Elevated concentrations of neurofilament light chain in the cerebrospinal fluid of bipolar disorder patients.
Bipolar disorder (BD) is characterized by mood swings between manic and depressive states. The etiology and pathogenesis of BD is unclear, but many of the affected cognitive domains, as well as neuroanatomical abnormalities, resemble symptoms and signs of small vessel disease. In small vessel disease, cerebrospinal fluid (CSF) markers reflecting damages in different cell types and subcellular structures of the brain have been established. Hence, we hypothesized that CSF markers related to small vessel disease may also be applicable as biomarkers for BD. To investigate this hypothesis, we sampled CSF from 133 patients with BD and 86 healthy controls. The concentrations of neurofilament light chain (NF-L), myelin basic protein (MBP), S100B, and heart-type fatty acid binding protein (H-FABP) were measured in CSF and analyzed in relation to diagnosis, clinical characteristics, and ongoing medications. Hereby we found an elevation of the marker of subcortical axonal damage, NF-L, in bipolar subjects. We also identified positive associations between NF-L and treatment with atypical antipsychotics, MBP and lamotrigine, and H-FABP and lithium. These findings indicate axonal damage as an underlying neuropathological component of bipolar disorder, although the clinical value of elevated NF-L remains to be validated in follow-up studies. The associations between current medications and CSF brain injury markers might aid in the understanding of both therapeutic and adverse effects of these drugs.
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Joel
J
Jakobsson
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Maria
M
Bjerke
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Carl Johan
CJ
Ekman
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Carl
C
Sellgren
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Anette G M
AG
Johansson
1] Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden [2] UCL Institute of Neurology, London, UK.
Henrik
H
Zetterberg
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Kaj
K
Blennow
1] Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden [2] Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden [3] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Mikael
M
Landén
D000328:Adult; D000367:Age Factors; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001369:Axons / Q000473:pathology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001714:Bipolar Disorder / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology; D001921:Brain / Q000473:pathology; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D016014:Linear Models; D018020:Lithium Compounds / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D004676:Myelin Basic Protein / Q000134:cerebrospinal fluid*; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D011569:Psychiatric Status Rating Scales; D011619:Psychotropic Drugs / Q000627:therapeutic use; D064568:S100 Calcium Binding Protein beta Subunit / Q000134:cerebrospinal fluid*; D012737:Sex Factors; D014227:Triazines / Q000627:therapeutic use
D014150:Antipsychotic Agents; D015415:Biomarkers; C493408:FABP3 protein, human; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D018020:Lithium Compounds; C499048:MBP protein, human; D004676:Myelin Basic Protein; D016900:Neurofilament Proteins; D011619:Psychotropic Drugs; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; D014227:Triazines; C044882:neurofilament protein L; D000077213:Lamotrigine