TABLE 2:

CLINICAL STUDIES-PBMC, MONOCYTES, POSTMORTEM BRAIN

MODEL	TARGET	DIAGNOSIS/TREATMENT	RESPONSE	PUBLICATION
PBMC	TLRs	MDD (n=30) HC (n=29)	↑ TLR3, 4, 5, 7 mRNA ↓ TLR1, 6 mRNA	Hung YY et al. (2014)
PBMC	TLRs	MDD (n=56) HC (n=35) SSRI, SNRI, NDRI Tetracyclic	↓ TLR3, 5, 7, 8, 9 mRNA baseline after trt ↓ TLR1, 2, 4, 6 mRNA below baseline after trt	Hung YY et al. (2016)
PBMC	TLRs	MDD (n=68) M (n=15); F (n=53) SSRI, SNRI	↓ TLR2, 3, 4, 6, 8, 9 and IL-6 mRNA after SSRI ↓TLR2, 5, 6 mRNA after SNRI	Hou T-Y et al. (2018)
PBMC,monocytes	TLR regulators	MDD (n=100) HC (n=53) M (n=21); F (n=79) SSRI, SNRI	↓ MyD88s, TNFAIP3 mRNA at baseline in MDD ↑ TNFAIP3 after SSRI TNFAIP3 predicted improvement (HAMD-17) ↓ LPS-induced IL-6 mRNA after fluoxetine (THP-1)	Hung YY et al. (2017)
Monocytes	TNFAIP3	MDD (n=91) M (n=20); F (n=71)	TNFAIP3 mRNA correlation with psychological anxiety (HAMD-17)	Chen RA et al. (2018)
CD14+Monocytes	TLR negative regulators	MDD (n=34) HC (n=33)	↑ All TLR mRNA except TLR3, 5 ↓ TOLLIP, MyD88s, NOD2, TNFAIP3 mRNA ↑TNFAIP3 mRNA after antidepressant trt	Hung YY (2018)
WBC	TLR4	MDD (n=51) M (n=15); F (n=36)	Psychological anxiety, weight loss predict TLR4 mRNA levels (HAMD-17)	Wu MK et al. (2015)
PBMC	TLR4 TLR proteins	MDD (n=50) HC (n=30)	↑ TLR4 mRNA/protein, NF- κB mRNA; no change CBT ↑ IL-6 and CRP; no change CBT	Keri S. et al. (2014)
Postmortem-DLPFC	TLR3/4	DS (n=22); DNS (n=12); NC (n=20)	↑ TLR3, 4 mRNA DS and DNS ↑ TLR3, 4 protein in DS	Pandey GN et al. (2014)
Postmortem-PFC	TLRs	DS (n=24); DNS (n=12); NC (n=24)	↑ TLR2, 3 mRNA in DS and TLR3, 4, 7 in DNS ↑ TLR2-4, 6, 10 protein in DS	Pandey GN et al. (2019)
Postmortem-DLPFC	TLR4 TLR proteins	MDD (n=30) Antidepressant (n=15); anti-free (n=15) HC (n=30) SSRI, SNRI, Tricyclics	No change in TLR4 protein ↑ HSP70, p38 and JNK MAPK ↓ Nrf2 (anti-oxidant), DUSP2 (MAPK regulator)	Martin-Hernandez D. et al. (2018)

Abbreviations- PBMC: peripheral blood mononuclear cells; CD14: cluster of differentiation 14; WBC: whole blood cells; DL(PFC): dorsolateral prefrontal cortex; TLR4: toll-like receptor 4; MDD: major depressive disorder; HC: healthy controls; SSRI: serotonin-selective reuptake inhibitor; SNRI: norepinephrine-selective reuptake inhibitor; NDRI; norepinephrine-dopamine reuptake inhibitor; M: male; F: female; DS: depressed suicide; DNS: depressed non-suicide; NC: normal control; mRNA: message ribonucleic acid; trt: treatment; IL-6: interleukin-6; MyD88s: myeloid differentiation primary response protein 88 (splice variant); TNFAIP3: TNF alpha induced protein 3; HAMD-17: Hamilton Depression Rating Scale; LPS: lipopolysaccharide; THP-1: human monocytic cell line; TOLLIP: toll-interacting protein; NOD2: Nucleotide-binding oligomerization domain-containing protein 2; NF-κB: nuclear Factor kappa-light-chain-enhancer of activated B cells; CBT: cognitive behavioral therapy; CRP: C-reactive protein; HSP70: heat shock protein 70; p38 MAPK: p38 mitogen-activated protein kinase; JNK: Jun N-terminal kinase; Nrf2: Nuclear factor erythroid 2-related factor 2; DUSP2: Dual specificity protein phosphatase 2