Tuberculosis and comorbid depression: Association with serum indoleamine 2,3-dioxygenase activity

Patients with tuberculosis (TB) may have depression as a comorbidity, which may be associated with poor treatment outcomes. Increased production of pro-inflammatory cytokines activating enzyme indoleamine 2,3-dioxygenase (IDO) has been reported in TB. We studied the association of IDO activity and comorbid depression in TB patients.

Newly diagnosed, treatment-naïve TB patients were evaluated for symptoms of depression using the Patient Health Questionnaire (PHQ)-9 scale. A PHQ-9 score of ≥5 was taken as an indicator for depression. Patients were further categorized into two groups based on their PHQ-9 scores, Group-I with a PHQ-9 score of <5 and Group-II with a PHQ-9 score ≥5. The serum kynurenine (KYN) and tryptophan (TRP) levels were determined using liquid chromatography-mass spectrometry (LC-MS) and the KYN/TRP ratio was taken as a measure for IDO activity.

A total of 106 TB patients and 106 healthy controls were enrolled in this study. Over 73.5% of TB patients had PHQ-9 scores of above 5 with an average score of 7.09 ± 2.83, a significant difference (P < 0.05) as compared to the average PHQ-9 scores of healthy controls (2.93 ± 1.20). Group-II TB patients had lower serum TRP 539.55 ± 194.31 ng/mL versus 1109.45 ± 186.04 ng/mL (P < 0.01) in Group-I; higher serum KYN 425.81 ± 65.51 ng/mL versus 250.06 ± 40.28 ng/mL (P < 0.01) and higher K/T ratio 0.906 ± 0.56 versus 0.251 ± 0.052 (P < 0.01). There was a significant linear correlation between PHQ-9 and serum KYN (r: 0.969; P: <0.01; R2: 0.909); serum TRP (r: 0.841; P: <0.01; R2: 0.745); and KYN/TRP ratio (r: 0.745; P < 0.01; R2: 0.618).

These findings suggest that in TB patients, induction of IDO activity may be relevant to the development of comorbid depression.