Peripheral neurofilament light chain and intracortical myelin in bipolar I disorder

Mohammad Ali; Bianca Wollenhaupt-Aguiar; Manpreet Sehmbi; Luciano Minuzzi; Nicholas A Bock; Benicio N Frey

doi:10.1016/j.jad.2025.01.045

Peripheral neurofilament light chain and intracortical myelin in bipolar I disorder

J Affect Disord. 2025 Jan 10:S0165-0327(25)00058-8. doi: 10.1016/j.jad.2025.01.045. Online ahead of print.

Authors

Mohammad Ali¹, Bianca Wollenhaupt-Aguiar², Manpreet Sehmbi³, Luciano Minuzzi⁴, Nicholas A Bock⁵, Benicio N Frey⁶

Affiliations

¹ MiNDS Neuroscience Graduate Program, McMaster University, Hamilton, ON, Canada; Centre for Clinical Neurosciences, McMaster University, Canada.
² Centre for Clinical Neurosciences, McMaster University, Canada.
³ MiNDS Neuroscience Graduate Program, McMaster University, Hamilton, ON, Canada.
⁴ Centre for Clinical Neurosciences, McMaster University, Canada; Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada; Mood Disorders Treatment and Research Centre and Women's Health Concerns Clinic, St. Joseph's Healthcare Hamilton, ON, Canada.
⁵ Department of Psychology, Neuroscience, and Behaviour, McMaster University, Hamilton, ON, Canada.
⁶ Centre for Clinical Neurosciences, McMaster University, Canada; Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada; Mood Disorders Treatment and Research Centre and Women's Health Concerns Clinic, St. Joseph's Healthcare Hamilton, ON, Canada. Electronic address: freybn@mcmaster.ca.

PMID: 39800065
DOI: 10.1016/j.jad.2025.01.045

Abstract

Background: Neurofilament light chain (NfL) is a cytoskeletal protein that supports neuronal structure. Blood NfL levels are reported to be higher in diseases where myelin is damaged. Studies investigating intracortical myelin (ICM) in bipolar disorder (BD) have reported deficits in ICM maturation over age. This study investigated the association between ICM and peripheral blood NfL levels in BD.

Methods: NfL was quantified using a high sensitivity ELISA kit in 72 BD and 71 healthy control (HC) participants. t-test was used to determine group difference in NfL levels between BD and HC, and ridge regression was performed to analyze NfL and ICM association in six brain regions that demonstrated ICM deficits including the dorsolateral motor cortex, dorsomedial motor cortex, dorsolateral premotor cortex, dorsomedial premotor cortex, caudal dorsolateral prefrontal cortex, caudal dorsomedial prefrontal cortex, and age in BD only. Regions within the occipital lobe and cingulum was also analyzed as control regions.

Results: BD individuals had higher serum NfL concentration compared to HC (p = 0.001). The ridge regression analysis including the six brain regions and age explained 26 % of the variance in NfL concentration, while the occipital lobe and cingulum along with age explained only 7 % and 2 % of the variance, respectively.

Limitations: This was a cross-sectional correlational study so causation cannot be inferred. Also, this study focused on a limited number of brain regions previously associated with changes in ICM in BD.

Conclusion: This study corroborates previous research, which found increased NfL in CSF and blood in BD compared to HC. This demonstrates the potential utility of NfL as a marker of brain morphology deficits in BD.

Keywords: Biomarkers; Bipolar disorder; Intracortical myelin; Myelin; Neurofilament light chain.