The Relationship Between Brain-Derived Neurotrophic Factor and Serotonin in Major Depressive and Bipolar Disorders: A Cross-Sectional Analysis

Background Mood disorders like major depressive disorder (MDD) and bipolar disorder (BD) involve complex interactions between brain-derived neurotrophic factor (BDNF) and serotonin. While extensive research has explored these factors individually, their combined effects and interactions in these disorders are less understood. This study uniquely addresses this gap by examining how BDNF and serotonin interact and relate to mood disorder severity, providing new insights into their joint role in MDD and BD. Objectives The objective of this study was to examine the correlation between serum BDNF and plasma serotonin levels and to assess how these correlations relate to the severity of symptoms and overall disease severity in MDD and BD. Methodology This cross-sectional study, conducted at the Khyber Medical University, Peshawar, from January to September 2023, examined the correlation between BDNF and serotonin in individuals with MDD and BD. Participants (n = 63) aged 18-65 were recruited based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, excluding those with neurological disorders, substance abuse, or severe medical illness. A control group of 21 healthy individuals was matched by age and gender. Data collection involved demographic details, clinical history, and comorbid diagnoses assessed using the Mini International Neuropsychiatric Interview (MINI). Mood disorder severity was measured using the Hamilton Depression Rating Scale (HAM-D) for MDD and the Young Mania Rating Scale (YMRS) for BD, along with additional assessments (Beck Depression Inventory, Global Assessment of Functioning). Serum BDNF and serotonin levels were analyzed using enzyme-linked immunosorbent assay (ELISA) kits. Statistical analyses included t-tests, Mann-Whitney U tests, Pearson correlations, and subgroup analyses to assess relationships between biomarkers, mood disorder severity, and influencing factors. Results BDNF levels were found to be 20.1 ± 5.3 ng/mL in MDD, 18.5 ± 4.7 ng/mL in BD, and 25.9 ± 6.2 ng/mL in controls. Serotonin levels were 45.8 ± 12.6 ng/mL in MDD, 43.2 ± 11.4 ng/mL in BD, and 52.1 ± 14.3 ng/mL in controls. In the MDD group, significant negative correlations were observed between BDNF levels and mood disorder severity (r = -0.32, p = 0.045), whereas serotonin levels did not show significant correlations (r = -0.21, p = 0.23). In the BD group, BDNF levels also showed a significant negative correlation with manic symptoms (r = -0.28, p = 0.048), but serotonin levels showed no significant correlation. Subgroup analyses revealed that participants under 40 years had higher BDNF levels (22.8 ± 5.6 ng/mL) compared to those aged 40 and above (19.7 ± 4.3 ng/mL). Females showed higher BDNF levels (24.5 ± 6.3 ng/mL) than males (19.3 ± 3.8 ng/mL). Participants not on medication had higher BDNF levels (23.6 ± 5.1 ng/mL) compared to those on medication (17.9 ± 4.2 ng/mL). Those without comorbidities also had higher BDNF levels (23.8 ± 5.9 ng/mL) than those with comorbidities (18.2 ± 4.5 ng/mL), while serotonin levels varied similarly across these subgroups. Conclusion Lower BDNF levels are associated with mood disorders and symptom severity, indicating their potential as a biomarker.