PMID- 28039552 OWN - NLM STAT- MEDLINE DCOM- 20180130 LR - 20181113 IS - 1433-8491 (Electronic) IS - 0940-1334 (Print) IS - 0940-1334 (Linking) VI - 267 IP - 5 DP - 2017 Aug TI - Cerebrospinal fluid microglia and neurodegenerative markers in twins concordant and discordant for psychotic disorders. PG - 391-402 LID - 10.1007/s00406-016-0759-5 [doi] AB - 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 beta-amyloid metabolism (AbetaX-38, AbetaX-40, AbetaX-42 and Abeta1-42), soluble amyloid precursor proteins (sAPP-alpha and sAPP-beta), 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, AbetaX-42, Abeta1-42, 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. FAU - Johansson, Viktoria AU - Johansson V AUID- ORCID: 0000-0003-3775-7245 AD - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. viktoria.johansson@ki.se. FAU - Jakobsson, Joel AU - Jakobsson J AD - Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden. FAU - Fortgang, Rebecca G AU - Fortgang RG AD - Department of Psychology, Yale University, New Haven, USA. FAU - Zetterberg, Henrik AU - Zetterberg H AD - Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden. AD - UCL Institute of Neurology, Queen Square, London, UK. FAU - Blennow, Kaj AU - Blennow K AD - Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden. FAU - Cannon, Tyrone D AU - Cannon TD AD - Department of Psychology, Yale University, New Haven, USA. AD - Department of Psychiatry, Yale University, New Haven, USA. FAU - Hultman, Christina M AU - Hultman CM AD - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. FAU - Wetterberg, Lennart AU - Wetterberg L AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. FAU - Landen, Mikael AU - Landen M AD - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. AD - Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden. LA - eng PT - Journal Article PT - Twin Study DEP - 20161230 PL - Germany TA - Eur Arch Psychiatry Clin Neurosci JT - European archives of psychiatry and clinical neuroscience JID - 9103030 RN - 0 (Amyloid beta-Peptides) RN - 0 (Biomarkers) RN - 0 (CCL2 protein, human) RN - 0 (CHI3L1 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Chitinase-3-Like Protein 1) RN - 0 (Lipopolysaccharide Receptors) SB - IM MH - Adult MH - Amyloid beta-Peptides/blood/*cerebrospinal fluid MH - Biomarkers/blood/*cerebrospinal fluid MH - Chemokine CCL2/blood/cerebrospinal fluid MH - Chitinase-3-Like Protein 1/blood/cerebrospinal fluid MH - *Diseases in Twins MH - Female MH - Genetic Predisposition to Disease MH - Humans MH - Lipopolysaccharide Receptors/*metabolism MH - Male MH - Middle Aged MH - Psychometrics MH - Psychotic Disorders/blood/*cerebrospinal fluid/genetics/psychology MH - Statistics as Topic MH - Twins, Dizygotic MH - Twins, Monozygotic PMC - PMC5509775 OTO - NOTNLM OT - Biomarker OT - Bipolar disorder OT - Cerebrospinal fluid OT - Neuroinflammation OT - Schizophrenia OT - Twin study COIS- 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 Landen have no financial interests to declare. EDAT- 2017/01/01 06:00 MHDA- 2018/01/31 06:00 PMCR- 2016/12/30 CRDT- 2017/01/01 06:00 PHST- 2016/06/08 00:00 [received] PHST- 2016/12/13 00:00 [accepted] PHST- 2017/01/01 06:00 [pubmed] PHST- 2018/01/31 06:00 [medline] PHST- 2017/01/01 06:00 [entrez] PHST- 2016/12/30 00:00 [pmc-release] AID - 10.1007/s00406-016-0759-5 [pii] AID - 759 [pii] AID - 10.1007/s00406-016-0759-5 [doi] PST - ppublish SO - Eur Arch Psychiatry Clin Neurosci. 2017 Aug;267(5):391-402. doi: 10.1007/s00406-016-0759-5. Epub 2016 Dec 30.