Altered tryptophan catabolite concentrations in major depressive disorder and associated changes in hippocampal subfield volumes

Doolin, Kelly; Allers, Kelly A.; Pleiner, Sina; Liesener, André; Farrell, Chloë; Tozzi, Leonardo; O’Hanlon, Erik; Roddy, Darren; Frodl, Thomas; Harkin, Andrew; O’Keane, Veronica

doi:10.1016/j.psyneuen.2018.05.019

Cited by 73 publications

(43 citation statements)

References 55 publications

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“…This clinical data fit well with results from animal experiments: Depressive-like behavior related to immune activation was demonstrated to be associated with an upregulation of IDO1 (205)(206)(207) as well as KMO (208)(209)(210). Peripheral administration of lipopolysaccharide activated IDO, resulting in a distinct depressive-like behavioral syndrome (205).…”

Section: Fatigue and Depression Are Related To Immune Activation In Csupporting

confidence: 85%

Inflammation-Induced Tryptophan Breakdown is Related With Anemia, Fatigue, and Depression in Cancer

et al. 2020

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Many patients with cancer suffer from anemia, depression, and an impaired quality of life (QoL). These patients often also show decreased plasma tryptophan levels and increased kynurenine concentrations in parallel with elevated concentrations of Th1 type immune activation marker neopterin. In the course of anti-tumor immune response, the pro-inflammatory cytokine interferon gamma (IFN-γ) induces both, the enzyme indoleamine 2,3-dioxygenase (IDO) to degrade tryptophan and the enzyme GTP-cyclohydrolase I to form neopterin. High neopterin concentrations as well as an increased kynurenine to tryptophan ratio (Kyn/Trp) in the blood of cancer patients are predictive for a worse outcome. Inflammation-mediated tryptophan catabolism along the kynurenine pathway is related to fatigue and anemia as well as to depression and a decreased QoL in patients with solid tumors. In fact, enhanced tryptophan breakdown might greatly contribute to the development of anemia, fatigue, and depression in cancer patients. IDO activation and stimulation of the kynurenine pathway exert immune regulatory mechanisms, which may impair anti-tumor immune responses. In addition, tumor cells can degrade tryptophan to weaken immune responses directed against them. High IDO expression in the tumor tissue is associated with a poor prognosis of patients. The efficiency of IDO-inhibitors to inhibit cancer progression is currently tested in combination with established chemotherapies and with immune checkpoint inhibitors. Inflammation-mediated tryptophan catabolism and its possible influence on the development and persistence of anemia, fatigue, and depression in cancer patients are discussed.

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Section: Fatigue and Depression Are Related To Immune Activation In Csupporting

confidence: 85%

Inflammation-Induced Tryptophan Breakdown is Related With Anemia, Fatigue, and Depression in Cancer

et al. 2020

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“…Kynurenine pathway activation and associated elevated immune response has been shown to be associated with smaller hippocampi in MDD. 85 Abnormal membrane turnover in the hippocampus in MDD is greater in patients with highly recurrent illness and is further evidenced by magnetic resonance spectroscopy (MRS) studies. 86 Following from the shift to a pro-inflammatory state and the production of neurotoxic end-products, as well as a direct effect from chronic stress, perturbations in neurotransmission also occur in the pathogenesis of MDD.…”

Section: Stress Neurotoxicity and Temporal Lobe Structures In Mddmentioning

confidence: 99%

Hippocampal and Amygdalar Volume Changes in Major Depressive Disorder: A Targeted Review and Focus on Stress

et al. 2020

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Medial temporal lobe structures have long been implicated in the pathogenesis of major depressive disorder. Although findings of smaller hippocampal and amygdalar volumes are common, inconsistencies remain in the literature. In this targeted review, we examine recent and significant neuroimaging papers examining the volumes of these structures in major depressive disorder. A targeted PubMed/Google Scholar search was undertaken focusing on volumetric neuroimaging studies of the hippocampus and amygdala in major depressive disorder. Where possible, mean volumes and accompanying standard deviations were extracted allowing computation of Cohen’s ds effect sizes. Although not a meta-analysis, this allows a broad comparison of volume changes across studies. Thirty-nine studies in total were assessed. Hippocampal substructures and amygdale substructures were investigated in 11 and 2 studies, respectively. The hippocampus was more consistently smaller than the amygdala across studies, which is reflected in the larger cumulative difference in volume found with the Cohen’s ds calculations. The left and right hippocampi were, respectively, 92% and 91.3% of the volume found in controls, and the left and right amygdalae were, respectively, 94.8% and 92.6% of the volume of controls across all included studies. The role of stress in temporal lobe structure volume reduction in major depressive disorder is discussed.

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“…Compared to their non-fatigued counterparts, survivors with CF are characterized by metabolic changes that may be associated with a low grade inflammatory status. The essential amino acid Trp is the precursor of melatonin and serotonin, and has received much attention in investigations of depression and other psychiatric disorders [39,40]. Trp is mainly catabolized along the kynurenine pathway that produces intermediate compounds, collectively referred to as kynurenines, with a variety of effects, including neuro-and immunomodulation [37].…”

Section: Discussionmentioning

confidence: 99%

Metabolic analysis of amino acids and vitamin B6 pathways in lymphoma survivors with cancer related chronic fatigue

et al. 2020

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Chronic cancer-related fatigue (CF) is a common and distressing condition in a subset of cancer survivors and common also after successful treatment of malignant lymphoma. The etiology and pathogenesis of CF is unknown, and lack of biomarkers hampers development of diagnostic tests and successful therapy. Recent studies on the changes of amino acid levels and other metabolites in patients with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) have pointed to possible central defects in energy metabolism. Here we report a comprehensive analysis of serum concentrations of amino acids, including metabolites of tryptophan, the kynurenine pathway and vitamin B6 in a well characterized national Norwegian cohort of lymphoma survivors after high-dose therapy and autologous stem cell transplantation. Among the 20 standard amino acids in humans, only tryptophan levels were significantly lower in both males and females with CF compared to non-fatigued survivors, a strikingly different pattern than seen in CFS/ME. Markers of tryptophan degradation by the kynurenine pathway (kynurenine/tryptophan ratio) and activation of vitamin B6 catabolism (pyridoxic acid/(pyridoxal + pyridoxal 5'-phosphate), PAr index) differed in survivors with or without CF and correlated with known markers of immune activation and inflammation, such as neopterin, C-reactive protein and Interleukin-6. Among personal traits and clinical findings assessed simultaneously in participating survivors, higher neuroticism score, obesity and higher PAr index were significantly associated with increased risk of CF. Collectively, these data point to low grade immune activation and inflammation as a basis for CF in lymphoma survivors.

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Altered tryptophan catabolite concentrations in major depressive disorder and associated changes in hippocampal subfield volumes

Cited by 73 publications

References 55 publications

Inflammation-Induced Tryptophan Breakdown is Related With Anemia, Fatigue, and Depression in Cancer

Inflammation-Induced Tryptophan Breakdown is Related With Anemia, Fatigue, and Depression in Cancer

Hippocampal and Amygdalar Volume Changes in Major Depressive Disorder: A Targeted Review and Focus on Stress

Metabolic analysis of amino acids and vitamin B6 pathways in lymphoma survivors with cancer related chronic fatigue

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