kynurenine and Schizophrenia studies

Kynurenine: A metabolite of the essential amino acid tryptophan metabolized via the tryptophan-kynurenine pathway.
kynurenine : A ketone that is alanine in which one of the methyl hydrogens is substituted by a 2-aminobenzoyl group.

Schizophrenia: A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior.

Research Excerpts

Excerpt	Relevance	Reference
"The tryptophan catabolite (TRYCAT) pathway is implicated in the pathophysiology of schizophrenia (SCZ) since the rate-limiting enzyme indoleamine-dioxygenase (IDO) may be induced by inflammatory and oxidative stress mediators."	9.22	The tryptophan catabolite or kynurenine pathway in schizophrenia: meta-analysis reveals dissociations between central, serum, and plasma compartments. ( Al-Hakeim, HK; Almulla, AF; Maes, M; Solmi, M; Tunvirachaisakul, C; Vasupanrajit, A; Verkerk, R, 2022)
"The kynurenine (KYN) pathway is postulated to play various roles in immune system dysregulation of schizophrenia (SCZ)."	9.12	Dysregulation of kynurenine pathway and potential dynamic changes of kynurenine in schizophrenia: A systematic review and meta-analysis. ( Cao, B; Chen, Y; McIntyre, RS; Pan, Z; Ren, Z; Wang, D, 2021)
"These results emphasize how different inflammatory markers can unbalance the tryptophan/kynurenine pathway in schizophrenia."	9.05	Effects of inflammation on the kynurenine pathway in schizophrenia - a systematic review. ( Elyamany, O; Mulert, C; Pedraz-Petrozzi, B; Rummel, C, 2020)
"The kynurenine pathway (KP) has been proposed as indirect link between systemic immune responses and clinical symptom development in schizophrenia spectrum disorders (SSD)."	9.05	Blood-based kynurenine pathway alterations in schizophrenia spectrum disorders: A meta-analysis. ( Coppens, V; De Picker, L; Kampen, JK; Morrens, M, 2020)
"Phencyclidine (PCP) is a dissociative anesthetic that induces psychotic symptoms and neurocognitive deficits in rodents similar to those observed in schizophrenia patients."	9.01	Linking phencyclidine intoxication to the tryptophan-kynurenine pathway: Therapeutic implications for schizophrenia. ( Fujigaki, H; Mouri, A; Nabeshima, T; Saito, K; Yamamoto, Y, 2019)
"The brain concentration of kynurenic acid (KYNA), a metabolite of the kynurenine pathway of tryptophan degradation and antagonist at both the glycine coagonist site of the N-methyl-D-aspartic acid receptor (NMDAR) and the alpha7 nicotinic acetylcholine receptor (alpha7nAChR), is elevated in the prefrontal cortex (PFC) of individuals with schizophrenia."	8.86	Cortical kynurenine pathway metabolism: a novel target for cognitive enhancement in Schizophrenia. ( Schwarcz, R; Wonodi, I, 2010)
"The tryptophan-kynurenine pathway is of major interest in psychiatry and is altered in patients with depression, schizophrenia and panic disorder."	8.12	The immune-kynurenine pathway in social anxiety disorder. ( Butler, MI; Clarke, G; Cryan, JF; Dinan, TG; Long-Smith, C; Moloney, GM; Morkl, S; O'Mahony, SM, 2022)
"Our study results suggest that the baseline MNFT levels in the kynurenine pathway of tryptophan metabolism may be predictive of the treatment response to olanzapine in schizophrenia."	8.12	Kynurenine pathway metabolites and therapeutic response to olanzapine in female patients with schizophrenia: A longitudinal study. ( Guan, X; Li, X; Liu, H; Wu, F; Xiu, M; Xu, J, 2022)
"To develop a method for determining cinnabarinic acid (CA) and its immediate precursor 3-hydroxyanthranylic acid (3HAA) in blood plasma and to study their concentrations in patients with schizophrenia before and after treatment."	8.12	[Cinnabarinic acid as a potential prognostic marker of schizophrenia]. ( Baymeeva, NV; Brusov, OS; Oleichik, IV; Shilov, YE; Sizov, SV; Tyurin, IA, 2022)
"A number of tryptophan metabolites known to be neuroactive have been examined for their potential associations with cognitive deficits in schizophrenia."	8.02	Effects of neuroactive metabolites of the tryptophan pathway on working memory and cortical thickness in schizophrenia. ( Chiappelli, J; Cui, Y; Hong, LE; Huang, J; Kochunov, P; Tan, S; Tan, Y; Tian, B; Tian, L; Tong, J; Wang, Z; Yang, F; Zhang, P; Zhou, Y, 2021)
"There is evidence suggesting that tryptophan (TRP)-kynurenine (KYN) pathway dysregulation is involved in the pathophysiology of schizophrenia and is regulated by inflammatory cytokines."	8.02	Association of the kynurenine pathway metabolites with clinical, cognitive features and IL-1β levels in patients with schizophrenia spectrum disorder and their siblings. ( Alptekin, K; Atbaşoğlu, C; Erdağ, E; Gülöksüz, S; Hakan, MT; Küçükhüseyin, Ö; Noyan, H; Rutten, BPF; Saka, MC; Tüzün, E; Üçok, A; van Os, J; Yaylım, İ, 2021)
"Tryptophan and its catabolites (TRYCATs) have been suggested to link peripheral immune system activation and central neurotransmitter abnormalities with relevance to the etio-pathophysiology of schizophrenia (SZ) and major depressive disorder (MDD)."	8.02	Quinolinic acid is associated with cognitive deficits in schizophrenia but not major depressive disorder. ( Cathomas, F; Guetter, K; Kaiser, S; Klaus, F; Seifritz, E, 2021)
" The KP metabolite kynurenic acid (KYNA) is increased in the brains of people with schizophrenia."	7.96	Dysregulation of kynurenine metabolism is related to proinflammatory cytokines, attention, and prefrontal cortex volume in schizophrenia. ( Balzan, R; Boerrigter, D; Bruggemann, J; Galletly, C; Guillemin, GJ; Jacobs, KR; Kindler, J; Lenroot, R; Lim, CK; Liu, D; O'Donnell, M; Weickert, CS; Weickert, TW, 2020)
"Although prone to residual confounding, the present results suggest the kynurenine pathway of tryptophan metabolism, noradrenergic and purinergic system dysfunction as trait factors in schizophrenia spectrum and bipolar disorders."	7.96	Metabolic dysfunctions in the kynurenine pathway, noradrenergic and purine metabolism in schizophrenia and bipolar disorders. ( Agartz, I; Andreassen, OA; Bogdanov, M; Dieset, I; Djurovic, S; Hope, S; Jönsson, EG; Kaddurah-Daouk, R; Matson, W; Melle, I; Smeland, OB; Steen, NE; Vedal, TSJ, 2020)
"Abnormalities in the kynurenine pathway (KP) of tryptophan degradation, leading to the dysfunction of neuroactive KP metabolites in the brain, have been implicated in the pathophysiology of schizophrenia (SZ)."	7.88	Influence of plasma cytokines on kynurenine and kynurenic acid in schizophrenia. ( Chiappelli, J; Hong, LE; Notarangelo, FM; Pocivavsek, A; Rowland, LM; Schwarcz, R; Thomas, MAR, 2018)
"Aim & Objective: To delineate the associations between executive impairments and changes in tryptophan catabolite (TRYCAT) patterning, negative symptoms and deficit schizophrenia."	7.88	The Effects of Tryptophan Catabolites on Negative Symptoms and Deficit Schizophrenia are Partly Mediated by Executive Impairments: Results of Partial Least Squares Path Modeling. ( Kanchanatawan, B; Maes, M, 2018)
"Evidence has shown that the kynurenine pathway (KP) plays a role in the onset of oxidative stress and also in the pathophysiology of schizophrenia."	7.88	The inhibition of the kynurenine pathway prevents behavioral disturbances and oxidative stress in the brain of adult rats subjected to an animal model of schizophrenia. ( Barichello, T; Becker, IRT; Ceretta, LB; Dal-Pizzol, F; Kaddurah-Daouk, R; Oses, JP; Petronilho, F; Quevedo, J; Réus, GZ; Scaini, G; Zugno, AI, 2018)
"Several studies suggest a pathophysiologically relevant association between increased brain levels of the neuroinhibitory tryptophan metabolite kynurenic acid and cognitive dysfunctions in people with schizophrenia."	7.88	Maternal genotype determines kynurenic acid levels in the fetal brain: Implications for the pathophysiology of schizophrenia. ( Beggiato, S; Giorgini, F; Notarangelo, FM; Sathyasaikumar, KV; Schwarcz, R, 2018)
"Several lines of evidence suggest that up-regulation of immune response and alterations of kynurenine pathway function are involved in pathogenesis of schizophrenia."	7.85	Correlations of Kynurenic Acid, 3-Hydroxykynurenine, sIL-2R, IFN-α, and IL-4 with Clinical Symptoms During Acute Relapse of Schizophrenia. ( Flis, M; Kandefer-Szerszeń, M; Karakuła-Juchnowicz, H; Kocki, T; Rosa, W; Szymona, K; Urbańska, EM; Zdzisińska, B, 2017)
"The kynurenine pathway of tryptophan metabolism has been implicated in the pathophysiology of psychiatric disorders, including schizophrenia."	7.81	Xanthurenic Acid Activates mGlu2/3 Metabotropic Glutamate Receptors and is a Potential Trait Marker for Schizophrenia. ( Battaglia, G; Bruno, V; Capi, M; Caruso, A; Cavallari, M; Comparelli, A; Corigliano, V; Curto, M; De Blasi, A; De Carolis, A; De Fusco, A; Di Menna, L; Fazio, F; Girardi, P; Gradini, R; Iacovelli, L; Lionetto, L; Miele, J; Napoletano, F; Nicoletti, F; Nisticò, R; Scaccianoce, S; Simmaco, M; Ulivieri, M; Zappulla, C, 2015)
"The levels of kynurenic acid (KYNA), an endogenous negative modulator of alpha7 nicotinic acetylcholine receptors (α7nAChRs), are elevated in the brains of patients with schizophrenia (SZ)."	7.81	Elevated levels of kynurenic acid during gestation produce neurochemical, morphological, and cognitive deficits in adulthood: implications for schizophrenia. ( Bortz, DM; Bruno, JP; Fredericks, PJ; Jørgensen, CV; Leuner, B; Pershing, ML; Pocivavsek, A; Schwarcz, R; Vunck, SA, 2015)
"The kynurenic acid (KYNA) hypothesis for schizophrenia is partly based on studies showing increased brain levels of KYNA in patients."	7.78	Increased levels of kynurenine and kynurenic acid in the CSF of patients with schizophrenia. ( Dahl, ML; Engberg, G; Erhardt, S; Holtze, M; Linderholm, KR; Olsson, SK; Samuelsson, M; Skogh, E, 2012)
"The levels of kynurenic acid (KYNA), an astrocyte-derived metabolite of the branched kynurenine pathway (KP) of tryptophan degradation and antagonist of α7 nicotinic acetylcholine and N-methyl-D-aspartate receptors, are elevated in the prefrontal cortex (PFC) of individuals with schizophrenia (SZ)."	7.77	Impaired kynurenine pathway metabolism in the prefrontal cortex of individuals with schizophrenia. ( McMahon, RP; Rassoulpour, A; Roberts, RC; Sathyasaikumar, KV; Schwarcz, R; Stachowski, EK; Wonodi, I, 2011)
"Prior studies of mRNA expression, protein expression, and pathway metabolite levels have implicated dysregulation of the kynurenine pathway in the etiology of schizophrenia and bipolar disorder."	7.75	Two complex genotypes relevant to the kynurenine pathway and melanotropin function show association with schizophrenia and bipolar disorder. ( Leonard, S; Miller, CL; Murakami, P; Ross, RG; Ruczinski, I; Sinkus, M; Sullivan, B, 2009)
"Kynurenic acid (KYNA) is an endogenous compound implicated in the pathophysiology of schizophrenia."	7.75	Elevated levels of kynurenic acid change the dopaminergic response to amphetamine: implications for schizophrenia. ( Andersson, AS; Engberg, G; Erhardt, S; Holtze, M; Larsson, K; Linderholm, KR; Nilsson-Todd, LK; Olsson, E; Olsson, SK; Schwieler, L, 2009)
"Increased concentrations of kynurenine pathway metabolites have been reported by several groups for disorders involving psychosis, including schizophrenia and bipolar disorder."	7.74	Alterations in kynurenine precursor and product levels in schizophrenia and bipolar disorder. ( Cwik, M; Llenos, IC; Miller, CL; Walkup, J; Weis, S, 2008)
"Markers of the kynurenine pathway were studied in postmortem frontal cortex obtained from individuals with schizophrenia and controls."	7.72	Expression of the kynurenine pathway enzyme tryptophan 2,3-dioxygenase is increased in the frontal cortex of individuals with schizophrenia. ( Barillo, MM; Dulay, JR; Llenos, IC; Miller, CL; Weis, S; Yolken, RH, 2004)
"Schizophrenia is a chronic psychotic disease burdened by cognitive deficits which hamper daily functioning causing disability and costs for society."	7.01	Importance of the dysregulation of the kynurenine pathway on cognition in schizophrenia: a systematic review of clinical studies. ( Bosia, M; Comai, S; Guillemin, GJ; Sapienza, J; Spangaro, M, 2023)
"Schizophrenia is a neuropsychiatric disorder characterized by various symptoms including autonomic imbalance."	6.72	A Potential Interface between the Kynurenine Pathway and Autonomic Imbalance in Schizophrenia. ( Büki, A; Horvath, G; Kekesi, G; Vécsei, L, 2021)
"Schizophrenia is associated with general inflammation and disruption of glutamatergic and dopaminergic signalling."	6.53	Kynurenines, Gender and Neuroinflammation; Showcase Schizophrenia. ( de Bie, J; Guillemin, GJ; Lim, CK, 2016)
"Patients with treatment-resistant schizophrenia (TRS) suffer severe, long-term psychotic symptoms and chronic stress."	5.72	Elevated salivary kynurenic acid levels related to enlarged choroid plexus and severity of clinical phenotypes in treatment-resistant schizophrenia. ( Chiappelli, J; Hong, LE; Huang, J; Kochunov, P; Li, Y; Tan, S; Tan, Y; Tian, B; Tian, L; Tong, J; Wang, Z; Yang, F; Zhang, P; Zhou, Y, 2022)
"The kynurenine pathway (KP) has been linked to alterations in glutamatergic and monoaminergic neurotransmission and to SZ symptomatology through the production of the metabolites quinolinic acid (QA) and kynurenic acid (KYNA)."	5.62	Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology. ( Afia, AB; Artuch, R; Garcia-Bueno, B; Haro, JM; Leza, JC; MacDowell, KS; Ormazabal, A; Ramos, B; Vila, È, 2021)
"Cinnabarinic acid (CA) is a kynurenine metabolite that activates mGlu4 metabotropic glutamate receptors."	5.56	The Trace Kynurenine, Cinnabarinic Acid, Displays Potent Antipsychotic-Like Activity in Mice and Its Levels Are Reduced in the Prefrontal Cortex of Individuals Affected by Schizophrenia. ( Antenucci, N; Battaglia, G; Bruno, V; Chocyk, A; Cieslik, P; Curto, M; Di Menna, L; Fazio, F; Fucile, S; Giannino, G; Iacovelli, L; Liberatore, F; Lionetto, L; Martinello, K; Mascio, G; Nicoletti, F; Pilc, A; Pittaluga, A; Simmaco, M; Traficante, A; Ulivieri, M; Vergassola, M; Wierońska, JM, 2020)
"The etiology of schizophrenia is still unclear."	5.48	Kynurenine is correlated with IL-1β in plasma of schizophrenia patients. ( Costa, AC; Gattaz, WF; Joaquim, HPG; Talib, LL, 2018)
"Schizophrenia is associated with abnormalities in the structure and functioning of white matter, but the underlying neuropathology is unclear."	5.43	Tryptophan Metabolism and White Matter Integrity in Schizophrenia. ( Can, A; Chiappelli, J; Du, X; Fuchs, D; Hong, LE; Kochunov, P; Lowry, CA; Postolache, TT; Rowland, LM; Savransky, A; Shukla, DK; Tagamets, M; Wijtenburg, SA, 2016)
"Schizophrenia is characterized by complex and dynamically interacting perturbations in multiple neurochemical systems."	5.36	Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia. ( Dougherty, GG; Kaddurah-Daouk, R; Keshavan, MS; Krishnan, RR; Matson, WR; McEvoy, J; Montrose, DM; Reddy, RD; Rozen, S; Yao, JK, 2010)
"Schizophrenia is a common, debilitating mental illness that has persisted over the generations."	5.35	The evolution of schizophrenia: a model for selection by infection, with a focus on NAD. ( Miller, CL, 2009)
"The tryptophan catabolite (TRYCAT) pathway is implicated in the pathophysiology of schizophrenia (SCZ) since the rate-limiting enzyme indoleamine-dioxygenase (IDO) may be induced by inflammatory and oxidative stress mediators."	5.22	The tryptophan catabolite or kynurenine pathway in schizophrenia: meta-analysis reveals dissociations between central, serum, and plasma compartments. ( Al-Hakeim, HK; Almulla, AF; Maes, M; Solmi, M; Tunvirachaisakul, C; Vasupanrajit, A; Verkerk, R, 2022)
"Cytokine imbalances especially between T helper type (Th) 1 and Th2 and tryptophan breakdown were reported to be involved in the pathophysiology of schizophrenia."	5.14	Cytokine changes and tryptophan metabolites in medication-naïve and medication-free schizophrenic patients. ( Kim, YK; Leonard, B; Myint, AM; Scharpe, S; Steinbusch, H; Verkerk, R, 2009)
"The kynurenine (KYN) pathway is postulated to play various roles in immune system dysregulation of schizophrenia (SCZ)."	5.12	Dysregulation of kynurenine pathway and potential dynamic changes of kynurenine in schizophrenia: A systematic review and meta-analysis. ( Cao, B; Chen, Y; McIntyre, RS; Pan, Z; Ren, Z; Wang, D, 2021)
"These results emphasize how different inflammatory markers can unbalance the tryptophan/kynurenine pathway in schizophrenia."	5.05	Effects of inflammation on the kynurenine pathway in schizophrenia - a systematic review. ( Elyamany, O; Mulert, C; Pedraz-Petrozzi, B; Rummel, C, 2020)
"The kynurenine pathway (KP) has been proposed as indirect link between systemic immune responses and clinical symptom development in schizophrenia spectrum disorders (SSD)."	5.05	Blood-based kynurenine pathway alterations in schizophrenia spectrum disorders: A meta-analysis. ( Coppens, V; De Picker, L; Kampen, JK; Morrens, M, 2020)
"Phencyclidine (PCP) is a dissociative anesthetic that induces psychotic symptoms and neurocognitive deficits in rodents similar to those observed in schizophrenia patients."	5.01	Linking phencyclidine intoxication to the tryptophan-kynurenine pathway: Therapeutic implications for schizophrenia. ( Fujigaki, H; Mouri, A; Nabeshima, T; Saito, K; Yamamoto, Y, 2019)
"Future research on the cerebral cell-type specific distribution of kynurenine metabolites and their brain-regional concentration imbalances will be required to connect peripheral immune changes, the hypotheses of blood-brain barrier dysfunction and glial pathology with concepts of altered neurotransmission in schizophrenia and major depression."	4.88	Bridging the gap between the immune and glutamate hypotheses of schizophrenia and major depression: Potential role of glial NMDA receptor modulators and impaired blood-brain barrier integrity. ( Bernstein, HG; Bogerts, B; Gos, T; Myint, AM; Sarnyai, Z; Steiner, J; Walter, M, 2012)
"The exact pathophysiological mechanism leading to dopaminergic dysfunction in schizophrenia is still unclear, but inflammation is postulated to be a key player: a dysfunction in the activation of the type 1 immune response seems to be associated with decreased activity of the key enzyme in tryptophan/kynurenine metabolism, indoleamine 2,3- dioxygenase (IDO), resulting in increased production of kynurenic acid - a N-methyl-D-aspartate (NMDA) antagonist in the central nervous system (CNS) - and reduced glutamatergic neurotransmission."	4.88	Immunological treatment options for schizophrenia. ( Müller, N; Myint, AM; Schwarz, MJ, 2012)
"The brain concentration of kynurenic acid (KYNA), a metabolite of the kynurenine pathway of tryptophan degradation and antagonist at both the glycine coagonist site of the N-methyl-D-aspartic acid receptor (NMDAR) and the alpha7 nicotinic acetylcholine receptor (alpha7nAChR), is elevated in the prefrontal cortex (PFC) of individuals with schizophrenia."	4.86	Cortical kynurenine pathway metabolism: a novel target for cognitive enhancement in Schizophrenia. ( Schwarcz, R; Wonodi, I, 2010)
"Our study results suggest that the baseline MNFT levels in the kynurenine pathway of tryptophan metabolism may be predictive of the treatment response to olanzapine in schizophrenia."	4.12	Kynurenine pathway metabolites and therapeutic response to olanzapine in female patients with schizophrenia: A longitudinal study. ( Guan, X; Li, X; Liu, H; Wu, F; Xiu, M; Xu, J, 2022)
"To develop a method for determining cinnabarinic acid (CA) and its immediate precursor 3-hydroxyanthranylic acid (3HAA) in blood plasma and to study their concentrations in patients with schizophrenia before and after treatment."	4.12	[Cinnabarinic acid as a potential prognostic marker of schizophrenia]. ( Baymeeva, NV; Brusov, OS; Oleichik, IV; Shilov, YE; Sizov, SV; Tyurin, IA, 2022)
"The tryptophan-kynurenine pathway is of major interest in psychiatry and is altered in patients with depression, schizophrenia and panic disorder."	4.12	The immune-kynurenine pathway in social anxiety disorder. ( Butler, MI; Clarke, G; Cryan, JF; Dinan, TG; Long-Smith, C; Moloney, GM; Morkl, S; O'Mahony, SM, 2022)
"Tryptophan and its catabolites (TRYCATs) have been suggested to link peripheral immune system activation and central neurotransmitter abnormalities with relevance to the etio-pathophysiology of schizophrenia (SZ) and major depressive disorder (MDD)."	4.02	Quinolinic acid is associated with cognitive deficits in schizophrenia but not major depressive disorder. ( Cathomas, F; Guetter, K; Kaiser, S; Klaus, F; Seifritz, E, 2021)
"A number of tryptophan metabolites known to be neuroactive have been examined for their potential associations with cognitive deficits in schizophrenia."	4.02	Effects of neuroactive metabolites of the tryptophan pathway on working memory and cortical thickness in schizophrenia. ( Chiappelli, J; Cui, Y; Hong, LE; Huang, J; Kochunov, P; Tan, S; Tan, Y; Tian, B; Tian, L; Tong, J; Wang, Z; Yang, F; Zhang, P; Zhou, Y, 2021)
"There is evidence suggesting that tryptophan (TRP)-kynurenine (KYN) pathway dysregulation is involved in the pathophysiology of schizophrenia and is regulated by inflammatory cytokines."	4.02	Association of the kynurenine pathway metabolites with clinical, cognitive features and IL-1β levels in patients with schizophrenia spectrum disorder and their siblings. ( Alptekin, K; Atbaşoğlu, C; Erdağ, E; Gülöksüz, S; Hakan, MT; Küçükhüseyin, Ö; Noyan, H; Rutten, BPF; Saka, MC; Tüzün, E; Üçok, A; van Os, J; Yaylım, İ, 2021)
"Risks of autoimmune processes causing schizophrenia are associated with several factors: an impaired functioning of dopaminergic and glutamatergic systems in the brain, kynurenine pathway disorder with overproduction of quinolinic, anthranilic, and kynurenic acids (possibly altering both neurons and T-regulators), increased intestinal permeability, as well as food antigens' effects, stress and infections with various pathogens at different stages of ontogenesis."	4.02	Autoimmune Concept of Schizophrenia: Historical Roots and Current Facets. ( Butoma, BG; Churilov, LP; Gilburd, B; Mayorova, MA; Petrova, NN; Shoenfeld, Y, 2021)
"Although prone to residual confounding, the present results suggest the kynurenine pathway of tryptophan metabolism, noradrenergic and purinergic system dysfunction as trait factors in schizophrenia spectrum and bipolar disorders."	3.96	Metabolic dysfunctions in the kynurenine pathway, noradrenergic and purine metabolism in schizophrenia and bipolar disorders. ( Agartz, I; Andreassen, OA; Bogdanov, M; Dieset, I; Djurovic, S; Hope, S; Jönsson, EG; Kaddurah-Daouk, R; Matson, W; Melle, I; Smeland, OB; Steen, NE; Vedal, TSJ, 2020)
"Distinct abnormalities in kynurenine pathway (KP) metabolism have been reported in various psychiatric disorders, including schizophrenia (SZ)."	3.96	Exposure to elevated embryonic kynurenine in rats: Sex-dependent learning and memory impairments in adult offspring. ( Baratta, AM; Buck, SA; Pocivavsek, A, 2020)
" The KP metabolite kynurenic acid (KYNA) is increased in the brains of people with schizophrenia."	3.96	Dysregulation of kynurenine metabolism is related to proinflammatory cytokines, attention, and prefrontal cortex volume in schizophrenia. ( Balzan, R; Boerrigter, D; Bruggemann, J; Galletly, C; Guillemin, GJ; Jacobs, KR; Kindler, J; Lenroot, R; Lim, CK; Liu, D; O'Donnell, M; Weickert, CS; Weickert, TW, 2020)
"Several studies suggest a pathophysiologically relevant association between increased brain levels of the neuroinhibitory tryptophan metabolite kynurenic acid and cognitive dysfunctions in people with schizophrenia."	3.88	Maternal genotype determines kynurenic acid levels in the fetal brain: Implications for the pathophysiology of schizophrenia. ( Beggiato, S; Giorgini, F; Notarangelo, FM; Sathyasaikumar, KV; Schwarcz, R, 2018)
"Evidence has shown that the kynurenine pathway (KP) plays a role in the onset of oxidative stress and also in the pathophysiology of schizophrenia."	3.88	The inhibition of the kynurenine pathway prevents behavioral disturbances and oxidative stress in the brain of adult rats subjected to an animal model of schizophrenia. ( Barichello, T; Becker, IRT; Ceretta, LB; Dal-Pizzol, F; Kaddurah-Daouk, R; Oses, JP; Petronilho, F; Quevedo, J; Réus, GZ; Scaini, G; Zugno, AI, 2018)
"Aim & Objective: To delineate the associations between executive impairments and changes in tryptophan catabolite (TRYCAT) patterning, negative symptoms and deficit schizophrenia."	3.88	The Effects of Tryptophan Catabolites on Negative Symptoms and Deficit Schizophrenia are Partly Mediated by Executive Impairments: Results of Partial Least Squares Path Modeling. ( Kanchanatawan, B; Maes, M, 2018)
"Abnormalities in the kynurenine pathway (KP) of tryptophan degradation, leading to the dysfunction of neuroactive KP metabolites in the brain, have been implicated in the pathophysiology of schizophrenia (SZ)."	3.88	Influence of plasma cytokines on kynurenine and kynurenic acid in schizophrenia. ( Chiappelli, J; Hong, LE; Notarangelo, FM; Pocivavsek, A; Rowland, LM; Schwarcz, R; Thomas, MAR, 2018)
" Depression is hypothesized to be causally associated with an imbalance in the kynurenine pathway, with an increased metabolism down the 3-hydroxykynurenine (3HK) branch of the pathway leading to increased levels of the neurotoxic metabolite, quinolinic acid (QA), which is a putative N-methyl-d-aspartate (NMDA) receptor agonist."	3.85	Serum kynurenic acid is reduced in affective psychosis. ( Bliss, SA; Dantzer, R; Drevets, WC; Ford, BN; McMillin, JR; Morris, HM; Savitz, JB; Suzuki, H; Teague, TK; Wurfel, BE, 2017)
"Several lines of evidence suggest that up-regulation of immune response and alterations of kynurenine pathway function are involved in pathogenesis of schizophrenia."	3.85	Correlations of Kynurenic Acid, 3-Hydroxykynurenine, sIL-2R, IFN-α, and IL-4 with Clinical Symptoms During Acute Relapse of Schizophrenia. ( Flis, M; Kandefer-Szerszeń, M; Karakuła-Juchnowicz, H; Kocki, T; Rosa, W; Szymona, K; Urbańska, EM; Zdzisińska, B, 2017)
"Levels of kynurenic acid (KYNA), an endogenous negative modulator of alpha 7 nicotinic acetylcholine receptors (α7nAChRs) and antagonist at glutamatergic N-methyl-D-aspartate receptors (NMDARs), are elevated in the brain of patients with schizophrenia (SZ)."	3.83	Prenatal kynurenine exposure in rats: age-dependent changes in NMDA receptor expression and conditioned fear responding. ( Bruno, JP; Lindquist, DH; Pershing, ML; Phenis, D; Pocivavsek, A; Schwarcz, R; Valentini, V, 2016)
"The kynurenine pathway of tryptophan metabolism has been implicated in the pathophysiology of psychiatric disorders, including schizophrenia."	3.81	Xanthurenic Acid Activates mGlu2/3 Metabotropic Glutamate Receptors and is a Potential Trait Marker for Schizophrenia. ( Battaglia, G; Bruno, V; Capi, M; Caruso, A; Cavallari, M; Comparelli, A; Corigliano, V; Curto, M; De Blasi, A; De Carolis, A; De Fusco, A; Di Menna, L; Fazio, F; Girardi, P; Gradini, R; Iacovelli, L; Lionetto, L; Miele, J; Napoletano, F; Nicoletti, F; Nisticò, R; Scaccianoce, S; Simmaco, M; Ulivieri, M; Zappulla, C, 2015)
"The levels of kynurenic acid (KYNA), an endogenous negative modulator of alpha7 nicotinic acetylcholine receptors (α7nAChRs), are elevated in the brains of patients with schizophrenia (SZ)."	3.81	Elevated levels of kynurenic acid during gestation produce neurochemical, morphological, and cognitive deficits in adulthood: implications for schizophrenia. ( Bortz, DM; Bruno, JP; Fredericks, PJ; Jørgensen, CV; Leuner, B; Pershing, ML; Pocivavsek, A; Schwarcz, R; Vunck, SA, 2015)
"Neurotoxic metabolites of the kynurenine pathway are thought to be implicated in the pathogenesis of schizophrenia."	3.80	[A study of IL-1Β and IDO gene polymorphisms in patients with schizophrenia]. ( Gabaeva, MV; Ganisheva, TK; Golimbet, VE; Kasparov, SV; Kolesina, NIu; Korovaĭtseva, GI; Savel'eva, TM; Snegireva, AA; Velikaia, NV, 2014)
"The kynurenic acid (KYNA) hypothesis for schizophrenia is partly based on studies showing increased brain levels of KYNA in patients."	3.78	Increased levels of kynurenine and kynurenic acid in the CSF of patients with schizophrenia. ( Dahl, ML; Engberg, G; Erhardt, S; Holtze, M; Linderholm, KR; Olsson, SK; Samuelsson, M; Skogh, E, 2012)
"Impaired α7 nicotinic acetylcholine receptor (nAChR) function and GABAergic transmission in the hippocampus and elevated brain levels of kynurenic acid (KYNA), an astrocyte-derived metabolite of the kynurenine pathway, are key features of schizophrenia."	3.78	Regulation of GABAergic inputs to CA1 pyramidal neurons by nicotinic receptors and kynurenic acid. ( Albuquerque, EX; Alkondon, M; Banerjee, J; Pereira, EF, 2012)
"The association between the pro-inflammatory state of schizophrenia and increased tryptophan degradation into kynurenine has been reported."	3.77	Reversal of imbalance between kynurenic acid and 3-hydroxykynurenine by antipsychotics in medication-naïve and medication-free schizophrenic patients. ( Kim, YK; Leonard, BE; Mueller, HH; Myint, AM; Scharpé, S; Schwarz, MJ; Steinbusch, HW; Verkerk, R; Zach, J, 2011)
"The levels of kynurenic acid (KYNA), an astrocyte-derived metabolite of the branched kynurenine pathway (KP) of tryptophan degradation and antagonist of α7 nicotinic acetylcholine and N-methyl-D-aspartate receptors, are elevated in the prefrontal cortex (PFC) of individuals with schizophrenia (SZ)."	3.77	Impaired kynurenine pathway metabolism in the prefrontal cortex of individuals with schizophrenia. ( McMahon, RP; Rassoulpour, A; Roberts, RC; Sathyasaikumar, KV; Schwarcz, R; Stachowski, EK; Wonodi, I, 2011)
"A facile fluorometric assay using D-kynurenine as a substrate was utilized for evaluating the inhibition of D-amino acid oxidase (DAAO), which is one of the products of a susceptibility gene for schizophrenia, by commercial antipsychotic drugs, namely, chlorpromazine (CPZ), carbamazepine, sulpiride, quetiapine, and imipramine."	3.77	Inhibition of D-amino acid oxidase activity by antipsychotic drugs evaluated by a fluorometric assay using D-kynurenine as substrate. ( Fukushima, T; Iwasa, S; Nakabayashi, M; Song, Z; Tabara, H; Yokoyama, Y, 2011)
"Kynurenic acid (KYNA) is an endogenous compound implicated in the pathophysiology of schizophrenia."	3.75	Elevated levels of kynurenic acid change the dopaminergic response to amphetamine: implications for schizophrenia. ( Andersson, AS; Engberg, G; Erhardt, S; Holtze, M; Larsson, K; Linderholm, KR; Nilsson-Todd, LK; Olsson, E; Olsson, SK; Schwieler, L, 2009)
"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."	3.75	Kynurenine pathway in psychosis: evidence of increased tryptophan degradation. ( Barry, S; Clarke, G; Dinan, TG; Scully, P, 2009)
"Prior studies of mRNA expression, protein expression, and pathway metabolite levels have implicated dysregulation of the kynurenine pathway in the etiology of schizophrenia and bipolar disorder."	3.75	Two complex genotypes relevant to the kynurenine pathway and melanotropin function show association with schizophrenia and bipolar disorder. ( Leonard, S; Miller, CL; Murakami, P; Ross, RG; Ruczinski, I; Sinkus, M; Sullivan, B, 2009)
"The upregulation of the initiating step of the kynurenine pathway was demonstrated in postmortem anterior cingulated cortex from individuals with schizophrenia and bipolar disorder."	3.74	Tryptophan breakdown pathway in bipolar mania. ( Kim, YK; Leonard, BE; Myint, AM; Park, SH; Scharpé, S; Steinbusch, HW; Verkerk, R, 2007)
" The proposed HPLC method was applied to determine KYN levels in the plasma of ketamine-treated rats--the animal model of schizophrenia."	3.74	Determination of kynurenine levels in rat plasma by high-performance liquid chromatography with pre-column fluorescence derivatization. ( Fukushima, T; Imai, K; Mitsuhashi, S; Santa, T; Tomiya, M; Toyo'oka, T, 2007)
"Increased concentrations of kynurenine pathway metabolites have been reported by several groups for disorders involving psychosis, including schizophrenia and bipolar disorder."	3.74	Alterations in kynurenine precursor and product levels in schizophrenia and bipolar disorder. ( Cwik, M; Llenos, IC; Miller, CL; Walkup, J; Weis, S, 2008)
"Markers of the kynurenine pathway were studied in postmortem frontal cortex obtained from individuals with schizophrenia and controls."	3.72	Expression of the kynurenine pathway enzyme tryptophan 2,3-dioxygenase is increased in the frontal cortex of individuals with schizophrenia. ( Barillo, MM; Dulay, JR; Llenos, IC; Miller, CL; Weis, S; Yolken, RH, 2004)
" In rats, chronic (6-months) treatment with haloperidol did not cause an increase in kynurenate levels in the frontal cortex, indicating that the elevation observed in schizophrenia is not due to antipsychotic medication."	3.71	Increased cortical kynurenate content in schizophrenia. ( Medoff, D; Rassoulpour, A; Roberts, RC; Schwarcz, R; Tamminga, CA; Wu, HQ, 2001)
"Schizophrenia is a chronic psychotic disease burdened by cognitive deficits which hamper daily functioning causing disability and costs for society."	3.01	Importance of the dysregulation of the kynurenine pathway on cognition in schizophrenia: a systematic review of clinical studies. ( Bosia, M; Comai, S; Guillemin, GJ; Sapienza, J; Spangaro, M, 2023)
"Schizophrenia is a major psychotic disorder affecting nearly 23."	2.72	Role and Perspectives of Inflammation and C-Reactive Protein (CRP) in Psychosis: An Economic and Widespread Tool for Assessing the Disease. ( Aamir, A; Awan, HA; Awan, S; De Berardis, D; de Filippis, R; Di Giannantonio, M; Diwan, MN; Fornaro, M; Irfan, M; Martinotti, G; Pettorruso, M; Ullah, I; Vellante, F; Ventriglio, A, 2021)
"Schizophrenia is a neuropsychiatric disorder characterized by various symptoms including autonomic imbalance."	2.72	A Potential Interface between the Kynurenine Pathway and Autonomic Imbalance in Schizophrenia. ( Büki, A; Horvath, G; Kekesi, G; Vécsei, L, 2021)
"Schizophrenia is associated with general inflammation and disruption of glutamatergic and dopaminergic signalling."	2.53	Kynurenines, Gender and Neuroinflammation; Showcase Schizophrenia. ( de Bie, J; Guillemin, GJ; Lim, CK, 2016)
"Patients with treatment-resistant schizophrenia (TRS) suffer severe, long-term psychotic symptoms and chronic stress."	1.72	Elevated salivary kynurenic acid levels related to enlarged choroid plexus and severity of clinical phenotypes in treatment-resistant schizophrenia. ( Chiappelli, J; Hong, LE; Huang, J; Kochunov, P; Li, Y; Tan, S; Tan, Y; Tian, B; Tian, L; Tong, J; Wang, Z; Yang, F; Zhang, P; Zhou, Y, 2022)
"The kynurenine pathway (KP) has been linked to alterations in glutamatergic and monoaminergic neurotransmission and to SZ symptomatology through the production of the metabolites quinolinic acid (QA) and kynurenic acid (KYNA)."	1.62	Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology. ( Afia, AB; Artuch, R; Garcia-Bueno, B; Haro, JM; Leza, JC; MacDowell, KS; Ormazabal, A; Ramos, B; Vila, È, 2021)
"Cinnabarinic acid (CA) is a kynurenine metabolite that activates mGlu4 metabotropic glutamate receptors."	1.56	The Trace Kynurenine, Cinnabarinic Acid, Displays Potent Antipsychotic-Like Activity in Mice and Its Levels Are Reduced in the Prefrontal Cortex of Individuals Affected by Schizophrenia. ( Antenucci, N; Battaglia, G; Bruno, V; Chocyk, A; Cieslik, P; Curto, M; Di Menna, L; Fazio, F; Fucile, S; Giannino, G; Iacovelli, L; Liberatore, F; Lionetto, L; Martinello, K; Mascio, G; Nicoletti, F; Pilc, A; Pittaluga, A; Simmaco, M; Traficante, A; Ulivieri, M; Vergassola, M; Wierońska, JM, 2020)
"The etiology of schizophrenia is still unclear."	1.48	Kynurenine is correlated with IL-1β in plasma of schizophrenia patients. ( Costa, AC; Gattaz, WF; Joaquim, HPG; Talib, LL, 2018)
"Schizophrenia is associated with abnormalities in the structure and functioning of white matter, but the underlying neuropathology is unclear."	1.43	Tryptophan Metabolism and White Matter Integrity in Schizophrenia. ( Can, A; Chiappelli, J; Du, X; Fuchs, D; Hong, LE; Kochunov, P; Lowry, CA; Postolache, TT; Rowland, LM; Savransky, A; Shukla, DK; Tagamets, M; Wijtenburg, SA, 2016)
"Only kynurenine-treated rats were impaired in acquiring the extra-dimensional shift (saline, 8."	1.38	Acute elevations of brain kynurenic acid impair cognitive flexibility: normalization by the alpha7 positive modulator galantamine. ( Alexander, KS; Bruno, JP; Schwarcz, R; Wu, HQ, 2012)
"Schizophrenia is characterized by complex and dynamically interacting perturbations in multiple neurochemical systems."	1.36	Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia. ( Dougherty, GG; Kaddurah-Daouk, R; Keshavan, MS; Krishnan, RR; Matson, WR; McEvoy, J; Montrose, DM; Reddy, RD; Rozen, S; Yao, JK, 2010)
"Schizophrenia is a common, debilitating mental illness that has persisted over the generations."	1.35	The evolution of schizophrenia: a model for selection by infection, with a focus on NAD. ( Miller, CL, 2009)

Research

Studies (104)

Authors

Clinical Trials (8)

Trial Overview

Trial Outcomes

Change in Level of Cognition

Timeframe	Studies, this research(%)	All Research%
pre-1990	9 (8.65)	18.7374
1990's	2 (1.92)	18.2507
2000's	15 (14.42)	29.6817
2010's	50 (48.08)	24.3611
2020's	28 (26.92)	2.80

Authors	Studies
Afia, AB	1
Vila, È	1
MacDowell, KS	1
Ormazabal, A	1
Leza, JC	1
Haro, JM	1
Artuch, R	1
Ramos, B	1
Garcia-Bueno, B	1
Büki, A	1
Kekesi, G	2
Horvath, G	2
Vécsei, L	3
Butler, MI	1
Long-Smith, C	1
Moloney, GM	1
Morkl, S	1
O'Mahony, SM	1
Cryan, JF	1
Clarke, G	3
Dinan, TG	2
Huang, J	3
Zhang, P	3
Zhou, Y	3
Tong, J	3
Cui, Y	2
Tan, S	3
Wang, Z	3
Yang, F	3
Kochunov, P	4
Tian, B	3
Tian, L	3
Hong, LE	5
Tan, Y	3
Ullah, I	1
Awan, HA	1
Aamir, A	1
Diwan, MN	1
de Filippis, R	1
Awan, S	1
Irfan, M	1
Fornaro, M	1
Ventriglio, A	1
Vellante, F	1
Pettorruso, M	1
Martinotti, G	1
Di Giannantonio, M	1
De Berardis, D	1
Almulla, AF	1
Vasupanrajit, A	1
Tunvirachaisakul, C	1
Al-Hakeim, HK	1
Solmi, M	1
Verkerk, R	5
Maes, M	2
Guan, X	1
Xu, J	1
Xiu, M	1
Li, X	1
Liu, H	1
Wu, F	1
Li, Y	1
Chiappelli, J	4
Sakamoto, T	1
Odera, K	1
Onozato, M	1
Sugasawa, H	1
Takahashi, R	1
Fujimaki, Y	1
Fukushima, T	3
Sapienza, J	3
Spangaro, M	3
Guillemin, GJ	6
Comai, S	3
Bosia, M	3
Shilov, YE	1
Baymeeva, NV	1
Brusov, OS	1
Oleichik, IV	1
Sizov, SV	1
Tyurin, IA	1
Hare, SM	1
Adhikari, BM	1
Mo, C	1
Chen, S	1
Wijtenburg, SA	2
Seneviratne, C	1
Kane-Gerard, S	1
Sathyasaikumar, KV	3
Notarangelo, FM	3
Schwarcz, R	12
Kelly, DL	3
Rowland, LM	4
Buchanan, RW	1
Wang, Y	1
Fang, X	1
Wang, G	1
Tang, W	1
Liu, S	1
Yang, Y	1
Chen, J	1
Ling, Y	1
Zhou, C	1
Zhang, X	1
Zhang, C	1
Su, KP	1
Zhu, F	1
Guo, R	1
Wang, W	1
Ju, Y	1
Wang, Q	1
Ma, Q	1
Sun, Q	1
Fan, Y	1
Xie, Y	1
Yang, Z	1
Jie, Z	1
Zhao, B	1
Xiao, L	1
Yang, L	1
Zhang, T	1
Liu, B	1
Guo, L	1
He, X	1
Chen, Y	2
Chen, C	1
Gao, C	1
Xu, X	1
Yang, H	1
Wang, J	1
Dang, Y	1
Madsen, L	1
Brix, S	1
Kristiansen, K	1
Jia, H	1
Ma, X	1
Zádor, F	1
Nagy-Grócz, G	1
Dvorácskó, S	1
Szűcs, E	1
Tömböly, C	1
Benyhe, S	1
Pedraz-Petrozzi, B	1
Elyamany, O	1
Rummel, C	1
Mulert, C	1
Zhang, Z	1
Zhang, M	1
Luo, Y	1
Ni, X	1
Lu, H	1
Wen, Y	1
Fan, N	1
Ulivieri, M	2
Wierońska, JM	1
Lionetto, L	3
Martinello, K	1
Cieslik, P	1
Chocyk, A	1
Curto, M	3
Di Menna, L	2
Iacovelli, L	2
Traficante, A	1
Liberatore, F	1
Mascio, G	1
Antenucci, N	1
Giannino, G	1
Vergassola, M	1
Pittaluga, A	1
Bruno, V	2
Battaglia, G	2
Fucile, S	1
Simmaco, M	3
Nicoletti, F	3
Pilc, A	1
Fazio, F	3
Buck, SA	1
Baratta, AM	1
Pocivavsek, A	5
Morrens, M	1
De Picker, L	2
Kampen, JK	1
Coppens, V	1
Marx, W	1
McGuinness, AJ	1
Rocks, T	1
Ruusunen, A	1
Cleminson, J	1
Walker, AJ	1
Gomes-da-Costa, S	1
Lane, M	1
Sanches, M	1
Diaz, AP	1
Tseng, PT	1
Lin, PY	1
Berk, M	1
O'Neil, A	1
Jacka, F	1
Stubbs, B	1
Carvalho, AF	1
Quevedo, J	2
Soares, JC	1
Fernandes, BS	1
Cao, B	1
Ren, Z	1
Pan, Z	1
McIntyre, RS	1
Wang, D	1
Noyan, H	1
Erdağ, E	1
Tüzün, E	1
Yaylım, İ	1
Küçükhüseyin, Ö	1
Hakan, MT	1
Gülöksüz, S	1
Rutten, BPF	1
Saka, MC	1
Atbaşoğlu, C	1
Alptekin, K	1
van Os, J	1
Üçok, A	1
Mayorova, MA	1
Butoma, BG	1
Churilov, LP	1
Gilburd, B	1
Petrova, NN	1
Shoenfeld, Y	1
Cathomas, F	1
Guetter, K	1
Seifritz, E	1
Klaus, F	1
Kaiser, S	1
Bartoli, F	1
Cioni, RM	1
Callovini, T	1
Cavaleri, D	1
Crocamo, C	1
Carrà, G	1
Wurfel, BE	1
Drevets, WC	1
Bliss, SA	1
McMillin, JR	1
Suzuki, H	1
Ford, BN	1
Morris, HM	1
Teague, TK	1
Dantzer, R	1
Savitz, JB	1
Koola, MM	1
Sklar, J	1
Davis, W	1
Nikiforuk, A	1
Meissen, JK	1
Sawant-Basak, A	1
Aaronson, ST	1
Kozak, R	1
Réus, GZ	1
Becker, IRT	1
Scaini, G	1
Petronilho, F	1
Oses, JP	1
Kaddurah-Daouk, R	4
Ceretta, LB	1
Zugno, AI	1
Dal-Pizzol, F	1
Barichello, T	1
Hahn, B	1
Reneski, CH	1
Joaquim, HPG	1
Costa, AC	1
Gattaz, WF	1
Talib, LL	1
van den Brink, WJ	1
Palic, S	1
Köhler, I	1
de Lange, ECM	1
Thomas, MAR	1
Tufvesson-Alm, M	1
Schwieler, L	4
Goiny, M	1
Erhardt, S	6
Engberg, G	6
Kanchanatawan, B	1
Li, C	1
Wang, A	1
Wang, C	1
Ramamurthy, J	1
Zhang, E	1
Guadagno, E	1
Trakadis, Y	1
Beggiato, S	1
Giorgini, F	1
Fujigaki, H	1
Mouri, A	1
Yamamoto, Y	1
Nabeshima, T	1
Saito, K	1
Corigliano, V	2
Comparelli, A	2
Ferracuti, S	1
Baldessarini, RJ	1
Steen, NE	1
Dieset, I	1
Hope, S	1
Vedal, TSJ	1
Smeland, OB	1
Matson, W	1
Agartz, I	1
Melle, I	1
Djurovic, S	1
Jönsson, EG	1
Bogdanov, M	1
Andreassen, OA	1
Kindler, J	1
Lim, CK	3
Weickert, CS	2
Boerrigter, D	1
Galletly, C	1
Liu, D	1
Jacobs, KR	1
Balzan, R	1
Bruggemann, J	1
O'Donnell, M	1
Lenroot, R	1
Weickert, TW	1
Oxenkrug, G	1
Bernstein, HG	2
Guest, PC	1
van der Hart, M	1
Roeser, J	1
Summergrad, P	1
Steiner, J	2
Johansson, AS	1
Owe-Larsson, B	1
Asp, L	1
Kocki, T	2
Adler, M	1
Hetta, J	1
Gardner, R	1
Lundkvist, GB	1
Urbanska, EM	2
Karlsson, H	1
Zavitsanou, K	1
Purves-Tyson, T	1
Karl, T	1
Kassiou, M	1
Banister, SD	1
Golimbet, VE	1
Korovaĭtseva, GI	1
Gabaeva, MV	1
Velikaia, NV	1
Snegireva, AA	1
Kasparov, SV	1
Kolesina, NIu	1
Ganisheva, TK	1
Savel'eva, TM	1
Pershing, ML	2
Bortz, DM	1
Fredericks, PJ	1
Jørgensen, CV	1
Vunck, SA	1
Leuner, B	1
Bruno, JP	4
Larsson, MK	1
Skogh, E	2
Kegel, ME	1
Orhan, F	1
Abdelmoaty, S	1
Finn, A	1
Bhat, M	1
Samuelsson, M	2
Lundberg, K	1
Dahl, ML	2
Sellgren, C	1
Schuppe-Koistinen, I	1
Svensson, C	1
Okusaga, O	2
Duncan, E	1
Langenberg, P	1
Brundin, L	1
Fuchs, D	4
Groer, MW	1
Giegling, I	2
Stearns-Yoder, KA	2
Hartmann, AM	2
Konte, B	2
Friedl, M	2
Brenner, LA	2
Lowry, CA	3
Rujescu, D	2
Postolache, TT	3
Cavallari, M	1
Zappulla, C	1
Napoletano, F	1
Capi, M	1
Scaccianoce, S	1
Caruso, A	1
Miele, J	1
De Fusco, A	1
De Carolis, A	1
Gradini, R	1
Nisticò, R	1
De Blasi, A	1
Girardi, P	1
Kosten, L	1
Verhaeghe, J	1
Thomae, D	1
Wyffels, L	1
Van Eetveldt, A	1
Dedeurwaerdere, S	1
Stroobants, S	1
Staelens, S	1
Shukla, DK	1
Tagamets, M	1
Du, X	1
Savransky, A	1
Can, A	1
Sekine, A	1
Kuroki, Y	1
Urata, T	1
Mori, N	1
Fukuwatari, T	1
Imbeault, S	1
de Bie, J	1
Reeves, G	1
Groer, M	1
Cook, TB	1
Pandey, JP	1
Hoisington, AJ	1
Eaton, WW	1
Phenis, D	1
Valentini, V	1
Lindquist, DH	1
Shovestul, BJ	1
Glassman, M	1
McMahon, RP	2
Liu, F	1
Szymona, K	1
Zdzisińska, B	1
Karakuła-Juchnowicz, H	1
Kandefer-Szerszeń, M	1
Flis, M	1
Rosa, W	1
Barry, S	1
Scully, P	1
Olsson, SK	3
Andersson, AS	1
Linderholm, KR	2
Holtze, M	2
Nilsson-Todd, LK	1
Olsson, E	1
Larsson, K	1
Miller, CL	5
Costantino, G	1
Kim, YK	3
Myint, AM	8
Scharpe, S	3
Steinbusch, H	1
Leonard, B	1
Yao, JK	2
Dougherty, GG	2
Reddy, RD	2
Keshavan, MS	2
Montrose, DM	2
Matson, WR	2
Rozen, S	1
Krishnan, RR	1
McEvoy, J	2
Murakami, P	1
Ruczinski, I	1
Ross, RG	1
Sinkus, M	1
Sullivan, B	1
Leonard, S	1
Wu, HQ	3
Pereira, EF	2
Pellicciari, R	1
Albuquerque, EX	2
Bechter, K	1
Reiber, H	1
Herzog, S	1
Tumani, H	1
Maxeiner, HG	1
Wonodi, I	2
Anderson, G	1
Stachowski, EK	1
Roberts, RC	2
Rassoulpour, A	2
Akagbosu, CO	1
Evans, GC	1
Gulick, D	1
Suckow, RF	1
Bucci, DJ	1
Condray, R	1
Haas, GL	1
Müller, N	3
Schwarz, MJ	4
Mueller, HH	1
Zach, J	1
Steinbusch, HW	2

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Proof-of Concept Trial of Galantamine and Memantine for Cognitive Impairments in Schizophrenia: Is the Combination Effective?[NCT02234752]	Phase 2	3 participants (Actual)	Interventional	2014-09-30	Terminated (stopped due to Funding no longer available and PI no longer working at the institution)
A Longitudinal Study of Inflammatory Pathways in Depression[NCT04159207]		160 participants (Anticipated)	Observational	2019-10-01	Recruiting
Kynurenine Pathway Metabolites as Novel Translational Biological Markers of Irritable Bowel Syndrome: Relationship to Gastrointestinal Function, Cognition and Co-morbid Depression[NCT01304355]		85 participants (Anticipated)	Observational	2011-01-31	Recruiting
Pilot Study of Glycine Augmentation in Carriers of a Mutation in the Gene Encoding Glycine Decarboxylase[NCT01720316]	Phase 2	2 participants (Actual)	Interventional	2012-12-10	Completed
Targeting a Genetic Mutation in Glycine Metabolism With D-cycloserine[NCT02304432]	Early Phase 1	2 participants (Actual)	Interventional	2015-09-27	Completed
A Randomised Double Blind Placebo Controlled 12 Week Trial of Methotrexate Added to Treatment As Usual in Early Schizophrenia[NCT02074319]	Phase 1	92 participants (Actual)	Interventional	2013-12-31	Completed
Vortioxetine Monotherapy for Major Depressive Disorder in Type 2 Diabetes: Role of Inflammation, Kynurenine Pathway, and Structural and Functional Brain Connectivity as Biomarkers[NCT03580967]	Phase 4	0 participants (Actual)	Interventional	2019-07-01	Withdrawn (stopped due to COVID-19 Pandemic interfered with Pt recruitment)
The Effects of Glycine Transport Inhibition on Brain Glycine Concentration[NCT00538070]		68 participants (Actual)	Interventional	2007-08-31	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

The primary outcome measure will be the change in level of cognition as measured by the MATRICS Consensus Cognitive Battery (MCCB). In schizophrenia, usual composite scores are 20-39. In healthy controls, usual composite scores are normalized to 40-60. Higher values of composite scores mean better cognition. Test scores are normalized to healthy controls, therefore no min-max range is available. Final scores calculated by MATRICS Consensus Cognitive Battery software. Exact minimum/maximum are not known to provider. Overall composite scores are reported. (NCT02234752)
Timeframe: Baseline and 6-Weeks

Free Tryptophan (TRP)

Intervention	units on a scale (Number)
	Baseline Participant 1	Week 6 Participant 1	Baseline Participant 2	Week 6 Participant 2	Baseline Participant 3
Galantamine ER, Memantine XR	48	48	32	25	9

The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. (NCT02234752)
Timeframe: Baseline and 6-Weeks

KYN/TRP

Intervention	µM (Mean)
	Baseline tryptophan Participant 1	Week-6 tryptophan Participant 1	Baseline tryptophan Participant 2	Week-6 tryptophan Participant 2	Baseline tryptophan Participant 3
KP Metabolites Values	51.94	55.72	32.17	24.96	35.07

The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. AUC ratio reported. (NCT02234752)
Timeframe: Baseline and 6-Weeks

KYNA/KYN

Intervention	AUC Ratio (Number)
	Baseline KYN/TRP Participant 1	Week-6 KYN/TRP Participant 1	Baseline KYN/TRP Participant 2	Week-6 KYN/TRP Participant 2	Baseline KYN/TRP Participant 3
KP Metabolites Values	1.21	1.31	1.06	0.8	0.79

The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. AUC ratio reported. (NCT02234752)
Timeframe: Baseline and 6-Weeks

Kynurenic Acid (KYNA)

Intervention	AUC Ratio (Number)
	Baseline KYNA/KYN Participant 1	Week-6 KYNA/KYN Participant 1	Baseline KYNA/KYN Participant 2	Week-6 KYNA/KYN Participant 2	Baseline KYNA/KYN Participant 3
KP Metabolites Values	0.075	0.050	0.121	0.114	0.152

The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. MS* AUC is mass spectrometry times area under the curve. (NCT02234752)
Timeframe: Baseline and 6-Weeks

Kynurenine (KYN)

Intervention	MS* AUC (Mean)
	Baseline KYNA Participant 1	Week-6 KYNA Participant 1	Baseline KYNA Participant 2	Week-6 KYNA Participant 2	Baseline KYNA Participant 3
KP Metabolites Values	103911	83737	95139	73280	93163

The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. (NCT02234752)
Timeframe: Baseline and 6-Weeks

PIC/KYN

Intervention	µM (Mean)
	Baseline KYN Participant 1	Week-6 KYN Participant 1	Baseline KYN Participant 2	Week-6 KYN Participant 2	Baseline KYN Participant 3
KP Metabolites Values	1.62	1.85	0.86	0.71	0.76

The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. AUC ratio reported. (NCT02234752)
Timeframe: Baseline and 6-Weeks

Picolinic Acid (PIC)

Intervention	AUC Ratio (Number)
	Baseline PIC/KYN Participant 1	Week-6 PIC/KYN Participant 1	Baseline PIC/KYN Participant 2	Week-6 PIC/KYN Participant 2	Baseline PIC/KYN Participant 3
KP Metabolites Values	0.0317	0.0175	0.1039	0.0989	0.0655

Auditory Evoked Potentials - P50 Ratio (P50 S2/P50 S1 Amplitude) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT

Intervention	MS* AUC (Mean)
	Baseline PIC Participant 1	Week-6 PIC Participant 1	Baseline PIC Participant 2	Week-6 PIC Participant 2	Baseline PIC Participant 3
KP Metabolites Values	44021	29542	81883	63745	40189

Auditory evoked potentials amplitude: P50 ratio (S2/S1). Participants were assessed at baseline and in week 6 of open-label glycine treatment. (NCT01720316)
Timeframe: Recordings at baseline and week 6 of glycine

Auditory Evoked Potentials in Amplitude (Degrees Measured in Microvolts) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT

Intervention	ratio (Number)
Auditory ERPs Amplitude (Deg) Baseline: Subject 2	44.51
Auditory ERPs Amplitude (Deg) 6 Weeks of Glycine: Subject 2	35.67

Auditory evoked potentials amplitude: P300 at fz, cz, and pz; N100 at fz and cz; P200 at fz and cz; P50 S1 and S2 amplitude; mismatch negativity (MMN) at fz and cz. Participants were assessed at baseline and in week 6 of open-label glycine treatment. (NCT01720316)
Timeframe: Recordings at baseline and week 6 of glycine

Auditory Evoked Potentials in Gammas Oscillations (the Power Spectrum is Measured in Microvolts Squared) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT

Intervention	microvolts (Number)
	P300 amplitude at fz	P300 amplitude at cz	P300 amplitude at pz	N100 amplitude at fz	N100 amplitude at cz	P200 amplitude at fz	P200 amplitude at cz	P50 S1 amplitude	P50 S2 amplitude	MMN amplitude at fz	MMN amplitude at cz
Auditory ERPs Amplitude (Deg) 6 Weeks of Glycine: Subject 2	3.74	6.6	5.57	-4.71	-3.89	6.29	7.8	2.2	0.78	-1.004	-1.322
Auditory ERPs Amplitude (Deg) Baseline: Subject 2	-0.635	6.53	5.34	-3.93	-3.62	1.662	6.59	2.76	1.23	-3.356	-4.13

Auditory evoked potentials gamma: G40 hz phase locking at fz and cz; G20 hz phase locking response at fz and cz G30 hz phase locking response at fz and cz. Participants were assessed at baseline and in week 6 of open-label glycine treatment. (NCT01720316)
Timeframe: Recordings at baseline and week 6 of glycine

Auditory Evoked Potentials in Latency (Msec) at BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF TREATMENT WITH GLYCINE

Intervention	microvolts squared (Number)
	G40 fz	G40 cz	G20 fz	G20 cz	G30 fz	G30 cz
Auditory ERPs Gamma 6 Weeks of Glycine: Subject 2	0.255	0.29	0.107	0.108	0.177	0.242
Auditory ERPs Gamma Baseline: Subject 2	0.135	0.168	0.023	0.03	0.19	0.163

Auditory evoked potentials latency: P300 at fz, cz, and pz); N100 at fz and cz); P200 at fz and cz. Participants were assessed at baseline and in week of open-label glycine treatment. (NCT01720316)
Timeframe: Recordings at baseline and week 6 of glycine

Brain GABA Metabolite Levels (GABA/Creatine Ratio: GABA/Cr) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT

Intervention	msec (Number)
	P300 latency at fz	P300 latency at cz	P300 latency at pz	N100 latency at fz	N100 latency at cz	P200 latency at fz	P200 latency at cz
Auditory ERPs Latency (ms) 6 Weeks of Glycine: Subject 2	300.78	293	294.92	94	94	205	203
Auditory ERPs Latency (ms) Baseline: Subject 2	279.3	279.3	279.3	97.66	91.8	197.27	193.4

Magnetic resonance spectroscopy GABA/Cr. Participants were assessed 1) pre-glycine treatment (baseline) and 2) in week 6 of open-label glycine treatment measured in posterior occipital cortex. (NCT01720316)
Timeframe: Baseline and week 6 of glycine

Brain Glutamate Metabolite Levels (Glutamate/Creatine Ratio: Glu/Cr) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT

Intervention	ratio (Number)
	Baseline GABA/Cr	Week 6 of glycine tx GABA/Cr
Subject1: Brain GABA/CR Ratio- Baseline/Week 6 of Glycine	0.16	0.22
Subject2: Brain GABA/CR Ratio- Baseline/Week 6 of Glycine	0.27	0.24

magnetic resonance spectroscopy - glutamate metabolite level. Participants were assessed 1) pre-glycine treatment and in week 6 of open-label glycine treatment. Measured in posterior occipital cortex. (NCT01720316)
Timeframe: baseline and week 6 of glycine

Brain Glycine/CR Ratio

Intervention	ratio (Number)
	Baseline brain glutamate/Cr ratio	Week 6 brain glutamate/Cr ratio
Subject1: Brain Glutamate/CR Ratio- Baseline/Week 6 of Glycine	0.98	0.84
Subject2: Brain Glutamate/CR Ratio- Baseline/Week 6 of Glycine	2.053	1.13

magnetic resonance spectroscopy: glycine/creatine ratio. Participants were assessed at 1) BASELINE PRE-GLYCINE TREATMENT: pre-glycine challenge drink, 60 minutes post challenge drink, 80 minutes post challenge drink, 100 minutes post challenge drink, and 120 minutes post challenge drink (0.4 g/kg up to max of 30 g); and 2) IN WEEK 6 OF OPEN-LABEL GLYCINE TREATMENT: pre-glycine dose, and 60 minutes, 80 minutes, 100 minutes and 120 minutes post daily dose of glycine. Measured in posterior occipital cortex (NCT01720316)
Timeframe: baseline (pre-challenge, 60, 80, 100, 120 minutes post-challenge), and week 6 of glycine (pre-dose and 60, 80, 100, 120 minutes post-dose

Brief Psychiatric Rating Scale (BPRS) Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks Positive and Negative Symptom Scores at Baseline and at 2, 4, and 6 Weeks During Intervention 1, Intervention 2, and During Open-label Glycine

Intervention	ratio (Number)
	Baseline - pre-challenge drink	Baseline 60 minutes post challenge drink	Baseline 80 minutes post challenge drink	Baseline 100 minutes post challenge drink	Baseline 120 minutes post challenge drink	Week 6 of glycine - pre-glycine dose	Week 6 of glycine - 60 minutes post glycine dose	Week 6 of glycine - 80 minutes post glycine dose	Week 6 of glycine - 100 minutes post glycine dose	Week 6 of glycine - 120 minutes post glycine dose
Subject 2:Brain Glycine/CR Ratio at Baseline/Week 6 of Glycine	0.5691	0.3918	0.6428	0.6363	0.9559	0.3235	0.3807	0.5591	0.4142	0.3545
Subject1: Brain Glycine/CR Ratio at Baseline/Week 6 of Glycine	0.2558	0.6157	0.6631	0.5938	0.6953	0.6573	0.2983	0.4577	0.5751	0.3842

Total BPRS score measures severity of 18 psychiatric symptoms. Each symptom is scored 1-7 with the total score ranging from 18-126. 18 means no symptoms and 126 means very severe symptoms. (NCT01720316)
Timeframe: baseline and at 2 weeks, 4 weeks, and 6 weeks within and after each treatment period

Clinical Global Impression (CGI) Severity Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks Within Each Treatment Period

Intervention	units on a scale (Number)
	BPRS at baseline	BPRS at 2 weeks intervention 1	BPRS at 4 weeks intervention 1	BPRS at 6 weeks intervention 1	BPRS, end of washout1	BPRS at 2 weeks intervention 2	BPRS at 4 weeks intervention 2	BPRS at 6 weeks intervention 2	BPRS, end of washout2	BPRS at 2 weeks open label	BPRS at 4 weeks open label	BPRS at 6 weeks open label	BPRS, end of washout3
Glycine, Then Placebo	39	38	32	21	22	37	31	37	32	23	22	21	19
Placebo, Then Glycine	46	38	39	28	34	32	20	23	24	20	18	19	23

Clinical Global Impression (CGI) severity scores measure severity of mental illness on a scale of 1-7 where 1 means normal, not at all ill, 2 means borderline mentally ill, 3 means mildly ill, 4 means moderately ill, 5 means markedly ill, 6 means severely ill and 7 means among the most extremely ill patients. (NCT01720316)
Timeframe: CGI at baseline and at 2 weeks, 4 weeks, and 6 weeks per treatment period

Clinical Global Impression (CGI) Therapeutic Effect Scores at 2 Weeks, 4 Weeks, and 6 Weeks Within Each Treatment Period

Intervention	units on a scale (Number)
	CGI severity score at baseline	CGI severity score at 2 weeks intervention 1	CGI severity score at 4 weeks intervention 1	CGI severity score at 6 weeks intervention 1	CGI severity score, end of washout1	CGI severity score at 2 weeks intervention 2	CGI severity score at 4 weeks intervention 2	CGI severity score at 6 weeks intervention 2	CGI severity score, end of washout2	CGI severity score at 2 weeks open label	CGI severity score at 4 weeks open label	CGI severity score at 6 weeks open label	CGI severity score, end of washout3
Glycine, Then Placebo	4	4	3	2	2	4	4	4	4	3	3	2	2
Placebo, Then Glycine	4	4	4	4	4	4	4	3	3	3	3	2	2

Clinical Global Impression (CGI) therapeutic effect scores measure degree of improvement as marked (1), moderate (5), minimal (9) or unchanged/worse (13). (NCT01720316)
Timeframe: at 2 weeks, 4 weeks, and 6 weeks within each treatment period

Depression Symptom Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks Within Each Treatment Period

Intervention	score (Number)
	CGI therapeutic effect at 2 weeks intervention 1	CGI therapeutic effect at 4 weeks intervention 1	CGI therapeutic effect at 6 weeks intervention 1	CGI therapeutic effect, end of washout1	CGI therapeutic effect at 2 weeks intervention 2	CGI therapeutic effect at 4 weeks intervention 2	CGI therapeutic effect at 6 weeks intervention 2	CGI therapeutic effect, end of washout2	CGI therapeutic effect at 2 weeks open label	CGI therapeutic effect at 4 weeks open label	CGI therapeutic effect at 6 weeks open label	CGI therapeutic effect, end of washout3
Glycine, Then Placebo	13	5	5	5	13	13	13	13	5	5	1	1
Placebo, Then Glycine	5	5	5	5	13	5	5	5	1	1	1	1

Hamilton Depression Scale measures severity of depression symptoms. The sum of ratings for 9 depression symptoms are measured on a scale from 0-2 with 0 meaning no symptoms and 2 meaning some level of severity of that specific symptom. The rating for 1 depression symptom is measured on a scale from 0-3 with 0 meaning no symptoms and 3 meaning a severe level of that specific symptom. The sum of ratings for 11 depression symptoms are measured on a scale from 0-4 with 0 meaning no symptoms and 4 meaning a severe level of that specific symptom. The three sums are added to produce an overall depression rating scale score ranging from 0-65. (NCT01720316)
Timeframe: baseline and at 2 weeks, 4 weeks, and 6 weeks within each treatment period

Glycine Plasma Amino Acid Levels at Baseline, During Glycine Treatment, During Placebo Treatment and During Open-label Glycine

Intervention	units on a scale (Number)
	Depression symptoms at baseline	Depression symptoms at 2 weeks intervention 1	Depression symptoms at 4 weeks intervention 1	Depression symptoms at 6 weeks intervention 1	Depression symptoms, end of washout1	Depression symptoms at 2 weeks intervention 2	Depression symptoms at 4 weeks intervention 2	Depression symptoms at 6 weeks intervention 2	Depression symptoms, end of washout2	Depression symptoms at 2 weeks open label	Depression symptoms at 4 weeks open label	Depression symptoms at 6 weeks open label	Depression symptoms, end of washout3
Glycine, Then Placebo	18	17	11	3	1	19	5	7	3	2	2	1	2
Placebo, Then Glycine	12	5	5	0	3	3	2	1	1	1	1	1	0

Plasma glycine levels; normal range is 122-467 nM/mL (NCT01720316)
Timeframe: At baseline, during glycine treatment, during placebo treatment and during open-label glycine

Mania Symptom Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks Within Each Treatment Period

Intervention	nM/mL (Number)
	Baseline	Glycine double-blind	Placebo	Glycine open-label
Glycine Then Placebo	216	410	194	516
Placebo Then Glycine	271	761	347	634

Young Mania Rating Scale (YMRS) measures severity of manic symptoms. The sum of ratings for 7 symptoms of mania is measured on a scale from 0-4 and the sum of 4 symptoms of mania is measured on a scale from 0-8 to yield a total score ranging from 0-60, with 0 meaning no manic symptoms and 60 meaning severe manic symptoms. (NCT01720316)
Timeframe: baseline and at 2 weeks, 4 weeks, and 6 weeks within each treatment period

Neurocognitive Function at Baseline, During Glycine Treatment, During Placebo Treatment and During Open-label Glycine

Intervention	units on a scale (Number)
	Manic symptoms at baseline	Manic symptoms at 2 weeks intervention 1	Manic symptoms at 4 weeks intervention 1	Manic symptoms at 6 weeks intervention 1	Manic symptoms, end of washout1	Manic symptoms at 2 weeks intervention 2	Manic symptoms at 4 weeks intervention 2	Manic symptoms at 6 weeks intervention 2	Manic symptoms, end of washout2	Manic symptoms at 2 weeks open label	Manic symptoms at 4 weeks open label	Manic symptoms at 6 weeks open label	Manic symptoms, end of washout3
Glycine, Then Placebo	4	1	0	0	0	17	0	2	2	1	0	0	0
Placebo, Then Glycine	7	7	6	0	0	0	0	0	0	0	0	0	0

Scores on each of 8 domains of cognitive function (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning/problem solving, social cognition, overall composite). Scores are T scores ranging from 0-100, with 50 representing the mean for a population based on a normal distribution; standard deviation of 10. Only overall composite score is entered. (NCT01720316)
Timeframe: At baseline, during glycine treatment, during placebo treatment and during open-label glycine

Positive and Negative Symptom Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks During Intervention 1 (Glycine or Placebo), Intervention 2 (Glycine or Placebo), and During Open-label Glycine

Intervention	units on a scale (Number)
	Participant 1	Participant 2
Baseline	45	48
Composite Score on Glycine, Double-blind	52	52
Composite Score on Glycine, Open-label	49	46
Composite Score on Placebo	52	55

Positive and Negative Symptom Scale (PANSS) measures positive and negative symptoms of schizophrenia. The sum of ratings for seven positive symptoms are measured on a scale from 7-49 with 7 meaning no symptoms and 49 meaning severe symptoms. (NCT01720316)
Timeframe: baseline and at 2 weeks, 4 weeks, and 6 weeks within each treatment period and after each treatment period

Auditory Evoked Potentials - P50 Ratio (P50 S2/S1) (Amplitude)

Intervention	units on a scale (Number)
	Positive symptoms at baseline	Positive symptoms at 2 weeks intervention 1	Positive symptoms at 4 weeks intervention 1	Positive symptoms at 6 weeks intervention 1	Positive symptoms, end of washout1	Positive symptoms at 2 weeks intervention 2	Positive symptoms at 4 weeks intervention 2	Positive symptoms at 6 weeks intervention 2	Positive symptoms, end of washout2	Positive symptoms at 2 weeks open label	Positive symptoms at 4 weeks open label	Positive symptoms at 6 weeks open label	Positive symptoms, end of washout3
Glycine, Then Placebo	13	12	9	8	7	12	11	14	14	9	9	7	7
Placebo, Then Glycine	19	20	19	13	13	12	10	11	11	8	7	8	8

Auditory evoked potential amplitude: P50 ratio (P50 S2/S1) (NCT02304432)
Timeframe: Baseline and Week 8 of DCS treatment

Auditory Evoked Potentials in Amplitude (Degrees Measured in Microvolts)

Intervention	ratio (Number)
	P50 ratio: Baseline	P50 ratio: Week 8 of DCS
First Open Label DCS	44.51	30

Auditory evoked potential amplitude: P300 at fz, cz, and pz; N100 at fz and cz; P200 at fz and cz; P50 S1 and S2; mismatch negativity (MMN) at fz and cz. (NCT02304432)
Timeframe: Baseline and Week 8 of DCS treatment

Auditory Evoked Potentials in Gamma Oscillations (the Power Spectrum is Measured in Microvolts Squared)

Intervention	microvolts (Number)
	P300 at fz: Baseline	P300 at cz: Baseline	P300 at pz: Baseline	N100 at fz: Baseline	N100 at cz: Baseline	P200 at fz: Baseline	P200 at cz: Baseline	P50 S1: Baseline	P50 S2: Baseline	MMN at fz: Baseline	MMN at cz: Baseline	P300 at fz: Week 8 of DCS	P300 at cz: Week 8 of DCS	P300 at pz: Week 8 of DCS	N100 at fz: Week 8 of DCS	N100 at cz: Week 8 of DCS	P200 at fz: Week 8 of DCS	P200 at cz: Week 8 of DCS	P50 S1: Week 8 of DCS	P50 S2: Week 8 of DCS	MMN at fz: Week 8 of DCS	MMN at cz: Week 8 of DCS
First Open Label DCS	-0.635	6.529	5.340	-3.926	-3.615	1.662	6.591	2.759	1.23	-3.356	-4.130	3.030	6.810	6.620	-3.260	-3.940	8.200	8.160	1.36	0.4	-3.330	-1.540

Auditory evoked potential gamma: G40 hz phase locking at fz and cz; G30 hz phase locking at fz and cz; G20 hz phase locking at fz and cz (NCT02304432)
Timeframe: Baseline and Week 8 of DCS treatment

Auditory Evoked Potentials in Latency (Msec)

Intervention	microvolts squared (Number)
	G40 hz phase locking at fz: Baseline	G40 hz phase locking at cz: Baseline	G30 hz phase locking at fz: Baseline	G30 hz phase locking at cz: Baseline	G20 hz phase locking at fz: Baseline	G20 hz phase locking at cz: Baseline	G40 hz phase locking at fz: Week 8 of DCS	G40 hz phase locking at cz: Week 8 of DCS	G30 hz phase locking at fz: Week 8 of DCS	G30 hz phase locking at cz: Week 8 of DCS	G20 hz phase locking at fz: Week 8 of DCS	G20 hz phase locking at cz: Week 8 of DCS
First Open Label DCS	0.135	0.168	0.190	0.163	0.023	0.030	0.344	0.381	0.168	0.19	0.01	-0.01

Auditory evoked potential latency: P300 at fz, cz, and pz; N100 at fz and cz; P200 at fz and cz. (NCT02304432)
Timeframe: Baseline and Week 8 of DCS treatment

Brain Glycine/CR Ratio

Intervention	msec (Number)
	P300 at fz: Baseline	P300 at cz: Baseline	P300 at pz: Baseline	N100 at fz: Baseline	N100 at cz: Baseline	P200 at fz: Baseline	P200 at cz: Baseline	P300 at fz: Week 8 of DCS	P300 at cz: Week 8 of DCS	P300 at pz: Week 8 of DCS	N100 at fz: Week 8 of DCS	N100 at cz: Week 8 of DCS	P200 at fz: Week 8 of DCS	P200 at cz: Week 8 of DCS
First Open Label DCS	279.297	279.297	279.297	97.656	91.797	197.266	193.359	294.920	294.000	294	87.9	88.000	212.890	212.000

Proton magnetic resonance spectroscopy at 4T: brain glycine/CR ratio. Participants were assessed at baseline (pre-glycine challenge dose and 60, 80, 100 and 120 minutes post glycine dose) and in week 8 of of open-label DCS treatment: pre-DCS dose, and 60, 80, 100 and 120 minutes post DCS dose. Measured in posterior occipital cortex. (NCT02304432)
Timeframe: Baseline and Week 8 of DCS treatment

Brief Psychiatric Rating Scale (BPRS) Scores

Intervention	ratio (Median)
	Baseline	Baseline at 60 minutes	Baseline at 80 minutes	Baseline at 100 minutes	Baseline at 120 minutes	Week 8 of DCS: Baseline	Week 8 of DCS: 60 minutes	Week 8 of DCS: 80 minutes	Week 8 of DCS: 100 minutes	Week 8 of DCS: 120 minutes
Open Label DCS	0.41245	0.50375	0.65295	0.61505	0.8256	0.10977	0.248885	0.32609	0.32052	0.312155

Total BPRS score measures severity of 18 psychiatric symptoms. Each symptom is scored 1-7 with the total score ranging from 18-126. 18 means no symptoms and 126 means very severe symptoms. (NCT02304432)
Timeframe: Baseline & at 2, 4, 6 & 8 Weeks during open-label phase 1 and every 2 weeks up to 24 weeks during open label phase 2

Brief Psychiatric Rating Scale (BPRS) Scores

Intervention	units on a scale (Median)
	Baseline BPRS	2 weeks BPRS	4 weeks BPRS	6 weeks BPRS	8 weeks BPRS	10 weeks BPRS	12 weeks BPRS	14 weeks BPRS	16 weeks BPRS	18 weeks BPRS	20 weeks BPRS	22 weeks BPRS	24 weeks BPRS
First Open Label DCS	37	25	26	24	24.5	NA	NA	NA	NA	NA	NA	NA	NA
Second Open Label DCS	31.5	30.5	28	25.5	26	26.5	26	25.5	28.5	27	25	24.5	26.5

Total BPRS score measures severity of 18 psychiatric symptoms. Each symptom is scored 1-7 with the total score ranging from 18-126. 18 means no symptoms and 126 means very severe symptoms. (NCT02304432)
Timeframe: Baseline, 2, 4, & 6 weeks (crossover periods)

Clinical Global Impression (CGI) Severity Scores

Intervention	units on a scale (Number)
	Baseline BPRS for first intervention	2 weeks BPRS for first intervention	4 weeks BPRS for first intervention	6 weeks BPRS for first intervention	Baseline BPRS for second intervention	2 weeks BPRS for second intervention	4 weeks BPRS for second intervention	6 weeks BPRS for second intervention
DCS First, Then Placebo	26	25	25	26	39	45	45	38
Placebo First, Then DCS	29	35	33	35	36	30	27	28

CGI severity scores measure severity of mental illness on a scale of 1-7 where 1 means normal, not at all ill, 2 means borderline mentally ill, 3 means mildly ill, 4 means moderately ill, 5 means markedly ill, 6 means severely ill and 7 means among the most extremely ill patients. (NCT02304432)
Timeframe: Baseline & at 2, 4, 6 & 8 Weeks during open-label phase 1 and every 2 weeks up to 24 weeks during open label phase 2

Clinical Global Impression (CGI) Severity Scores

Intervention	units on a scale (Median)
	Baseline CGI	2 weeks CGI	4 weeks CGI	6 weeks CGI	8 weeks CGI	10 weeks CGI	12 weeks CGI	14 weeks CGI	16 weeks CGI	18 weeks CGI	20 weeks CGI	22 weeks CGI	24 weeks CGI
First Open Label DCS	4	2	2	2	2	NA	NA	NA	NA	NA	NA	NA	NA
Second Open Label DCS	2.5	2.5	2.5	2.5	2.5	3	2.5	2	2.5	2.5	2.5	2.5	2.5

Depression Symptom Scores

Intervention	units on a scale (Number)
	Baseline CGI for first intervention	2 weeks CGI for first intervention	4 weeks CGI for first intervention	6 weeks CGI for first intervention	Baseline CGI for second intervention	2 weeks CGI for second intervention	4 weeks CGI for second intervention	6 weeks CGI for second intervention
DCS First, Then Placebo	2	2	2	2	3	3	3	3
Placebo First, Then DCS	1	3	3	3	3	2	2	2

Hamilton Depression Scale (HAM) measures severity of depression symptoms. The sum of the ratings for 9 depression symptoms is measured on a scale of 0-2 with 0 meaning no depression symptoms and 2 meaning some level of severity of that specific symptom. The rating for one depression symptom is measured on a scale of 0-3 with 0 meaning no depression symptoms and 3 meaning a severe level of that specific symptom. The sum of ratings for 11 depression symptoms is measured on a scale of 0-4, with 0 meaning no symptoms and 4 meaning a severe level of that specific symptom. The three sums are added to produce an overall depression rating scale score ranging from 0-65. Higher scores indicate worse depression symptoms. (NCT02304432)
Timeframe: Baseline & at 2, 4, 6 & 8 Weeks during open-label phase 1 and every 2 weeks up to 24 weeks during open label phase 2

Depression Symptom Scores

Intervention	units on a scale (Median)
	Baseline HAM	2 weeks HAM	4 weeks HAM	6 weeks HAM	8 weeks HAM	10 weeks HAM	12 weeks HAM	14 weeks HAM	16 weeks HAM	18 weeks HAM	20 weeks HAM	22 weeks HAM	24 weeks HAM
First Open Label DCS	5	1.5	1	0.5	1.5	NA	NA	NA	NA	NA	NA	NA	NA
Second Open Label DCS	0.5	1	1	0	2.5	0	0	0	3.5	0	0	0	0

Mania Symptom Scores

Intervention	units on a scale (Number)
	Baseline HAM for first intervention	2 weeks HAM for first intervention	4 weeks HAM for first intervention	6 weeks HAM for first intervention	Baseline HAM for second intervention	2 weeks HAM for second intervention	4 weeks HAM for second intervention	6 weeks HAM for second intervention
DCS First, Then Placebo	0	1	0	0	2	12	9	2
Placebo First, Then DCS	4	5	2	10	0	0	0	0

Young Mania Rating Scale (YMRS) measures severity of manic symptoms. The sum of the ratings for 7 symptoms of mania is measured on a scale of 0-4 and the sumof 4 symptoms of mania is measured on a scale of 0-8 to yield a total score ranging from 0-60, with 0 meaning no manic symptoms and 60 meaning severe manic symptoms. (NCT02304432)
Timeframe: Baseline & at 2, 4, 6 & 8 Weeks during open-label phase 1 and every 2 weeks up to 24 weeks during open label phase 2

Mania Symptom Scores

Intervention	units on a scale (Median)
	Baseline YMRS	2 weeks YMRS	4 weeks YMRS	6 weeks YMRS	8 weeks YMRS	10 weeks YMRS	12 weeks YMRS	14 weeks YMRS	16 weeks YMRS	18 weeks YMRS	20 weeks YMRS	22 weeks YMRS	24 weeks YMRS
First Open Label DCS	2	1	1	0	0	NA	NA	NA	NA	NA	NA	NA	NA
Second Open Label DCS	0	0	0	0	0	0	0	0	0	0	0	0	1

Neurocognitive Function

Intervention	units on a scale (Number)
	Baseline YMRS for first intervention	2 weeks YMRS for first intervention	4 weeks YMRS for first intervention	6 weeks YMRS for first intervention	Baseline YMRS for second intervention	2 weeks YMRS for second intervention	4 weeks YMRS for second intervention	6 weeks YMRS for second intervention
DCS First, Then Placebo	0	0	0	0	0	0	0	0
Placebo First, Then DCS	1	0	0	0	4	1	1	1

Scores on each of 8 domains of cognitive function (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning/problem solving, social cognition, overall composite). Scores are T scores ranging from 0-100, with 50 representing the mean for a population based on a normal distribution, standard deviation of 10. Higher scores signify better functioning. (NCT02304432)
Timeframe: Baseline and Week 8 of open-label DCS treatment

Positive and Negative Symptom Scores

Intervention	T scores (Median)
	Baseline Processing Speed	Baseline Attention/Vigilance	Baseline Working Memory	Baseline Verbal Learning	Baseline Visual Learning	Baseline Reasoning/Problem Solving	Baseline Social Cognition	Baseline Overall Composite Score	Week 8 of open-label DCS Processing Speed	Week 8 of open-label DCS Attention/Vigilance	Week 8 of open-label DCS Working Memory	Week 8 of open-label DCS Verbal Learning	Week 8 of open-label DCS Visual Learning	Week 8 of open-label DCS Reasoning/Problem Solving	Week 8 of open-label DCS Social Cognition	Week 8 of open-label DCS Overall Composite Score
Open Label DCS	48.5	44.5	38.5	54	50.5	52.5	48	46.5	52.5	47.5	50.5	43.5	54.5	66.5	44.5	51.5

Positive and Negative Symptom Scale (PANSS) measures positive and negative symptoms of schizophrenia. The sum of ratings for seven positive symptoms is measured on a scale from 7-49 with 7 meaning no symptoms and 49 meaning severe symptoms.The sum of ratings for seven negative symptoms is measured on a scale from 7-49 with 7 meaning no symptoms and 49 meaning severe symptoms. (NCT02304432)
Timeframe: Baseline & at 2, 4, 6 & 8 Weeks during open-label phase 1 and every 2 weeks up to 24 weeks during open label phase 2

Positive and Negative Symptom Scores

Article	Year
A Potential Interface between the Kynurenine Pathway and Autonomic Imbalance in Schizophrenia. International journal of molecular sciences, 2021, Sep-16, Volume: 22, Issue:18 Topics: Animals; Autonomic Nervous System; Humans; Kynurenic Acid; Kynurenine; Schizophrenia	2021
Role and Perspectives of Inflammation and C-Reactive Protein (CRP) in Psychosis: An Economic and Widespread Tool for Assessing the Disease. International journal of molecular sciences, 2021, Dec-02, Volume: 22, Issue:23 Topics: Biomarkers; Blood-Brain Barrier; C-Reactive Protein; Humans; Inflammation; Kynurenine; Risk Factors;	2021
The tryptophan catabolite or kynurenine pathway in schizophrenia: meta-analysis reveals dissociations between central, serum, and plasma compartments. Molecular psychiatry, 2022, Volume: 27, Issue:9 Topics: Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Kynurenic Acid; Kynurenine; Quinolinic Acid; Schizophr	2022
Importance of the dysregulation of the kynurenine pathway on cognition in schizophrenia: a systematic review of clinical studies. European archives of psychiatry and clinical neuroscience, 2023, Volume: 273, Issue:6 Topics: Cognition; Humans; Kynurenic Acid; Kynurenine; Psychotic Disorders; Quality of Life; Schizophrenia	2023
Importance of the dysregulation of the kynurenine pathway on cognition in schizophrenia: a systematic review of clinical studies. European archives of psychiatry and clinical neuroscience, 2023, Volume: 273, Issue:6 Topics: Cognition; Humans; Kynurenic Acid; Kynurenine; Psychotic Disorders; Quality of Life; Schizophrenia	2023
Importance of the dysregulation of the kynurenine pathway on cognition in schizophrenia: a systematic review of clinical studies. European archives of psychiatry and clinical neuroscience, 2023, Volume: 273, Issue:6 Topics: Cognition; Humans; Kynurenic Acid; Kynurenine; Psychotic Disorders; Quality of Life; Schizophrenia	2023
Importance of the dysregulation of the kynurenine pathway on cognition in schizophrenia: a systematic review of clinical studies. European archives of psychiatry and clinical neuroscience, 2023, Volume: 273, Issue:6 Topics: Cognition; Humans; Kynurenic Acid; Kynurenine; Psychotic Disorders; Quality of Life; Schizophrenia	2023
Kynurenines and the Endocannabinoid System in Schizophrenia: Common Points and Potential Interactions. Molecules (Basel, Switzerland), 2019, Oct-15, Volume: 24, Issue:20 Topics: Animals; Biomarkers; Disease Susceptibility; Endocannabinoids; Humans; Kynurenine; Metabolic Network	2019
Effects of inflammation on the kynurenine pathway in schizophrenia - a systematic review. Journal of neuroinflammation, 2020, Feb-15, Volume: 17, Issue:1 Topics: Humans; Inflammation; Kynurenine; Psychotic Disorders; Schizophrenia	2020
Blood-based kynurenine pathway alterations in schizophrenia spectrum disorders: A meta-analysis. Schizophrenia research, 2020, Volume: 223 Topics: Aged; Humans; Kynurenic Acid; Kynurenine; Quinolinic Acid; Schizophrenia; Tryptophan	2020
The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a meta-analysis of 101 studies. Molecular psychiatry, 2021, Volume: 26, Issue:8 Topics: Bipolar Disorder; Depressive Disorder, Major; Humans; Kynurenic Acid; Kynurenine; Schizophrenia	2021
Dysregulation of kynurenine pathway and potential dynamic changes of kynurenine in schizophrenia: A systematic review and meta-analysis. Neuroscience and biobehavioral reviews, 2021, Volume: 123 Topics: Humans; Kynurenic Acid; Kynurenine; Quinolinic Acid; Schizophrenia; Tryptophan	2021
Access to the CNS: Biomarker Strategies for Dopaminergic Treatments. Pharmaceutical research, 2018, Feb-15, Volume: 35, Issue:3 Topics: Animals; Biomarkers; Disease Models, Animal; Dopamine Agents; Drug Development; Humans; Hypothalamo-	2018
Metabolomics in patients with psychosis: A systematic review. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 2018, Volume: 177, Issue:6 Topics: 3-Hydroxybutyric Acid; Aspartic Acid; Biomarkers; Bipolar Disorder; Creatine; Female; Glutamic Acid;	2018
Linking phencyclidine intoxication to the tryptophan-kynurenine pathway: Therapeutic implications for schizophrenia. Neurochemistry international, 2019, Volume: 125 Topics: Animals; Brain; Humans; Kynurenine; Phencyclidine; Schizophrenia; Signal Transduction; Tryptophan	2019
The kynurenine pathway in schizophrenia and bipolar disorder. Neuropharmacology, 2017, Volume: 112, Issue:Pt B Topics: Bipolar Disorder; Humans; Kynurenine; Metabolic Networks and Pathways; Schizophrenia	2017
Kynurenines, Gender and Neuroinflammation; Showcase Schizophrenia. Neurotoxicity research, 2016, Volume: 30, Issue:3 Topics: Animals; Humans; Kynurenine; Neuroimmunomodulation; Schizophrenia; Sex Characteristics	2016
Pharmacological manipulation of kynurenic acid: potential in the treatment of psychiatric disorders. CNS drugs, 2009, Volume: 23, Issue:2 Topics: Animals; Cognition Disorders; Excitatory Amino Acid Antagonists; Humans; Kynurenic Acid; Kynurenine;	2009
New promises for manipulation of kynurenine pathway in cancer and neurological diseases. Expert opinion on therapeutic targets, 2009, Volume: 13, Issue:2 Topics: Animals; Drug Delivery Systems; Drug Discovery; Humans; Huntington Disease; Indoleamine-Pyrrole 2,3,	2009
Cortical kynurenine pathway metabolism: a novel target for cognitive enhancement in Schizophrenia. Schizophrenia bulletin, 2010, Volume: 36, Issue:2 Topics: alpha7 Nicotinic Acetylcholine Receptor; Animals; Astrocytes; Cognition Disorders; Disease Models, A	2010
Cortical kynurenine pathway metabolism: a novel target for cognitive enhancement in Schizophrenia. Schizophrenia bulletin, 2010, Volume: 36, Issue:2 Topics: alpha7 Nicotinic Acetylcholine Receptor; Animals; Astrocytes; Cognition Disorders; Disease Models, A	2010
Cortical kynurenine pathway metabolism: a novel target for cognitive enhancement in Schizophrenia. Schizophrenia bulletin, 2010, Volume: 36, Issue:2 Topics: alpha7 Nicotinic Acetylcholine Receptor; Animals; Astrocytes; Cognition Disorders; Disease Models, A	2010
Cortical kynurenine pathway metabolism: a novel target for cognitive enhancement in Schizophrenia. Schizophrenia bulletin, 2010, Volume: 36, Issue:2 Topics: alpha7 Nicotinic Acetylcholine Receptor; Animals; Astrocytes; Cognition Disorders; Disease Models, A	2010
Kynurenine pathway in schizophrenia: pathophysiological and therapeutic aspects. Current pharmaceutical design, 2011, Volume: 17, Issue:2 Topics: Animals; Anti-Inflammatory Agents; Antipsychotic Agents; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenas	2011
Bridging the gap between the immune and glutamate hypotheses of schizophrenia and major depression: Potential role of glial NMDA receptor modulators and impaired blood-brain barrier integrity. The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, 2012, Volume: 13, Issue:7 Topics: Blood-Brain Barrier; Depressive Disorder, Major; Glutamic Acid; Humans; Inflammation; Kynurenine; Ne	2012
Immunological treatment options for schizophrenia. Current pharmaceutical biotechnology, 2012, Volume: 13, Issue:8 Topics: Animals; Antipsychotic Agents; Astrocytes; Cyclooxygenase 2 Inhibitors; Humans; Kynurenine; Microgli	2012
Kynurenines: from the perspective of major psychiatric disorders. The FEBS journal, 2012, Volume: 279, Issue:8 Topics: Animals; Bipolar Disorder; Depressive Disorder, Major; Humans; Kynurenine; Schizophrenia	2012
Inflammation in schizophrenia. Advances in protein chemistry and structural biology, 2012, Volume: 88 Topics: Antipsychotic Agents; Brain; Humans; Inflammation; Kynurenine; Macrophages; Microglia; Monocytes; Sc	2012
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Kynurenines in neurodegenerative disorders: therapeutic consideration. Advances in experimental medicine and biology, 2004, Volume: 541 Topics: AIDS Dementia Complex; Animals; Central Nervous System Diseases; Down Syndrome; Enzyme Inhibitors; H	2004
Kynurenic acid antagonists and kynurenine pathway inhibitors. Expert opinion on investigational drugs, 2001, Volume: 10, Issue:4 Topics: Brain Ischemia; Epilepsy; Excitatory Amino Acid Antagonists; Humans; Kynurenic Acid; Kynurenine; Neu	2001
The role of amines in the etiology of schizophrenia. Comprehensive psychiatry, 1968, Volume: 9, Issue:2 Topics: Adrenochrome; Amines; Amphetamine; Brain Chemistry; Dopamine; Epinephrine; Humans; Indoles; Kynureni	1968

Article	Year
Tryptophan challenge in individuals with schizophrenia and healthy controls: acute effects on circulating kynurenine and kynurenic acid, cognition and cerebral blood flow. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2023, Volume: 48, Issue:11 Topics: Animals; Cerebrovascular Circulation; Cognition; Cross-Over Studies; Humans; Kynurenic Acid; Kynuren	2023
Kynurenine pathway in schizophrenia: Galantamine-memantine combination for cognitive impairments. Schizophrenia research, 2018, Volume: 193 Topics: Adolescent; Adult; Cognitive Dysfunction; Drug Therapy, Combination; Female; Galantamine; Humans; Ky	2018
Cytokine changes and tryptophan metabolites in medication-naïve and medication-free schizophrenic patients. Neuropsychobiology, 2009, Volume: 59, Issue:2 Topics: Adult; Antipsychotic Agents; Cytokines; Female; Humans; Kynurenine; Male; Schizophrenia; Time Factor	2009
3-Hydroxykynurenine and clinical symptoms in first-episode neuroleptic-naive patients with schizophrenia. The international journal of neuropsychopharmacology, 2011, Volume: 14, Issue:6 Topics: Adolescent; Adult; Antipsychotic Agents; Brief Psychiatric Rating Scale; Chromatography, High Pressu	2011
A multidimensional approach to analysis of cerebrospinal fluid biogenic amines in schizophrenia: I. Comparisons with healthy control subjects and neuroleptic-treated/unmedicated pairs analyses. Psychiatry research, 1994, Volume: 52, Issue:3 Topics: Adult; Biogenic Amines; Chromatography, High Pressure Liquid; Chronic Disease; Dopamine; Double-Blin	1994
A multidimensional approach to analysis of cerebrospinal fluid biogenic amines in schizophrenia: II. Correlations with psychopathology. Psychiatry research, 1994, Volume: 52, Issue:3 Topics: Adult; Biogenic Amines; Dopamine; Double-Blind Method; Female; Haloperidol; Humans; Kynurenine; Male	1994
A controlled study of tryptophan-benserazide in schizophrenia. Communications in psychopharmacology, 1978, Volume: 2, Issue:1 Topics: Adult; Aged; Benserazide; Chlorpromazine; Clinical Trials as Topic; Double-Blind Method; Drug Therap	1978

Article	Year
Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology. Journal of neuroinflammation, 2021, Sep-12, Volume: 18, Issue:1 Topics: Cerebellum; Humans; Kynurenic Acid; Kynurenine; Prefrontal Cortex; Schizophrenia	2021
The immune-kynurenine pathway in social anxiety disorder. Brain, behavior, and immunity, 2022, Volume: 99 Topics: Female; Humans; Kynurenic Acid; Kynurenine; Male; Phobia, Social; Schizophrenia; Tryptophan	2022
Serum kynurenine metabolites might not be associated with risk factors of treatment-resistant schizophrenia. Journal of psychiatric research, 2022, Volume: 145 Topics: Diffusion Tensor Imaging; Humans; Kynurenic Acid; Kynurenine; Risk Factors; Schizophrenia; Schizophr	2022
Kynurenine pathway metabolites and therapeutic response to olanzapine in female patients with schizophrenia: A longitudinal study. CNS neuroscience & therapeutics, 2022, Volume: 28, Issue:10 Topics: Antipsychotic Agents; Benzodiazepines; Chromatography, Liquid; Female; Humans; Kynurenine; Longitudi	2022
Elevated salivary kynurenic acid levels related to enlarged choroid plexus and severity of clinical phenotypes in treatment-resistant schizophrenia. Brain, behavior, and immunity, 2022, Volume: 106 Topics: Antipsychotic Agents; Choroid Plexus; Humans; Kynurenic Acid; Kynurenine; Phenotype; Schizophrenia;	2022
Direct Fluorescence Evaluation of d-Amino Acid Oxidase Activity Using a Synthetic d-Kynurenine Derivative. Analytical chemistry, 2022, 10-25, Volume: 94, Issue:42 Topics: Animals; D-Amino-Acid Oxidase; Fluorometry; Kynurenic Acid; Kynurenine; Schizophrenia; Swine	2022
[Cinnabarinic acid as a potential prognostic marker of schizophrenia]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 2022, Volume: 122, Issue:12 Topics: 3-Hydroxyanthranilic Acid; Female; Humans; Kynurenine; Oxazines; Prognosis; Schizophrenia	2022
The association between inflammation and kynurenine pathway metabolites in electroconvulsive therapy for schizophrenia: Implications for clinical efficacy. Brain, behavior, and immunity, 2023, Volume: 113 Topics: Electroconvulsive Therapy; Humans; Interleukin-18; Kynurenic Acid; Kynurenine; RNA, Messenger; Schiz	2023
Transplantation of microbiota from drug-free patients with schizophrenia causes schizophrenia-like abnormal behaviors and dysregulated kynurenine metabolism in mice. Molecular psychiatry, 2020, Volume: 25, Issue:11 Topics: Animals; Case-Control Studies; Dopamine; Fecal Microbiota Transplantation; Gastrointestinal Microbio	2020
Preliminary comparative analysis of kynurenine pathway metabolites in chronic ketamine users, schizophrenic patients, and healthy controls. Human psychopharmacology, 2020, Volume: 35, Issue:4 Topics: Adult; Case-Control Studies; Chromatography, High Pressure Liquid; Female; Humans; Ketamine; Kynuren	2020
The Trace Kynurenine, Cinnabarinic Acid, Displays Potent Antipsychotic-Like Activity in Mice and Its Levels Are Reduced in the Prefrontal Cortex of Individuals Affected by Schizophrenia. Schizophrenia bulletin, 2020, 12-01, Volume: 46, Issue:6 Topics: Adult; Animals; Antipsychotic Agents; Behavior, Animal; Cells, Cultured; Disease Models, Animal; Ele	2020
Exposure to elevated embryonic kynurenine in rats: Sex-dependent learning and memory impairments in adult offspring. Neurobiology of learning and memory, 2020, Volume: 174 Topics: Animals; Brain; Disease Models, Animal; Female; Kynurenine; Male; Memory; Rats, Wistar; Schizophreni	2020
Association of the kynurenine pathway metabolites with clinical, cognitive features and IL-1β levels in patients with schizophrenia spectrum disorder and their siblings. Schizophrenia research, 2021, Volume: 229 Topics: Cognition; Humans; Kynurenic Acid; Kynurenine; Schizophrenia; Siblings	2021
Effects of neuroactive metabolites of the tryptophan pathway on working memory and cortical thickness in schizophrenia. Translational psychiatry, 2021, 04-01, Volume: 11, Issue:1 Topics: Humans; Kynurenic Acid; Kynurenine; Memory, Short-Term; Quinolinic Acid; Schizophrenia; Tryptophan	2021
Autoimmune Concept of Schizophrenia: Historical Roots and Current Facets. Psychiatria Danubina, 2021,Spring, Volume: 33, Issue:1 Topics: Antipsychotic Agents; Humans; Kynurenic Acid; Kynurenine; Psychotic Disorders; Schizophrenia	2021
Quinolinic acid is associated with cognitive deficits in schizophrenia but not major depressive disorder. Scientific reports, 2021, 05-11, Volume: 11, Issue:1 Topics: Adult; Case-Control Studies; Cognition; Cognitive Dysfunction; Depressive Disorder, Major; Female; H	2021
The kynurenine pathway in schizophrenia and other mental disorders: Insight from meta-analyses on the peripheral blood levels of tryptophan and related metabolites. Schizophrenia research, 2021, Volume: 232 Topics: Bipolar Disorder; Humans; Kynurenic Acid; Kynurenine; Schizophrenia; Tryptophan	2021
Serum kynurenic acid is reduced in affective psychosis. Translational psychiatry, 2017, 05-02, Volume: 7, Issue:5 Topics: Adult; Affective Disorders, Psychotic; Bipolar Disorder; Corpus Striatum; Cytokines; Depression; Dep	2017
The inhibition of the kynurenine pathway prevents behavioral disturbances and oxidative stress in the brain of adult rats subjected to an animal model of schizophrenia. Progress in neuro-psychopharmacology & biological psychiatry, 2018, Feb-02, Volume: 81 Topics: Animals; Antipsychotic Agents; Brain; Disease Models, Animal; Enzyme Inhibitors; Indoleamine-Pyrrole	2018
Prenatal kynurenine treatment in rats causes schizophrenia-like broad monitoring deficits in adulthood. Psychopharmacology, 2018, Volume: 235, Issue:3 Topics: Age Factors; Animals; Attention; Brain; Cognition; Cognition Disorders; Female; Kynurenine; Locomoti	2018
Kynurenine is correlated with IL-1β in plasma of schizophrenia patients. Journal of neural transmission (Vienna, Austria : 1996), 2018, Volume: 125, Issue:5 Topics: Adult; Female; Humans; Interleukin-1beta; Kynurenine; Male; Schizophrenia; Tryptophan	2018
Influence of plasma cytokines on kynurenine and kynurenic acid in schizophrenia. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2018, Volume: 43, Issue:8 Topics: Adolescent; Adult; Cytokines; Female; Humans; Kynurenic Acid; Kynurenine; Male; Middle Aged; Psychot	2018
Importance of kynurenine 3-monooxygenase for spontaneous firing and pharmacological responses of midbrain dopamine neurons: Relevance for schizophrenia. Neuropharmacology, 2018, Volume: 138 Topics: Action Potentials; Animals; Antipsychotic Agents; Dopaminergic Neurons; Dose-Response Relationship,	2018
The Effects of Tryptophan Catabolites on Negative Symptoms and Deficit Schizophrenia are Partly Mediated by Executive Impairments: Results of Partial Least Squares Path Modeling. CNS & neurological disorders drug targets, 2018, Volume: 17, Issue:6 Topics: Adolescent; Adult; Aged; Analysis of Variance; Cognition Disorders; Executive Function; Female; Huma	2018
Maternal genotype determines kynurenic acid levels in the fetal brain: Implications for the pathophysiology of schizophrenia. Journal of psychopharmacology (Oxford, England), 2018, Volume: 32, Issue:11 Topics: Animals; Brain; Cognitive Dysfunction; Female; Genotype; Kynurenic Acid; Kynurenine; Kynurenine 3-Mo	2018
Serum xanthurenic acid levels: Reduced in subjects at ultra high risk for psychosis. Schizophrenia research, 2019, Volume: 208 Topics: Adolescent; Adult; Disease Progression; Female; Humans; Hydroxyindoleacetic Acid; Kynurenic Acid; Ky	2019
Metabolic dysfunctions in the kynurenine pathway, noradrenergic and purine metabolism in schizophrenia and bipolar disorders. Psychological medicine, 2020, Volume: 50, Issue:4 Topics: Adolescent; Adult; Bipolar Disorder; Female; Humans; Kynurenine; Male; Metabolic Networks and Pathwa	2020
Dysregulation of kynurenine metabolism is related to proinflammatory cytokines, attention, and prefrontal cortex volume in schizophrenia. Molecular psychiatry, 2020, Volume: 25, Issue:11 Topics: Adult; Attention; Cytokines; Female; Humans; Inflammation Mediators; Kynurenic Acid; Kynurenine; Mal	2020
Plasma xanthurenic acid in a context of insulin resistance and obesity in schizophrenia. Schizophrenia research, 2019, Volume: 211 Topics: Case-Control Studies; Humans; Insulin Resistance; Kynurenic Acid; Kynurenine; Obesity; Schizophrenia	2019
Activation of kynurenine pathway in ex vivo fibroblasts from patients with bipolar disorder or schizophrenia: cytokine challenge increases production of 3-hydroxykynurenine. Journal of psychiatric research, 2013, Volume: 47, Issue:11 Topics: Adult; Bipolar Disorder; Cells, Cultured; Cytokines; Female; Fibroblasts; Gene Expression Regulation	2013
Effect of maternal immune activation on the kynurenine pathway in preadolescent rat offspring and on MK801-induced hyperlocomotion in adulthood: amelioration by COX-2 inhibition. Brain, behavior, and immunity, 2014, Volume: 41 Topics: Animals; Brain; Celecoxib; Cyclooxygenase 2 Inhibitors; Disease Models, Animal; Dizocilpine Maleate;	2014
[A study of IL-1Β and IDO gene polymorphisms in patients with schizophrenia]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 2014, Volume: 114, Issue:5 Topics: Adult; Alleles; Female; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Interleukin-1beta; Kynurenine;	2014
Elevated levels of kynurenic acid during gestation produce neurochemical, morphological, and cognitive deficits in adulthood: implications for schizophrenia. Neuropharmacology, 2015, Volume: 90 Topics: alpha7 Nicotinic Acetylcholine Receptor; Animals; Attention; Brain; Cognition; Dendritic Spines; Die	2015
Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia--significance for activation of the kynurenine pathway. Journal of psychiatry & neuroscience : JPN, 2015, Volume: 40, Issue:2 Topics: Adult; Astrocytes; Cells, Cultured; Cerebral Cortex; Chronic Disease; Female; Humans; Interleukin-6;	2015
Combined Toxoplasma gondii seropositivity and high blood kynurenine--Linked with nonfatal suicidal self-directed violence in patients with schizophrenia. Journal of psychiatric research, 2016, Volume: 72 Topics: Adult; Female; Humans; Kynurenine; Male; Odds Ratio; Schizophrenia; Self-Injurious Behavior; Suicide	2016
Xanthurenic Acid Activates mGlu2/3 Metabotropic Glutamate Receptors and is a Potential Trait Marker for Schizophrenia. Scientific reports, 2015, Dec-08, Volume: 5 Topics: Adult; Aged; Animals; Biomarkers; Brain; Case-Control Studies; Female; HEK293 Cells; Humans; Kynuren	2015
Multiprobe molecular imaging of an NMDA receptor hypofunction rat model for glutamatergic dysfunction. Psychiatry research. Neuroimaging, 2016, Feb-28, Volume: 248 Topics: Animals; Brain; Disease Models, Animal; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Glut	2016
Tryptophan Metabolism and White Matter Integrity in Schizophrenia. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016, Volume: 41, Issue:10 Topics: Adult; Analysis of Variance; Anisotropy; Diffusion Tensor Imaging; Female; Glutamic Acid; Humans; Ky	2016
Inhibition of Large Neutral Amino Acid Transporters Suppresses Kynurenic Acid Production Via Inhibition of Kynurenine Uptake in Rodent Brain. Neurochemical research, 2016, Volume: 41, Issue:9 Topics: alpha7 Nicotinic Acetylcholine Receptor; Amino Acid Transport Systems, Neutral; Animals; Brain; Kynu	2016
Kynurenine and Tryptophan Levels in Patients With Schizophrenia and Elevated Antigliadin Immunoglobulin G Antibodies. Psychosomatic medicine, 2016, Volume: 78, Issue:8 Topics: Adult; Female; Gliadin; Humans; Immunoglobulin G; Kynurenine; Male; Middle Aged; Schizophrenia; Tryp	2016
Prenatal kynurenine exposure in rats: age-dependent changes in NMDA receptor expression and conditioned fear responding. Psychopharmacology, 2016, Volume: 233, Issue:21-22 Topics: Age Factors; alpha7 Nicotinic Acetylcholine Receptor; Animals; Brain; Cognition; Conditioning, Psych	2016
Pilot study examining the relationship of childhood trauma, perceived stress, and medication use to serum kynurenic acid and kynurenine levels in schizophrenia. Schizophrenia research, 2017, Volume: 185 Topics: Adult; Adult Survivors of Child Abuse; Antipsychotic Agents; Female; Humans; Kynurenic Acid; Kynuren	2017
Correlations of Kynurenic Acid, 3-Hydroxykynurenine, sIL-2R, IFN-α, and IL-4 with Clinical Symptoms During Acute Relapse of Schizophrenia. Neurotoxicity research, 2017, Volume: 32, Issue:1 Topics: Adult; Antipsychotic Agents; Clozapine; Female; Humans; Interferon-alpha; Interleukin-4; Kynurenic A	2017
Kynurenine pathway in psychosis: evidence of increased tryptophan degradation. Journal of psychopharmacology (Oxford, England), 2009, Volume: 23, Issue:3 Topics: Adult; Chromatography, High Pressure Liquid; Enzyme-Linked Immunosorbent Assay; Female; Humans; Indo	2009
Elevated levels of kynurenic acid change the dopaminergic response to amphetamine: implications for schizophrenia. The international journal of neuropsychopharmacology, 2009, Volume: 12, Issue:4 Topics: Animals; Brain Chemistry; Data Interpretation, Statistical; Dextroamphetamine; Dopamine; Dopamine Up	2009
The evolution of schizophrenia: a model for selection by infection, with a focus on NAD. Current pharmaceutical design, 2009, Volume: 15, Issue:1 Topics: Biological Evolution; Humans; Kynurenine; Models, Biological; NAD; Schizophrenia; Selection, Genetic	2009
Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia. Molecular psychiatry, 2010, Volume: 15, Issue:9 Topics: Adolescent; Adult; Antipsychotic Agents; Female; Humans; Hydroxyindoleacetic Acid; Kynurenine; Male;	2010
Two complex genotypes relevant to the kynurenine pathway and melanotropin function show association with schizophrenia and bipolar disorder. Schizophrenia research, 2009, Volume: 113, Issue:2-3 Topics: Adult; Aged; Aged, 80 and over; Bipolar Disorder; Black or African American; Databases, Genetic; Fem	2009
The astrocyte-derived alpha7 nicotinic receptor antagonist kynurenic acid controls extracellular glutamate levels in the prefrontal cortex. Journal of molecular neuroscience : MN, 2010, Volume: 40, Issue:1-2 Topics: alpha7 Nicotinic Acetylcholine Receptor; Animals; Astrocytes; Cholinesterase Inhibitors; Enzyme Inhi	2010
Cerebrospinal fluid analysis in affective and schizophrenic spectrum disorders: identification of subgroups with immune responses and blood-CSF barrier dysfunction. Journal of psychiatric research, 2010, Volume: 44, Issue:5 Topics: Adult; Cohort Studies; Female; Humans; Immunoglobulins; International Classification of Diseases; Ky	2010
Increased levels of kynurenine and kynurenic acid in the CSF of patients with schizophrenia. Schizophrenia bulletin, 2012, Volume: 38, Issue:3 Topics: Adult; Antipsychotic Agents; Benzodiazepines; Humans; Kynurenic Acid; Kynurenine; Male; Middle Aged;	2012
Neuronal-immune interactions in mediating stress effects in the etiology and course of schizophrenia: role of the amygdala in developmental co-ordination. Medical hypotheses, 2011, Volume: 76, Issue:1 Topics: Amygdala; Humans; Hydrocortisone; Kynurenine; Schizophrenia; Stress, Psychological	2011
Impaired kynurenine pathway metabolism in the prefrontal cortex of individuals with schizophrenia. Schizophrenia bulletin, 2011, Volume: 37, Issue:6 Topics: Adult; Aged; Animals; Antipsychotic Agents; Case-Control Studies; Female; Humans; Kynurenine; Kynure	2011
Exposure to kynurenic acid during adolescence produces memory deficits in adulthood. Schizophrenia bulletin, 2012, Volume: 38, Issue:4 Topics: alpha7 Nicotinic Acetylcholine Receptor; Animals; Excitatory Amino Acid Antagonists; Fear; Kynurenic	2012
Reversal of imbalance between kynurenic acid and 3-hydroxykynurenine by antipsychotics in medication-naïve and medication-free schizophrenic patients. Brain, behavior, and immunity, 2011, Volume: 25, Issue:8 Topics: Adult; Algorithms; Antipsychotic Agents; Chromatography, High Pressure Liquid; Diagnostic and Statis	2011
Inhibition of D-amino acid oxidase activity by antipsychotic drugs evaluated by a fluorometric assay using D-kynurenine as substrate. Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 2011, Volume: 131, Issue:7 Topics: Antipsychotic Agents; Chlorpromazine; D-Amino-Acid Oxidase; Dibenzothiazepines; Dose-Response Relati	2011
Acute elevations of brain kynurenic acid impair cognitive flexibility: normalization by the alpha7 positive modulator galantamine. Psychopharmacology, 2012, Volume: 220, Issue:3 Topics: alpha7 Nicotinic Acetylcholine Receptor; Animals; Brain; Cognition; Cognition Disorders; Disease Mod	2012
Regulation of GABAergic inputs to CA1 pyramidal neurons by nicotinic receptors and kynurenic acid. The Journal of pharmacology and experimental therapeutics, 2012, Volume: 341, Issue:2 Topics: Aconitine; alpha7 Nicotinic Acetylcholine Receptor; Animals; Bungarotoxins; CA1 Region, Hippocampal;	2012
Development and validation of a single analytical method for the determination of tryptophan, and its kynurenine metabolites in rat plasma. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2012, Jun-01, Volume: 898 Topics: 3-Hydroxyanthranilic Acid; Animals; Charcoal; Chromatography, High Pressure Liquid; Depression; Kynu	2012
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INVESTIGATIONS ON THE TRYPTOPHANE METABOLISM (VIA KYNURENINE) IN SCHIZOPHRENIC PATIENTS. Acta psychiatrica Scandinavica, 1964, Volume: 40, Issue:3 Topics: Amino Acids; Humans; Kynurenine; Schizophrenia; Tryptophan; Urine; Xanthurenates	1964
Expression of the kynurenine pathway enzyme tryptophan 2,3-dioxygenase is increased in the frontal cortex of individuals with schizophrenia. Neurobiology of disease, 2004, Volume: 15, Issue:3 Topics: Adult; Aged; Blotting, Western; Dioxygenases; Enzyme-Linked Immunosorbent Assay; Female; Frontal Lob	2004
Upregulation of the initiating step of the kynurenine pathway in postmortem anterior cingulate cortex from individuals with schizophrenia and bipolar disorder. Brain research, 2006, Feb-16, Volume: 1073-1074 Topics: Adult; Analysis of Variance; Bipolar Disorder; Chromatography, High Pressure Liquid; Demography; Dep	2006
Tryptophan breakdown pathway in bipolar mania. Journal of affective disorders, 2007, Volume: 102, Issue:1-3 Topics: Adult; Aspartic Acid; Bipolar Disorder; Brief Psychiatric Rating Scale; Female; Gyrus Cinguli; Human	2007
Determination of kynurenine levels in rat plasma by high-performance liquid chromatography with pre-column fluorescence derivatization. Analytica chimica acta, 2007, Feb-19, Volume: 584, Issue:2 Topics: Animals; Chromatography, High Pressure Liquid; Fluorescence; Ketamine; Kynurenine; Male; Rats; Rats,	2007
Alterations in kynurenine precursor and product levels in schizophrenia and bipolar disorder. Neurochemistry international, 2008, Volume: 52, Issue:6 Topics: 3-Hydroxyanthranilic Acid; Adult; Biomarkers; Bipolar Disorder; Brain; Chromatography, High Pressure	2008
Increased cortical kynurenate content in schizophrenia. Biological psychiatry, 2001, Oct-01, Volume: 50, Issue:7 Topics: Adult; Aged; Aged, 80 and over; Animals; Antipsychotic Agents; Female; Frontal Lobe; Haloperidol; Hu	2001
Monoamine mechanisms in chronic schizophrenia: post-mortem neurochemical findings. The British journal of psychiatry : the journal of mental science, 1979, Volume: 134 Topics: Aged; Brain Chemistry; Catechol O-Methyltransferase; Chronic Disease; Dopamine; Dopamine beta-Hydrox	1979
Brain tryptophan metabolism in schizophrenia: a post mortem study of metabolites of the serotonin and kynurenine pathways in schizophrenic and control subjects. Psychopharmacology, 1979, Apr-25, Volume: 62, Issue:3 Topics: Aged; Aging; Brain; Female; Humans; Hydroxyindoleacetic Acid; Kynurenine; Male; Middle Aged; Myocard	1979
Relationship of dietary tryptophan and niacin to tryptophan metabolism in schizophrenics and nonschizophrenics. The American journal of clinical nutrition, 1974, Volume: 27, Issue:6 Topics: Acetates; Aminohippuric Acids; Diet; Female; Humans; Hydroxyindoleacetic Acid; Indican; Indoles; Kyn	1974

Intervention	units on a scale (Median)
	Baseline positive	Baseline negative	2 weeks positive	2 weeks negative	4 weeks positive	4 weeks negative	6 weeks positive	6 weeks negative	8 weeks positive	8 weeks negative	10 weeks positive	10 weeks negative	12 weeks positive	12 weeks negative	14 weeks positive	14 weeks negative	16 weeks positive	16 weeks negative	18 weeks positive	18 weeks negative	20 weeks positive	20 weeks negative	22 weeks positive	22 weeks negative	24 weeks positive	24 weeks negative
First Open Label DCS	14.5	14.5	10	12	10.5	12	9	12	9	12	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
Second Open Label DCS	11	14	11	14	10.5	13.5	9	13	9.5	12	10.5	13	11	12	10	12	10.5	12	10.5	12	10.5	12	9.5	12	10	12

Intervention	units on a scale (Number)
	Baseline positive for first intervention	Baseline negative symptoms for first intervention	2 weeks positive for first intervention	2 weeks negative for first intervention	4 weeks positive for first intervention	4 weeks negative for first intervention	6 weeks positive for first intervention	6 weeks negative for first intervention	Baseline positive for second intervention	Baseline negative for second intervention	2 weeks positive for second intervention	2 weeks negative for second intervention	4 weeks positive for second intervention	4 weeks negative for second intervention	6 weeks positive for second intervention	6 weeks negative for second intervention
DCS First, Then Placebo	10	15	10	15	10	15	10	15	15	18	15	18	15	18	14	18
Placebo First, Then DCS	11	9	12	15	11	13	13	13	13	13	10	11	9	11	9	11

kynurenine and Schizophrenia

Research Excerpts

Research

Studies (104)

Authors

Clinical Trials (8)

Trial Overview

Trial Outcomes

Change in Level of Cognition

Free Tryptophan (TRP)

KYN/TRP

KYNA/KYN

Kynurenic Acid (KYNA)

Kynurenine (KYN)

PIC/KYN

Picolinic Acid (PIC)

Auditory Evoked Potentials - P50 Ratio (P50 S2/P50 S1 Amplitude) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT

Auditory Evoked Potentials in Amplitude (Degrees Measured in Microvolts) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT

Auditory Evoked Potentials in Gammas Oscillations (the Power Spectrum is Measured in Microvolts Squared) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT

Auditory Evoked Potentials in Latency (Msec) at BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF TREATMENT WITH GLYCINE

Brain GABA Metabolite Levels (GABA/Creatine Ratio: GABA/Cr) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT

Brain Glutamate Metabolite Levels (Glutamate/Creatine Ratio: Glu/Cr) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT

Brain Glycine/CR Ratio

Brief Psychiatric Rating Scale (BPRS) Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks Positive and Negative Symptom Scores at Baseline and at 2, 4, and 6 Weeks During Intervention 1, Intervention 2, and During Open-label Glycine

Clinical Global Impression (CGI) Severity Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks Within Each Treatment Period

Clinical Global Impression (CGI) Therapeutic Effect Scores at 2 Weeks, 4 Weeks, and 6 Weeks Within Each Treatment Period

Depression Symptom Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks Within Each Treatment Period

Glycine Plasma Amino Acid Levels at Baseline, During Glycine Treatment, During Placebo Treatment and During Open-label Glycine

Mania Symptom Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks Within Each Treatment Period

Neurocognitive Function at Baseline, During Glycine Treatment, During Placebo Treatment and During Open-label Glycine

Positive and Negative Symptom Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks During Intervention 1 (Glycine or Placebo), Intervention 2 (Glycine or Placebo), and During Open-label Glycine

Auditory Evoked Potentials - P50 Ratio (P50 S2/S1) (Amplitude)

Auditory Evoked Potentials in Amplitude (Degrees Measured in Microvolts)

Auditory Evoked Potentials in Gamma Oscillations (the Power Spectrum is Measured in Microvolts Squared)

Auditory Evoked Potentials in Latency (Msec)

Brain Glycine/CR Ratio

Brief Psychiatric Rating Scale (BPRS) Scores

Brief Psychiatric Rating Scale (BPRS) Scores

Clinical Global Impression (CGI) Severity Scores

Clinical Global Impression (CGI) Severity Scores

Depression Symptom Scores

Depression Symptom Scores

Mania Symptom Scores

Mania Symptom Scores

Neurocognitive Function

Positive and Negative Symptom Scores

Positive and Negative Symptom Scores

Reviews

Trials

Other Studies