Increased plasma levels of competing amino acids, rather than lowered plasma tryptophan levels, are associated with a non-response to treatment in major depression.
Lowered plasma tryptophan (TRP) and TRP/competing amino acid (CAA) ratio may be involved in the pathophysiology of major depression (MDD). Increased cortisol and immune-inflammatory mediators in MDD may affect the availability of TRP to the brain. We investigated whether baseline or post-treatment TRP, CAAs and TRP/CAA ratio are associated with a treatment response in MDD and whether these effects may be mediated by cortisol or immune biomarkers. We included 50 medication-free MDD patients with a depressive episode (DSM diagnosis) and assessed symptom severity with the Inventory of Depressive Symptomatology (IDS) before and after treatment as usual for 12 weeks (endpoint). Plasma levels of TRP, CAAs, the ratio, cortisol, CRP and 6 selected cytokines were assayed. The primary outcome was a 50% reduction in the IDS, while the secondary was a remission of the depressive episode. In IDS non-responders, CAAs increased and the TRP/CAA ratio decreased, while in IDS responders CAAs decreased and the TRP/CAA ratio increased from baseline to endpoint. In patients who were still depressed at endpoint TRP and CAAs levels had increased from baseline, while in remitted patients no such effects were found. Increases in CAAs were inversely correlated with changes in interleukin-1 receptor antagonist levels. The results show that increased CAA levels from baseline to endpoint are associated with a non-response to treatment in MDD patients. This suggests that the mechanism underpinning the CAA-related treatment resistance may be related to changes in immune pathways. CAA levels and amino acid metabolism may be new drug targets in depression.
['Ormstad|Heidi|H|', 'Dahl|Johan|J|', 'Verkerk|Robert|R|', 'Andreassen|Ole A|OA|', 'Maes|Michael|M|']
D000328:Adult D000596:Amino Acids D000928:Antidepressive Agents D015415:Biomarkers D016207:Cytokines D003865:Depressive Disorder, Major D039721:Diagnostic and Statistical Manual of Mental Disorders D015536:Down-Regulation D004351:Drug Resistance D005260:Female D005500:Follow-Up Studies D006801:Humans D008137:Longitudinal Studies D008297:Male D008875:Middle Aged D009664:Norway D010044:Outpatient Clinics, Hospital D010352:Patient Dropouts D011569:Psychiatric Status Rating Scales D012074:Remission Induction D014364:Tryptophan D015854:Up-Regulation
Tryptophan Depression Indoleamine 2,3-dioxygenase Inflammation Kynurenine Serotonin