSH concentrations, but no correlations between CSF somatostatin and serum GH or prolactin, or with plasma cortisol before or after dexamethasone.
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PMID:Low levels of somatostatin in human CSF mark depressive episodes. 614 88

Rats which had been primed with the serotonin depletor, p-chlorophenylalanine, and sacrificed months later were found to have the same resting levels of brain serotonin and norepinephrine as unprimed controls. However, when treated with the monoamine oxidase inhibitor, tranylcypromine, the former showed a significantly lower accumulation of these biogenic amines than their tranylcypromine-treated unprimed counterparts. These findings indicate that brain serotonin, which had been lowered at the outset by p-chlorophenylalanine, had returned to normal levels but that the priming procedure might have resulted in a long-term decrease in the turnover rates of serotonin as well as norepinephrine. Primed animals may prove suitable as models of disturbed biogenic amine metabolism with possible relevance to schizophrenia and other brain dysfunctions.
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PMID:Serotonin and norepinephrine: long-term decrease in rate of synthesis in brain of rats primed with p-chlorophenylalanine. 616 15

One hundred and ten patients with Research Diagnostic Criteria (RDC) diagnoses of major depressive disorders were assessed for present or recent suicidal ideation and behavior and for suicidal acts earlier in life before current depression using the Schedule for Affective Disorders and Schizophrenia (SADS). Suicidal scores were correlated uni- and bivariately with levels of CSF monoamine metabolites (HVA, 5HIAA, MHPG), urinary MHPG, the proportion post-/predexamethasone plasma cortisol at 1100 h, and platelet MAO activity (all standardized to same sex, age, height and weight). Results indicate that all 3 monoamine metabolites and their interactions are involved in various aspects of suicidality, at least in unipolar patients. MHPG and 5HIAA (both low or both high) were involved in current or recent suicidal ideation, and low HVA was mainly associated with past potential lethality of suicidal acts. Current hypercortisolism was found in patients that earlier in life had tried to commit dangerous suicides. Bipolar patients (depressives with a history of manic or hypomanic episodes) had earlier in life significantly more, and more dangerous, suicidal attempts than the unipolars.
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PMID:Life at risk: markers of suicidality in depression. 620 42

Vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK) and gastrin in the cerebrospinal fluid (CSF) were studied in patients with endogenous depression, non-endogenous depression, mania, schizophrenia and a control group. All patients were classified according to ICD-9 and the group of depressions was further classified according to the Newcastle Rating Scales for depression (Carney et al. 1965) (N-I). In the group of non-endogenously depressed patients, CSF-VIP levels (median 16 pmol/l) were found to be significantly lower than those of controls (median = 32 pmol/l) and endogenous depressives (36 pmol/l). In the non-endogenous group, it appeared that the low CSF-VIP was due to a group of patients who, during a past or present depressive episode, had been diagnosed as suffering from endogenous depression. Moreover, this group was clinically characterized by 'dysphoric/hysterical features', 'reversed diurnal variation' (i.e. worse in the evening), and 'lack of clearly circumscribed episodes'. In many aspects this group seems similar to the atypical depressives described as monoamine oxidase inhibitor responders. Concerning CSF-CCK and CSF-gastrin, no significant differences between the examined groups were demonstrated.
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PMID:Vasoactive intestinal polypeptide decreased in cerebrospinal fluid (CSF) in atypical depression. Vasoactive intestinal polypeptide, cholecystokinin and gastrin in CSF in psychiatric disorders. 624 Dec 14


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