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Serum Neurofilament Light (sNfL) as Biomarker for Bipolar Disorder? (2024 Study)

Bipolar Disorder (BD), a complex psychiatric condition, is under constant study to better understand its pathophysiology and improve diagnostic and treatment strategies.

Recent research has focused on the role of serum neurofilament light (sNfL), a marker for neuro-axonal injury, in BD.


  • Individuals with BD for more than three years exhibit higher sNfL levels compared to those with a shorter illness duration and healthy controls.
  • A positive correlation exists between current manic symptoms and increased sNfL levels.
  • sNfL, typically elevated in various neurological disorders, is now being explored as a potential biomarker in psychiatric conditions like BD.
  • The study suggests that sNfL levels could reflect the illness duration in BD, hinting at its utility in predicting disease progression and treatment response.

Source: Journal of Affective Disorders (2024)

Neurofilament Light (NFL) & Psychiatric Disorders: Links

Neurofilament light (NfL) is one of the key components in the architecture of neurons, specifically forming part of the neuronal cytoskeleton.

Neurofilaments are a type of intermediate filament, integral to maintaining neuronal shape and size, and are crucial for efficient nerve conduction.

Among these, the light chain of neurofilament, known as NfL, is noteworthy due to its lower molecular weight and specific roles.

Functions & Significance of NfL

The primary function of NfL is to support the structural integrity and radial growth of axons, which is vital for proper nerve signal transmission.

NfL plays a critical role in neuronal health and functionality.

Its stability and abundance are crucial for maintaining the nervous system’s normal function.

In the context of neurology, elevated levels of NfL, particularly in the cerebrospinal fluid (CSF) and blood, are indicative of neuro-axonal damage and degeneration.

This elevation is observed in various neurological conditions such as multiple sclerosis, Alzheimer’s disease, and amyotrophic lateral sclerosis, where NfL serves as a biomarker for neuronal injury.

NfL in Psychiatric Disorders

Traditionally, the focus on NfL has been predominantly in neurological disorders.

However, recent research has expanded to include psychiatric conditions.

The rationale stems from the understanding that psychiatric disorders, like their neurological counterparts, may involve neuroinflammatory and neurodegenerative processes that could affect neuronal integrity.

Studies have started to explore elevated NfL levels in psychiatric disorders as a potential indicator of underlying neurobiological changes.

This is particularly significant given that psychiatric conditions, unlike many neurological diseases, often lack concrete biomarkers for diagnosis and monitoring.

Neurofilament Light in Bipolar Disorder: Why study it?

A growing body of evidence suggests that neurobiological changes, particularly in the brain’s white matter and neuronal structures, play a significant role in BD’s pathophysiology.

Neurofilament light is a unique biomarker that could help us better understand bipolar disorder.

  • Neurodegenerative Processes: BD has been associated with neurodegenerative processes, which may contribute to the progressive nature of the disorder. As NfL is a known marker of neuro-axonal injury, its levels could reflect these neurodegenerative changes in BD.
  • Axonal Integrity: Given NfL’s role in maintaining axonal integrity, changes in its levels could indicate alterations in white matter integrity, which have been observed in BD.
  • Diagnostic and Prognostic Potential: Identifying biomarkers like NfL in BD could aid in early diagnosis, monitor disease progression, and potentially predict treatment responses. This is particularly crucial in BD, where objective biomarkers are scarce.
  • Understanding Mood Episodes: The correlation between NfL levels and the frequency of mood episodes (especially manic episodes) in BD could offer insights into how these episodes impact brain health. This understanding could lead to more targeted therapies.

Serum Neurofilament Light (SNFL) in Bipolar Disorder (2024 Study)

Queissner et al. investigated the potential relationship between serum neurofilament light (sNfL) levels and various clinical states of Bipolar Disorder (BD).

This study sought to determine whether sNfL could serve as a biomarker for BD, particularly focusing on its correlation with the duration of illness, the number of manic and depressive episodes, and the overall severity of the disorder.


  • Participants: The study included 51 patients diagnosed with BD and 35 healthy controls (HC). Participants were former in- or out-patients of a psychiatric department.
  • Clinical Assessments: The study used the Hamilton Depression Scale (HAM-D) and the Young Mania Rating Scale (YMRS) for mood assessments. The duration of illness was established based on diagnosis date, self-report, and medical records.
  • Biomarker Analysis: sNfL levels were quantified using a commercial ultrasensitive single molecule array (Simoa) technique. This advanced method ensured high sensitivity in detecting sNfL concentrations in serum samples.
  • Statistical Analysis: The study employed various statistical tools, including partial correlations and linear regression models, to analyze the relationship between sNfL levels and clinical parameters. Adjustments were made for potential confounders like age, illness duration, and BMI.


  • Correlation with Manic Episodes: A significant positive correlation was found between the number of past manic episodes and sNfL levels, controlled for age and illness duration.
  • Impact of Illness Duration: Patients with more than three years of illness duration showed significantly higher sNfL levels compared to those with a shorter duration and to healthy controls.
  • Depressive Episodes: No significant association was observed between the number of depressive episodes and sNfL levels.
  • General sNfL Levels: In overall terms, sNfL levels did not significantly differ between BD patients and healthy controls.


  • Study Design: The study’s cross-sectional nature and reliance on a single sNfL measurement point limit the ability to infer causality or track changes over time.
  • Retrospective Data: The reliance on patient self-report and medical records for historical data such as the number of past episodes could introduce recall bias.
  • Medication Effects: The study did not account for the potential impact of psychiatric medications on sNfL levels, which could be a significant confounding factor.
  • Narrow Focus: The exclusion of patients with severe comorbidities and drug abuse history might limit the generalizability of the findings to the broader BD population.
  • Biomarker Specificity: The lack of significant difference in general sNfL levels between BD patients and healthy controls raises questions about the specificity of sNfL as a biomarker for BD.

Details of Results: Neurofilament Light in Bipolar Disorder (2024)

sNfL & Manic Episodes

  • The study revealed a significant positive correlation between the number of past manic episodes in BD patients and their sNfL levels. Specifically, this relationship held true even after adjusting for age and the duration of illness, with a Pearson correlation coefficient (r) of 0.390 and a p-value of 0.03.
  • Furthermore, a linear regression model validated this association, indicating a substantial link between manic episodes and increased sNfL levels, suggesting that each manic episode might contribute to neuro-axonal damage.

Illness Duration & sNfL Levels

  • A critical finding was the differentiation of sNfL levels based on the duration of illness. Patients with BD for over three years exhibited significantly higher sNfL levels (mean 18.59, SD 11.98) than those with a shorter duration of illness and healthy controls.
  • This elevation was statistically significant (p = 0.03), emphasizing a potential cumulative effect of the disorder on neuro-axonal integrity over time.

No Association with Depressive Episodes

  • Contrasting with the findings on manic episodes, the study did not find a significant correlation between the number of depressive episodes and sNfL levels (r = 0.311, p > 0.05).
  • This suggests that the neuro-axonal damage reflected by sNfL may be more closely linked to manic rather than depressive phases of BD.

What are the potential implications of the findings? (sNfL & BD)

  • Understanding Bipolar Disorder Pathophysiology: The correlation between increased sNfL levels and manic episodes suggests a potential neurodegenerative component in BD, particularly during manic phases. This could shift the focus towards understanding and treating the neurobiological aspects of mania.
  • Biomarker for Disease Progression: The association between illness duration and elevated sNfL levels indicates that sNfL could be a valuable biomarker for tracking the progression of BD, possibly reflecting ongoing neuro-axonal damage over time.
  • Tailoring Treatment Strategies: These findings could influence treatment strategies, emphasizing early intervention to prevent or mitigate neuro-axonal damage, especially in patients with frequent manic episodes.
  • Future Research and Clinical Trials: The study paves the way for further research, including longitudinal studies, to explore the dynamics of sNfL in BD. It also underscores the need for clinical trials to evaluate interventions targeting neurodegenerative processes in BD.

Why Neurofilament Light May Be Abnormal in Bipolar Disorder (Possible Mechanisms)

The abnormal levels of neurofilament light (NfL) in individuals with Bipolar Disorder (BD) point towards intricate neurobiological mechanisms at play.

Neuroinflammatory Hypothesis

BD is increasingly associated with neuroinflammatory processes. Neuroinflammation can lead to neuronal damage and axonal degeneration, reflected in elevated NfL levels.

During manic episodes, inflammatory responses may be more pronounced, possibly due to stress-related neurobiological changes, contributing to higher NfL levels.

Oxidative Stress & Neuronal Damage

Oxidative stress, a state of imbalance between free radicals and antioxidants in the body, is thought to play a role in BD.

This imbalance can lead to cellular damage, particularly in neurons, causing axonal injury and thus increasing NfL levels. Manic episodes, in particular, might exacerbate oxidative stress, further elevating NfL.

White Matter Abnormalities

Studies have shown white matter abnormalities in individuals with BD.

White matter is rich in axons, and any disruption in its integrity could lead to increased NfL levels.

These abnormalities might progress as the illness duration increases, explaining higher NfL levels in those with a longer history of BD.

Glutamatergic Neurotoxicity

Glutamate, a key neurotransmitter in the brain, is often dysregulated in BD.

Excessive glutamate can lead to excitotoxicity, a process damaging to neurons and axons.

This glutamatergic neurotoxicity could be a contributing factor to the elevated NfL levels observed in BD patients.

Neurodegenerative Changes

BD might have a neurodegenerative component, especially in chronic stages.

The progressive nature of neurodegeneration could lead to ongoing axonal damage, reflected in the increased levels of NfL over time.

Impact of Pharmacological Treatments

Long-term use of certain psychiatric medications could potentially influence neuronal health.

While medications are designed to stabilize mood and prevent episodes, they might also have unintended effects on neuronal structures, potentially influencing NfL levels.

Genetic Susceptibility

Genetic factors may predispose individuals to both BD and greater vulnerability to neuronal damage.

Certain genetic profiles could influence the body’s response to stress and neuroinflammation, leading to variations in NfL levels among those with BD.

Stress-Related Neuronal Impact

Chronic stress, often associated with BD, can have detrimental effects on brain structure and function.

Stress hormones and their impact on the brain might contribute to the disruption of neuronal integrity, influencing NfL levels.

Takeaway: Serum Neurofilament Light in Bipolar Disorder

The study’s in-depth exploration into the relationship between serum neurofilament light (sNfL) levels and Bipolar Disorder (BD) provides groundbreaking insights into the neurobiological underpinnings of this complex mental health condition.

The significant correlation between increased sNfL levels and the frequency of manic episodes, along with the impact of illness duration, suggests a neurodegenerative component in BD.

These findings not only enhance our understanding of BD’s pathophysiology but also open up new avenues for targeted treatments and preventive strategies.

However, the absence of a similar correlation with depressive episodes and the limitations of the study highlight the need for further research.

This study lays a foundation for future investigations, potentially revolutionizing the management and perception of BD in psychiatry.


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