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. 2017 Aug;267(5):391-402.
doi: 10.1007/s00406-016-0759-5. Epub 2016 Dec 30.

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

Viktoria Johansson  1 , Joel Jakobsson  2 , Rebecca G Fortgang  3 , Henrik Zetterberg  2   4 , Kaj Blennow  2 , Tyrone D Cannon  3   5 , Christina M Hultman  6 , Lennart Wetterberg  7 , Mikael Landén  6   2
Affiliations

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

Viktoria Johansson et al. Eur Arch Psychiatry Clin Neurosci. 2017 Aug.

Abstract

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.

Keywords: Biomarker; Bipolar disorder; Cerebrospinal fluid; Neuroinflammation; Schizophrenia; Twin study.

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Conflict of interest statement

Tyrone Cannon is a consultant to Boehringer Ingelheim Pharmaceuticals and Kaj Blennow has served as consultant and at advisory boards for Fujirebio Europe, IBL International and Roche Diagnostics. Viktoria Johansson, Joel Jakobsson, Rebecca G Fortgang, Henrik Zetterberg, Christina M Hultman, Lennart Wetterberg, and Mikael Landén have no financial interests to declare.

Figures

Fig. 1
Fig. 1
Comparison of sCD14 levels between the twin pairs where the probands are affected with schizophrenia or bipolar disorder and the co-twins are not affected and the line represents each pair (n = 11)
Fig. 2
Fig. 2
Correlations of the difference scores between the twin pairs (n = 17) of CSF/serum albumin ratio in relation to the CSF markers sCD14 and YKL-40
See this image and copyright information in PMC

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