Non-Invasive Brain Stimulation Effects on Biomarkers of Tryptophan Metabolism: A Scoping Review and Meta-Analysis
Abstract
:1. Introduction
1.1. Rationale
1.2. Objective
2. Methods
2.1. Eligibility Criteria
2.2. Information Sources
2.3. Search Strategy
2.4. Selection and Data Collection
2.5. Data Items
2.6. Qualitative Synthesis Methods
2.7. Quantitative Synthesis Methods by Bayesian Meta-Analysis
3. Results
3.1. Selection of Sources of Evidence
3.2. Characteristics of Included Studiess
3.3. Qualitative Synthesis Results
3.4. Quantitative Synthesis Results by Bayesian Meta-Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
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Patient | Human or animal models; can be healthy or with an underlying health condition. |
Intervention | NIBS techniques: ECT, rTMS, or tDCS |
Comparison | Biomarkers of interest assessed: tryptophan (TRP), kynurenine (KYN), formylkynurenine, kynurenic acid (KA), quinolinic acid (QA), NAD+, 3-hydroxykynurenine (3-HK), xanthurenic acid (XA), picolinic acid (PA), anthranilic acid (AA), serotonin (5-HT), oxitriptan, 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), N-acetyl-5-HT, or melatonin. Measures of their concentrations must be reported and compared to baseline levels, e.g., measures obtained before and again during or after NIBS, or comparison of animal models that received active versus sham NIBS. Studies without a control group can be included, so long as baseline measures are clearly defined. |
Outcome | Biomarkers must measure serotonin or kynurenine pathway activation, sampled peripherally or centrally (e.g., CSF, plasma/serum, microdialysis, brain tissue analysis in animal models). Changes in health condition will be collected if available (e.g., in humans, clinical scales; in rodents, task specific performance) |
Study | Design | Protocol | Participants | Demographics | Source | Timing of Post-NIBS Sampling | Biomarker | Result |
---|---|---|---|---|---|---|---|---|
ECT | ||||||||
Aarsland et al., 2019 [33] | pretest-posttest | Site: right unilateral Seizure length: *median 50.7 s, IQR 16 s Session N: *max. 20 Session freq.: 3/week | depression (uni- and bipolar, with and without psychotic symptoms) | N: 21 M:F: 44:56% * Age: median 46, IQR 21.0 * | serum | 1–2 weeks after the last session (median 10 days, IQR 6) | TRP | ns |
KYN | ns | |||||||
KA | ns | |||||||
3-HK | ns | |||||||
QA | ns | |||||||
PA | ↑ | |||||||
XA | ns | |||||||
AA | ns | |||||||
KYN/TRP | ns | |||||||
KA/KYN | ns | |||||||
KA/3-HK | ns | |||||||
QA/KA | ns | |||||||
XA/3-HK | ns | |||||||
PA/QA | ↑ | |||||||
Aberg-Wistedt et al., 1986 [34] | pretest-posttest | Site: bifrontotemporal Seizure length: 45.0 ± 8.2 s * Session N: 8.0 ± 3.1 * Session freq.: 3/week | depression (unipolar, without psychotic symptoms) | N: 11 M:F: 33:67% * Age: 56 ± 16.2 * | CSF | 3 weeks after the last session | 5-HIAA | ns |
Allen et al., 2018 [35] | pretest-posttest | Site: bitemporal Session N: max. 6 Session freq.: 2/week | TRD (unipolar) | N: 18 M:F: 33:67% Age: 57.5 ± 14.7 | plasma | 4–7 days after the last session | TRP | ns |
KYN | ns | |||||||
KA | ns | |||||||
KYN/TRP | ns | |||||||
KA/KYN | ns | |||||||
D’Elia et al., 1977 [36] | pretest-posttest | Site: nondominant unilateral Session N: mean 6.1, range 3–12 | depression (uni- and bipolar) | N: 24 M:F: 38:63% Age: 48.0 ± 12.5, range 22–64 | serum | mean of levels sampled before each session from the second to the last. | TRP | ns |
Guloksuz et al., 2015 [37] | pretest-posttest | Site: bifrontotemporal Seizure length: mean 52 s, range 10–200 s Session N: mean 6.1, range 3–11 Session freq.: 2/week | TRD (uni- and bipolar) | N: 19 M:F: 32:68% Age: 52.6 ± 14.4, range 23–74 | serum | before every other session | TRP | ns |
KYN | ns | |||||||
KA | ↑ | |||||||
3-HK | ns | |||||||
5-HIAA | ns | |||||||
KYN/TRP | ↑ | |||||||
KA/KYN | ↑ | |||||||
KA/3-HK | ↑ | |||||||
5-HIAA/KYN | ns | |||||||
Hasani et al., 2019 [38] | parallel | Site: bifrontotemporal Session N: 6–8 Session freq.: every other day | TRD (unipolar) | Exp. group N: 21 Age: 35.24 ± 14.17 Control group N: 15 Age: 33.26 ± 13.59 | plasma | 16 days after the first session | 5-HT | ↑ (posttest) |
30 days after the first session | ↑ (posttest) | |||||||
Hoekstra et al., 2001 [39] | pretest-posttest | Site: unilateral and bifrontotemporal Session N: mean 11 Session freq.: 2/week | TRD (unipolar, with and without psychotic symptoms) | N: 20 M:F: 35:65% Age: 52 ± 13.1 | plasma | the morning after the final session | TRP | ns |
Hoffmann et al., 1985 [40] | pretest-posttest | Site: bitemporal Session N: mean 11, range 6–19 * Session freq.: 3/week | depression (uni- and bipolar, with and without psychotic symptoms) | N: 7 all male Age: 46 ± 11.2, range 29–61 | CSF | 12 days after the last session | 5-HIAA | ns |
Hofmann et al., 1996 [41] | pretest-posttest | Site: bifrontotemporal Seizure length: 40.48 ± 14.12 s Session N: 1 | depression (unipolar) | N: 31 M:F: 29:71% Age: 37.22 ± 13.98 | serum | 1 min after the session | 5-HIAA | ns |
1 h after the session | ↓ | |||||||
2 h after the session | ↓ | |||||||
Jori et al., 1975 [42] | pretest-posttest | Session N: 4–8 | depression (with psychotic symptoms) | N: 12 M:F: 88:12% * Age: mean 45, range 25–63 * | CSF | 7 days after the final session | 5-HIAA | ↑ |
Kirkegaard, Møller and Bjørum, 1978 [43] | pretest-posttest | Site: unilateral Session N: 10.5 ± 2.6 Session freq.: 2/week | depression (uni- and bipolar) | N: 10 M:F: 30:70% Age: mean 63 | CSF | - | TRP | ns |
plasma | TRP | ↓ | ||||||
free TRP | ns | |||||||
free/total TRP | ↑ | |||||||
Lestra et al., 1998 [44] | pretest-posttest | Session N: 5–9 Session freq.: every 3 or 4 days | depression (unipolar) | N: 6 M:F: 43:57% * Age: range 27–70 * | platelet pellet | 10 days after the last session | 5-HT | ns |
Mokhtar et al., 1997 [45] | pretest-posttest | Site: bilateral Seizure length: 20 s in nine, a mild fit in one Session N: 1 | depression (uni- and bipolar) | N: 10 M:F: 50:50% Age: mean 48.5, SEM 4.3 | serum | 15 min after the session | TRP | ns |
30 min after the session | ns | |||||||
45 min after the session | ↓ | |||||||
1 h after the session | ↓ | |||||||
Nikisch and Mathé, 2008 [46] | pretest-posttest | Site: unilateral Session N: 8 Session freq.: 2/week | TRD (unipolar, with and without psychotic symptoms) | N: 6 M:F: 83:17% Age: 40 ± 8 | CSF | 1 week after the last session | 5-HIAA | ↑ |
Olajossy et al., 2017 [47] | pretest-posttest | Site: bifrontotemporal Session N: 12 Session freq.: 2/week | recurrent depressive disorder | N: 32 M:F: 41:59% Age: 49.41 ± 12.73 | serum | 30 min after the first, sixth, and 12th sessions | KA | ns |
depression in bipolar disorder | N: 11 M:F: 36:64% Age: 44.73 ± 13.83 | ns | ||||||
schizoaffective disorder | N: 7 M:F: 43:57% Age: 33.29 ± 8.56 | ns | ||||||
Palmio et al., 2005 [48] | pretest-posttest | Site: bilateral Seizure length: 45.7 ± 13.2, range 21–66 Session N: 3.8 ± 2.2, range 1–7 | depression (unipolar, with and without psychotic symptoms) | N: 10 M:F: 30:70% Age: 55.6 ± 15.8, range 28–73 | plasma | 2 h after the last session | TRP | ↑ |
6 h after the last session | ↑ | |||||||
24 h after the last session | ↑ | |||||||
48 h after the last session | ns | |||||||
Rudorfer et al., 1988 [49] | pretest-posttest | Site: uni- and bilateral Seizure length: at least 25 s Session N: 14.3 ± 1.2, range 13–15 | depression (unipolar) | N: 3 all female Age: 48.7 ± 22.0, range 35–74 | CSF | 4–5 days after the last session | 5-HIAA | No statistical tests: levels reportedly increased in 2 of 3 patients. |
Rudorfer et al., 1991 [50] | pretest-posttest | Site: uni- and bilateral Seizure length: at least 25 s Session N: 13.6 ± 3.3, range 9–19 | TRD (unipolar) | N: 8 M:F: 25:75% Age: 53.1 ± 13.2, range 35–71 | CSF | 5–10 days after the last session | 5-HIAA | ns |
Ryan et al., 2020 [51] | pretest-posttest | Site: unilateral and bitemporal Session N: 7.97 ± 2.46 Session freq.: 2/week | depression (uni- and bipolar, with and without psychotic symptoms) | N: 94 M:F: 38:62% Age: 55.48 ± 14.72 | plasma | 1–3 days after the last session | XA/3-HK | ns |
Ryan et al., 2020 [52] | pretest-posttest | Site: unilateral and bitemporal Session N: 7.96 ± 2.47 Session freq.: 2/week | depression (uni- and bipolar, with and without psychotic symptoms) | N: 94 M:F: 38:62% Age: 55.48 ± 14.72 | plasma | 1–3 days after the last session | TRP | ns |
KYN | ns | |||||||
KA | ns | |||||||
3-HK | ns | |||||||
QA | ns | |||||||
PA | ns | |||||||
XA | ns | |||||||
AA | ns | |||||||
KYN/TRP | ns | |||||||
KA/KYN | ns | |||||||
QA/KA | ns | |||||||
QA/KYN | ns | |||||||
Sawa, 1981 [53] | pretest-posttest | Session N: 1 | depression (uni- and bipolar) | N: 9 M:F: 44:56% Age: 40.7 ± 11.8, range 20–52 | plasma | 1 min after the session | TRP | ns |
free TRP | ↑ | |||||||
5 min after the session | TRP | ↓ | ||||||
free TRP | ns | |||||||
10 min after the session | TRP | ↓ | ||||||
free TRP | ns | |||||||
30 min after the session | TRP | ns | ||||||
free TRP | ns | |||||||
1 h after the session | TRP | ns | ||||||
free TRP | ↓ | |||||||
Schwieler et al., 2016 [54] | pretest-posttest | Site: right unilateral Session N: 3 | TRD (unipolar) | N: 15 M:F: 58:42% * Age: median 41.0, IQR 25.0–54.0 * | plasma | - | TRP | ↓ |
KYN | ↓ $ | |||||||
KA | ns | |||||||
QA | ↓ | |||||||
KYN/TRP | ns | |||||||
QA/KA | ↓ | |||||||
Smith and Strömgren, 1981 [55] | pretest-posttest | Site: nondominant unilateral Session freq.: 4/week | depression | N: 13 M:F: 69:31% Age: 42.7 ± 12.5, range 24–61 | serum | 9 am on the day after the last session | TRP | ns |
Stelmasiak and Curzon, 1974 [56] | pretest-posttest | Site: unilateral Session N: 1 | depression | N: 18 M:F: 39:61% Age: mean 48, range 20–70 | plasma | 1 min after the session | TRP | ns |
free TRP | ↑ | |||||||
15 min after the session | TRP | ns | ||||||
free TRP | ↑ | |||||||
30 min after the session | TRP | ns | ||||||
free TRP | ns | |||||||
1 h after the session | TRP | ns | ||||||
free TRP | ns | |||||||
Udayakumar et al., 1981 [57] | pretest-posttest | Site: bitemporal Session N: 1 | schizophrenia | N: 29 M:F: 66:34% Age: 27.4 ± 8.0, range 14–49 | CSF | 5 min after the session | 5-HT | ↑ |
48–72 h after the session | ns | |||||||
Whalley, Yates and Christie, 1980 [58] | pretest-posttest | Session N: 4–9 * | depression (unipolar, without psychotic symptoms) | N: 11 M:F: 25:75% * Age: 49 ± 13.9 * | plasma | 10 min after the first session | TRP | ↓ |
free TRP | ns | |||||||
immediately before the last session | TRP | ns # | ||||||
free TRP | ns # | |||||||
12 weeks after the last session | TRP | ns $ | ||||||
free TRP | ns $ | |||||||
TMS | ||||||||
Leblhuber et al., 2021 [59] | pretest-posttest | Site: medial frontopolar cortex Pulse freq.: 20 Hz Intensity: 1.5 T Pulse N: 2400 Session N: 10 Session freq.: 5/week | TRD (unipolar) | N: 21 M:F: 48:52% Age: 59.4 ± 15.7 | serum | - | TRP | ns |
KYN | ns | |||||||
KYN/TRP | ns | |||||||
Leblhuber, Steiner and Fuchs, 2019 [60] | parallel | Site: bilateral prefrontal cortex Pulse freq.: 3 Hz Intensity: 0.08 T Pulse N: 30 min Session N: 10 Session freq.: 5/week | TRD (geriatric) | Exp. group N: 19 M:F: 45:55% * Age: mean 71.9, SEM 2.92 Control group N: 10 M:F: 45:55% * Age: mean 73.3, SEM 2.69 | serum | immediately after the last session | TRP | ns (group x time) |
KYN | ns (group x time) | |||||||
KYN/TRP | ns (group x time) | |||||||
Leblhuber et al., 2018 [61] | pretest-posttest | Site: bilateral prefrontal cortex Pulse freq.: 3 Hz Intensity: above 100% MT Session N: 10 | TRD (geriatric) | N: 10 M:F: 40:60% Age: 69 ± 8.78 | serum | - | TRP | ns |
KYN | ns | |||||||
KYN/TRP | ns | |||||||
Liu et al., 2022 [62] | parallel | Site: bilateral dorsolateral and ventrolateral prefrontal cortex Pulse freq.: 0.5 Hz Intensity: 0.70 T Session N: 8 Session freq.: 5/week | post-stroke depression | Exp. group N: 35 M:F: 57:43% Age: 55.61 ± 6.84 Control group N: 35 M:F: 66:34% Age: 50.20 ± 6.28 | serum | 8 weeks after the last session | 5-HT | ↑ (posttest) |
Lu et al., 2018 [63] | pretest-posttest | Site: bilateral dorsolateral prefrontal cortex Pulse freq.: 1 Hz Intensity: 80% MT Pulse N: 750 Session N: 10 Session freq.: 5/week | generalized anxiety disorders | N: 28 M:F: 39:61% Age: 45.5 ± 12.67, range 27–72 | serum | 1 h after the last session | 5-HT | ↑ |
Maestú et al., 2013 [64] | parallel | Site: 33 stimulation coils distributed evenly across an EEG cap Pulse freq.: 8 Hz Intensity: 43 nT Pulse N: 20 min Session N: 8 Session freq.: 1/week | fibromyalgia | Exp. group N: 28 all female Age: 40.7 ± 6.7 * Control group N: 26 all female Age: 40.7 ± 6.7 * | blood | - | 5-HT | ns (group x time) |
Miniussi et al., 2005 [65] | pretest-posttest | Site: left dorsolateral prefrontal cortex Pulse freq.: 17 Hz Intensity: 110% MT Pulse N: 408 Session N: 5 Session freq.: 1/day | TRD (uni- and bipolar, with and without psychotic symptoms) | N: 10 M:F: 25:75% * Age: mean 58 | plasma | the day of the last session | 5-HT | ns |
5-HIAA | ns | |||||||
Pulse freq.: 1 Hz Pulse N: 400 | N: 10 M:F: 25:75% * Age: mean 52 | 5-HT | ns | |||||
5-HIAA | ns | |||||||
Niimi et al., 2020 [66] | parallel | Site: primary motor cortex of the unaffected hemisphere Pulse freq.: 1 Hz Intensity: 90% MT Pulse N: 1200 Session N: 22 Session freq.: 2/day | stroke | Exp. group N: 62 M:F: 66:34% Age: 62.3 ± 11.0 Control group N: 33 M:F: 52:48% Age: 66.2 ± 10.8 | serum | - | TRP | ns |
KYN | ns | |||||||
KYN/TRP | ns | |||||||
Sibon et al., 2007 [67] | crossover | Site: left dorsolateral prefrontal cortex Pulse freq.: 10 Hz Intensity: 90% MT Pulse N: 450 Session N: 1 | healthy | N: 10 M:F: 50:50% Age: 24.7 ± 5.14, range 18–40 | plasma | - | TRP | ns |
free TRP | ns | |||||||
Tateishi et al., 2021 [68] | pretest-posttest | Site: left dorsolateral prefrontal cortex Pulse freq.: 10 Hz Intensity: 100% MT Pulse N: 1600 Session N: 30 Session freq.: 5/week | TRD (unipolar) | N: 13 M:F: 31:69% Age: 54.9 ± 14.3 | plasma | - | TRP | ↑ |
oxitriptan | ns | |||||||
5-HT | ↓ | |||||||
melatonin | ns | |||||||
KYN | ns | |||||||
KA | ns | |||||||
3-HK | ns | |||||||
KYN/TRP | ns | |||||||
Tateishi et al., 2022 [69] | pretest-posttest | Site: left dorsolateral prefrontal cortex Pulse freq.: 10 Hz Intensity: 100% MT Pulse N: 1600 Session N: 30 Session freq.: 5/week | TRD (unipolar) | N: 5 Age: 48.0 ± 13.9, range 30–72 | CSF | - | TRP | ns |
5-HT | ns | |||||||
KYN | ↑ | |||||||
KA | ns | |||||||
3-HK | ns | |||||||
tDCS | ||||||||
Hadoush et al., 2021 [70] | pretest-posttest | Site: bilateral primary motor cortex and bilateral dorsolateral prefrontal cortex Polarity: anodal Electrode size: 25 cm2 Intensity: 1 mA Duration: 20 min Session N: 10 Session freq.: 5/week | Parkinson’s disease | N: 25 M:F: 76:24% Age: mean 61.5, range 30–80 | serum | - | melatonin | ↓ |
Study | Design | Protocol | Subjects | Demographics | Source | Timing of Post-NIBS Sampling | Biomarker | Result |
---|---|---|---|---|---|---|---|---|
ECT | ||||||||
Evans et al., 1976 [71] | parallel | Site: ear clips Session N: 1 | healthy Sprague-Dawley rats | Exp. group N: - all male Control group N: - all male | brain tissue | 30 min after the session | TRP | ns (posttest) |
5-HT | ns (posttest) | |||||||
5-HIAA | ns (posttest) | |||||||
Exp. group N: 5 Control group N: 5 | 1 h after the session | 5-HT | ns (posttest) | |||||
Exp. group N: 6 Control group N: 5 | 3 h after the session | TRP | ns (posttest) | |||||
Exp. group N: 14 Control group N: 14 | 5-HT | ns (posttest) * | ||||||
5-HIAA | ↑ (posttest) | |||||||
Exp. group N: 3 Control group N: 3 | 6 h after the session | 5-HT | ns (posttest) | |||||
Exp. group N: 4 Control group N: 5 | 24 h after the session | TRP | ns (posttest) | |||||
5-HT | ns (posttest) | |||||||
5-HIAA | ns (posttest) | |||||||
Gur et al., 2002 [72] | parallel | Site: ear clips Session N: 10 Session freq.: 1/day | healthy Albino rats | Exp. group N: 13 all male Control group N: 16 all male | microdialysis (ventral hippocampus) | 48 h after the last session | 5-HT | ns (posttest) |
microdialysis (anterior hypothalamus) | 24 h after the last session | ns (posttest) | ||||||
Juckel et al., 1999 [73] | pretest-posttest | Site: left medial prefrontal cortex Session N: 1 | healthy, anesthetized Sprague-Dawley rats | N: 6 all male | microdialysis (left amygdala) | during the session | 5-HT | ↑ |
Site: left medial prefrontal cortex | healthy, anesthetized Sprague-Dawley rats | N: 6 | microdialysis (left ventral hippocampus) | ↑ | ||||
Site: left medial prefrontal cortex | healthy, behaving Sprague-Dawley rats | N: 3 | microdialysis (left ventral hippocampus) | ↑ | ||||
Site: right medial prefrontal cortex | healthy, anesthetized Sprague-Dawley rats | N: 4 | microdialysis (left ventral hippocampus) | ↑ | ||||
Site: right medial prefrontal cortex | healthy, anesthetized Sprague-Dawley rats | N: 3 | microdialysis (right ventral hippocampus) | ↑ | ||||
Karoum et al., 1986 [74] | pretest-posttest | Site: ear clips Session N: 10 Session freq.: 1/day | healthy Sprague-Dawley rats | N: 5 all male | brain tissue (caudate nucleus) | 20 h after the last session | 5-HT | ns |
5-HIAA | ns | |||||||
5-HIAA/5-HT | ns | |||||||
1 week after the last session | 5-HT | ns | ||||||
5-HIAA | ns | |||||||
5-HIAA/5-HT | ns | |||||||
brain tissue (frontal cortex) | 20 h after the last session | 5-HT | ns | |||||
5-HIAA | ns | |||||||
5-HIAA/5-HT | ns | |||||||
1 week after the last session | 5-HT | ↑ | ||||||
5-HIAA | ns | |||||||
5-HIAA/5-HT | ns | |||||||
urine | nights between sessions | 5-HIAA | ↓ | |||||
nights in the first week after the last session | ↓ | |||||||
Khanna et al.,, 1971 [75] | parallel | Site: temples Session N: 15 Session freq.: 1/day | healthy dogs later with ECT-induced cardiac abnormalities | Exp. group N: 19 Control group N: 10 | myocardium tissue | the day after the last session | 5-HT | ↑ (posttest) |
healthy dogs later without ECT-induced cardiac abnormalities | Exp. group N: 11 Control group N: 10 | ns (posttest) | ||||||
Madhav et al., 2000 [76] | parallel | Site: ear clips Session N: 5 Session freq.: every other day | Sprague-Dawley rats with serotonergic lesion in the right cingulum bundle (via which the hippocampus receives serotonergic innervation) | Exp. group N: 4 all male Control group N: 4 all male | brain tissue (right hippocampus) | 18 days after the last session | 5-HT | ns (posttest) |
5-HIAA | ↑ (posttest) | |||||||
5-HIAA/5-HT | ns (posttest) | |||||||
McIntyre and Oxenkrug, 1984 [77] | parallel | Site: ear clips Seizure length: 20–25 s Session N: 7 Session freq.: 1/day | healthy Sprague-Dawley rats | Exp. group N: 14 all male Control group N: 7 all male | brain tissue (hypothalamus) | 9 pm of the day of the last session | TRP | ns (posttest) |
5-HT | ↓ (posttest) | |||||||
5-HIAA | ns (posttest) | |||||||
Exp. group N: 13 Control group N: 7 | brain tissue (pineal gland) | TRP | ns (posttest) | |||||
5-HT | ↓ (posttest) | |||||||
5-HIAA | ns (posttest) | |||||||
N-acetyl-5-HT | ns (posttest) | |||||||
melatonin | ns (posttest) | |||||||
Session N: 1 | Exp. group N: 8 Control group N: 7 | brain tissue (hypothalamus) | TRP | ns (posttest) | ||||
5-HT | ns (posttest) | |||||||
5-HIAA | ↓ (posttest) | |||||||
Exp. group N: 7 Control group N: 7 | brain tissue (pineal gland) | TRP | ns (posttest) | |||||
5-HT | ns (posttest) | |||||||
5-HIAA | ns (posttest) | |||||||
N-acetyl-5-HT | ns (posttest) | |||||||
melatonin | ns (posttest) | |||||||
Shields, 1972 [78] | parallel | Session N: 8 | healthy rats | Exp. group N: 8 Control group N: 8 | brain tissue | 24 h after the last session | 5-HT | ns (posttest) |
5-HIAA | ns (posttest) | |||||||
Exp. group N: 8 Control group N: 7 | 5-HT | ns (posttest) | ||||||
5-HIAA | ns (posttest) | |||||||
Session N: 12 | Exp. group N: 7 Control group N: 8 | 5-HT | ns (posttest) | |||||
5-HIAA | ns (posttest) | |||||||
Session N: 16 | Exp. group N: 6 Control group N: 8 | 5-HT | ns (posttest) | |||||
5-HIAA | ns (posttest) | |||||||
Session N: 1 | Exp. group N: 8 Control group N: 8 | 3 h after the session | TRP | ns (posttest) | ||||
5-HT | ns (posttest) | |||||||
5-HIAA | ↑ (posttest) * | |||||||
Sugrue, 1983 [79] | parallel | Site: ear clips Session N: 10 Session freq.: 1/day | healthy Sprague-Dawley rats | Exp. group N: at least 5 all male Control group N: 40–48 all male | brain tissue (cortex) | 6.5 h after the last session | 5-HT | ns (posttest) |
5-HIAA | ↑ (posttest) | |||||||
Tagliamonte et al., 1972 [80] | parallel | Site: ear clips Seizure length: 15 s Session N: 2 Session freq.: 30 min interval | healthy Wistar rats | Exp. group N: 24 all male Control group N: 150 all male | plasma | 1 h after the first session | TRP | ns (posttest) |
brain tissue | TRP | ↑ (posttest) | ||||||
5-HT | ns (posttest) | |||||||
5-HIAA | ↑ (posttest) | |||||||
Session N: 1 | Exp. group N: 21 Control group N: 150 | plasma | TRP | ns (posttest) | ||||
brain tissue | TRP | ↑ (posttest) | ||||||
5-HT | ns (posttest) | |||||||
5-HIAA | ↑ (posttest) | |||||||
Yoshida et al., 1997 [81] | parallel | Site: ear clips Seizure length: 20–25 s Session N: 8 Session freq.: 1/day | healthy Wistar rats | Exp. group N: 6 all male Control group N: 6 all male | microdialysis (striatum) | 0–180 after the first session | 5-HIAA | ↑ (posttest/pretest) |
immediately before the last session | ↑ (posttest) | |||||||
Yoshida et al., 1998 [82] | parallel | Site: ear clips Seizure length: 20–25 s Session N: 8 Session freq.: 1/day | healthy Wistar rats | Exp. group N: 6 all male Control group N: 6 all male | microdialysis (frontal cortex) | 0–180 after the first session | 5-HIAA | ↑ (posttest/pretest) |
immediately before the last session | ↑ (posttest) | |||||||
TMS | ||||||||
Ben-Shachar et al., 1997 [83] | parallel | Pulse freq.: 25 Hz Intensity: 2.3 T Pulse N: 50 Session N: 1 | healthy Sprague-Dawley rats | Exp. group N: 16–20 all male Control group N: 16–20 all male | brain tissue (frontal cortex) | 10 s after the session | 5-HT | ns (posttest) |
5-HIAA | ns (posttest) | |||||||
5-HIAA/5-HT | ns (posttest) | |||||||
brain tissue (hippocampus) | 5-HT | ↑ (posttest) | ||||||
5-HIAA | ↑ (posttest) | |||||||
5-HIAA/5-HT | ns (posttest) | |||||||
brain tissue (striatum) | 5-HT | ns (posttest) | ||||||
5-HIAA | ns (posttest) | |||||||
5-HIAA/5-HT | ns (posttest) | |||||||
brain tissue (midbrain) | 5-HT | ns (posttest) | ||||||
5-HIAA | ns (posttest) | |||||||
5-HIAA/5-HT | ns (posttest) | |||||||
Ben-Shachar et al., 1999 [84] | parallel | Pulse freq.: 15 Hz Intensity: 2 T Pulse N: 52 Session N: 10 Session freq.: 1/day | healthy Sprague-Dawley rats | Exp. group N: 18–20 all male Control group N: 18–20 all male | brain tissue (frontal cortex) | 4 h after the last session | 5-HT | ns (posttest) |
brain tissue (hippocampus) | ns (posttest) | |||||||
brain tissue (striatum) | ns (posttest) | |||||||
brain tissue (midbrain) | ns (posttest) | |||||||
El Arfani et al., 2017 [85] | parallel | Site: prefrontal cortex Pulse freq.: 20 Hz Intensity: 110% MT Pulse N: 1560 Session N: 20 Session freq.: 5/day | healthy Sprague-Dawley rats | Exp. group N: 6 all male Control group N: 6 all male | brain tissue (striatum) | the day after the last session | 5-HT | ns (posttest) |
5-HIAA | ↓ (posttest) | |||||||
Gur et al., 2000 [86] | parallel | Pulse freq.: 15 Hz Intensity: 1.12 T Pulse N: 600 Session N: 10 Session freq.: 1/day | healthy Albino rats | Exp. group N: 10 all male Control group N: 10 all male | microdialysis (left prefrontal cortex) | the morning after the last session | 5-HT | ns (posttest) |
Heath et al., 2018 [87] | parallel | Site: bifrontal cortex Pulse freq.: 10 Hz Intensity: 12 mT Pulse N: 1800 Session N: 20 Session freq.: 5/week | C57BL/6J mice with olfactory bulbectomy (modelling agitated depression) | Exp. group N: 11 all male Control group N: 9 all male | plasma | 24 h after the last session | TRP | ns (posttest) |
plasma | 5-HT | ns (posttest) | ||||||
Intensity: 90 mT | Exp. group N: 5 Control group N: 3 | brain tissue (frontal cortex) | 5-HT | ns (posttest) | ||||
Exp. group N: 10 Control group N: 9 | plasma | TRP | ns (posttest) | |||||
plasma | 5-HT | ↓ (posttest) | ||||||
Intensity: 1.2 T | Exp. group N: 9 Control group N: 9 | plasma | TRP | ns (posttest) | ||||
plasma | 5-HT | ns (posttest) | ||||||
Kanno et al., 2003 [88] | parallel | Site: frontal brain Pulse freq.: 25 Hz Intensity: 0.6 T Pulse N: 125 Session N: 3 Session freq.: 1/day | healthy Wistar rats | Exp. group N: 8 all male Control group N: 7 all male | microdialysis (prefrontal cortex) | - | 5-HT | ns (posttest) |
Kanno et al., 2003 [89] | parallel | Site: frontal brain Pulse freq.: 25 Hz Intensity: 0.6 T Pulse N: 500 Session N: 1 | healthy Wistar rats | Exp. group N: 6 all male Control group N: 6 all male | microdialysis (right prefrontal cortex) | during and 0–160 min after the session | 5-HT | ↓ (posttest) |
Kanno et al., 2004 [90] | parallel | Site: frontal brain Pulse freq.: 25 Hz Intensity: 0.6 T Pulse N: 500 Session N: 1 | healthy Wistar rats | Exp. group N: 6 all male Control group N: 6 all male | microdialysis (right dorsolateral striatum) | during and 0–160 min after the session | 5-HT | ns (posttest) |
Keck et al., 2000 [91] | parallel | Site: left frontal cortex Pulse freq.: 20 Hz Intensity: 130% MT Pulse N: 1000 Session N: 1 | healthy Wistar rats | Exp. group N: 8 all male Control group N: 6 all male | microdialysis (right dorsal hippocampus) | during and 0–30 and 30–60 min after the session | 5-HT | ns (group x time) |
5-HIAA | ns (group x time) | |||||||
Kim et al., 2016 [92] | parallel | Site: right prefrontal cortex Pulse freq.: 10 Hz Intensity: 100% MT Pulse N: 1000 Session N: 15 Session freq.: 5/week | SHR/Izm rats (spontaneously hypertensive, modelling ADHD) | Exp. group N: 9 all male Control group N: 8 all male | brain tissue (prefrontal cortex) | 7 h 50 min after the last session | 5-HT | ns (posttest) |
Löffler et al., 2012 [93] | parallel | Site: cerebral cortex Pulse freq.: 20 Hz Intensity: 130% MT Pulse N: 300 Session N: 1 | healthy Wistar rats | Exp. group N: 8 all male Control group N: 6 all male | microdialysis (nucleus accumbens shell) | 0–160 min after the session | 5-HT | ↑ (posttest/pretest) |
5-HIAA | ns (posttest/pretest) | |||||||
Peng et al., 2018 [94] | parallel | Site: vertex Pulse freq.: 1 Hz Intensity: 0.84 T Session N: 7 Session freq.: 1/day | Sprague-Dawley rats with chronic unpredictable stress (modelling depression) | Exp. group N: 10 all male Control group N: 10 all male | brain tissue (prefrontal cortex) | 24 h after the last session | 5-HT | ns (posttest) |
5-HIAA | ns (posttest) | |||||||
Intensity: 1.26 T | Exp. group N: 10 Control group N: 10 | 5-HT | ns (posttest) | |||||
5-HIAA | ns (posttest) | |||||||
Pulse freq.: 5 Hz Intensity: 0.84 T | Exp. group N: 10 Control group N: 10 | 5-HT | ↑ (posttest) | |||||
5-HIAA | ↓ (posttest) | |||||||
Intensity: 1.26 T | Exp. group N: 10 Control group N: 10 | 5-HT | ↑ (posttest) | |||||
5-HIAA | ↓ (posttest) | |||||||
Pulse freq.: 10 Hz Intensity: 0.84 T | Exp. group N: 10 Control group N: 10 | 5-HT | ↑ (posttest) | |||||
5-HIAA | ↓ (posttest) | |||||||
Intensity: 1.26 T | Exp. group N: 10 Control group N: 10 | 5-HT | ↑ (posttest) | |||||
5-HIAA | ↓ (posttest) | |||||||
Poh et al., 2019 [95] | parallel | Site: lambda Pulse freq.: 10 Hz Intensity: 12 mT Pulse N: 6000 Session N: 1 | healthy C57BL/6J mice | Exp. group N: 5 M:F: 60:40% Control group N: 5 M:F: 60:40% | brain tissue (cortex) | immediately after the session | 5-HT | ns (posttest) |
5-HIAA | ns (posttest) | |||||||
5-HIAA/5-HT | ↓ (posttest) | |||||||
brain tissue (hippocampus) | 5-HT | ns (posttest) | ||||||
5-HIAA | ns (posttest) | |||||||
5-HIAA/5-HT | ns (posttest) | |||||||
brain tissue (striatum) | 5-HT | ns (posttest) | ||||||
5-HIAA | ns (posttest) | |||||||
5-HIAA/5-HT | ns (posttest) | |||||||
Intensity: 1.2 T Pulse N: 3600 | Exp. group N: 6 M:F: 50:50% Control group N: 5 M:F: 60:40% | brain tissue (cortex) | 5-HT | ns (posttest) | ||||
5-HIAA | ns (posttest) | |||||||
5-HIAA/5-HT | ns (posttest) | |||||||
brain tissue (hippocampus) | 5-HT | ns (posttest) | ||||||
5-HIAA | ns (posttest) | |||||||
5-HIAA/5-HT | ns (posttest) | |||||||
brain tissue (striatum) | 5-HT | ns (posttest) | ||||||
5-HIAA | ns (posttest) | |||||||
5-HIAA/5-HT | ns (posttest) | |||||||
Wang et al., 2022 [96] | parallel | Site: center of skull Pulse freq.: 10 Hz Intensity: 90% MT Pulse N: 1000 Session N: 40 Session freq.: 5/week | Sprague-Dawley rats with spinal cord contusion injury | Exp. group N: 10 all female Control group N: 10 all female | ventral horn sections of the lumbar spinal cord | - | 5-HT | ns (posttest) |
tDCS | ||||||||
Tanaka et al., 2013 [97] | parallel | Site: cortex Polarity: cathodal Electrode size: 5 mm × 5 mm Intensity: 800 μA Duration: 10 min Session N: 1 | healthy Sprague-Dawley rats | Exp. group N: 7 all male Control group N: 7 all male | microdialysis (striatum) | during and 0–390 min after the session | 5-HT | ns (posttest/pretest) |
Polarity: anodal | Exp. group N: 7 Control group N: 7 | ns (posttest/pretest) |
Metabolite | Source | Studies | r | Effect BF10 | Heterogeneity BF10 | Publication Bias BF10 |
---|---|---|---|---|---|---|
ECT | ||||||
TRP | plasma | N: 8 [35,39,43,48,52,53,56,58] | 0.5 | 0.216 | 10.191 | 0.645 |
0.7 | 0.278 | 39.36 | 0.891 | |||
0.9 | 0.183 | >100 | 7.014 | |||
KA | plasma | N: 2 [35,52] | 0.5 | 0.174 | 0.568 | 0.656 |
0.7 | 0.174 | 0.629 | 0.978 | |||
0.9 | 0.269 | 2.267 | 1.015 | |||
KA/KYN | plasma | N: 2 [35,52] | 0.5 | 0.174 | 0.468 | 0.461 |
0.7 | 0.178 | 0.46 | 0.461 | |||
0.9 | 0.309 | 0.782 | 0.517 | |||
TMS | ||||||
TRP | plasma | N: 2 [62,63] | 0.5 | 0.279 | 0.699 | 0.633 |
0.7 | 0.242 | 0.732 | 0.683 | |||
0.9 | 0.197 | 1.306 | 1.271 | |||
5-HT | serum | N: 2 [62,63]) | 0.5 | 5.46 | 0.804 | 1.598 |
0.7 | 5.377 | 0.777 | 1.678 | |||
0.9 | 9.232 | 0.79 | 1.504 |
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Giron, C.G.; Lin, T.T.Z.; Kan, R.L.D.; Zhang, B.B.B.; Yau, S.Y.; Kranz, G.S. Non-Invasive Brain Stimulation Effects on Biomarkers of Tryptophan Metabolism: A Scoping Review and Meta-Analysis. Int. J. Mol. Sci. 2022, 23, 9692. https://doi.org/10.3390/ijms23179692
Giron CG, Lin TTZ, Kan RLD, Zhang BBB, Yau SY, Kranz GS. Non-Invasive Brain Stimulation Effects on Biomarkers of Tryptophan Metabolism: A Scoping Review and Meta-Analysis. International Journal of Molecular Sciences. 2022; 23(17):9692. https://doi.org/10.3390/ijms23179692
Chicago/Turabian StyleGiron, Cristian G., Tim T. Z. Lin, Rebecca L. D. Kan, Bella B. B. Zhang, Suk Yu Yau, and Georg S. Kranz. 2022. "Non-Invasive Brain Stimulation Effects on Biomarkers of Tryptophan Metabolism: A Scoping Review and Meta-Analysis" International Journal of Molecular Sciences 23, no. 17: 9692. https://doi.org/10.3390/ijms23179692