Table 3.

Psychological stress and psychopathology affect GR gene methylation

	Study	Experimental Group	Species	Sex (% male)	Sample size	DNA Methylation Assessment	Tissue(s)	Age at Sample Collection	16	17	NGFI-A site?	110
Animal Studies	1 Desarnaud et al. 2008 (22)	Social defeat and exposure to rat	Mouse	NR	5 animals per group	Sodium bisulfite treatment (EZ DNA Methylation Kit, Zymo Research) + sequencing (ABI Prism 3100 Genetic Analyzer, Applied Biosystems)	Hippocampus	NR		no Δ a	Y
	2 Witzmann et al. 2012 (24)	Acute or chronic stress	Rat	100	6 animals per group	Sodium bisulfite treatment (EpiTect Bisulphite kit, Qiagen) + pyrosequencing (Pyromark ID using Pyrogold reagents, Biotage)	Paraventricular nucleus (PVN) Hippocampus Adrenal Pituitary	10–12-week-old		↑b	Yc
	3 Tran et al. 2013 (50)	Repeated (7 day) water avoidance stress	Rat	100	6 animals per group	Sodium bisulfite treatment (EZ DNA Methylation-Gold kit, Zymo Research) + pyrosequencing (EpigenDX)	Amygdala	Adult		↑	Y

	Study	Experimental Group	Sex (% male)	Sample size	DNA Methylation Assessment	Tissue(s)	Age at Sample Collection	1D	1J	1E	1B	1F	NGFI-A site?	1C	1H	Other
Human Peripheral Studies	4 De Rooij et al. 2012 (51)	Variations in acute stress reactivity	47	675	Methylation-sensitive enzymatic restriction (AciI and HinfI) + qPCR (SYBR Green, Sigma)	Blood	55–60							no Δs
	5 Dammann et al. 2011 (52)	Borderline personality disorder	Control: 0 BPD: 8	Control: 11 BPD: 26	COBRA and/or Sodium bisulfite treatment + pyrosequencing (PyroMark Q24, Qiagen)	Blood	33					↑	N
	6 Steiger et al. 2013 (21)	Bulimia nervosa with childhood abuse	0	BN with childhood abuse: 32 BN without childhood abuse: 32 No BN or abuse: 32	Sodium bisulfite treatment (EpiTect Bisulfite Kit, Qiagen) + EpiTYPER platform (Sequenom)	Blood	BN: 26.05 (mean) No eating disorder: 23.67 (mean)				no Δ	no Δ	Y	↑d	↓e
	7 Yehuda et al. 2013 (53)	Combat veterans with PTSD and prolonged exposure to psychotherapy: responders and non- responders	88	Responders: 8 Non-responders: 8	Sodium bisulfite treatment (EpiTect Bisulfite Kit, Qiagen)+ sequencing (Genewiz)	Blood	Responders: 41 Non-responders: 58					no Δ f	Y
	8 Labonté et al. 2014 (55)	Post-traumatic stress disorder and negative trauma experience	50	PTSD: 30 Controls: 16	Sodium bisulfite treatment (EpiTect Bisulfite Kit, Qiagen) + Epityper (Sequenom)	Blood	PTSD: 43.4 Controls: 36.9				↓			↓	no Δ
	9 Yehuda et al. 2014 (54)	Combat veterans with or without post-traumatic stress disorder	100	PTSD: 61 Controls: 61	Sodium bisulfite treatment (EpiTect Bisulfite Kit, Qiagen) + Sequencing (Genewiz)	Blood	PTSD: 34.2 Controls: 33.0					↓	Y
	10 Na et al. 2014 (56)	Major Depression Disorder	MDD: 24 Controls: 29	Total: 117 MDD: 45 Controls: 72	Sodium bisulfite treatment (EZ DNA Methylation-Gold kit, Zymo Research) + Pyrosequencing (Pyromark ID, Varionostic)	Blood	18–65 MDD: 41.6 (median) Controls: 40.72 (median)					↓g	Y
Human Central Studies	11 Alt et al. 2010 (30)	Lifetime diagnosis of major depressive disorder	MDD: 67 Controls: 50	MDD: 6 Controls: 6	Sodium bisulfite treatment (EpiTect Bisulfite Kit, Qiagen) + Pyrosequencing (Pyromark ID, Varionostic)	Amygdala Hippocampus Inferior prefrontal gyrus Cingulate gyrus Nucleus accumbens	MDD: 75.5 Controls: 72.5		no Δs	no Δs	no Δs	no Δs	Y

^ano detectable methylation on NR3C1 CpGs.

^bAcute stress group – ↑ methylation at several CpG sites in hippocampus only; Chronic stress group – ↑ methylation in response to psychosocial stress in adrenal and pituitary, ↑ methylation in adrenal and ↓ methylation in the pituitary in response to restraint stress.

^cAcute stress – hippocampus only; Chronic stress – adrenal only.

^dCpGs 10 & 21; BN vs. no eating disorder.

^eIn BN+BPD vs. BN no BPD/no eating disorder.

^fNo change over time and no difference between responders and non-responders.

^gCpGs 3 & 4.