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Kynurenine depression

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https://www.readbyqxmd.com/read/29777939/variation-of-genes-encoding-kat1-aadat-and-ido1-as-a-potential-risk-of-depression-development
#1
Paulina Wigner, Piotr Czarny, Ewelina Synowiec, Michał Bijak, Monika Talarowska, Piotr Galecki, Janusz Szemraj, Tomasz Sliwinski
Numerous data suggests that the disorders of tryptophan catabolites (TRYCATs) pathway, including a decreased level of tryptophan or evaluated concentration of harmful TRYCATs -kynurenine, quinolinic acid, 3-hydroxyanthranilic acid, 3-hydroxytryptophan - may cause the occurrence of DD symptoms. In this work, we assessed the relationship between single-nucleotide polymorphisms (SNPs) of KAT1, KAT2 and IDO1 gene encoding, and the risk of depression development. Our study was performed on the DNA isolated from peripheral blood of 281 depressed patients and 236 controls...
May 16, 2018: European Psychiatry: the Journal of the Association of European Psychiatrists
https://www.readbyqxmd.com/read/29775873/psychosocial-stress-and-inflammation-driving-tryptophan-breakdown-in-children-and-adolescents-a-cross-sectional-analysis-of-two-cohorts
#2
Nathalie Michels, Gerard Clarke, Loreto Olavarria-Ramirez, Sonia Gómez-Martínez, Ligia Esperanza Díaz, Ascensión Marcos, Kurt Widhalm, Livia A Carvalho
BACKGROUND: Tryptophan breakdown is an important mechanism in several diseases e.g. inflammation and stress-induced inflammation have been associated with the development of depression via enhanced tryptophan breakdown. Depression is a major public health problem which commonly starts during adolescence, thus identifying underlying mechanisms during early life is crucial in prevention. The aim of this work was to verify whether independent and interacting associations of psychosocial stress and inflammation on tryptophan breakdown already exist in children and adolescents as a vulnerable age group...
May 15, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29753175/changes-in-the-tryptophan-kynurenine-axis-in-association-to-therapeutic-response-in-clinically-depressed-patients-undergoing-psychiatric-rehabilitation
#3
B Reininghaus, K Riedrich, N Dalkner, S A Bengesser, A Birner, M Platzer, C Hamm, J M Gostner, D Fuchs, E Z Reininghaus
INTRODUCTION: In recent decades a number of studies have shown an association between the Tryptophan (Trp)-Kynurenine (Kyn) axis and neuropsychiatric disorders. However, the role of the Trp-Kyn pathway on the affective status in a general psychiatric cohort requires clarification. This study aimed to measure peripheral changes in Trp, Kyn and the Kyn/Trp-ratio as well as in the inflammatory markers high sensitive C-reactive protein (hsCRP) and interleukine-6 (IL-6) in individuals undergoing a six-week course of intensive treatment program comparing subgroups of treatment responders and non-responders...
May 6, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29734055/kynurenine-pathway-metabolic-balance-influences-microglia-activity-targeting-kynurenine-monooxygenase-to-dampen-neuroinflammation
#4
Allison M Garrison, Jennifer M Parrott, Arnulfo Tuñon, Jennifer Delgado, Laney Redus, Jason C O'Connor
Chronic stress or inflammation increases tryptophan metabolism along the kynurenine pathway (KP), and the generation of neuroactive kynurenine metabolites contributes to subsequent depressive-like behaviors. Microglia regulate KP balance by preferentially producing oxidative metabolites, including quinolinic acid. Research has focused on the interplay between cytokines and HPA axis-derived corticosteroids in regulating microglial activity and effects of KP metabolites directly on neurons; however, the potential role that KP metabolites have directly on microglial activity is unknown...
April 22, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29731182/effect-of-probiotic-and-prebiotic-vs-placebo-on-psychological-outcomes-in-patients-with-major-depressive-disorder-a-randomized-clinical-trial
#5
Asma Kazemi, Ahmad Ali Noorbala, Kamal Azam, Mohammad Hadi Eskandari, Kurosh Djafarian
BACKGROUND: Disturbance in the equilibrium of the gut microbiota has been involved in the pathophysiology of depression. Probiotics have the potential to healthfully modulate the gut microbiome. Prebiotics could also be effective by stimulation of growth of some bacterial species in the gut microbiota. OBJECTIVE: The aim of this double blind clinical trial, was to compare the effect of supplementation with the probiotic and prebiotic on the Beck Depression Inventory (BDI) score as a primary outcome as well as the kynurenine/tryptophan ratio and tryptophan/branch chain amino acids (BCAAs) ratio as secondary outcomes in patients with major depressive disorder (MDD)...
April 24, 2018: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/29725904/chronic-mild-stress-alters-kynurenine-pathways-changing-the-glutamate-neurotransmission-in-frontal-cortex-of-rats
#6
David Martín-Hernández, Hiram Tendilla-Beltrán, José L M Madrigal, Borja García-Bueno, Juan C Leza, Javier R Caso
Immune stimulation might be involved in the pathophysiology of major depressive disorder (MDD). This stimulation induces indoleamine 2,3-dioxygenase (IDO), an enzyme that reduces the tryptophan bioavailability to synthesize serotonin. IDO products, kynurenine metabolites, exert neurotoxic/neuroprotective actions through glutamate receptors. Thus, we study elements of these pathways linked to kynurenine metabolite activity examining whether antidepressants (ADs) can modulate them. Male Wistar rats were exposed to chronic mild stress (CMS), and some of them were treated with ADs...
May 3, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29705843/neuroimmune-imbalances-and-yin-yang-dynamics-in-stress-anxiety-and-depression
#7
Qing Yan
Evidences from psychoneuroimmunology (PNI) and systems biology studies support a conceptual framework of "Yin-Yang dynamics" for understanding the "whole mind-body system." The Yin-Yang dynamical balances in the stress response networks may be critical for health and diseases, especially mental health and psychiatric disorders. Specifically, the neuroimmune imbalances have been found as the important features and potential biomarkers of stress, anxiety, depression, and systemic inflammation...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29683396/reduced-peripheral-availability-of-tryptophan-and-increased-activation-of-the-kynurenine-pathway-and-cortisol-correlate-with-major-depression-and-suicide
#8
Amel Messaoud, Mensi Rym, Wahiba Douki, Fadoua Neffati, Mohamed Fadhel Najjar, Gabriella Gobbi, Flavia Valtorta, Lotfi Gaha, Stefano Comai
OBJECTIVES: Patients affected by major depression (MDD) are at high risk of suicide. The metabolism of tryptophan (Trp) along the serotonin (5-HT) and kynurenine (Kyn) pathways was found dysfunctional in MDD and in suicide. However, a clear biological framework linking dysfunctions in Trp metabolism via 5-HT and Kyn, cortisol, and the activities of tryptophan and indoleamino 2,3-dioxygenase (TDO, IDO) enzymes has not been yet clarified in MDD with or without suicidal behaviors. METHODS: We analyzed peripheral markers of Trp via 5-HT and Kyn pathways, Kyn/Trp ratio as a measure of TDO/IDO activities, cortisol, and psychopathology in 73 non-suicidal and 56 suicidal MDD patients, and in 40 healthy controls...
April 23, 2018: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/29608993/kynurenine-pathway-in-depression-a-systematic-review-and-meta-analysis
#9
REVIEW
Kamiyu Ogyu, Kaoruhiko Kubo, Yoshihiro Noda, Yusuke Iwata, Sakiko Tsugawa, Yuki Omura, Masataka Wada, Ryosuke Tarumi, Eric Plitman, Sho Moriguchi, Takahiro Miyazaki, Hiroyuki Uchida, Ariel Graff-Guerrero, Masaru Mimura, Shinichiro Nakajima
Abnormalities of the kynurenine (KYN) pathway may be implicated in the pathophysiology of depression. However, the relationships between depression and each metabolite of the KYN pathway remain uncertain. Therefore, we conducted a meta-analysis about the levels of the metabolites of KYN pathway between patients with depression and controls. Out of 899 initial records, we identified 22 articles to form the empirical basis. Seventeen, 10, and 18 studies examined levels of kynurenic acid (KYNA), quinolinic acid (QUIN), and KYN, respectively...
March 30, 2018: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/29524456/from-feedback-loop-transitions-to-biomarkers-in-the-psycho-immune-neuroendocrine-network-detecting-the-critical-transition-from-health-to-major-depression
#10
REVIEW
N J C Stapelberg, R Pratt, D L Neumann, D H K Shum, S Brandis, V Muthukkumarasamy, B Stantic, M Blumenstein, J P Headrick
BACKGROUND: Biological pathways underlying major depressive disorder (MDD) can be viewed as systems biology networks. The psycho-immune-neuroendocrine (PINE) network comprises central nervous, immune, endocrine and autonomic systems, integrating biological mechanisms of MDD. Such networks exhibit recurrent motifs with specific functions, including positive and negative feedback loops, and are subject to critical transitions, influenced by feedback loop transitions (FLTs). AIMS: We aim to identify critical feedback loops and their FLTs, as well sentinel network nodes (SNNs), key network nodes that drive FLTs, within the PINE network...
March 8, 2018: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/29508147/glutamate-and-its-receptors-as-therapeutic-targets-for-migraine
#11
REVIEW
Jan Hoffmann, Andrew Charles
There is substantial evidence indicating a role for glutamate in migraine. Levels of glutamate are higher in the brain and possibly also in the peripheral circulation in migraine patients, particularly during attacks. Altered blood levels of kynurenines, endogenous modulators of glutamate receptors, have been reported in migraine patients. Population genetic studies implicate genes that are involved with glutamate signaling in migraine, and gene mutations responsible for familial hemiplegic migraine and other familial migraine syndromes may influence glutamate signaling...
April 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29487480/modulation-of-tryptophan-and-serotonin-metabolism-as-a-biochemical-basis-of-the-behavioral-effects-of-use-and-withdrawal-of-androgenic-anabolic-steroids-and-other-image-and-performance-enhancing-agents
#12
Abdulla A-B Badawy
Modulation of tryptophan (Trp) metabolism may underpin the behavioral effects of androgenic-anabolic steroids (AAS) and associated image and performance enhancers. Euphoria, arousal, and decreased anxiety observed with moderate use and exercise may involve enhanced cerebral serotonin synthesis and function by increased release of albumin-bound Trp and estrogen-mediated liver Trp 2,3-dioxygenase (TDO) inhibition and enhancement of serotonin function. Aggression, anxiety, depression, personality disorders, and psychosis, observed on withdrawal of AAS or with use of large doses, can be caused by decreased serotonin synthesis due to TDO induction on withdrawal, excess Trp inhibiting the 2 enzymes of serotonin synthesis, and increased cerebral levels of neuroactive kynurenines...
2018: International Journal of Tryptophan Research: IJTR
https://www.readbyqxmd.com/read/29475018/kynurenine-pathway-metabolism-and-the-neurobiology-of-treatment-resistant-depression-comparison-of-multiple-ketamine-infusions-and-electroconvulsive-therapy
#13
A P Allen, M Naughton, J Dowling, A Walsh, R O'Shea, G Shorten, L Scott, D M McLoughlin, J F Cryan, G Clarke, T G Dinan
Current first-line antidepressants can take weeks or months to decrease depressive symptoms. Low dose ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, shows potential for a more rapid antidepressant effect, with efficacy also evident in previously treatment-resistant populations. However, a greater understanding of the physiological mechanisms underlying such effects is required. We assessed the potential impact of ketamine infusion on neurobiological drivers of kynurenine pathway metabolism in major depression (HPA axis hyperactivity, inflammation) in patients with treatment-resistant depression compared to gender-matched healthy controls...
May 2018: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/29454180/tryptophan-kynurenine-and-lipid-related-metabolites-as-blood-biomarkers-for-first-episode-drug-na%C3%A3-ve-patients-with-major-depressive-disorder-an-exploratory-pilot-case-control-study
#14
Nobuki Kuwano, Takahiro A Kato, Daiki Setoyama, Mina Sato-Kasai, Norihiro Shimokawa, Kohei Hayakawa, Masahiro Ohgidani, Noriaki Sagata, Hiroaki Kubo, Junji Kishimoto, Dongchon Kang, Shigenob Kanba
BACKGROUND: Early intervention in depression has been critical to prevent its negative impact including suicide. Recent blood biomarker studies for major depressive disorder (MDD) have suggested that tryptophan-kynurenine and lipid related metabolites are involved in the pathophysiology of MDD. However, there have been limited studies investigating these blood biomarkers in first-episode drug-naïve MDD, which are particularly important for early intervention in depression. METHODS: As an exploratory pilot case-control study, we examined the above blood biomarkers, and analyzed how these biomarkers are associated with clinical variables in first-episode drug-naïve MDD patients, based on metabolome/lipidome analysis...
April 15, 2018: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29377288/effects-of-anti-inflammatory-drugs-on-the-expression-of-tryptophan-metabolism-genes-by-human-macrophages
#15
Tim Regan, Andrew C Gill, Sara M Clohisey, Mark W Barnett, Carmine M Pariante, Neil A Harrison, David A Hume, Edward T Bullmore, Tom C Freeman
Several lines of evidence link macrophage activation and inflammation with (monoaminergic) nervous systems in the etiology of depression. IFN treatment is associated with depressive symptoms, whereas anti-TNFα therapies elicit positive mood. This study describes the actions of 2 monoaminergic antidepressants (escitalopram, nortriptyline) and 3 anti-inflammatory drugs (indomethacin, prednisolone, and anti-TNFα antibody) on the response of human monocyte-derived macrophages (MDMs) from 6 individuals to LPS or IFN-α...
April 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29368666/tryptophan-supplementation-and-serotonin-function-genetic-variations-in-behavioural-effects
#16
E L Gibson
The neurotransmitter serotonin has a role in affective disorders such as depression and anxiety, as well as sleep, cognitive function and appetite. This review examines the evidence that serotonin-related genotypes may moderate the behavioural effects of supplementation with the serotonin precursor amino acid l-tryptophan (TRP), on which synthesis of serotonin (or 5-hydroxytryptamine; 5-HT) depends. However, 95 % of serotonin is synthesised and used in the periphery, and TRP is also metabolised via non-5-HT routes such as the kynurenine pathway...
January 25, 2018: Proceedings of the Nutrition Society
https://www.readbyqxmd.com/read/29366745/glycyrrhizic-acid-ameliorates-the-kynurenine-pathway-in-association-with-its-antidepressant-effect
#17
Bo Wang, Yong-Jie Lian, Xin Dong, Wei Peng, Lin-Lin Liu, Wen-Jun Su, Hong Gong, Ting Zhang, Chun-Lei Jiang, Jia-Si Li, Yun-Xia Wang
Our previous study implied the role of central high mobility group box 1 (HMGB1) in lipopolysaccharide (LPS)-induced depressive-like behaviors that could partially abrogate by glycyrrhizic acid (GZA). Here, we considered the potential mechanism underlying GZA ameliorating chronic stress-induced depression both in vivo and in vitro. Depression model was established with the 4-week chronic unpredictable mild stress (CUMS) mice. Sucrose preference test, tail suspension test and open field test were performed to reflect depressive-like behaviors...
January 26, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29327354/a-validated-liquid-chromatography-high-resolution-tandem-mass-spectrometry-method-for-the-simultaneous-quantitation-of-tryptophan-kynurenine-kynurenic-acid-and-quinolinic-acid-in-human-plasma
#18
Kathrin Arnhard, Florian Pitterl, Barbara Sperner-Unterweger, Dietmar Fuchs, Therese Koal, Herbert Oberacher
Tryptophan (TRP) catabolism via the kynurenine pathway is considered to represent a major link between inflammation and various diseases, including neurodegenerative disorders, depression, schizophrenia, multiple sclerosis, cardiovascular disease, and cancer. The kynurenine pathway and levels of TRP and its metabolites kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QUIN) are well regulated under physiological conditions but may be altered as part of the activated immune response. A simple, sensitive, and specific liquid chromatography-time of flight mass spectrometry method was developed for determining levels of the four compounds in human plasma samples...
January 12, 2018: Electrophoresis
https://www.readbyqxmd.com/read/29317604/beta-defensin-1-aryl-hydrocarbon-receptor-and-plasma-kynurenine-in-major-depressive-disorder-metabolomics-informed-genomics
#19
Duan Liu, Balmiki Ray, Drew R Neavin, Jiabin Zhang, Arjun P Athreya, Joanna M Biernacka, William V Bobo, Daniel K Hall-Flavin, Michelle K Skime, Hongjie Zhu, Gregory D Jenkins, Anthony Batzler, Krishna R Kalari, Felix Boakye-Agyeman, Wayne R Matson, Swati S Bhasin, Taisei Mushiroda, Yusuke Nakamura, Michiaki Kubo, Ravishankar K Iyer, Liewei Wang, Mark A Frye, Rima Kaddurah-Daouk, Richard M Weinshilboum
Major depressive disorder (MDD) is a heterogeneous disease. Efforts to identify biomarkers for sub-classifying MDD and antidepressant therapy by genome-wide association studies (GWAS) alone have generally yielded disappointing results. We applied a metabolomics-informed genomic research strategy to study the contribution of genetic variation to MDD pathophysiology by assaying 31 metabolites, including compounds from the tryptophan, tyrosine, and purine pathways, in plasma samples from 290 MDD patients. Associations of metabolite concentrations with depressive symptoms were determined, followed by GWAS for selected metabolites and functional validation studies of the genes identified...
January 10, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29307018/the-role-of-tryptophan-metabolism-in-postpartum-depression
#20
REVIEW
Kai-Ming Duan, Jia-Hui Ma, Sai-Ying Wang, ZhengDong Huang, YingYong Zhou, HeYa Yu
The Postpartum depression (PPD) is the most common postpartum psychiatric disorder, afflicting approximately 10%-20% of new mothers. Clinical symptoms of the PPD include depressive disorder, agitation, insomnia, anxiety and confusion, resulting in an increase in suicidal tendencies, thereby having significant impacts on the puerpera, newborn and their family. A growing body of data indicate a role for alterations in tryptophan metabolism in the PPD. The metabolism of tryptophan produces an array of crucial factors that can differentially regulate key physiological processes linked to the PPD...
January 6, 2018: Metabolic Brain Disease
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