Table 3.
mTORC1-related biomarkers in clinical studies. Summarized are mTORC1-related biomarkers, which are close relative to mTORC1 (mTORC1-proximal), farther downstream the mTORC1 (mTORC1-distal), and upstream of mTORC1. Presented data are based on clinical studies in MDD in which the pharmacological treatment deemed successful and resulted in fast mood improvement, unless stated otherwise..
| References | Treatment | Classic AD | Biomarker (time after dosing) | Matrix | Baseline Biomarker | Treatment response | Sample size (m/f) | p | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| mTORC1-proximal | mTORC1-distal | Upstream | C/P | Biomarker | Mood | C | P | |||||
| Denk and colleagues 75 | ket | No | mTOR (ph, 100 min) | PBMCs | NA/100% | 500%↑ | MADRS, 4↓ | NA | 1 (f) | NA | ||
| BDI, 3↓ | ||||||||||||
| Haile and colleagues 76 | ket | No | BDNF (pr, 240 min) | Plasma | ~2.5 ng/ml | ~3.5 ng/ml↑ | MADRS, ~12↓ | NA | 15 | 0.03 | ||
| Allen and colleagues 77 | ket | No | BDNF (pr, 1 week) | Serum | ~19/~10 ng/ml | ~15 ng/ml↑ | HAMD, ~10 ↓ | 10/10 | 9/8 | <0.05 a | ||
| <0.001b,c | ||||||||||||
| <0.03 d | ||||||||||||
| Szuster-Ciesielska and colleagues 78 | NA | NA | Apoptosis (Bcl-2/Bax pr) | PBMCs | 0.969 ± 0.05/0.746 ± 0.1 | NA | NA | 15/15 | 14/15 | <0.05b,* | ||
| Eilat and colleagues 79 | NA | NA | Apoptosis (apoptotic cells) | PBMCs | 0.5%–24.85%/1%–27% | NA | NA | 6/1 | 6/1 | <0.05 b | ||
| Amidfar and colleagues 80 | NA | NA | Apoptosis (Bcl2/Bax mRNA) | PBMCs | 1/0.776 ± 0.08; 0.36 ± 0.04 | NA | NA | 15/15 | 13/17; 7/236 | <0.001 e | ||
| <0.001 b | ||||||||||||
PBMC, peripheral blood mononuclear cell; ph, phosphorylated protein; pr, protein; mRNA, gene expression; m, male; f, female; C, control group; P, patient group; V, measured biomarker value; Dep, depression scale score; NA, not applicable; NR, not reported; ket, ketamine; mid, midazolam; escita, escitalopram; cita, citalopram; ser, sertraline; par, paroxetine; ven, venlafaxine; desven, desvenlafaxine; flu, fluoxetine; mir, mirtazapine; clom, clomipramine; traz, trazodone; ago, agomelatine; benzo, benzodiazepines. For all other abbreviations, see list of abbreviations.
~Approximation.
↓Decrease compared with previous state.
↑Increase compared with previous state.
Difference from (baseline) biomarker.
Difference from controls.
Difference from (baseline) mood/depression score.
Correlation between biomarker and mood.
Difference from other patient subgroup.
Measurement performed once.