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. 2025 Apr 25;30(10):4529–4542. doi: 10.1038/s41380-025-03038-5

Table 4.

Epigenome-wide suggestive (p < 1E–5) DNA methylation changes (Mean Diff.) from T0 (baseline) to T1 (post-treatment) and to T2 (6-month follow-up), respectively, in a responders to cognitive-behavioral therapy (CBT) in patients with anxiety disorders (T0–T1: N = 133; T0–T2: N = 141).

T0–T1
CpG T-Value P-Value Mean Diff. T0–T1 Nearest Gene Annotation Previous Functional Evidence Reference
T0–T2
CpG T-Value P-Value Mean Diff. T0-T2 Nearest Gene Annotation Previous Functional Evidence Reference
cg04624514 −4.739 5.212E–06 −0.00085 (−0.1%) TMCC1

• CircTmcc1 contributed to the secretion of proinflammatory mediators and glutamate metabolism in astrocytes and subsequently modulated an improvement in spatial memory by mediating neuronal synaptic plasticity

• Associated with anxiety disorders in granulocytes in a cross-anxiety disorder EWAS

[25, 94]
cg00666772 4.659 7.317E–06 −0.00018 (−0.02%) OCA2 • Associated with anxiety disorders in monocytes in a cross-anxiety disorder EWAS [25]
cg21601852 4.612 8.917E–06 −0.0011 (0.12%) ADIPOR2

• Adiponectin-deficient mice exhibited normal contextual fear conditioning but displayed slower extinction learning

• Infusions of adiponectin into the dentate gyrus of the hippocampus in fear-conditioned mice facilitated extinction of contextual fear

• Targeting adiponectin/AdipoR2 have been suggested to strengthen extinction-based exposure therapies

• Adiponectin-KO mice displayed increased anxiety at 9 and 18 months

• Associated with anxiety disorders in granulocytes in a cross-anxiety disorder EWAS

[25, 9597]
cg21474639 4.597 9.472E–06 −0.00041 (−0.05%) EIF3B

Mean Diff.: negative values indicate a decrease in methylation from T0–T2.

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