Neurofilament Light Chain Correlation With Severity of Symptoms and Cognitive Decline in Mood Disorders

Cytoskeletal integrity, represented by neurofilament light chain (NfL), has emerged as a critical biomarker for neuroaxonal injury, with growing evidence linking it to mood disorders such as major depressive disorder (MDD) and bipolar disorder (BD). Neurofilaments are structural proteins essential for maintaining neuronal stability, and NfL, the smallest subunit, is released into extracellular fluids like cerebrospinal fluid (CSF) and blood following neuronal damage. Recent advancements in immunoassay technologies have enabled the reliable quantification of NfL in peripheral blood, providing a minimally invasive method to assess brain pathology (1).

Mood disorders are characterized by structural brain alterations, including reduced white matter integrity and gray matter volume loss, suggesting underlying neuroaxonal damage. Elevated blood NfL levels have been reported in patients with Major Depressive Disorder and Bipolar Disorder , with increases ranging from 1.2 to 2.5-fold compared to healthy controls, indicating a potential link between cytoskeletal disruption and mood disorder pathology (1,2).

In MDD, higher NfL levels have been associated with cognitive dysfunction and white matter abnormalities, highlighting the role of cytoskeletal integrity in disease severity (3).

Similarly, in Bipolar Disorder, elevated NfL levels have been linked to cognitive deficits and structural brain changes, particularly during acute episodes, further supporting the involvement of neuroaxonal injury in mood disorder progression (2,4).

However, the interpretation of NfL levels in mood disorders is complicated by factors such as age, body mass index (BMI), and cardiovascular risk factors, which influence NfL variability (1). Despite these challenges, NfL holds promise as a biomarker for assessing cytoskeletal integrity and monitoring disease progression in mood disorders, offering new insights into their neurobiological underpinnings. Further research is needed to elucidate the mechanisms driving NfL release and its clinical utility in psychiatric practice.

Participants will be divided into three groups (A) Patients with Major depressive episode (B) Patients with Bipolar Disorder Manic Episode

• Inclusion criteria:

• age 15-50 years old
• both sexes will be included
• meet the Diagnostic And Statistical Manual Of Mental Disorders Fifth Edition (DSM-5) criteria for major depressive disorder or Bipolar disorder
• Exclusion criteria:

• Major Medical or Neurological Diseases.
• History of Traumatic Brain Injury, Major Fracture.
• Alcohol or Substance Use Disorder. (C) Healthy control

a. Inclusion criteria:

• age- and sex-matching with group A, B
• Healthy Control without any of major physical conditions or psychiatric disorder