title: Cerebrospinal fluid microglia and neurodegenerative markers in twins concordant and discordant for psychotic disorders.
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.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. viktoria.johansson@ki.se.
authors.forename: Viktoria
authors.identifier: http://orcid.org/0000-0003-3775-7245
authors.initials: V
authors.lastname: Johansson
authors.affiliation: Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Joel
authors.initials: J
authors.lastname: Jakobsson
authors.affiliation: Department of Psychology, Yale University, New Haven, USA.
authors.forename: Rebecca G
authors.initials: RG
authors.lastname: Fortgang
authors.affiliation: Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.|UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Department of Psychology, Yale University, New Haven, USA.|Department of Psychiatry, Yale University, New Haven, USA.
authors.forename: Tyrone D
authors.initials: TD
authors.lastname: Cannon
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Hultman
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Wetterberg
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Landén
mesh_terms: D000328:Adult; D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid*; D018932:Chemokine CCL2 / Q000097:blood / Q000134:cerebrospinal fluid; D000071451:Chitinase-3-Like Protein 1 / Q000097:blood / Q000134:cerebrospinal fluid; D004200:Diseases in Twins; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011594:Psychometrics; D011618:Psychotic Disorders / Q000097:blood / Q000134:cerebrospinal fluid* / Q000235:genetics / Q000523:psychology; D013223:Statistics as Topic; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C111835:CCL2 protein, human; C084533:CHI3L1 protein, human; D018932:Chemokine CCL2; D000071451:Chitinase-3-Like Protein 1; D018950:Lipopolysaccharide Receptors
keywords: Biomarker; Bipolar disorder; Cerebrospinal fluid; Neuroinflammation; Schizophrenia; Twin study