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• Serum Brain Derived Neurotrophic factor assayed in an African population amongst patients with Major Depressive Episode (with the absence of any chronic medical illness, alcohol and substance misuse and acute medical illness) and compared to age and sex matched controls. • Mean serum BDNF was found to be lower in patients with MDE as compared to controls. • Mean serum BDNF in patients with MDE increased after 8 weeks of treatment to levels similar with healthy age and sex matched controls. • Serum BDNF can thus be a potential biomarker for Major Depressive Disorder. Current views on the etiology of Major Depressive Diorder(MDD) emphasizes environmental and biological interplay. Recent studies have implicated reduction in Brain Derived Neurotrophic Factor (BDNF) in the pathophysiology and as a biomarker of major depression (Neurotrophin Hypothesis of Depression). This study aimed at showing that the Neurotrophin hypothesis of depression is relevant in the pathophysiology of Major Depressive Episode in Southern Nigeria. Consecutive consenting patients diagnosed with Major Depressive Episode (MDE) using the Structured Clinical Interview for DSM (SCID) and age and sex matched controls were enrolled into this study. Serum BDNF was measured prior to commencement of treatment as baseline and 8 weeks after treatment. Depression severity was rated with the Hamilton Depression Rating Scale (HAM-D) and Patient Health Questionnaire (PHQ-9). Seventy-five cases and 75 age and sex matched controls were recruited. The mean ± SD of serum BDNF of depressed patients (26.09 ng/ml ± 1.96) was significantly lower than those of age and sex matched controls (28.13 ng/ml ± 1.47) P < 0.01. The study had a follow up rate of 48% after 8 weeks of treatment. Serum BDNF post treatment was significantly higher than baseline. This was a single center study with a high drop-out rate. The result of this study adds to the mounting evidence in support of the neurotrophin hypothesis of depression. [ABSTRACT FROM AUTHOR]