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Samuelsson, Martin
Publications (10 of 23) Show all publications
Schwieler, L., Samuelsson, M., Frye, M. A., Bhat, M., Schuppe-Koistinen, I., Jungholm, O., . . . Erhardt, S. (2016). Electroconvulsive therapy suppresses the neurotoxic branch of the kynurenine pathway in treatment-resistant depressed patients. Journal of Neuroinflammation, 13(51)
Open this publication in new window or tab >>Electroconvulsive therapy suppresses the neurotoxic branch of the kynurenine pathway in treatment-resistant depressed patients
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2016 (English)In: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 13, no 51Article in journal (Refereed) Published
Abstract [en]

Background: Neuroinflammation is increasingly recognized as contributing to the pathogenesis of depression. Key inflammatory markers as well as kynurenic acid (KYNA) and quinolinic acid (QUIN), both tryptophan metabolites, have been associated with depressive symptoms and suicidality. The aim of the present study is to investigate the peripheral concentration of cytokines and tryptophan and kynurenine metabolites in patients with unipolar treatment-resistant depression before and after electroconvulsive therapy (ECT), the most effective treatment for depression. Methods: Cytokines in plasma from patients with major depressive disorder (MDD; n = 19) and healthy volunteers (n = 14) were analyzed with electrochemiluminescence detection. Tryptophan and kynurenine metabolites were detected with high-performance liquid chromatography (HPLC) and LC/MS. KYNA was analyzed in a second healthy control cohort (n = 22). Results: Patients with MDD had increased plasma levels of interleukin (IL)-6 compared to healthy volunteers (P < 0.05). We also found an altered kynurenine metabolism in these patients displayed by decreased plasma levels of KYNA (P < 0.0001) as well as a significantly increased QUIN/KYNA ratio (P < 0.001). Plasma levels of tryptophan, kynurenine, and QUIN did not differ between patients and controls. Treatment with ECT was associated with a significant decrease in the plasma levels of tryptophan (P < 0.05), kynurenine (P < 0.01), and QUIN (P < 0.001), whereas plasma levels of KYNA did not change. The QUIN/KYNA ratio was found to significantly decrease in ECT-treated patients (P < 0.05). There was a significant inverse correlation between symptom severity and kynurenine levels at baseline (r = -0.67, P = 0.002). Conclusions: This study confirms an imbalanced kynurenine pathway in MDD supporting the hypothesis of a netstimulation of N-methyl-D-aspartic acid (NMDA) receptors in the disorder. Treatment with ECT profoundly decreased QUIN, an NMDA-receptor agonist previously suggested to be implicated in the pathogenesis of depression, an effect that might have bearing for the good clinical outcome of ECT.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2016
Keywords
NMDA receptor; Cytokines; ECT; Quinolinic acid; Inflammation; IL-6; Kynurenic acid; Treatment-resistant depression
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-126251 (URN)10.1186/s12974-016-0517-7 (DOI)000370952400001 ()26925576 (PubMedID)
Note

Funding Agencies|Swedish Medical Research Council [2009-7053; 2013-2838, K2014-62X-14647-12-51]; Swedish Brain Foundation; Svenska Lakaresallskapet; Petrus och Augusta Hedlunds Stiftelse; Ostergotland County Council; AstraZeneca-Karolinska Institutet Joint Research Program in Translational Science; Karolinska Institutet (KID); Swedish Federal Government under the LUA/ALF [ALF 20130032]; Linkoping University Hospital; Karolinska Institutet

Available from: 2016-03-21 Created: 2016-03-21 Last updated: 2017-11-30
Ventorp, F., Barzilay, R., Erhardt, S., Samuelsson, M., Traskman-Bendz, L., Janelidze, S., . . . Brundin, L. (2016). The CD44 ligand hyaluronic acid is elevated in the cerebrospinal fluid of suicide attempters and is associated with increased blood-brain barrier permeability. Journal of Affective Disorders, 193, 349-354
Open this publication in new window or tab >>The CD44 ligand hyaluronic acid is elevated in the cerebrospinal fluid of suicide attempters and is associated with increased blood-brain barrier permeability
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2016 (English)In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 193, p. 349-354Article in journal (Refereed) Published
Abstract [en]

Background: The glycosaminoglycan hyaluronic acid (HA) is an important component of the extracellular matrix (ECM) in the brain. CD44 is a cell adhesion molecule that binds to HA in the ECM and is present on astrocytes, microglia and certain neurons. Cell adhesion molecules have been reported to be involved in anxiety and mood disorders. CD44 levels are decreased in the cerebrospinal fluid (CSF) of depressed individuals, and the CD44 gene has been identified in brain GWAS studies as a possible risk gene for suicidal behavior. Method: We measured the CSF levels of HA and the soluble CD44 (sCD44) in suicide attempters (n=94) and in healthy controls (n=45) using ELISA and electrochemiluminescence assays. We also investigated other proteins known to interact with CD44, such as osteopontin and the matrix metalloproteinases MMP1, MMP3 and MMP9. Results: The suicide attempters had higher CSF levels of HA (p=.003) and MMP9 (p=.004). The CSF levels of HA correlated with BBB-permeability (rho=0.410, p<.001) and MMP9 correlated with sCD44 levels (rho=0.260, p=.005). Limitations: Other relevant biological contributors to suicidal behavior is not addressed in parallel to the specific role of CD44-HA signaling. The gender distribution of the patients from whom CSF was analyzed was uneven. Conclusions: Increased BBB-permeability and HA levels might be a results of increased neuroinflammation and can play a role in the pathobiology of suicidal behavior. The CD44 signaling pathway might be considered a novel target for intervention in mood disorders. (C) 2016 Elsevier B.V. All rights reserved.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2016
Keywords
Suicide; CSF; Hyaluronic acid; CD44; MMP9; Inflammation
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-125668 (URN)10.1016/j.jad.2015.12.069 (DOI)000369586000049 ()26796235 (PubMedID)
Available from: 2016-03-02 Created: 2016-02-29 Last updated: 2017-11-30
Bay-Richter, C., Linderholm, K. R., Lim, C. K., Samuelsson, M., Traskman-Bendz, L., Guillemin, G. J., . . . Brundin, L. (2015). A role for inflammatory metabolites as modulators of the glutamate N-methyl-D-aspartate receptor in depression and suicidality. Brain, behavior, and immunity, 43, 110-117
Open this publication in new window or tab >>A role for inflammatory metabolites as modulators of the glutamate N-methyl-D-aspartate receptor in depression and suicidality
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2015 (English)In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 43, p. 110-117Article in journal (Refereed) Published
Abstract [en]

Background: Patients with depression and suicidality suffer from low-grade neuroinflammation. Proinflammatory cytokines activate indoleamine 2,3-dioxygenase, an initial enzyme of the kynurenine pathway. This pathway produces neuroactive metabolites, including quinolinic- and kynurenic acid, binding to the glutamate N-methyl-D-aspartate-receptor, which is hypothesized to be part of the neural mechanisms underlying symptoms of depression. We therefore hypothesized that symptoms of depression and suicidality would fluctuate over time in patients prone to suicidal behavior, depending on the degree of inflammation and kynurenine metabolite levels in the cerebrospinal fluid (CSF). Methods: We measured cytokines and kynurenine metabolites in CSF, collected from suicide attempters at repeated occasions over 2 years (total patient samples n = 143, individuals n = 30) and healthy controls (n = 36). The association between the markers and psychiatric symptoms was assessed using the Montgomery Asberg Depression Rating Scale and the Suicide Assessment Scale. Results: Quinolinic acid was increased and kynurenic acid decreased over time in suicidal patients versus healthy controls. Furthermore, we found a significant association between low kynurenic acid and severe depressive symptoms, as well as between high interleukin-6 levels and more severe suicidal symptoms. Conclusions: We demonstrate a long-term dysregulation of the kynurenine pathway in the central nervous system of suicide attempters. An increased load of inflammatory cytokines was coupled to more severe symptoms. We therefore suggest that patients with a dysregulated kynurenine pathway are vulnerable to develop depressive symptoms upon inflammatory conditions, as a result the excess production of the NMDA-receptor agonist quinolinic acid. This study provides a neurobiological framework supporting the use of NMDA-receptor antagonists in the treatment of suicidality and depression. (C) 2014 Elsevier Inc. All rights reserved.

Place, publisher, year, edition, pages
ACADEMIC PRESS INC ELSEVIER SCIENCE, 2015
Keywords
Suicide; Glutamate; Quinolinic acid; Kynurenic acid; Interleukin-6; Cerebrospinal fluid
National Category
Basic Medicine
Identifiers
urn:nbn:se:liu:diva-121771 (URN)10.1016/j.bbi.2014.07.012 (DOI)000360592700015 ()25124710 (PubMedID)
Note

Funding Agencies|Michigan State University; Van Andel Research Institute; Swedish Research Council [2009-4284, 2011-4787, 2002-5297, 2008-2922, 2009-7052, 2013-2838]; Province of Scania clinical state grants (ALF); Australian Research Council; National Health and Medical Research Council, Australia

Available from: 2015-10-06 Created: 2015-10-05 Last updated: 2018-01-11
Schwieler, L., Larsson, M. K., Skogh, E., Kegel, M. E., Orhan, F., Abdelmoaty, S., . . . Engberg, G. (2015). Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia - significance for activation of the kynurenine pathway.. Journal of Psychiatry & Neuroscience, 40(2), 126-13
Open this publication in new window or tab >>Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia - significance for activation of the kynurenine pathway.
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2015 (English)In: Journal of Psychiatry & Neuroscience, ISSN 1180-4882, E-ISSN 1488-2434, Vol. 40, no 2, p. 126-13Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Accumulating evidence indicates that schizophrenia is associated with brain immune activation. While a number of reports suggest increased cytokine levels in patients with schizophrenia, many of these studies have been limited by their focus on peripheral cytokines or confounded by various antipsychotic treatments. Here, well-characterized patients with schizophrenia, all receiving olanzapine treatment, and healthy volunteers were analyzed with regard to cerebrospinal fluid (CSF) levels of cytokines. We correlated the CSF cytokine levels to previously analyzed metabolites of the kynurenine (KYN) pathway.

METHODS: We analyzed the CSF from patients and controls using electrochemiluminescence detection with regard to cytokines. Cell culture media from human cortical astrocytes were analyzed for KYN and kynurenic acid (KYNA) using high-pressure liquid chromatography or liquid chromatography/mass spectrometry.

RESULTS: We included 23 patients and 37 controls in our study. Patients with schizophrenia had increased CSF levels of interleukin (IL)-6 compared with healthy volunteers. In patients, we also observed a positive correlation between IL-6 and the tryptophan:KYNA ratio, indicating that IL-6 activates the KYN pathway. In line with this, application of IL-6 to cultured human astrocytes increased cell medium concentration of KYNA.

LIMITATIONS: The CSF samples had been frozen and thawed twice before analysis of cytokines. Median age differed between patients and controls. When appropriate, all present analyses were adjusted for age.

CONCLUSION: We have shown that IL-6, KYN and KYNA are elevated in patients with chronic schizophrenia, strengthening the idea of brain immune activation in patients with this disease. Our concurrent cell culture and clinical findings suggest that IL-6 induces the KYN pathway, leading to increased production of the N-methyl-D-aspartate receptor antagonist KYNA in patients with schizophrenia.

Place, publisher, year, edition, pages
CMA-CANADIAN MEDICAL ASSOC, 2015
National Category
Neurosciences
Identifiers
urn:nbn:se:liu:diva-116363 (URN)10.1503/jpn.140126 (DOI)000351206800008 ()25455350 (PubMedID)
Available from: 2015-03-26 Created: 2015-03-26 Last updated: 2018-01-11Bibliographically approved
Janelidze, S., Suchankova, P., Ekman, A., Erhardt, S., Sellgren, C., Samuelsson, M., . . . Brundin, L. (2015). Low IL-8 is associated with anxiety in suicidal patients: genetic variation and decreased protein levels. Acta Psychiatrica Scandinavica, 131(4), 269-278
Open this publication in new window or tab >>Low IL-8 is associated with anxiety in suicidal patients: genetic variation and decreased protein levels
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2015 (English)In: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 131, no 4, p. 269-278Article in journal (Refereed) Published
Abstract [en]

ObjectiveRecent studies indicate that inflammation may play a role in the pathophysiology of suicidality. Interleukin-8 (IL-8) is a chemokine that in addition to its function in the immune system also exert neuroprotective properties. The involvement of this chemokine in neuropsychiatric conditions is incompletely known. MethodWe measured plasma and cerebrospinal fluid (CSF) IL-8, as well as the genotype frequency of a single nucleotide polymorphism (-251A/T, rs4073) in the promoter region of the IL8 gene, in suicide attempters (n=206) and healthy controls (n=578). ResultsPlasma and CSF levels of IL-8 were significantly lower in suicide attempters with anxiety than in healthy controls. IL-8 in both plasma and CSF correlated negatively with symptoms of anxiety. Compared with the population-based cohort, the IL-8-251T allele was more prevalent among female suicide attempters. Furthermore, suicide attempters carrying this allele showed more severe anxiety. This correlative study warrants further mechanistic studies on the effects of IL-8 in the central nervous system. ConclusionWe suggest that IL-8 might be involved in the biological mechanisms mediating resilience to anxiety. Thus, our findings highlight the chemokine IL-8 as a potential target for future development of anti-anxiety treatments and suicide prevention.

Place, publisher, year, edition, pages
Wiley: 12 months, 2015
Keywords
depression; inflammation; chemokine; biomarker
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-116942 (URN)10.1111/acps.12339 (DOI)000351147200008 ()25251027 (PubMedID)
Note

Funding Agencies|Swedish Research Council [2009-7052, 2013-2838]; Swedish Brain Foundation; Soderstrom-Konig Foundation; Sjobring Foundation; Fysiografiska Society; province of Scania state grants (ALF)

Available from: 2015-04-13 Created: 2015-04-10 Last updated: 2017-12-04
Kegel, M. E., Bhat, M., Skogh, E., Samuelsson, M., Lundberg, K., Dahl, M.-L., . . . Erhardt, S. (2014). Imbalanced Kynurenine Pathway in Schizophrenia. International Journal of Tryptophan Research, 7, 15-22
Open this publication in new window or tab >>Imbalanced Kynurenine Pathway in Schizophrenia
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2014 (English)In: International Journal of Tryptophan Research, ISSN 1178-6469, Vol. 7, p. 15-22Article in journal (Refereed) Published
Abstract [en]

Several studies suggest a role for kynurenic acid (KYNA) in the pathophysiology of schizophrenia. It has been proposed that increased brain KYNA levels in schizophrenia result from a pathological shift in the kynurenine pathway toward enhanced KYNA formation, away from the other branch of the pathway leading to quinolinic acid (QUIN). Here we investigate the levels of QUIN in cerebrospinal fluid (CSF) of patients with schizophrenia and healthy controls, and relate those to CSF levels of KYNA and other kynurenine metabolites from the same individuals. CSF QUIN levels from stable outpatients treated with olanzapine (n = 22) and those of controls (n = 26) were analyzed using liquid chromatography-mass spectrometry. No difference in CSF QUIN levels between patients and controls was observed (20.6 ± 1.5 nM vs. 18.2 ± 1.1 nM, P = 0.36). CSF QUIN was positively correlated to CSF kynurenine and CSF KYNA in patients but not in controls. The CSF QUIN/KYNA ratio was lower in patients than in controls (P = 0.027). In summary, the present study offers support for an over-activated and imbalanced kynurenine pathway, favoring the production of KYNA over QUIN in patients with schizophrenia.

Place, publisher, year, edition, pages
Libertas Academica, 2014
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-110785 (URN)10.4137/IJTR.S16800 (DOI)
Available from: 2014-09-22 Created: 2014-09-22 Last updated: 2017-12-05Bibliographically approved
Janelidze, S., Ventorp, F., Erhardt, S., Hansson, O., Minthon, L., Flax, J., . . . Brundin, L. (2013). Altered chemokine levels in the cerebrospinal fluid and plasma of suicide attempters. Psychoneuroendocrinology, 38(6), 853-862
Open this publication in new window or tab >>Altered chemokine levels in the cerebrospinal fluid and plasma of suicide attempters
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2013 (English)In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 38, no 6, p. 853-862Article in journal (Refereed) Published
Abstract [en]

Chemokines constitute a class of small inflammatory proteins that control the chemotaxis of leukocytes. They are also present in the central nervous system (CNS) and contribute to diverse physiological functions, such as the regulation of cell migration, axonal growth and neuronal survival. It is to date not known whether chemokines in the CNS are affected in psychiatric disorders. In this study, chemokine levels were measured in the cerebrospinal fluid (CSF) of 137 psychiatric patients in conjunction to a suicide attempt, and 43 healthy controls. A subgroup of patients (n = 42) was followed up with blood samples 12 years after the initial CSF collection, when they did not show suicidal behavior. The follow-up chemokine levels were compared to those of psychiatric patients (n = 17) who had never attempted suicide. Ultrasensitive chemokine multiplex immunoassay was used to quantify eotaxin-1 (CCL11), interferon gamma-induced protein-10 (IP-10, CXCL10), macrophage inflammatory protein-1 beta (MIP-1 beta, CCL4), monocyte chemotactic protein-1 (MCP-1, CCL2), MCP-4 (CCL13) and thymus and activation regulated chemokine (TARC, CCL17). Patients were diagnosed using DSM-III-R/DSM-IV, and assessed using the Comprehensive Psychopathological Rating Scale (CPRS), including subscales, and the Suicidal Intent Scale (SIS). CSF eotaxin-1, MIP-1 beta, MCP-1, MCP-4 and TARC were significantly lower in suicide attempters than in healthy controls. Low chemokine levels were specifically associated with psychotic symptoms and pain. In the samples collected at follow-up, TARC was significantly lower in suicide attempters compared to psychiatric patients who had never attempted suicide. We also found a positive correlation between blood TARC and brain-derived neurotrophic factor (BDNF) levels. Our study thus provides evidence of reduced chemokine levels in suicide attempters, both in the acute suicidal setting, and at long-term, compared to non-attempters. These results warrant future studies on the detailed neurobiological functions of chemokines in psychiatric patients. (C) 2012 Elsevier Ltd. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2013
Keywords
Chemokines; Suicide attempt; Depression; Inflammation; Cerebrospinal fluid; Eotaxin-1; MIP-1 beta; MCP-1; MCP-4; TARC
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-103411 (URN)10.1016/j.psyneuen.2012.09.010 (DOI)000319540000012 ()
Available from: 2014-01-20 Created: 2014-01-20 Last updated: 2017-12-06
Erhardt, S., Lim, C. K., Linderholm, K. R., Janelidze, S., Lindqvist, D., Samuelsson, M., . . . Brundin, L. (2013). Connecting Inflammation with Glutamate Agonism in Suicidality. Neuropsychopharmacology, 38(5), 743-752
Open this publication in new window or tab >>Connecting Inflammation with Glutamate Agonism in Suicidality
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2013 (English)In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 38, no 5, p. 743-752Article in journal (Refereed) Published
Abstract [en]

The NMDA-receptor antagonist ketamine has proven efficient in reducing symptoms of suicidality, although the mechanisms explaining this effect have not been detailed in psychiatric patients. Recent evidence points towards a low-grade inflammation in brains of suicide victims. Inflammation leads to production of quinolinic acid (QUIN) and kynurenic acid (KYNA), an agonist and antagonist of the glutamatergic N-methyl-D-aspartate (NMDA) receptor, respectively. We here measured QUIN and KYNA in the cerebrospinal fluid (CSF) of 64 medication-free suicide attempters and 36 controls, using gas chromatography mass spectrometry and high-performance liquid chromatography. We assessed the patients clinically using the Suicide Intent Scale and the Montgomery Asberg Depression Rating Scale (MADRS). We found that QUIN, but not KYNA, was significantly elevated in the CSF of suicide attempters (Pandlt;0.001). As predicted, the increase in QUIN was associated with higher levels of CSF interleukin-6. Moreover, QUIN levels correlated with the total scores on Suicide Intent Scale. There was a significant decrease of QUIN in patients who came for follow-up lumbar punctures within 6 months after the suicide attempt. In summary, we here present clinical evidence of increased QUIN in the CSF of suicide attempters. An increased QUIN/KYNA quotient speaks in favor of an overall NMDA-receptor stimulation. The correlation between QUIN and the Suicide Intent Scale indicates that changes in glutamatergic neurotransmission could be specifically linked to suicidality. Our findings have important implications for the detection and specific treatment of suicidal patients, and might explain the observed remedial effects of ketamine. Neuropsychopharmacology (2013) 38, 743-752; doi:10.1038/npp.2012.248; published online 9 January 2013

Place, publisher, year, edition, pages
Nature Publishing Group: Open Access Hybrid Model Option A, 2013
Keywords
quinolinic acid, suicide, depression, glutamate, cytokine
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-91010 (URN)10.1038/npp.2012.248 (DOI)000316161300004 ()
Note

Funding Agencies|Swedish Research Council|2009-42842011-47872002-52972008-29222009-70522011-4795|Province of Scania clinical state grants (ALF)||American Foundation for Suicide Prevention|2-DIG-00030-0608-1208|Rebecca Cooper Foundation||National Health Medical Research Council in Australia (NHMRC)||

Available from: 2013-04-11 Created: 2013-04-11 Last updated: 2017-12-06
Samuelsson, M., Skogh, E., Lundberg, K., Vrethem, M. & Öllinger, K. (2013). Taurine and glutathione in plasma and cerebrospinal fluid in olanzapine treated patients with schizophrenia. Psychiatry Research, 210(3), 819-824
Open this publication in new window or tab >>Taurine and glutathione in plasma and cerebrospinal fluid in olanzapine treated patients with schizophrenia
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2013 (English)In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 210, no 3, p. 819-824Article 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
Keywords
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
Linderholm, K. R., Skogh, E., Olsson, S. K., Dahl, M.-L., Holtze, M., Engberg, G., . . . Erhardt, S. (2012). Increased Levels of Kynurenine and Kynurenic Acid in the CSF of Patients With Schizophrenia. Schizophrenia Bulletin, 38(3), 426-432
Open this publication in new window or tab >>Increased Levels of Kynurenine and Kynurenic Acid in the CSF of Patients With Schizophrenia
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2012 (English)In: Schizophrenia Bulletin, ISSN 0586-7614, E-ISSN 1745-1701, Vol. 38, no 3, p. 426-432Article in journal (Refereed) Published
Abstract [en]

Background: The kynurenic acid (KYNA) hypothesis for schizophrenia is partly based on studies showing increased brain levels of KYNA in patients. KYNA is an endogenous metabolite of tryptophan (TRP) produced in astrocytes and antagonizes N-methyl-D-aspartate and alpha7* nicotinic receptors. Methods: The formation of KYNA is determined by the availability of substrate, and hence, we analyzed KYNA and its precursors, kynurenine (KYN) and TRP, in the cerebrospinal fluid (CSF) of patients with schizophrenia. CSF from male patients with schizophrenia on olanzapine treatment (n = 16) was compared with healthy male volunteers (n = 29). Results: KYN and KYNA concentrations were higher in patients with schizophrenia (60.7 +/- 4.37nM and 2.03 +/- 0.23nM, respectively) compared with healthy volunteers (28.6 +/- 1.44nM and 1.36 +/- 0.08nM, respectively), whereas TRP did not differ between the groups. In all subjects, KYN positively correlated to KYNA. Conclusion: Our results demonstrate increased levels of CSF KYN and KYNA in patients with schizophrenia and further support the hypothesis that KYNA is involved in the pathophysiology of schizophrenia.

Place, publisher, year, edition, pages
Oxford University Press, 2012
Keywords
psychosis, kynurenate, olanzapine, cerebrospinal fluid, tryptophan
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-66972 (URN)10.1093/schbul/sbq086 (DOI)000303169000011 ()20729465 (PubMedID)
Available from: 2011-03-23 Created: 2011-03-23 Last updated: 2017-12-11
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