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Taurine and Glutathione in cerebrospinal fluid and plasma from patients with psychiatric disorders and healthy controls
Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A growing body of results indicate that immunological alterations and oxidative stress are of importance in various mental disorders. The inflammatory changes are possible to detect both in plasma and cerebrospinal fluid (CSF), and different psychiatric disorder exhibit similar changes indicating a common underlying mechanism. The antioxidants are of importance to regulate the redox balance and control the inflammatory processes but the causal relationship between psychiatric disorders and increased oxidative stress is however not fully clarified. Two important antioxidants; taurine and glutathione (GSH), have been suggested to have central nervous system (CNS)-protective properties. They have been found to fluctuate in several mental disorders including schizophrenia and depression but the clinical relevance need further studies.

The general aim of this thesis was to increase the understanding of taurine and the GSH in depression and schizophrenia, two major mental disorders, in comparison to healthy controls.

Correlations between glutathione and taurine levels in blood and CSF were analyzed in healthy male volunteers and we identified a complex pattern of associations showing that the CSF concentration was influenced by body mass index (BMI), age, intraspinal pressure, plasma concentrations the previous day and possible genetic factors. Electroconvulsive therapy (ECT) is used in the treatment of severely depressed patients. In blood collected before the first and after the third ECT, we found a significant decrease in plasma taurine in patients responding to the treatment, while total glutathione was unaltered. In a group of olanzapine treated patients with schizophrenia or schizoaffective disorders, we analysed taurine and glutathione in plasma and CSF and compared with healthy male and female volunteers. We observed increased plasma taurine levels in patients compared with controls, but no difference in CSF taurine and no alteration in glutathione.

This thesis indicates that taurine might play a role in mental disorders such as depression and schizophrenia. Increased knowledge about the complex regulation of taurine and glutathione might provide new insights into the impact of redox balance in the pathophysiology of psychiatric disorder and contribute to a future personalization of the treatment.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2012. , 65 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1316
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-84609ISBN: 978-91-7519-850-7 (print)OAI: oai:DiVA.org:liu-84609DiVA: diva2:560604
Public defence
2012-11-09, Eken, Campus US, Linköpings universitet, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2012-10-15 Created: 2012-10-15 Last updated: 2017-08-30Bibliographically approved
List of papers
1. Taurine in plasma and CSF: a study in healthy male volunteers
Open this publication in new window or tab >>Taurine in plasma and CSF: a study in healthy male volunteers
2009 (English)In: Amino Acids, ISSN 0939-4451, E-ISSN 1438-2199, Vol. 36, no 3, 529-533 p.Article in journal (Refereed) Published
Abstract [en]

In order to explore the interrelationship between plasma and cerebrospinal fluid taurine concentrations, three consecutive 6-ml fractions of cerebrospinal fluid were drawn from 30 healthy male volunteers in the early morning after 8 h in the fasting condition. Repeated plasma samples were drawn over 24 h the day before lumbar puncture. Taurine in plasma and cerebrospinal fluid was determined by high performance liquid chromatography. The subjects were categorized as extensive or poor metabolizers with respect to the cytochrome P450 2D6 genotype. The taurine cerebrospinal fluid/plasma ratio at 8 a.m. was negatively influenced by the plasma taurine concentration at 4 p.m. the previous day. It was also negatively influenced by body mass index and positively by the intraspinal pressure. Three poor metabolizers of cytochrome P450 2D6 had higher plasma taurine areas under the curve than 27 extensive metabolizers. Hypothetically, cytochrome P450 2D6 influences the transport of taurine across the blood-brain barrier.

Keyword
Taurine, Cerebrospinal fluid, Plasma, Cytochrome P450 2D6, Genotype
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-17389 (URN)10.1007/s00726-008-0115-9 (DOI)
Available from: 2009-03-21 Created: 2009-03-21 Last updated: 2017-12-13
2. Glutathione in the blood and cerebrospinal fluid: A study in healthy male volunteers
Open this publication in new window or tab >>Glutathione in the blood and cerebrospinal fluid: A study in healthy male volunteers
2011 (English)In: Neuropeptides, ISSN 0143-4179, E-ISSN 1532-2785, Vol. 45, no 4, 287-292 p.Article in journal (Refereed) Published
Abstract [en]

Glutathione (GSH) is an important regulator of intracellular redox homeostasis. In the brain, glutathione is considered a major antioxidant, which is also found at high concentrations in the extracellular environment. Altered GSH balance in plasma, blood and cerebrospinal fluid (CSF) has been observed in several disorders suggesting that an impaired antioxidant function is part of the pathophysiology. The aim of the present study was to investigate a possible relationship between glutathione in plasma and CSF. Blood samples were collected from 26 healthy male volunteers at 8 a.m., noon, 4 p.m. and 8 p.m. At 8 a.m. the following morning, blood was drawn and three 6-ml fractions of CSF were collected by lumbar puncture. In CSF, a disrupted gradient was found showing the highest glutathione concentration in the second compared to the first and third fraction (P andlt; 0.002). Moreover, correlation and regression analyses between glutathione in plasma and CSF revealed an association between the third fraction CSF and plasma glutathione 8 p.m. the day before lumbar puncture. Thus, if carefully standardised due to the disrupted gradient in CSF, it might be possible to estimate glutathione levels in CSF by analysing plasma in healthy males.

Place, publisher, year, edition, pages
Elsevier, 2011
Keyword
Glutathione, Plasma, Blood, Cerebrospinal fluid, Lumbar puncture
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-71560 (URN)10.1016/j.npep.2011.05.004 (DOI)000295349600005 ()
Note
Funding Agencies|Ostergotland County Council||Available from: 2011-10-21 Created: 2011-10-21 Last updated: 2017-12-08
3. Taurine and glutathione levels in plasma before and after ECT treatment
Open this publication in new window or tab >>Taurine and glutathione levels in plasma before and after ECT treatment
2012 (English)In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 198, no 1, 53-57 p.Article in journal (Refereed) Published
Abstract [en]

Taurine has been shown to be elevated in plasma and lymphocytes of depressed patients, but the level normalises after successful drug therapy. During depression, levels of glutathione (GSH) are decreased in the plasma and blood. This study was performed to examine taurine and GSH levels in depressed patients before and after electroconvulsive therapy (ECT). Fasting blood samples were collected from 23 patients before the first and after the third ECT treatment. The severity of depression was estimated with the Montgomery–Åsberg Depression Rating Scale (MADRS). We analysed GSH in blood and the levels of taurine and total GSH in plasma. After three ECTs, a significant decrease in MADRS scores was found for the entire group. Simultaneously, the decrease in the plasma taurine levels was significant for the seven responders but not for the sixteen non-responders. We observed no differences in blood or plasma GSH levels after three ECT treatments when compared to values before the therapy. Plasma taurine levels decrease significantly after three ECT treatments in patients who respond to treatment. GSH levels were not affected by ECT treatment. The results indicate that taurine may play a role in the pathophysiology of depression.

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam., 2012
Keyword
ECT; Taurine; Glutathione; Depression
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-84600 (URN)10.1016/j.psychres.2012.02.016 (DOI)000313848200010 ()
Available from: 2012-10-15 Created: 2012-10-15 Last updated: 2017-12-07Bibliographically approved
4. Taurine and glutathione in plasma and cerebrospinal fluid in olanzapine treated patients with schizophrenia
Open this publication in new window or tab >>Taurine and glutathione in plasma and cerebrospinal fluid in olanzapine treated patients with schizophrenia
Show others...
2013 (English)In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 210, no 3, 819-824 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: Oxidative stress has been implicated in the pathophysiology of schizophrenia. Taurine and glutathione (GSH) have antioxidant and central nervous system protective properties and are proposed to be involved in the pathology of schizophrenia. The aim of this study was to compare the blood and cerebrospinal fluid (CSF) levels of taurine and GSH in patients with schizophrenia medicated with oral olanzapine compared with controls.

Methods: In total, 37 patients with schizophrenia being medicated with olanzapine and 45 healthy volunteers were recruited. Taurine and GSH levels were analysed in plasma and CSF and correlated to symptoms and level of function.

Results: Plasma taurine levels were elevated in patients compared with controls (p=0.000003). No differences were found between patients and controls regarding taurine in CSF or GSH concentrations in plasma and CSF.

Conclusion: The significantly higher levels of plasma but not CSF taurine in patients with schizophrenia treated with olanzapine compared with controls may implicate the involvement of taurine in the pathophysiology of the disease. The absence of GSH differences in plasma and CSF between patients and controls is interesting in the perspective of earlier research proposing a dysregulation of GSH metabolism as a vulnerability factor for the development of schizophrenia.

Place, publisher, year, edition, pages
Elsevier, 2013
Keyword
Glutathione; taurine; schizophrenia; cerebrospinal fluid; olanzapine
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-84601 (URN)10.1016/j.psychres.2013.09.014 (DOI)000329417500024 ()
Available from: 2012-10-15 Created: 2012-10-15 Last updated: 2017-12-07Bibliographically approved

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