Elevated concentrations of neurofilament light chain in the cerebrospinal fluid of bipolar disorder patients

Neuropsychopharmacology. 2014 Sep;39(10):2349-56. doi: 10.1038/npp.2014.81. Epub 2014 Apr 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Antipsychotic Agents / therapeutic use
  • Axons / pathology
  • Biomarkers / cerebrospinal fluid
  • Bipolar Disorder / cerebrospinal fluid*
  • Bipolar Disorder / diagnosis
  • Bipolar Disorder / drug therapy
  • Bipolar Disorder / pathology
  • Brain / pathology
  • Fatty Acid Binding Protein 3
  • Fatty Acid-Binding Proteins / cerebrospinal fluid*
  • Female
  • Humans
  • Lamotrigine
  • Linear Models
  • Lithium Compounds / therapeutic use
  • Male
  • Middle Aged
  • Myelin Basic Protein / cerebrospinal fluid*
  • Neurofilament Proteins / cerebrospinal fluid*
  • Psychiatric Status Rating Scales
  • Psychotropic Drugs / therapeutic use
  • S100 Calcium Binding Protein beta Subunit / cerebrospinal fluid*
  • Sex Factors
  • Triazines / therapeutic use


  • Antipsychotic Agents
  • Biomarkers
  • FABP3 protein, human
  • Fatty Acid Binding Protein 3
  • Fatty Acid-Binding Proteins
  • Lithium Compounds
  • MBP protein, human
  • Myelin Basic Protein
  • Neurofilament Proteins
  • Psychotropic Drugs
  • S100 Calcium Binding Protein beta Subunit
  • S100B protein, human
  • Triazines
  • neurofilament protein L
  • Lamotrigine