Imbalanced Kynurenine Pathway in Schizophrenia

Kegel, Magdalena E.Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (författare)

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 Â± 1.5 nM vs. 18.2 Â± 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.

Bhat, MariaAstraZeneca, Research and Development, Innovative Medicines, Personalised Healthcare and Biomarkers, Translational Science Centre, Science for Life Laboratory, Solna, Sweden / Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (författare)
Skogh, ElisabethÖstergötlands Läns Landsting,Linköpings universitet,Avdelningen för neurovetenskap,Hälsouniversitetet,Psykiatriska kliniken(Swepub:liu)elisk66 (författare)
Samuelsson, MartinÖstergötlands Läns Landsting,Linköpings universitet,Avdelningen för neurovetenskap,Hälsouniversitetet,Psykiatriska kliniken(Swepub:liu)marsa78 (författare)
Lundberg, KristinaLinköpings universitet,Avdelningen för neurovetenskap,Hälsouniversitetet (författare)
Dahl, Marja-LiisaKarolinska Institutet (författare)
Sellgren, CarlKarolinska Institutet (författare)
Schwieler, LillyKarolinska Institutet (författare)
Engberg, GöranKarolinska Institutet (författare)
Schuppe-Koistinen, InaKarolinska Institutet (författare)
Erhardt, SophieKarolinska Institutet (författare)
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, SwedenAstraZeneca, Research and Development, Innovative Medicines, Personalised Healthcare and Biomarkers, Translational Science Centre, Science for Life Laboratory, Solna, Sweden / Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (creator_code:org_t)

Ingår i:International Journal of Tryptophan Research: Libertas Academica7, s. 15-221178-6469

Av författaren/redakt...: Kegel, Magdalena ...; Bhat, Maria; Skogh, Elisabeth; Samuelsson, Mart ...; Lundberg, Kristi ...; Dahl, Marja-Liis ...; visa fler...; Sellgren, Carl; Schwieler, Lilly; Engberg, Göran; Schuppe-Koistine ...; Erhardt, Sophie; visa färre...

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