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Cerebrospinal fluid microglia and neurodegenerative markers in twins concordant and discordant for psychotic disorders.

Artikel i vetenskaplig tidskrift
Författare Viktoria Johansson
Joel Jakobsson
Rebecca G Fortgang
Henrik Zetterberg
Kaj Blennow
Tyrone D Cannon
Christina M Hultman
Lennart Wetterberg
Mikael Landén
Publicerad i European archives of psychiatry and clinical neuroscience
Volym 267
Nummer/häfte 5
Sidor 391–402
ISSN 1433-8491
Publiceringsår 2017
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor 391–402
Språk en
Länkar dx.doi.org/10.1007/s00406-016-0759-...
www.ncbi.nlm.nih.gov/entrez/query.f...
Ämnesord Schizophrenia, Bipolar disorder, Biomarker, Cerebrospinal fluid, Twin study, Neuroinflammation
Ämneskategorier Neurokemi

Sammanfattning

Schizophrenia and bipolar disorder are debilitating psychiatric disorders with partially shared symptomatology including psychotic symptoms and cognitive impairment. Aberrant levels of microglia and neurodegenerative cerebrospinal fluid (CSF) markers have previously been found in schizophrenia and bipolar disorder. We aimed to analyze familial and environmental influences on these CSF markers and their relation to psychiatric symptoms and cognitive ability. CSF was collected from 17 complete twin pairs, nine monozygotic and eight dizygotic, and from one twin sibling. Two pairs were concordant for schizophrenia, and 11 pairs discordant for schizophrenia, schizoaffective disorder or bipolar disorder, and four pairs were not affected by psychotic disorders. Markers of microglia activation [monocyte chemoattractant protein-1 (MCP-1), chitinase 3-like protein 1 (YKL-40), and soluble cluster of differentiation 14 (sCD14)], markers of β-amyloid metabolism (AβX-38, AβX-40, AβX-42 and Aβ1-42), soluble amyloid precursor proteins (sAPP-α and sAPP-β), total tau (T-tau), phosphorylated tau (P-tau), and CSF/serum albumin ratio were measured in CSF using immunoassays. Heritability of the CSF markers was estimated, and associations to psychiatric and cognitive measurements were analyzed. Heritability estimates of the microglia markers were moderate, whereas several neurodegenerative markers showed high heritability. In contrast, AβX-42, Aβ1-42, P-tau and CSF/serum albumin ratio were influenced by dominant genetic variation. Higher sCD14 levels were found in twins with schizophrenia or bipolar disorder compared to their not affected co-twins, and higher sCD14-levels were associated with psychotic symptoms. The study provides support for a significant role of sCD14 in psychotic disorders and a possible role of microglia activation in psychosis.

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