Depression: Is Tryptophan Metabolism at the Core of the Issue?

In today’s broadcast we will be discussing how inflammation is gaining greater notoriety in the scientific literature as a primary cause of depression.  Yes, depression is multifactorial, but new research is demonstrating how inflammation leads to the abnormal breakdown of tryptophan leading to lower levels of serotonin.  However, the newest scientific research is demonstrating that rather than low serotonin levels, the “toxic” by products of tryptophan metabolism may be at the core of depression.
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1.Augmentation of antidepressant effects of venlafaxine by agomelatine in mice are independent of kynurenine pathway.
Thomas J, Khanam R, Vohora D.
Neurochem Int. 2016 Jun 13. pii: S0197-0186(16)30157-7. doi: 10.1016/j.neuint.2016.06.008. [Epub ahead of print]
PMID: 27311540 [PubMed – as supplied by publisher]
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2.Mechanisms of Inflammation-Associated Depression: Immune Influences on Tryptophan and Phenylalanine Metabolisms.
Strasser B, Sperner-Unterweger B, Fuchs D, Gostner JM.
Curr Top Behav Neurosci. 2016 Jun 9. [Epub ahead of print]
PMID: 27278641 [PubMed – as supplied by publisher]
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3.Increased plasma levels of competing amino acids, rather than lowered plasma tryptophan levels, are associated with a non-response to treatment in major depression.
Ormstad H, Dahl J, Verkerk R, Andreassen OA, Maes M.
Eur Neuropsychopharmacol. 2016 May 26. pii: S0924-977X(16)30046-3. doi: 10.1016/j.euroneuro.2016.05.005. [Epub ahead of print]
PMID: 27237997 [PubMed – as supplied by publisher]
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4.Quantitative profiling of neurotransmitter abnormalities in the hippocampus of rats treated with lipopolysaccharide: Focusing on kynurenine pathway and implications for depression.
Guo Y, Cai H, Chen L, Liang D, Yang R, Dang R, Jiang P.
J Neuroimmunol. 2016 Jun 15;295-296:41-6. doi: 10.1016/j.jneuroim.2016.04.006. Epub 2016 Apr 14.
PMID: 27235347 [PubMed – in process]
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5.Role of the Kynurenine Metabolism Pathway in Inflammation-Induced Depression: Preclinical Approaches.
Dantzer R.
Curr Top Behav Neurosci. 2016 May 26. [Epub ahead of print]
PMID: 27225497 [PubMed – as supplied by publisher]
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6.Role of Kynurenine Metabolism Pathway Activation in Major Depressive Disorders.
Savitz J.
Curr Top Behav Neurosci. 2016 May 25. [Epub ahead of print]
PMID: 27221627 [PubMed – as supplied by publisher]
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7.Depression in Autoimmune Diseases.
Pryce CR, Fontana A.
Curr Top Behav Neurosci. 2016 May 25. [Epub ahead of print]
PMID: 27221625 [PubMed – as supplied by publisher]
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8.Suicidality and Activation of the Kynurenine Pathway of Tryptophan Metabolism.
Bryleva EY, Brundin L.
Curr Top Behav Neurosci. 2016 May 25. [Epub ahead of print]
PMID: 27221623 [PubMed – as supplied by publisher]
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9.Female Flinders Sensitive Line rats show estrous cycle-independent depression-like behavior and altered tryptophan metabolism.
Eskelund A, Budac DP, Sanchez C, Elfving B, Wegener G.
Neuroscience. 2016 Aug 4;329:337-48. doi: 10.1016/j.neuroscience.2016.05.024. Epub 2016 May 19.
PMID: 27210075 [PubMed – in process]
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10.Adjuvant indoleamine 2,3-dioxygenase enzyme inhibition for comprehensive management of epilepsy and comorbid depression.
Singh T, Goel RK.
Eur J Pharmacol. 2016 May 14;784:111-120. doi: 10.1016/j.ejphar.2016.05.019. [Epub ahead of print]
PMID: 27189423 [PubMed – as supplied by publisher]
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11.Interactions between inflammatory mediators and corticosteroids regulate transcription of genes within the Kynurenine Pathway in the mouse hippocampus.
Brooks AK, Lawson MA, Smith RA, Janda TM, Kelley KW, McCusker RH.
J Neuroinflammation. 2016 May 3;13(1):98.
PMID: 27142940 [PubMed – as supplied by publisher] Free PMC Article
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12.Effects of Exhaustive Aerobic Exercise on Tryptophan-Kynurenine Metabolism in Trained Athletes.
Strasser B, Geiger D, Schauer M, Gatterer H, Burtscher M, Fuchs D.
PLoS One. 2016 Apr 28;11(4):e0153617. doi: 10.1371/journal.pone.0153617. eCollection 2016.
PMID: 27124720 [PubMed – in process] Free PMC Article
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13.Kynurenine pathway metabolites are associated with hippocampal activity during autobiographical memory recall in patients with depression.
Young KD, Drevets WC, Dantzer R, Teague TK, Bodurka J, Savitz J.
Brain Behav Immun. 2016 Aug;56:335-42. doi: 10.1016/j.bbi.2016.04.007. Epub 2016 Apr 29.
PMID: 27091600 [PubMed – in process]
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14.Polymorphism of Kynurenine Pathway-Related Genes, Kynurenic Acid, and Psychopathological Symptoms in HIV.
Douet V, Tanizaki N, Franke A, Li X, Chang L.
J Neuroimmune Pharmacol. 2016 Apr 12. [Epub ahead of print]
PMID: 27072370 [PubMed – as supplied by publisher]
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15.IgA/IgM responses to tryptophan and tryptophan catabolites (TRYCATs) are differently associated with prenatal depression, physio-somatic symptoms at the end of term and premenstrual syndrome.
Roomruangwong C, Kanchanatawan B, Sirivichayakul S, Anderson G, Carvalho AF, Duleu S, Geffard M, Maes M.
Mol Neurobiol. 2016 Apr 1. [Epub ahead of print]
PMID: 27037573 [PubMed – as supplied by publisher]
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16.Inflammation Models of Depression in Rodents: Relevance to Psychotropic Drug Discovery.
Remus JL, Dantzer R.
Int J Neuropsychopharmacol. 2016 Apr 27. pii: pyw028. doi: 10.1093/ijnp/pyw028. [Epub ahead of print] Review.
PMID: 27026361 [PubMed – as supplied by publisher] Free Article
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17.Overview of the role of vitamins and minerals on the kynurenine pathway in health and disease.
Majewski M, Kozlowska A, Thoene M, Lepiarczyk E, Grzegorzewski WJ.
J Physiol Pharmacol. 2016 Feb;67(1):3-19.
PMID: 27010891 [PubMed – in process] Free Article
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18.Microglia Transcriptome Changes in a Model of Depressive Behavior after Immune Challenge.
Gonzalez-Pena D, Nixon SE, O’Connor JC, Southey BR, Lawson MA, McCusker RH, Borras T, Machuca D, Hernandez AG, Dantzer R, Kelley KW, Rodriguez-Zas SL.
PLoS One. 2016 Mar 9;11(3):e0150858. doi: 10.1371/journal.pone.0150858. eCollection 2016.
PMID: 26959683 [PubMed – in process] Free PMC Article
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19.Direct effects of exercise on kynurenine metabolism in people with normal glucose tolerance or type 2 diabetes.
Mudry JM, Alm PS, Erhardt S, Goiny M, Fritz T, Caidahl K, Zierath JR, Krook A, Wallberg-Henriksson H.
Diabetes Metab Res Rev. 2016 Mar 4. doi: 10.1002/dmrr.2798. [Epub ahead of print]
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20.Kynurenine pathway metabolism and immune activation: Peripheral measurements in psychiatric and co-morbid conditions.
Strasser B, Becker K, Fuchs D, Gostner JM.
Neuropharmacology. 2016 Feb 26. pii: S0028-3908(16)30065-X. doi: 10.1016/j.neuropharm.2016.02.030. [Epub ahead of print] Review.
PMID: 26924709 [PubMed – as supplied by publisher]
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21.Kynurenine pathway metabolites and suicidality.
Bryleva EY, Brundin L.
Neuropharmacology. 2016 Jan 26. pii: S0028-3908(16)30033-8. doi: 10.1016/j.neuropharm.2016.01.034. [Epub ahead of print] Review.
PMID: 26820800 [PubMed – as supplied by publisher] Free Article
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22.Mast cells’ involvement in inflammation pathways linked to depression: evidence in mastocytosis.
Georgin-Lavialle S, Moura DS, Salvador A, Chauvet-Gelinier JC, Launay JM, Damaj G, Côté F, Soucié E, Chandesris MO, Barète S, Grandpeix-Guyodo C, Bachmeyer C, Alyanakian MA, Aouba A, Lortholary O, Dubreuil P, Teyssier JR, Trojak B, Haffen E, Vandel P, Bonin B; French Mast Cell Study Group, Hermine O, Gaillard R.
Mol Psychiatry. 2016 Jan 26. doi: 10.1038/mp.2015.216. [Epub ahead of print]
PMID: 26809839 [PubMed – as supplied by publisher]
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23.Mouse chronic social stress increases blood and brain kynurenine pathway activity and fear behaviour: Both effects are reversed by inhibition of indoleamine 2,3-dioxygenase.
Fuertig R, Azzinnari D, Bergamini G, Cathomas F, Sigrist H, Seifritz E, Vavassori S, Luippold A, Hengerer B, Ceci A, Pryce CR.
Brain Behav Immun. 2016 May;54:59-72. doi: 10.1016/j.bbi.2015.12.020. Epub 2015 Dec 24.
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24.Cognition and Emotions in Recurrent Depressive Disorders – The Role of Inflammation and the Kynurenine Pathway.
Talarowska M, Galecki P.
Curr Pharm Des. 2016;22(8):955-62.
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25.Indoleamine-2,3-Dioxygenase/Kynurenine Pathway as a Potential Pharmacological Target to Treat Depression Associated with Diabetes.
da Silva Dias IC, Carabelli B, Ishii DK, de Morais H, de Carvalho MC, Rizzo de Souza LE, Zanata SM, Brandão ML, Cunha TM, Ferraz AC, Cunha JM, Zanoveli JM.
Mol Neurobiol. 2015 Dec 15. [Epub ahead of print]
PMID: 26671617 [PubMed – as supplied by publisher]
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