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- Oxenstierna, G, et al.
(författare)
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Increased frequency of aberrant CSF circulation in schizophrenic patients compared to healthy volunteers
- 1996
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Ingår i: European psychiatry : the journal of the Association of European Psychiatrists. - : Cambridge University Press (CUP). - 0924-9338. ; 11:1, s. 16-20
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Tidskriftsartikel (refereegranskat)abstract
- In a previous cisternographic study of the cerebrospinal fluid (CSF) circulation in schizophrenic patients, indications for disturbed flow dynamics were found in 10 of 30 subjects. In order to replicate and investigate the clinical and pathophysiological significance of this finding, 39 schizophrenic patients and 42 healthy subjects were examined with an improved method for measurement of CSF circulation. 99mTc-DTPA was injected intrathecally and the gamma cisternograms were evaluated blindly. Correlations between cisternography findings and age, duration of disease, previous hospitalizations, positive or negative symptomatology, exposure to neuroleptics, psychiatric family history, CT findings and CSF levels of protein, tryptophan and monoamine metabolites, were calculated. Seven of the patients showed abnormalities in the cisternograms with a slow or obstructed flow of CSF over the convexities (P < 0.01) whereas none of the healthy volunteers showed abnormalities. There were no correlations between disturbed CSF circulation in the patients and the clinical and biochemical parameters, thus the significance of the deviations, similar to other biological aberrations found in schizophrenic patients, is not known. Recent developments in magnetic resonance imaging offer new possibilities to further examine CSF circulation abnormalities in schizophrenia.
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| 3. |
- Wiesel, F.-A., et al.
(författare)
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The complexity of using D2-dopamine antagonists in the treatment of patients with schizophrenia
- 2007
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Ingår i: European psychiatry. - : Elsevier Masson. - 0924-9338 .- 1778-3585. ; 22, s. S5-S6
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia is a complex disorder and the view that schizophrenia is caused by hyperdopaminergic activity is an oversimplification. In fact, there are clinical evidence in accordance with a hypodopaminergic condition. Thus, untreated patients show motor disturbances in line with a decreased dopamine activity in the extrapyramidal system, likewise cognitive deficits and negative symptoms. In our research we have explored the evidence of schizophrenia as a hyper- or hypodopaminergic condition. With Positron Emission Tomography (PET) we have not seen any evidence of increased D2-dopamine receptors in the brain of never medicated patients. The major dopamine metabolite homovanillic acid (HVA) was lowered in CSF in line with a decreased dopamine turnover in the brain. Tyrosine is precursor to the synthesis of dopamine and for that aim we have made transport studies in an in vitro model with fibroblasts to determine tyrosine kinetics. The results demonstrated that tyrosine transport is lower in patients with schizophrenia in comparison to healthy controls. Tyrosine kinetics measured with PET demonstrated dysregulation of tyrosine transport into the brain.We have found evidence of schizophrenia as a hypodopaminergic condition. This fact is a problem realizing that our antipsychotics are D2-dopamine antagonists, thus decreasing dopamine activity even further.The concept of schizophrenia as both a hypo- and hyperdopaminergic condition may explain why clozapine, a week D2-antagonist, works more efficiently than other antipsychotic compounds. It should be recognized that positive symptoms are, at least partly, related to changes in dopamine activity and therefore respond very efficiently to D2-dopamine antagonists.
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