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A genome-wide assoc...
A genome-wide association study of kynurenic acid in cerebrospinal fluid: implications for psychosis and cognitive impairment in bipolar disorder
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- Sellgren, C. M. (author)
- Karolinska Institutet
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- Kegel, M. E. (author)
- Karolinska Institutet
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- Bergen, S. E. (author)
- Karolinska Institutet
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- Ekman, C. J. (author)
- Karolinska Institutet
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Olsson, S. (author)
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Larsson, M. (author)
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Vawter, M. P. (author)
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- Backlund, L. (author)
- Karolinska Institutet
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- Sullivan, P. F. (author)
- Karolinska Institutet
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Sklar, P. (author)
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Smoller, J. W. (author)
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Magnusson, P. K. E. (author)
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- Hultman, C. M. (author)
- Karolinska Institutet
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- Walther-Jallow, L. (author)
- Karolinska Institutet
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- Svensson, C. I. (author)
- Karolinska Institutet
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- Lichtenstein, P. (author)
- Karolinska Institutet
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- Schalling, M. (author)
- Karolinska Institutet
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- Engberg, G. (author)
- Karolinska Institutet
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Erhardt, S. (author)
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- Landén, Mikael, 1966 (author)
- Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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(creator_code:org_t)
- 2015-12-15
- 2016
- English.
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:10, s. 1342-1350
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https://gup.ub.gu.se...
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Abstract
Subject headings
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- Elevated cerebrospinal fluid (CSF) levels of the glia-derived N-methyl-D-aspartic acid receptor antagonist kynurenic acid (KYNA) have consistently been implicated in schizophrenia and bipolar disorder. Here, we conducted a genome-wide association study based on CSF KYNA in bipolar disorder and found support for an association with a common variant within 1p21.3. After replication in an independent cohort, we linked this genetic variant-associated with reduced SNX7 expression-to positive psychotic symptoms and executive function deficits in bipolar disorder. A series of post-mortem brain tissue and in vitro experiments suggested SNX7 downregulation to result in a caspase-8-driven activation of interleukin-1 beta and a subsequent induction of the brain kynurenine pathway. The current study demonstrates the potential of using biomarkers in genetic studies of psychiatric disorders, and may help to identify novel drug targets in bipolar disorder.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- elevated levels
- schizophrenia
- brain
- interleukin-1-beta
- transcription
- flexibility
- activation
- expression
- dopamine
- families
- Biochemistry & Molecular Biology
- Neurosciences & Neurology
- Psychiatry
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
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Sellgren, C. M.
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Kegel, M. E.
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Bergen, S. E.
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Ekman, C. J.
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Olsson, S.
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Larsson, M.
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show more...
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Vawter, M. P.
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Backlund, L.
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Sullivan, P. F.
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Sklar, P.
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Smoller, J. W.
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Magnusson, P. K. ...
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Hultman, C. M.
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Walther-Jallow, ...
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Svensson, C. I.
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Lichtenstein, P.
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Schalling, M.
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Engberg, G.
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Erhardt, S.
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Landén, Mikael, ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Molecular Psychi ...
- By the university
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University of Gothenburg
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Karolinska Institutet