The association between plasma tryptophan catabolites and depression: the role of symptom profiles and inflammation

Background: Tryptophan catabolites ("TRYCATs") produced by the kynurenine pathway (KP) may play a role in depression pathophysiology. Studies comparing TRYCATs levels in depressed subjects and controls provided mixed findings. We examined the association of TRYCATs levels with 1) the presence of Major Depressive Disorder (MDD), 2) depressive symptom profiles and 3) inflammatory markers.Methods: The sample from the Netherlands Study of Depression and Anxiety included participants with current (n = 1100) or remitted (n = 753) MDD DSM-IV diagnosis and healthy controls (n = 642). Plasma levels of tryptophan (TRP), kynurenine (KYN), kynurenic acid (KynA), quinolinic acid (QA), C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor (TNF) were measured. Atypical/energy-related symptom (AES), melancholic symptom (MS) and anxious-distress symptom (ADS) profiles were derived from questionnaires.Results: After adjustment for age, sex, education, smoking status, alcohol consumption and chronic diseases, no significant differences in TRYCATs were found comparing MDD cases versus controls. The MS profile was associated (q < 0.05) with lower KynA (beta = -0.05), while AES was associated with higher KYN (beta = 0.05), QA (beta = 0.06) and TRP (beta = 0.06). Inflammatory markers were associated with higher KYN (CRP beta = 0.12, IL-6 beta = 0.08, TNF beta = 0.10) and QA (CRP beta = 0.21, IL-6 beta = 0.12, TNF beta = 0.18). Significant differences against controls emerged after selecting MDD cases with high (top 30%) CRP (KYN d = 0.20, QA d = 0.33) and high TNF (KYN d = 0.24; QA d = 0.39).Conclusions: TRYCATs levels were related to specific clinical and biological features, such as atypical symptoms or a proinflammatory status. Modulation of KP may potentially benefit a specific subset of depressed patients. Clinical studies should focus on patients with clear evidence of KP dysregulations.Stress-related psychiatric disorders across the life spa

THE NEUROANATOMY OF DEPRESSION: EVIDENCE FROM HUNTINGTON'S DISEASE

Neurological Motor Disorder

DIFFUSION TENSOR IMAGING IN HUNTINGTON'S DISEASE: IMPACT OF THE CONTROL FOR CORRUPTED DATA IN COMPARISONS AT THE GROUP LEVEL

Neurological Motor Disorder

A MULTICENTRE APPROACH FOR THE DETECTION OF PATTERNS OF IMPAIRMENT IN HUNTINGTON'S DISEASE BY USING DIFFUSION TENSOR IMAGING

Neurological Motor Disorder

The neuroanatomy of subthreshold depressive symptoms in Huntington's disease: a combined diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) study

Neurological Motor Disorder

6-, 9-AND 15-MONTH CHANGE IN CORTICAL THICKNESS AND REGION-OF-INTEREST VOLUME AND DIFFUSION METRICS IN HUNTINGTON'S DISEASE: INFORMING TRIAL DESIGN

Neurological Motor Disorder