Our findings also tentatively support consideration of several drug classes as therapeutic repurposing candidates for PTSD. For example, acetylcholine receptor antagonists could be considered given their association in cMAP with PLEKHM1. In a recent rodent study, the muscarinic receptor antagonist, scopolamine, augmented extinction in conjunction with exposure64 (although other studies suggest that positive allosteric modulation of M1 muscarinic activity enhances contextual fear conditioning)65. These results together suggest that a therapeutic role for cholinergic modulation in PTSD and other fear-related conditions, possibly in concert with exposure therapy, should be investigated. Angiotensin receptor antagonists, also identified as drug candidates through cMAP, have a strong preclinical rationale for use in PTSD66–68 and are, in fact, currently undergoing testing in a randomized placebo-controlled trial of losartan for PTSD (ClinicalTrials.gov Identifier: NCT02709018P).
