Kynurenine pathway in psychosis: evidence of increased tryptophan degradation
Abstract
The kynurenine pathway of tryptophan degradation may serve to integrate disparate abnormalities heretofore identified in research aiming to elucidate the complex aetiopathogenesis of psychotic disorders. Post-mortem brain tissue studies have reported elevated kynurenine and kynurenic acid in the frontal cortex and upregulation of the first step of the pathway in the anterior cingulate cortex of individuals with schizophrenia. In this study, we examined kynurenine pathway activity by measuring tryptophan breakdown, a number of pathway metabolites and interferon gamma (IFN-gamma), which is the preferential activator of the first-step enzyme, indoleamine dioxygenase (IDO), in the plasma of patients with major psychotic disorder. Plasma tryptophan, kynurenine pathway metabolites were measured using high-performance liquid chromatography (HPLC) in 34 patients with a diagnosis on the psychotic spectrum (schizophrenia or schizoaffective disorder) and in 36 healthy control subjects. IFN-gamma was measured using enzyme-linked immunosorbent assay (ELISA). The mean tryptophan breakdown index (kynurenine/tryptophan) was significantly higher in the patient group compared with controls (P < 0.05). IFN-gamma measures did not differ between groups (P = 0.23). No relationship was found between measures of psychopathology, symptom severity and activity in the first step in the pathway. A modest correlation was established between the tryptophan breakdown index and illness duration. These results provide evidence for kynurenine pathway upregulation, specifically involving the first enzymatic step, in patients with major psychotic disorder. Increased tryptophan degradation in psychoses may have potential consequences for the treatment of these disorders by informing the development of novel therapeutic compounds.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Dysregulation of the kynurenine pathway has been linked to several brain disorders, including depression, schizophrenia, and autism spectrum disorder.
“Dysregulation of the kynurenine pathway has been linked to several brain disorders, including depression (395), schizophrenia (396, 397), and ASD (398).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [397]
Cites
Scale for the Assessment of Negative Symptoms (SANS)*
(1989) · The British Journal of Psychiatry · doi:10.1192/s0007125000291502 · Cited by 2,706 · see citing works
Scale for Assessment of Positive Symptoms (SAPS) 1984
Andreasen, N. C. (1995) · Open Scholarship Institutional Repository (Washington University in St. Louis) · Cited by 2,423 · see citing works
Quinolinic Acid: An Endogenous Metabolite That Produces Axon-Sparing Lesions in Rat Brain
Schwarcz, R. M., Whetsell, W. O., & Mangano, R. M. (1983) · Science · doi:10.1126/science.6849138 · Cited by 1,269 · see citing works
Assessing Depression in Schizophrenia: The Calgary Depression Scale
Addington, D. E., Addington, J., & Maticka‐Tyndale, E. (1993) · The British Journal of Psychiatry · doi:10.1192/s0007125000292581 · Cited by 1,177 · see citing works
Frumento, G., Rotondo, R., Tonetti, M., Damonte, G., Benatti, U., & Ferrara, G. B. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020121 · Cited by 1,133 · see citing works
Relationship between interferon‐γ, indoleamine 2,3‐dioxygenase, and tryptophan catabolism
Taylor, M. W., & Feng, G. (1991) · The FASEB Journal · doi:10.1096/fasebj.5.11.1907934 · Cited by 1,060 · see citing works
Neuropharmacology of quinolinic and kynurenic acids.
Stone, T. W. (1993) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)00441-7 · Cited by 949 · see citing works
Blood–Brain Barrier Transport of Kynurenines: Implications for Brain Synthesis and Metabolism
Fukui, S., Schwarcz, R. M., Rapoport, S. I., Takada, Y., & Smith, Q. R. (1991) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1991.tb03460.x · Cited by 765 · see citing works
Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis on schizophrenia
Kim, J. S., Kornhuber, H. H., Schmid‐Burgk, W., & Holzmüller, B. (1980) · Neuroscience Letters · doi:10.1016/0304-3940(80)90178-0 · Cited by 694 · see citing works
Increased cortical kynurenate content in schizophrenia
Schwarcz, R., Rassoulpour, A., Wu, H.-Q., Medoff, D., Tamminga, C. A., & Roberts, R. C. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01078-2 · Cited by 590 · see citing works
Manipulation of Brain Kynurenines: Glial Targets, Neuronal Effects, and Clinical Opportunities
Schwarcz, R. M., & Pellicciari, R. (2002) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.034439 · Cited by 556 · see citing works
Monitoring tryptophan metabolism in chronic immune activation
Schröcksnadel, K., Wirleitner, B., Winkler, C., & Fuchs, D. (2006) · Clinica Chimica Acta · doi:10.1016/j.cca.2005.06.013 · Cited by 551 · see citing works
Kynurenine pathway in major depression: Evidence of impaired neuroprotection
Myint, A.-M., Kim, Y. K., Verkerk, R., Scharpé, S., Steinbusch, H., & Leonard, B. (2007) · Journal of Affective Disorders · doi:10.1016/j.jad.2006.07.013 · Cited by 527 · see citing works
Human macrophages convert l -tryptophan into the neurotoxin quinolinic acid
Heyes, M. P., Saito, K., & Markey, S. P. (1992) · Biochemical Journal · doi:10.1042/bj2830633 · Cited by 448 · see citing works
Tryptophan metabolism and brain function: focus on kynurenine and other indole metabolites
Moroni, F. (1999) · European Journal of Pharmacology · doi:10.1016/s0014-2999(99)00196-x · Cited by 347 · see citing works
Depression in first-episode schizophrenia
Koreen, A., Siris, S. G., Chakos, M., Alvir, J. M., Mayerhoff, D. I., & Lieberman, J. A. (1993) · American Journal of Psychiatry · doi:10.1176/ajp.150.11.1643 · Cited by 319 · see citing works
l-Kynurenine Its synthesis and possible regulatory function in brain
G�l, E. M., & Sherman, A. D. (1980) · Neurochemical Research · doi:10.1007/bf00964611 · Cited by 318 · see citing works
Tryptophan degradation and immune activation in Alzheimer's disease
Widner, B., Leblhuber, F., Walli, J., Tilz, G. P., Demel, U., & Fuchs, D. (2000) · Journal of Neural Transmission · doi:10.1007/s007020050029 · Cited by 287 · see citing works
Nicotinic Receptor Function in Schizophrenia
Leonard, S. S., Adams, C., Breese, C. R., Adler, L. E., Bickford, P. C., Byerley, W., Coon, H. H., Griffith, J. M., Miller, C., Myles‐Worsley, M., et al. (1996) · Schizophrenia Bulletin · doi:10.1093/schbul/22.3.431 · Cited by 263 · see citing works
Molecules in focus: Indoleamine 2,3-dioxygenase
King, N. J. C., & Thomas, S. R. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2007.01.004 · Cited by 260 · see citing works
Human microglia convert l -tryptophan into the neurotoxin quinolinic acid
Heyes, M. P., Achim, C. L., Wiley, C. A., Major, E. O., Saito, K., & Markey, S. P. (1996) · Biochemical Journal · doi:10.1042/bj3200595 · Cited by 260 · see citing works
Miller, C. L., Llenos, I. C., Dulay, J. R., & Weis, S. (2006) · Brain Research · doi:10.1016/j.brainres.2005.12.056 · Cited by 240 · see citing works
Magni, G., Amici, A., Emanuelli, M., Raffaelli, N., & Ruggieri, S. (1999) · Advances in enzymology and related areas of molecular biology/Advances in enzymology and related subjects · doi:10.1002/9780470123195.ch5 · Cited by 235 · see citing works
Miller, C. L., Llenos, I. C., Dulay, J. R., Barillo, M. M., Yolken, R. H., & Weis, S. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2003.12.015 · Cited by 232 · see citing works
Different kynurenine pathway enzymes limit quinolinic acid formation by various human cell types
Heyes, M. P., Chen, C. Y., Major, E. O., & Saito, K. (1997) · Biochemical Journal · doi:10.1042/bj3260351 · Cited by 215 · see citing works
Schizophrenia as an inflammation-mediated dysbalance of glutamatergic neurotransmission
Müller, N., & Schwarz, M. (2006) · Neurotoxicity Research · doi:10.1007/bf03033242 · Cited by 214 · see citing works
Review of immunological and immunopathological findings in schizophrenia.
Rothermundt, M., Arolt, V., & Bayer, T. (2001) · Brain, behavior, and immunity · doi:10.1006/brbi.2001.0648 · Cited by 200 · see citing works
A mechanism for increased quinolinic acid formation following acute systemic immune stimulation.
Saito, K., Crowley, J. S., Markey, S., & Heyes, M. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)82284-0 · Cited by 194 · see citing works
Hervé, C., Beyne, P., Jamault, H., & Delacoux, E. (1996) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/0378-4347(95)00341-x · Cited by 186 · see citing works
Induction of Tryptophan Degradation In Vitro and In Vivo : A γ-Interferon-Stimulated Activity
Byrne, G. I., LEHMANN, L. K., KIRSCHBAUM, J. G., Borden, E. C., Lee, C. M., & Brown, R. R. (1986) · Journal of Interferon Research · doi:10.1089/jir.1986.6.389 · Cited by 183 · see citing works
Bodaghi, B., Goureau, O., Zipeto, D., Laurent, L., Virelizier, J. L., & Michelson, S. (1999) · PubMed · Cited by 180 · see citing works
Sanni, L. A., Thomas, S. R., Tattam, B. N., Moore, D. E., Chaudhri, G., Stocker, R., & Hunt, N. H. (1998) · Europe PMC (PubMed Central) · Cited by 178 · see citing works
The role of immune function in schizophrenia: an overview
Müller, N., Riedel, M. K. M., Ackenheil, M., & Schwarz, M. (1999) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/pl00014187 · Cited by 158 · see citing works
Effects of phencyclidine on excitatory amino acid activation of spinal interneurones in the cat
Lodge, D., & Anis, N. A. (1982) · European Journal of Pharmacology · doi:10.1016/0014-2999(82)90022-x · Cited by 158 · see citing works
Bodaghi, B., Goureau, O., Zipeto, D., Laurent, L., Virelizier, J., & Michelson, S. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.2.957 · Cited by 154 · see citing works
Shepard, P. D., Joy, B., Prendeville, L. C., & Schwarcz, R. M. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300188 · Cited by 131 · see citing works
Biochemical and Medical Aspects of Tryptophan Metabolism
Nunn, P. B. (1981) · FEBS Letters · doi:10.1016/0014-5793(81)80451-6 · Cited by 105 · see citing works
Joseph, M. H., Baker, H. F., Crow, T. J., Riley, G. J., & Risby, D. (1979) · Psychopharmacology · doi:10.1007/bf00431959 · Cited by 80 · see citing works
Heyes, M. P., & Morrison, P. F. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.68010280.x · Cited by 79 · see citing works
Kynurenic acid antagonists and kynurenine pathway inhibitors
Stone, T. W. (2001) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.10.4.633 · Cited by 79 · see citing works
Purine, Kynurenine, Neopterin and Lipid Peroxidation Levels in Inflammatory Bowel Disease
Forrest, C. M., Youd, P. L., Kennedy, A., Gould, S. R., Darlington, L. G., & Stone, T. W. (2002) · Journal of Biomedical Science · doi:10.1007/bf02256538 · Cited by 77 · see citing works
Grant, R., Naif, H. M., Espinosa, M., & Kapoor, V. (2000) · Redox Report · doi:10.1179/135100000101535357 · Cited by 76 · see citing works
Kynurenic Acid And Schizophrenia
Erhardt, S., Schwieler, L., & Engberg, G. (2003) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-0135-0_18 · Cited by 74 · see citing works
Chronic neuroleptic treatment reduces endogenous kynurenic acid levels in rat brain
Ceresoli‐Borroni, G., Rassoulpour, A., Wu, H., Guidetti, P., & Schwarcz, R. M. (2006) · Journal of Neural Transmission · doi:10.1007/s00702-005-0432-z · Cited by 72 · see citing works
Avguštin, B., Wraber, B., & Tavčar, R. (2005) · PubMed · Cited by 65 · see citing works
Badawy, A. A. ‐., & Evans, M. (1976) · Biochemical Journal · doi:10.1042/bj1560381 · Cited by 55 · see citing works
Biochemical and medical aspects of tryptophan metabolism.
Hayaishi, O., Ishimura, Y., & Kido, R. (1980) · Cited by 53 · see citing works
Acute tryptophan depletion in schizophrenia
GOLIGHTLY, K. L., LLOYD, J. A., HOBSON, J. E., Gallagher, P., Mercer, G., & Young, A. H. (2001) · Psychological Medicine · doi:10.1017/s0033291799003062 · Cited by 46 · see citing works
Allegri, G., Costa, C., Bertazzo, A., Biasiolo, M., & Ragazzi, E. (2003) · Il Farmaco · doi:10.1016/s0014-827x(03)00140-x · Cited by 43 · see citing works
Acute Dietary Tryptophan Depletion: Effects on Schizophrenic Positive and Negative Symptoms
Sharma, R. P., Shapiro, L. E., Kamath, S. K., Soll, E. A., Watanabe, M. D., & Davis, J. M. (2008) · Neuropsychobiology · doi:10.1159/000119323 · Cited by 30 · see citing works
Induction of indoleamine 2,3-dioxygenase in primary human macrophages by HIV-1
Grant, R., Naif, H. M., Thuruthyil, S. J., Nasr, N., Littlejohn, T. K., Takikawa, O., & Kapoor, V. (2000) · Redox Report · doi:10.1179/135100000101535366 · Cited by 28 · see citing works
Depression in Kraepelinian schizophrenia
Kilzieh, N., Wood, A. E., Erdmann, J., Raskind, M. A., & Tapp, A. M. (2003) · Comprehensive Psychiatry · doi:10.1053/comp.2003.50002 · Cited by 24 · see citing works
Ino, K., & Kikkawa, F. (2008) · Springer eBooks · doi:10.1007/978-3-540-47648-1_3037 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Meta-Analysis of Cytokine Alterations in Schizophrenia: Clinical Status and Antipsychotic Effects
Miller, B. J., Buckley, P., Seabolt, W., Mellor, A., & Kirkpatrick, B. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.04.013 · Cited by 1,742 · see citing works
Goldsmith, D. R., Rapaport, M. H., & Miller, B. J. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.3 · Cited by 1,683 · see citing works
Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health
Berding, K., Vlckova, K., Marx, W., Schellekens, H., Stanton, C., Clarke, G., Jacka, F., Dinan, T. G., & Cryan, J. F. (2021) · Advances in Nutrition · doi:10.1093/advances/nmaa181 · Cited by 451 · see citing works
Self-citationThe role of pro-inflammatory cytokines in the neuroinflammation and neurogenesis of schizophrenia
Na, K., Jung, H., & Kim, Y. (2012) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2012.10.022 · Cited by 425 · see citing works
The kynurenine system and immunoregulation
Mándi, Y., & Vécsei, L. (2012) · Journal of neural transmission · doi:10.1007/s00702-011-0681-y · Cited by 382 · see citing works
Wang, A. K., & Miller, B. J. (2017) · Schizophrenia Bulletin · doi:10.1093/schbul/sbx035 · Cited by 389 · see citing works
Association of high-sensitivity C-reactive protein with <i>de novo</i> major depression
Pasco, J. A., Nicholson, G. C., Williams, L. J., Jacka, F. N., Henry, M. J., Kotowicz, M. A., Schneider, H. G., Leonard, B. E., & Berk, M. (2010) · British Journal of Psychiatry · doi:10.1192/bjp.bp.109.076430 · Cited by 321 · see citing works
Marx, W., McGuinness, A. J., Rocks, T., Ruusunen, A. A., Cleminson, J. R., Walker, A. J., Gomes‐da‐Costa, S., Lane, M. M., Sanches, M., Díaz, A. P., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-00951-9 · Cited by 327 · see citing works
Inflammation and Schizophrenia
Kirkpatrick, B. W., & Miller, B. J. (2013) · Schizophrenia Bulletin · doi:10.1093/schbul/sbt141 · Cited by 318 · see citing works
Morris, G., Berk, M., Carvalho, A. F., Caso, J. R., Sanz, Y., Walder, K. R., & Maes, M. H. J. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0004-2 · Cited by 307 · see citing works
Kindler, J., Lim, C. K., Weickert, C., Boerrigter, D., Galletly, C., Liu, D., Jacobs, K. R., Balzan, R., Bruggemann, J. M., O'Donnell, M., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0401-9 · Cited by 267 · see citing works
Cross talk: the microbiota and neurodevelopmental disorders
Kelly, J. R., Minuto, C., Cryan, J. F., Clarke, G., & Dinan, T. G. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00490 · Cited by 271 · see citing works
Kynurenic Acid in Schizophrenia: A Systematic Review and Meta-analysis
Plitman, E., Iwata, Y., Caravaggio, F., Nakajima, S., Chung, J. K., Gerretsen, P., Kim, J., Takeuchi, H., Chakravarty, M. M., Remington, G. J., et al. (2017) · Schizophrenia Bulletin · doi:10.1093/schbul/sbw221 · Cited by 252 · see citing works
Pillinger, T., D’Ambrosio, E., McCutcheon, R., & Howes, O. D. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0058-9 · Cited by 230 · see citing works
Towards an Immunophenotype of Schizophrenia: Progress, Potential Mechanisms, and Future Directions
Miller, B. J., & Goldsmith, D. R. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.211 · Cited by 182 · see citing works
Genomics of schizophrenia: time to consider the gut microbiome?
Dinan, T. G., Borre, Y. E., & Cryan, J. F. (2014) · Molecular Psychiatry · doi:10.1038/mp.2014.93 · Cited by 175 · see citing works
The Role of Tryptophan Metabolites in Neuropsychiatric Disorders
Davidson, M., Rashidi, N., Nurgali, K., & Apostolopoulos, V. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179968 · Cited by 180 · see citing works
Roomruangwong, C., Noto, C. D. S., Kanchanatawan, B., Anderson, G., Kubera, M., Carvalho, A. F., & Maes, M. H. J. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-01737-z · Cited by 162 · see citing works
Oades, R. D., Myint, A.-M., Dauvermann, M. R., SCHIMMELMANN, B. G., & Schwarz, M. (2010) · Behavioral and Brain Functions · doi:10.1186/1744-9081-6-32 · Cited by 148 · see citing works
Toxoplasma gondii antibody titers and history of suicide attempts in patients with schizophrenia
Okusaga, O. O., LANGENBERG, P. W., Sleemi, A., Vaswani, D., Giegling, I., Hartmann, A. M., Konte, B., Friedl, M., Groer, M. E., Yolken, R. H., et al. (2011) · Schizophrenia Research · doi:10.1016/j.schres.2011.08.006 · Cited by 129 · see citing works
Effects of inflammation on the kynurenine pathway in schizophrenia—a systematic review
Pedraz-Petrozzi, B., Elyamany, O., Rummel, C., & Mulert, C. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-1721-z · Cited by 119 · see citing works
A systematic, quantitative review of blood autoantibodies in schizophrenia
Ezeoke, A., Mellor, A. L., Buckley, P. F., & Miller, B. J. (2013) · Schizophrenia Research · doi:10.1016/j.schres.2013.07.029 · Cited by 115 · see citing works
The role of the gut microbiome in the development of schizophrenia
Kelly, J. R., Minuto, C., Cryan, J. F., Clarke, G. A., & Dinan, T. G. (2020) · Schizophrenia Research · doi:10.1016/j.schres.2020.02.010 · Cited by 119 · see citing works
Condray, R., Dougherty, G. G., Keshavan, M. S., Reddy, R. D., Haas, G. L., Montrose, D. M., Matson, W. R., McEvoy, J. P., Kaddurah-Daouk, R. F., & Yao, J. K. (2011) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145710001689 · Cited by 98 · see citing works
Pasco, J. A., Jacka, F. N., Williams, L. J., Henry, M. J., Nicholson, G. C., Kotowicz, M. A., & Berk, M. (2010) · Psychotherapy and Psychosomatics · doi:10.1159/000319530 · Cited by 95 · see citing works
The Gut–Brain Axis in Schizophrenia: The Implications of the Gut Microbiome and SCFA Production
Ju, S., Shin, Y., Han, S., Kwon, J., Choi, T. G., Kang, I., & Kim, S. S. (2023) · Nutrients · doi:10.3390/nu15204391 · Cited by 95 · see citing works
Alexander, K., Pocivavsek, A., Wu, H., Pershing, M. L., Schwarcz, R. M., & Bruno, J. P. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.01.063 · Cited by 85 · see citing works
The relationship between nicotine and psychosis
Quigley, H., & MacCabe, J. H. (2019) · Therapeutic Advances in Psychopharmacology · doi:10.1177/2045125319859969 · Cited by 90 · see citing works
Gut microbiota, kynurenine pathway and mental disorders – Review
Więdłocha, M., Marcinowicz, P., Janoska-Jaździk, M., & Szulc, A. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110145 · Cited by 87 · see citing works
Almulla, A. F., Vasupanrajit, A., Tunvirachaisakul, C., Al‐Hakeim, H. K., Solmi, M., Verkerk, R. M., & Maes, M. H. J. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01552-4 · Cited by 84 · see citing works
Tryptophan Metabolism and White Matter Integrity in Schizophrenia
Chiappelli, J., Postolache, T. T., Kochunov, P. V., Rowland, L. M., Wijtenburg, S. A., Shukla, D. K., Tagamets, M. A., Du, X. M., Savransky, A., Lowry, C. A., et al. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.66 · Cited by 84 · see citing works
Cao, B., Chen, Y., Ren, Z., Pan, Z., McIntyre, R., & Wang, D. (2021) · Neuroscience and Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.01.018 · Cited by 65 · see citing works
Tryptophan degradation in women with breast cancer: a pilot study
Lyon, D., Walter, J. M., Starkweather, A. R., Schubert, C. M., & McCain, N. L. (2011) · BMC Research Notes · doi:10.1186/1756-0500-4-156 · Cited by 71 · see citing works
The immune-kynurenine pathway in social anxiety disorder
Butler, M., Long-Smith, C. M., Moloney, G. M., Mörkl, S., O’Mahony, S. M., Cryan, J. F., Clarke, G. A., & Dinan, T. G. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.10.020 · Cited by 67 · see citing works
Wilson, J. R. A., Morandi, A., Girard, T., Thompson, J. L., Boomershine, C. S., Shintani, A., Ely, E. W., & Pandharipande, P. (2012) · Critical Care Medicine · doi:10.1097/ccm.0b013e318236f62d · Cited by 58 · see citing works
Feng-li, L., Chen, S., Wang, L., Jiang, R., Tian, H., Li, J., Yao, Y., & Zhuo, C. (2017) · Oncotarget · doi:10.18632/oncotarget.21284 · Cited by 66 · see citing works
Kanchanatawan, B., Sirivichayakul, S., Ruxrungtham, K., Carvalho, A. F., Geffard, M., Ormstad, H., Anderson, G., & Maes, M. H. J. (2017) · Molecular Neurobiology · doi:10.1007/s12035-017-0417-6 · Cited by 65 · see citing works
Pełka-Wysiecka, J., Kaczmarczyk, M., Bąba-Kubiś, A., Liśkiewicz, P., Wroński, M., Skonieczna-Żydecka, K., Marlicz, W., Misiak, B., Starzyńska, T., Kucharska-Mazur, J., et al. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8101605 · Cited by 59 · see citing works
“Although mechanisms underlying the potential effect of microbiota on the pathogenesis and course of SZ are yet to be determined, chronic inflammation [12] and altered tryptophan metabolism [13,14] have been suggested to be implicated in the pathogenesis of SZ.”
BackgroundKanai, M., Nakamura, T., & Funakoshi, H. (2009) · Neuroscience Research · doi:10.1016/j.neures.2009.02.004 · Cited by 55 · see citing works
Miller, C. L., Murakami, P. N., Ruczinski, I., Ross, R. G., Sinkus, M. L., Sullivan, B. F., & Leonard, S. S. (2009) · Schizophrenia Research · doi:10.1016/j.schres.2009.05.014 · Cited by 55 · see citing works
Szymona, K., Zdzisińska, B., Karakuła‐Juchnowicz, H., Kocki, T., Kandefer‐Szerszeń, M., Flis, M., Rosa, W., & Urbańska, E. M. (2017) · Neurotoxicity Research · doi:10.1007/s12640-017-9714-0 · Cited by 53 · see citing works
Fecal microbiota transplantation in non-communicable diseases: Recent advances and protocols
Hamamah, S., Gheorghita, R. E., Lobiuc, A., Sîrbu, I. O., & Covașă, M. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.1060581 · Cited by 53 · see citing works
Kanchanatawan, B., Sirivichayakul, S., Thika, S., Ruxrungtham, K., Carvalho, A. F., Geffard, M., Anderson, G., Noto, C. D. S., Ivanova, R., & Maes, M. H. J. (2017) · Metabolic Brain Disease · doi:10.1007/s11011-017-9982-7 · Cited by 51 · see citing works
Oades, R. D. (2011) · ADHD Attention Deficit and Hyperactivity Disorders · doi:10.1007/s12402-011-0062-2 · Cited by 51 · see citing works
Exposure to Kynurenic Acid During Adolescence Produces Memory Deficits in Adulthood
Akagbosu, C., Evans, G. C., Gulick, D., Suckow, R. F., & Bucci, D. J. (2010) · Schizophrenia Bulletin · doi:10.1093/schbul/sbq151 · Cited by 50 · see citing works
Influence of plasma cytokines on kynurenine and kynurenic acid in schizophrenia
Chiappelli, J., Notarangelo, F. M., Pocivavsek, A., Thomas, M. A. R., Rowland, L., Schwarcz, R., & Hong, L. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0038-4 · Cited by 46 · see citing works
Lee, M., Jayathilake, K., Dai, J., & Meltzer, H. (2011) · Psychiatry Research · doi:10.1016/j.psychres.2010.07.013 · Cited by 45 · see citing works
C-Reactive Protein Correlates with Negative Symptoms in Patients with Schizophrenia
Boozalis, T., Teixeira, A. L., Cho, R. Y.-J., & Okusaga, O. O. (2018) · Frontiers in Public Health · doi:10.3389/fpubh.2017.00360 · Cited by 45 · see citing works
Metabolomics in patients with psychosis: A systematic review
Li, C., Wang, A., Wang, C., Ramamurthy, J., Zhang, E. R., Guadagno, E., & Trakadis, Y. J. (2018) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32662 · Cited by 45 · see citing works
Ormstad, H., Bryn, V., Verkerk, R. M., Skjeldal, O. H., Halvorsen, B. L., Saugstad, O. D., Isaksen, J., & Maes, M. H. J. (2018) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527317666180720163221 · Cited by 43 · see citing works
Huang, X., Ding, W., Wu, F., Zhou, S., Deng, S., & Ning, Y. (2020) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s239763 · Cited by 43 · see citing works
Huang, J., Tong, J., Zhang, P., Zhou, Y., Cui, Y., Tan, S., Wang, Z., Yang, F., Kochunov, P. V., Chiappelli, J., et al. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01311-z · Cited by 41 · see citing works
Zhang, Y., Shi, H., Yang, G., Yang, Y., Li, W., Song, M., Shao, M., Su, X., & Lv, L. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01688-x · Cited by 37 · see citing works
Möller, M., du Preez, J. L., Emsley, R. A., & Harvey, B. H. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.02.021 · Cited by 36 · see citing works
Chiang, S. S. W., Riedel, M. J., Schwarz, M., & Mueller, N. (2013) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12040 · Cited by 35 · see citing works
Blood-based kynurenine pathway alterations in schizophrenia spectrum disorders: A meta-analysis
Morrens, M., Picker, L. D., Kampen, J. K., & Coppens, V. (2020) · Schizophrenia Research · doi:10.1016/j.schres.2020.09.007 · Cited by 35 · see citing works
New promises for manipulation of kynurenine pathway in cancer and neurological diseases
Costantino, G. (2009) · Expert opinion on therapeutic targets · doi:10.1517/14728220802665734 · Cited by 37 · see citing works
Physical Illnesses Before Diagnosed as Schizophrenia: A Nationwide Case-Control Study
Chen, Y., Pan, C., Chang, C.-K., Chen, P., Chang, H., Tai, M.-H., Su, S., Tsai, S., Chen, C., & Kuo, C. (2020) · Schizophrenia Bulletin · doi:10.1093/schbul/sbaa009 · Cited by 34 · see citing works
Skorobogatov, K., Autier, V., Foiselle, M., Richard, J., Boukouaci, W., Wu, C., Raynal, S., Carbonne, C., Laukens, K., Meysman, P., et al. (2023) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2022.100584 · Cited by 33 · see citing works
Kanchanatawan, B., Sirivichayakul, S., Carvalho, A. F., Anderson, G., Gałecki, P., & Maes, M. H. J. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.06.033 · Cited by 24 · see citing works
Kynurenine is correlated with IL-1β in plasma of schizophrenia patients
Joaquim, H. P. G., Costa, A. C., Gattaz, W. F., & Talib, L. L. (2018) · Journal of Neural Transmission · doi:10.1007/s00702-018-1838-8 · Cited by 24 · see citing works
Metabolomic profiling of the effects of allopurinol on Drosophila melanogaster
Bratty, M. A., Hobani, Y. H., Dow, J. A. T., & Watson, D. G. (2011) · Metabolomics · doi:10.1007/s11306-011-0275-6 · Cited by 22 · see citing works
Zajkowska, I., Niczyporuk, P., Urbaniak, A. D., Tomaszek, N., Modzelewski, S., & Waszkiewicz, N. (2024) · Nutrients · doi:10.3390/nu16142228 · Cited by 21 · see citing works
Hatzimanolis, A., Foteli, S., Xenaki, L., Selaković, M., Dimitrakopoulos, S., Vlachos, I. I., Kosteletos, I., Soldatos, R. F., Gazouli, M., Chatzipanagiotou, S., et al. (2024) · Schizophrenia · doi:10.1038/s41537-024-00483-z · Cited by 19 · see citing works
Sathyasaikumar, K. V., Notarangelo, F. M., Kelly, D. L., Rowland, L. M., Hare, S., Chen, S., Chen, M., Buchanan, R. W., & Schwarcz, R. M. (2022) · Pharmaceuticals · doi:10.3390/ph15081003 · Cited by 18 · see citing works
Metri, N., Butt, A. S., Murali, A., Steiner, G. Z., & Lim, C. K. (2023) · International Journal of Tryptophan Research · doi:10.1177/11786469231211184 · Cited by 16 · see citing works
Roomruangwong, C., Noto, C. D. S., Kanchanatawan, B., Anderson, G., Kubera, M., Carvalho, A. F., & Maes, M. H. J. (2018) · Preprints.org · doi:10.20944/preprints201809.0289.v1 · Cited by 15 · see citing works
Badawy, A. A. ‐. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3191-9 · Cited by 15 · see citing works
Zhang, Z., Zhang, M., Luo, Y., Ni, X., Lu, H., Wen, Y., & Fan, N. (2020) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.2738 · Cited by 15 · see citing works
Marković, M., Petronijević, N., Stašević, M., Karličić, I. S., Velimirović, M., Stojković, T., Ristić, S., Stojković, M., Milic, N. M., & Nikolić, T. (2023) · Cells · doi:10.3390/cells12242814 · Cited by 11 · see citing works
Indoleamine 2,3-dioxygenase (IDO)-activity in Severe Psychiatric Disorders: A Systemic Review
Fellendorf, F. T., Bonkat, N., Dalkner, N., Schönthaler, E. M. D., Manchia, M., Fuchs, D., & Reininghaus, E. Z. (2022) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026622666220718155616 · Cited by 12 · see citing works
Tao, W., Tian, J., Xu, T., Xu, S. L., Xie, H. Q., Zhou, Z., Guo, Z., Fu, H., Yin, X., Chen, Y., et al. (2018) · Environmental Pollution · doi:10.1016/j.envpol.2018.11.086 · Cited by 12 · see citing works
METABOLISMO DO TRIPTOFANO EM TRANSTORNOS MENTAIS: UM ENFOQUE NA ESQUIZOFRENIA
Carvalho, M. S., Yonamine, C. M., Mas, C. D., Nunes, D. F. S., & Hayashi, M. A. F. (2017) · VITTALLE - Revista de Ciências da Saúde · doi:10.14295/vittalle.v29i2.6550 · Cited by 11 · see citing works
Almulla, A. F., Vasupanrajit, A., Tunvirachaisakul, C., Al‐Hakeim, H. K., Solmi, M., Verkerk, R. M., & Maes, M. H. J. (2021) · medRxiv · doi:10.1101/2021.12.16.21267905 · Cited by 10 · see citing works
Effects of chronic physical illness on treatment outcomes among patients with schizophrenia
Filipčić, I. Š., Bajić, Ž., & Filipčić, I. (2019) · Current Opinion in Psychiatry · doi:10.1097/yco.0000000000000532 · Cited by 10 · see citing works
Huang, J., Zhang, P., Zhou, Y., Tong, J., Cui, Y., Tan, S., Wang, Z., Yang, F., Kochunov, P. V., Tian, B., et al. (2021) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2021.11.002 · Cited by 9 · see citing works
Huang, Z., Huang, Z., Du, Z., Gao, X., Jiang, Y., Zhou, Z., & Zhu, H. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2607817 · Cited by 9 · see citing works
Tryptophan Metabolism and the Microbiome-Gut-Brain Axis
Clarke, G. A., Villalobos-Manríquez, F., & Marin, D. C. (2021) · Oxford University Press eBooks · doi:10.1093/oxfordhb/9780190931544.013.13 · Cited by 7 · see citing works
Yang, C., Tian, Y., Yang, X., Liu, L., Chen, L., Xia, L., & Liu, H. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1337103 · Cited by 7 · see citing works
Verma, K., Amitabh, Prasad, D., Reddy, M. P., & Kohli, E. (2024) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.3c00632 · Cited by 5 · see citing works
Is Relapse in Schizophrenia an Immune-Mediated Effect?
Miller, B. J., & Buckley, P. F. (2012) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.10.2.115 · Cited by 6 · see citing works
Ramirez‐Hincapie, S., Giri, V., Keller, J., Kamp, H., Haake, V., Richling, E., & van Ravenzwaay, B. (2021) · Archives of Toxicology · doi:10.1007/s00204-021-03105-0 · Cited by 5 · see citing works
Chiang, S. S. W., Riedel, M. J., Gruber, R., Müller, N., & Schwarz, M. (2011) · The European Journal of Psychiatry · doi:10.4321/s0213-61632011000400002 · Cited by 5 · see citing works
Şizofreni Etyolojisinde Mikrobiyotanın Rolü
Kartalcı, Ş. (2017) · Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry · doi:10.18863/pgy.358105 · Cited by 7 · see citing works
Destigmatising mental illness, House style
Amanullah, S. (2010) · The British Journal of Psychiatry · doi:10.1192/bjp.197.5.377 · Cited by 2 · see citing works
Almulla, A. F., Vasupanrajit, A., Tunvirachaisakul, C., Al‐Hakeim, H. K., Solmi, M., Verkerk, R. M., & Maes, M. H. J. (2021) · Preprints.org · doi:10.20944/preprints202112.0301.v1 · Cited by 2 · see citing works
Afia, A. B., MacDowell, K. S., Martín‐Hernández, D., Zaafrane, F., Gaha, L., Leza, J. C., & Jrad, B. B. H. (2025) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-025-02172-z · Cited by 1 · see citing works
Miller, B. J., Buckley, P. F., Seabolt, W., Mellor, A. L., & Kirkpatrick, B. W. (2011) · Psiquiatría Biológica · doi:10.1016/j.psiq.2011.10.006 · Cited by 1 · see citing works
Quinolinate and related excitotoxins: mechanisms of neurotoxicity and disease relevance
Addae, J., & Stone, T. (2014) · Springer eBooks · doi:10.1007/978-1-4614-5836-4_127 · Cited by 8 · see citing works
endotóxico induzido por LPS e hipertriptofanemia
Migliorini, S. (2010)
Current awareness in human psychopharmacology
(2009) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.978
Skin-Gut-Breast Microbiota Axes
Drago, L. (2021) · MDPI eBooks · doi:10.3390/books978-3-0365-0899-3
VELİOĞLU, Z., Yıldırım, D. İ., & Eryılmaz, M. A. (2022) · Troia Medical Journal · doi:10.55665/troiamedj.1118052
Thirumalai, J., Mohammed, A. A. F., & Jeslin, G. N. (2026) · SN Comprehensive Clinical Medicine · doi:10.1007/s42399-026-02557-8
- Authors
- Barry, S., Clarke, G., Scully, P., & Dinan, T.
- Affiliations
- University College Cork (IE)
- Department of Psychiatry, The Alimentary Pharmabiotic Center, University College Cork, Cork, Ireland
- Corresponding author
- Barry, S
- ORCID
- Clarke, G
- Venue
- Journal of Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2008-06-18
- Volume
- 23
- Issue
- 3
- Pages
- 287-294
- ISSN
- 0269-8811 (ISSN-L)
- 1461-7285
- OpenAlex
- W2010473895
- Cited by
- 96
- References
- 53
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 10 · 2020: 9 · 2019: 5 · 2018: 8 · 2017: 10 · 2016: 4 · 2014: 2 · 2013: 5 · 2012: 3
- FWCI
- 2.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion)
- Funders
- Eli Lilly and Company
- Wellcome Trust
- Science Foundation Ireland
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- kynurenine pathway, tryptophan degradation, psychosis, schizophrenia, schizoaffective disorder, indoleamine 2,3-dioxygenase, interferon-gamma, kynurenine, kynurenic acid, plasma tryptophan, disease duration, aetiology of psychosis
- MeSH terms
- Adult, Chromatography, High Pressure Liquid, Enzyme-Linked Immunosorbent Assay, Female, Humans, Interferon-gamma, Kynurenine, Male, Middle Aged, Psychotic Disorders, Schizophrenia, Severity of Illness Index, Tryptophan, Up-Regulation, Indoleamine-Pyrrole 2,3,-Dioxygenase
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review