Tryptophan metabolites predict response after cognitive behavioral therapy for depression: A single-arm trial

•Tryptophan metabolites in relation to cognitive behavior therapy were firstly investigated.•5-HIAA, kynurenine, 3-HK, and kynurenine-tryptophan-ratio increased to endpoint.•all four parameters were indicative of treatment response. Cognitive behavioral therapy (CBT) is one of the most prominent standard treatments for depression. However, like with antidepressant drugs, a subgroup of patients remains unresponsive. Since an imbalance in serotonin and kynurenine pathway metabolites are involved in the pathophysiology of depression, this study investigates whether those may be useful biomarkers to predict therapy response. Adult drug-free patients with a diagnosed depressive episode underwent six weeks of cognitive behavioral therapy in a multimodal setting. Levels of biological parameters were measured at baseline and endpoint using Ultra Performance Liquid Chromatography. Similarly, depression severity was measured by MADRS. Levels of the serotonin metabolite 5-HIAA, kynurenine, the kynurenine metabolite 3-HK, and the kynurenine-tryptophan-ratio (Kyn/Trp) significantly increased until endpoint. Higher baseline levels of all four parameters were predictive for better response at endpoint. However, 3-HK levels were predictive for the continuous outcome of MADRS score change, while kynurenine and 5-HIAA levels were predictive for the binary outcome of response versus non-response, and Kyn/Trp and 5-HIAA for remission status. With this single-arm design, results are preliminary and effects at endpoint cannot causally be linked to the CBT intervention. This study shows that tryptophan metabolites may serve as biomarkers for treatment response to CBT to foster individualized treatment choices. However, classifying absolute levels as low or high in relation to other biomarkers is not possible. Controlled studies are needed.