SZ: total number of studies (max n=8) |
|
|
|
|
|
|
|
|
5 |
4 |
1 |
1 |
6 |
|
Erhardt,2525. Erhardt S, Blennow K, Nordin C, Skogh E, Lindström LH, Engberg G. Kynurenic acid levels are elevated in the cerebrospinal fluid of patients with schizophrenia. Neurosci Lett. 2001;313:96-8. Sweden |
Acute |
28/17 |
45/0 |
NA |
NA |
27/27 |
DSM-III-R |
Y (11), not specified |
|
|
|
|
|
KA levels increased in SZ patients vs. controls (p = 0.038). |
Holtze,2727. Holtze M, Saetre P, Engberg G, Schwieler L, Werge T, Andreassen OA, et al. Kynurenine 3-monooxygenase polymorphisms: relevance for kynurenic acid synthesis in patients with schizophrenia and healthy controls. J Psychiatry Neurosci. 2012;37:53-7. Sweden |
Stable |
17/33 |
38/12 |
NA |
NA |
33/28 |
NA |
Y (82), multiple types |
|
|
|
|
|
No major difference in KA levels in SZ patients vs. controls; however, a KMO SNP is identified and linked to elevated levels of KA in both SZ patients and controls (SNP: rs1053230) (p = 0.023). |
Issa,2828. Issa F, Gerhardt GA, Bartko JJ, Suddath RL, Lynch M, Gamache PH, et al. 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 Res. 1994;52:237-49. United States |
Acute |
24/12 |
23/13 |
25 |
NA |
30/31 |
DSM-III, DSM-III-R |
N |
|
|
|
|
|
This study controlled for freezer time. It is the only study in SZ to show increased levels of TRP in SZ patients (p < 0.01). This is also the only study with a large non-white population for SZ. There are no significant differences in KYN and 3-HK levels in SZ patients vs. controls. |
Kegel,2929. Kegel ME, Bhat M, Skogh E, Samuelsson M, Lundberg K, Dahl ML, et al. Imbalanced kynurenine pathway in schizophrenia. Int J Tryptophan Res. 2014;7:15-22. Sweden |
Stable |
21/26 |
30/17 |
100 |
25/24 |
38/25 |
DSM-IV, BPRS, GAF |
Y (100), olanzapine |
|
|
|
|
|
Nonsignificant trend for decreased levels of TRP in SZ patients, while KYN and KA levels are significantly increased (p < 0.01 and p = 0.012, respectively). Trend toward increased QA levels, but the QA/KA ratio is lower in SZ patients than in controls (p = 0.027). |
Linderholm,1313. Linderholm KR, Skogh E, Olsson SK, Dahl ML, Holtze M, Engberg G, et al. Increased levels of kynurenine and kynurenic acid in the CSF of patients with schizophrenia. Schizophr Bull. 2012;38:426-32. Sweden |
Stable |
16/29 |
45/0 |
NA |
NA |
37/25 |
DSM-IV, BPRS, GAF |
Y (100), olanzapine |
|
|
|
|
|
Nonsignificant decrease in TRP levels in SZ patients, while KYN and KA levels are significantly increased (p < 0.01). |
Nilsson,3030. Nilsson LK, Linderholm KR, Engberg G, Paulson L, Blennow K, Lindström LH, et al. Elevated levels of kynurenic acid in the cerebrospinal fluid of male patients with schizophrenia. Schizophr Res. 2005;80:315-22. Sweden |
Acute |
90/49 |
139/0 |
NA |
NA |
30/27 |
DSM-III-R |
Y (38), not specified |
|
|
|
|
|
KA levels in SZ patients are significantly increased (p = 0.031) in drug-naive (n=37), first-episode, or those on antipsychotics (n=34), but not in those with previous history of antipsychotic use who were drug-free at the time (n=19). |
Schwieler,3131. Schwieler L, Larsson MK, Skogh E, Kegel ME, Orhan F, Abdelmoaty S, et al. Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia--significance for activation of the kynurenine pathway. J Psychiatry Neurosci. 2015;40:126-33. Sweden |
Stable |
23/37 |
38/22 |
NA |
26/23 |
35/23 |
DSM-IV, BPRS, GAF |
Y (100), olanzapine, zopiclone, and lithium |
|
|
|
|
|
Nonsignificant trend toward decreased TRP levels and KYN:KA ratio. Significant decrease in TRP:KYN and TRP:KA ratios (p < 0.01), and significant increase in KYN and KA levels in SZ patients (p < 0.05). |
Gerner,2626. Gerner RH, Fairbanks L, Anderson GM, Young JG, Scheinin M, Linnoila M, et al. CSF neurochemistry in depressed, manic, and schizophrenic patients compared with that of normal controls. Am J Psychiatry. 1984;141:1533-40. United States |
Stable |
20/38 |
34/24 |
NA |
NA |
25/31 |
NA |
N |
|
|
|
|
|
No significant difference in TRP levels in SZ patients vs. controls. |
BD: total number of studies (max n=8) |
|
|
|
|
|
|
|
|
7 |
1 |
0 |
1 |
2 |
|
Bech,3333. Bech P, Kirkegaard C, Bock E, Johannesen M, Rafaelsen OJ. Hormones, electrolytes, and cerebrospinal fluid proteins in manic-melancholic patients. Neuropsychobiology. 1978;4:99-112. Denmark |
Depressed |
9/22 |
22/9 |
NA |
NA |
37/34(from MED) |
Beck’s Self-Rating Scale (1961) |
N |
|
|
|
|
|
No difference in TRP levels between patients and controls. Positive correlation between TRP and age (p < 0.01). |
Bech,3333. Bech P, Kirkegaard C, Bock E, Johannesen M, Rafaelsen OJ. Hormones, electrolytes, and cerebrospinal fluid proteins in manic-melancholic patients. Neuropsychobiology. 1978;4:99-112. Denmark |
Manic |
15/22 |
27/10 |
NA |
NA |
47/34(from MED) |
Biegel’s Manic-State Rating Scale (1971) |
N |
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|
|
|
|
No difference in TRP levels between patients and controls. Positive correlation between TRP and age (p < 0.01). |
Trepci,3636. Trepci A, Sellgren CM, Pålsson E, Brundin L, Khanlarkhani N, Schwieler L, et al. Central levels of tryptophan metabolites in subjects with bipolar disorder. Eur Neuropsychopharmacol. 2021;43:52-62. Sweden |
Euthymic |
101/80 |
79/102 |
NA |
25/23 (MED) |
43/33 (MED) |
DSM-IV |
Y (NA), multiple types |
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|
|
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|
Antidepressants significantly increased CSF levels of KYN, KA, and KYN:TRP ratio (p ≤ 0.02). Lamotrigine is also associated with increased levels of KYN (p = 0.03). Suicidal ideation is also associated with increased TRP levels and KYN:TRP ratio (p = 0.03 and p = 0.04, respectively). In general, KA levels are increased in bipolar patients compared to controls (p = 0.007). |
Ashcroft,3232. Ashcroft GW, Blackburn IM, Eccleston D, Glen AI, Hartley W, Kinloch NE, et al. Changes on recovery in the concentrations of tryptophan and the biogenic amine metabolites in the cerebrospinal fluid of patients with affective illness. Psychol Med. 1973;3:319-25. Scotland |
Depressed |
6/26 |
NA |
NA |
NA |
-/45 |
PSE, Hargreaves Rating Scale |
Y (NA), phenothiazine or butyrophenone groups |
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|
|
|
|
No significant difference in TRP levels in BD patients vs. controls. |
Ashcroft,3232. Ashcroft GW, Blackburn IM, Eccleston D, Glen AI, Hartley W, Kinloch NE, et al. Changes on recovery in the concentrations of tryptophan and the biogenic amine metabolites in the cerebrospinal fluid of patients with affective illness. Psychol Med. 1973;3:319-25. Scotland |
Manic |
7/26 |
NA |
NA |
NA |
-/45 |
PSE, Hargreaves Rating Scale |
Y (NA), ECT or phenothiazine or butyrophenone groups |
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|
|
|
|
No significant difference in TRP levels in BD patients vs. controls. |
Coppen,3434. Coppen A, Brooksbank BW, Peet M. Tryptophan concentration in the cerebrospinal fluid of depressive patients. Lancet. 1972;1:1393. England |
Manic |
3/14 |
8/9 |
NA |
NA |
46/52 |
NA |
NA; (100) lithium indicated, but not specified |
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|
|
|
|
Plasma levels of TRP are normal, but CSF concentrations of TRP are decreased in BD patients. |
Sellgren,3535. Sellgren CM, Gracias J, Jungholm O, Perlis RH, Engberg G, Schwieler L, et al. Peripheral and central levels of kynurenic acid in bipolar disorder subjects and healthy controls. Transl Psychiatry. 2019;9:37. Sweden |
Euthymic |
94/113 |
90/117 |
NA |
-/23 |
36/35 |
DSM-IV, MADRS, YMRS, ADE, MINI, D-KEFS |
Y (73) lithium, divalproex, olanzapine, quetiapine, lamotrigine |
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|
|
|
|
Selective increase in CSF levels of KA in BD patients with history of psychotic symptoms (p = 0.029). No significant difference in KA levels for BD patients in general compared to controls. |
Gerner,2626. Gerner RH, Fairbanks L, Anderson GM, Young JG, Scheinin M, Linnoila M, et al. CSF neurochemistry in depressed, manic, and schizophrenic patients compared with that of normal controls. Am J Psychiatry. 1984;141:1533-40. United States |
Manic |
15/38 |
28/25 |
NA |
NA |
34/31 |
RDC |
N |
|
|
|
|
|
No significant difference in TRP levels in BD patients vs. controls. |
|
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|
|
|
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|
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|
|
|
MDD: total number of studies (max n=11) |
|
|
|
|
|
|
|
|
9 |
4 |
1 |
2 |
2 |
|
Bech,3333. Bech P, Kirkegaard C, Bock E, Johannesen M, Rafaelsen OJ. Hormones, electrolytes, and cerebrospinal fluid proteins in manic-melancholic patients. Neuropsychobiology. 1978;4:99-112. Denmark |
Depressed |
9/22 |
22/9 |
NA |
NA |
56/34(from MED) |
Beck’s Self-Rating Scale (1961) |
N |
|
|
|
|
|
No difference in TRP levels between patients and controls. Positive correlation between TRP and age (p < 0.01). |
Paul,4242. Paul ER, Schwieler L, Erhardt S, Boda S, Trepci A, Kämpe R, et al. Peripheral and central kynurenine pathway abnormalities in major depression. Brain Behav Immun. 2022;101:136-45. Sweden |
Depressed |
36/33 |
22/47 |
NA |
25/24 (MED) |
31/26 (MED) |
MINI, ICD-10, DSM-V |
Y (44), not specified |
|
|
|
|
|
No significant differences in KYN, 3-HK, KA, or QA levels in depressed patients vs. controls. |
Curzon,3838. Curzon G, Kantamaneni BD, van Boxel P, Gillman PK, Bartlett JR, Bridges PK. Substances related to 5-hydroxytryptamine in plasma and in lumbar and ventricular fluids of psychiatric patients. Acta Psychiatr Scand Suppl. 1980;280:3-20. England |
Depressed |
14/10 |
NA |
NA |
NA |
51/51 |
Bridges & Bartlett (1977) |
Y (NA), diazepam, nitrazepam |
|
|
|
|
|
No significant difference in TRP levels in depressed patients vs. controls. |
Kaddurah-Daouk,4141. Kaddurah-Daouk R, Yuan P, Boyle SH, Matson W, Wang Z, Zeng ZB, et al. Cerebrospinal fluid metabolome in mood disorders-remission state has a unique metabolic profile. Sci Rep. 2012;2:667. United States |
Depressed |
15/18 |
16/17 |
NA |
27/29 |
38/40 |
MDRS, HAM-D, HAM-A |
N |
|
|
|
|
|
No significant difference in TRP levels in depressed patients vs. controls. |
Kaddurah-Daouk,4141. Kaddurah-Daouk R, Yuan P, Boyle SH, Matson W, Wang Z, Zeng ZB, et al. Cerebrospinal fluid metabolome in mood disorders-remission state has a unique metabolic profile. Sci Rep. 2012;2:667. United States |
Remission |
14/18 |
15/17 |
NA |
29/29 |
45/40 |
MDRS, HAM-D, HAM-A |
N |
|
|
|
|
|
No significant difference in TRP and KYN levels in MDD patients in remission vs. controls. There is likely a shift toward the KIM pathway in MDD patients in remission, based on decreased 5HIAA:TRP and 5HIAA:KYN ratios (p < 0.01). |
Erhardt,3939. Erhardt S, Lim CK, Linderholm KR, Janelidze S, Lindqvist D, Samuelsson M, et al. Connecting inflammation with glutamate agonism in suicidality. Neuropsychopharmacology. 2013;38:743-52. Sweden |
NA |
64/36 |
59/37 |
NA |
24/24 |
37/30 |
DSM-III-R, SCID I & II, MADRS, SIS |
N |
|
|
|
|
|
While there is no difference in KA levels of depressed patients with suicidal ideation vs. controls, QA levels are increased (p < 0.01). |
Banki,3737. Banki CM, Vojnik M, Molnar G. Cerebrospinal fluid amine metabolites, tryptophan and clinical parameters in depression. Part 1. Background variables. J Affect Disord. 1981;3:81-9. Hungary |
Depressed |
33/32 |
NA |
NA |
NA |
NA |
Taylor-Feighner System |
N |
|
|
|
|
|
No significant difference in TRP levels in depressed patients vs. controls. |
Ashcroft,3232. Ashcroft GW, Blackburn IM, Eccleston D, Glen AI, Hartley W, Kinloch NE, et al. Changes on recovery in the concentrations of tryptophan and the biogenic amine metabolites in the cerebrospinal fluid of patients with affective illness. Psychol Med. 1973;3:319-25. Scotland |
Depressed |
9/26 |
NA |
NA |
NA |
-/45 |
PSE, Hargreaves Rating Scale |
Y (NA), ECT or phenothiazine or butyrophenone groups |
|
|
|
|
|
No significant difference in TRP levels in depressed patients vs. controls. |
Hestad,4040. Hestad KA, Engedal K, Whist JE, Farup PG. The relationships among tryptophan, kynurenine, indoleamine 2,3-dioxygenase, depression, and neuropsychological performance. Front Psychol. 2017;8:1561. Norway |
Depressed |
44/31 |
30/45 |
NA |
NA |
45/44 |
ICD-10, F32-34 Spectra, DSM-IV, MADRS, 0 |
Y (51), not specified |
|
|
|
|
|
No significant differences in TRP and KYN levels nor in KYN:TRP ratio in depressed patients vs. controls. |
Coppen,3434. Coppen A, Brooksbank BW, Peet M. Tryptophan concentration in the cerebrospinal fluid of depressive patients. Lancet. 1972;1:1393. England |
Depressed |
10/14 |
9/15 |
NA |
NA |
52/52 |
NA |
NA |
|
|
|
|
|
Plasma levels of TRP were normal but CSF concentrations of TRP were decreased in depressed patients (p < 0.01). |
Coppen,3434. Coppen A, Brooksbank BW, Peet M. Tryptophan concentration in the cerebrospinal fluid of depressive patients. Lancet. 1972;1:1393. England |
Remission |
3/14 |
8/9 |
NA |
NA |
52/48 |
NA |
NA |
|
|
|
|
|
No significant difference in TRP levels in MDD patients in remission vs. controls. |