kynurenine has been researched along with Cognition Disorders in 17 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.
Cognition Disorders: Disorders characterized by disturbances in mental processes related to learning, thinking, reasoning, and judgment.
| Excerpt | Relevance | Reference |
|---|---|---|
| "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) |
| "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) |
| "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) |
| "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) |
| " Low xanthurenic acid occurred in both AD and with aging." | 3.85 | Kynurenine Pathway Metabolites in Alzheimer's Disease. ( Advani, R; Giil, LM; Midttun, Ø; Refsum, H; Smith, AD; Ueland, PM; Ulvik, A, 2017) |
| "Activation of indoleamine 2,3-dioxygenase (IDO) and higher concentrations of several kynurenine metabolites have been observed post-stroke, where they have been associated with increased mortality." | 3.77 | The relationship between indoleamine 2,3-dioxygenase activity and post-stroke cognitive impairment. ( Aviv, RI; Black, SE; Gold, AB; Herrmann, N; Kiss, A; Lanctôt, KL; Swardfager, W; Tennen, G, 2011) |
| "Chronic inflammation has been shown to contribute to the development of a wide variety of disorders by means of a number of proposed mechanisms." | 2.50 | The common inflammatory etiology of depression and cognitive impairment: a therapeutic target. ( Allison, DJ; Ditor, DS, 2014) |
| "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) |
| Timeframe | Studies, this research(%) | All Research% |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 2 (11.76) | 29.6817 |
| 2010's | 15 (88.24) | 24.3611 |
| 2020's | 0 (0.00) | 2.80 |
| Authors | Studies |
|---|---|
| Giil, LM | 1 |
| Midttun, Ø | 1 |
| Refsum, H | 1 |
| Ulvik, A | 1 |
| Advani, R | 1 |
| Smith, AD | 1 |
| Ueland, PM | 1 |
| Hahn, B | 1 |
| Reneski, CH | 1 |
| Pocivavsek, A | 3 |
| Schwarcz, R | 5 |
| Kanchanatawan, B | 1 |
| Maes, M | 1 |
| Wissmann, P | 1 |
| Geisler, S | 1 |
| Leblhuber, F | 1 |
| Fuchs, D | 1 |
| Stone, TW | 1 |
| Darlington, LG | 1 |
| Thomas, MA | 1 |
| Elmer, GI | 2 |
| Bruno, JP | 3 |
| Allison, DJ | 1 |
| Ditor, DS | 1 |
| Yi, SQ | 1 |
| Yang, M | 1 |
| Duan, KM | 1 |
| Zádori, D | 1 |
| Veres, G | 1 |
| Szalárdy, L | 1 |
| Klivényi, P | 1 |
| Fülöp, F | 1 |
| Toldi, J | 1 |
| Vécsei, L | 1 |
| Erhardt, S | 1 |
| Olsson, SK | 1 |
| Engberg, G | 1 |
| Wonodi, I | 1 |
| Gold, AB | 1 |
| Herrmann, N | 1 |
| Swardfager, W | 1 |
| Black, SE | 1 |
| Aviv, RI | 1 |
| Tennen, G | 1 |
| Kiss, A | 1 |
| Lanctôt, KL | 1 |
| Alexander, KS | 1 |
| Wu, HQ | 2 |
| Kandanearatchi, A | 1 |
| Brew, BJ | 1 |
| Schwarz, MJ | 1 |
| Guillemin, GJ | 1 |
| Teipel, SJ | 1 |
| Buerger, K | 1 |
| Hampel, H | 1 |
| Oxenkrug, GF | 1 |
| Trial | Phase | Enrollment | Study Type | Start Date | Status | ||
|---|---|---|---|---|---|---|---|
| Assessing the Efficacy of Transcutaneous Auricular Vagus Nerve Stimulation as an Anti-inflammatory Treatment Following Spinal Cord Injury[NCT05730049] | 30 participants (Anticipated) | Interventional | 2023-04-30 | Not yet 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 | ||
| [information is prepared from clinicaltrials.gov, extracted Sep-2024] | |||||||
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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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
| 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)
| 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
| 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 |
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, 2, 4, & 6 weeks (crossover periods)
| 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
| 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 |
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, 2, 4, & 6 weeks (crossover periods)
| 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
| 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 |
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, 2, 4, & 6 weeks (crossover periods)
| 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
| 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
| 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 |
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, 2, 4, & 6 weeks (crossover periods)
| 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 |
8 reviews available for kynurenine and Cognition Disorders
| Article | Year |
|---|---|
The kynurenine pathway as a therapeutic target in cognitive and neurodegenerative disorders.
Topics: Animals; Central Nervous System; Cognition Disorders; Drugs, Investigational; Enzyme Inhibitors; Hum | 2013 |
The common inflammatory etiology of depression and cognitive impairment: a therapeutic target.
Topics: Animals; Cognition Disorders; Depression; Humans; Inflammation; Kynurenine; Signal Transduction; Try | 2014 |
Immune-Mediated Metabolic Kynurenine Pathways Are Involved in the Postoperative Cognitive Dysfunction after Cardiopulmonary Bypass.
Topics: Biomarkers; Biosynthetic Pathways; Brain; Cardiopulmonary Bypass; China; Cognition Disorders; Humans | 2015 |
Inhibitors of the kynurenine pathway as neurotherapeutics: a patent review (2012-2015).
Topics: Animals; Central Nervous System Neoplasms; Cognition Disorders; Drug Design; Enzyme Inhibitors; Huma | 2016 |
Pharmacological manipulation of kynurenic acid: potential in the treatment of psychiatric disorders.
Topics: Animals; Cognition Disorders; Excitatory Amino Acid Antagonists; Humans; Kynurenic Acid; Kynurenine; | 2009 |
Cortical kynurenine pathway metabolism: a novel target for cognitive enhancement in Schizophrenia.
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.
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.
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.
Topics: alpha7 Nicotinic Acetylcholine Receptor; Animals; Astrocytes; Cognition Disorders; Disease Models, A | 2010 |
The kynurenine pathway and quinolinic acid: pivotal roles in HIV associated neurocognitive disorders.
Topics: Central Nervous System Diseases; Cognition Disorders; HIV; HIV Infections; Humans; Kynurenine; Quino | 2012 |
Genetic and hormonal regulation of tryptophan kynurenine metabolism: implications for vascular cognitive impairment, major depressive disorder, and aging.
Topics: Aging; Animals; Cognition Disorders; Cytokines; Depressive Disorder, Major; Hormones; Humans; Kynure | 2007 |
9 other studies available for kynurenine and Cognition Disorders
| Article | Year |
|---|---|
Kynurenine Pathway Metabolites in Alzheimer's Disease.
Topics: 3-Hydroxyanthranilic Acid; Aged; Aged, 80 and over; Aging; Alzheimer Disease; Cognition Disorders; C | 2017 |
Prenatal kynurenine treatment in rats causes schizophrenia-like broad monitoring deficits in adulthood.
Topics: Age Factors; Animals; Attention; Brain; Cognition; Cognition Disorders; Female; Kynurenine; Locomoti | 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.
Topics: Adolescent; Adult; Aged; Analysis of Variance; Cognition Disorders; Executive Function; Female; Huma | 2018 |
Immune activation in patients with Alzheimer's disease is associated with high serum phenylalanine concentrations.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cognition Disorders; Enzyme-Linked Immunosorbent Assay; | 2013 |
Continuous kynurenine administration during the prenatal period, but not during adolescence, causes learning and memory deficits in adult rats.
Topics: Age Factors; Animals; Avoidance Learning; Behavior, Animal; Cognition Disorders; Female; Hippocampus | 2014 |
The relationship between indoleamine 2,3-dioxygenase activity and post-stroke cognitive impairment.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Cognition Disorders; Cross-Sectional Studies; Enzyme Act | 2011 |
Acute elevations of brain kynurenic acid impair cognitive flexibility: normalization by the alpha7 positive modulator galantamine.
Topics: alpha7 Nicotinic Acetylcholine Receptor; Animals; Brain; Cognition; Cognition Disorders; Disease Mod | 2012 |
Pre- and postnatal exposure to kynurenine causes cognitive deficits in adulthood.
Topics: Age Factors; Analysis of Variance; Animals; Animals, Newborn; Chromatography, High Pressure Liquid; | 2012 |
Increased 3-hydroxykynurenine serum concentrations differentiate Alzheimer's disease patients from controls.
Topics: Aged; Alzheimer Disease; Biomarkers; Blood-Brain Barrier; Brain Chemistry; Chromatography, High Pres | 2013 |