Table 3.

Epigenome-wide DNA methylation at baseline associated with response to cognitive-behavioral therapy (CBT) at T1 (post-treatment) and at T2 (6-month follow-up) with suggestive significance (p ≤ 1E–5) in patients with anxiety disorders (T1: N = 336; T2: N = 306).

T1
CpG	Coefficienta	SE	Z-Value	P-Value b	Nearest Gene Annotation	Previous Functional Evidence	References
cg14814319	−4.685	0.969	−4.834	1.336E–06	RPSAP52	Associated with anxiety disorders in B-cells in a cross-anxiety disorder EWAS	[25]
cg10700019	4.548	0.952	4.776	1.791E–06	ZNF251	–	–
cg06730721	6.040	1.266	4.770	1.838E–06	ABCA7	No involvement in anxiety in Abca7 KO mice, but implicated in synaptic plasticity and cognition, as potentially relevant for CBT	[91, 92]
cg17982539	3.801	0.805	4.724	2.312E–06	LTBR	–	–
cg02325313	−2.662	0.585	−4.553	5.295E–06	ADRA2C	Adra2c mRNA levels were modulated by stress in a mouse model	[93]
cg01461856	−2.140	0.478	−4.472	7.737E–06	SLC47A2	Associated with anxiety disorders in granulocytes and B-cells in a cross-anxiety disorder EWAS	[25]
cg11888727	−4.062	0.909	−4.467	7.951E–06	SH3RF3	Associated with anxiety disorders in granulocytes in a cross-anxiety disorder EWAS	[25]
T2
cg12069641	1.659	0.366	4.528	5.949E–06	USP47	–	–
cg00032490	−1.892	0.424	−4.465	8.012E–06	ADGRD1	–	–
cg04793888	4.040	0.911	4.435	9.216E–06	PRSS58	–	–

Response to CBT was defined according to a T0–T1 or T0–T2 change of ≥ 50% in Hamilton Anxiety Rating Scale (HAM-A) scores (see “Treatment”).

^aa positive coefficient indicates higher methylation to predict increased response to CBT and vice versa.

^badjusted for absolute Hamilton Anxiety Rating Scale (HAM-A) score at T0, technical variance, age, sex, smoking status and comorbidity with depression.