Evidence that interactive effects of COMT and MTHFR moderate psychotic response to environmental stress

Peerbooms O, Rutten BPF, Collip D, Lardinois M, Lataster T, Thewissen V, Mafi Rad S, Drukker M, Kenis G, van Os J, Myin‐Germeys I, van Winkel R. Evidence that interactive effects of COMT and MTHFR moderate psychotic response to environmental stress. Objective: A functional interaction between Catechol‐O‐Methyltransferase (COMT) Val158Met and methylenetetrahydrofolate reductase (MTHFR) C677T has been shown to differentially affect cognition in patients with schizophrenia and healthy controls; the effect of COMT Val158Met × MTHFR interaction on resilience to stress in patients and controls remains to be examined. Method: A total of 98 patients with non‐affective psychotic disorder and 118 controls were genotyped for MTHFR C677T, MTHFR A1298C, and COMTVal158Met. Daily life reactivity to stress, modelled as the effect of daily life stress on psychotic experiences, was measured using the experience sampling method (ESM). Results: The MTHFR C677T genotype moderated the interaction between COMT Val158Met genotype and stress in patients (P