title: CSF neuroinflammatory biomarkers in bipolar disorder are associated with cognitive impairment.
abstract: Persistent cognitive impairment in the euthymic state of bipolar disorder is increasingly recognized. Mounting evidence also suggests an association between neuroinflammation and cognitive dysfunction. The purpose of this study was to test if cerebrospinal fluid (CSF) markers of neuroinflammation could account for cognitive impairment in bipolar disorder. Hierarchical linear regression models were applied to account for performance in five cognitive domains using CSF neuroinflammatory biomarkers as predictors in patients with bipolar disorder type I and II (N=78). The associations between these biomarkers and cognition were further tested in healthy age- and sex-matched controls (N=86). In patients with bipolar disorder, the CSF biomarkers accounted for a significant proportion of the variance in executive functions (42.8%, p=<.0005) independently of age, medication, disease status, and bipolar subtype. The microglial marker YKL-40 had a high impact (beta=-.99), and was the only biomarker that contributed individually. CSF biomarkers were not associated with cognitive performance in healthy controls. The CSF neuroinflammation biomarker YKL-40 is associated with executive performance in euthymic bipolar disorder, but not in healthy controls.
authors.affiliation: Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The Gothenburg University, Gothenburg, Sweden. Electronic address: sindre.rolstad@neuro.gu.se.
authors.forename: Sindre
authors.initials: S
authors.lastname: Rolstad
authors.affiliation: Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The Gothenburg University, Gothenburg, Sweden.
authors.forename: Joel
authors.initials: J
authors.lastname: Jakobsson
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carl
authors.initials: C
authors.lastname: Sellgren
authors.affiliation: Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The Gothenburg University, Gothenburg, Sweden.
authors.forename: Anniella
authors.initials: A
authors.lastname: Isgren
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carl Johan
authors.initials: CJ
authors.lastname: Ekman
authors.affiliation: Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The Gothenburg University, Gothenburg, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Bjerke
authors.affiliation: Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The Gothenburg University, Gothenburg, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The Gothenburg University, Gothenburg, Sweden; UCL Institute of Neurology, Queen Square, University College London, London, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The Gothenburg University, Gothenburg, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Pålsson
authors.affiliation: Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The Gothenburg University, Gothenburg, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Landén
mesh_terms: D054392:Adipokines / Q000134:cerebrospinal fluid*; D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001714:Bipolar Disorder / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000523:psychology*; D000071451:Chitinase-3-Like Protein 1; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000134:cerebrospinal fluid*; D056344:Executive Function / Q000502:physiology; D005260:Female; D006801:Humans; D037102:Lectins / Q000134:cerebrospinal fluid*; D016014:Linear Models; D008297:Male; D009483:Neuropsychological Tests
chemical_list: D054392:Adipokines; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins
keywords: Bipolar disorder; Cerebrospinal fluid; Inflammation; Neuropsychology