These authors contributed equally to this work.
Evidence that interactive effects of COMT and MTHFR moderate psychotic response to environmental stress
Article first published online: 30 NOV 2011
© 2011 John Wiley & Sons A/S
Acta Psychiatrica Scandinavica
Volume 125, Issue 3, pages 247–256, March 2012
How to Cite
Peerbooms, O., Rutten, B. P. F., Collip, D., Lardinois, M., Lataster, T., Thewissen, V., Mafi Rad, S., Drukker, M., Kenis, G., van Os, J., Myin-Germeys, I. and van Winkel, R. (2012), Evidence that interactive effects of COMT and MTHFR moderate psychotic response to environmental stress. Acta Psychiatrica Scandinavica, 125: 247–256. doi: 10.1111/j.1600-0447.2011.01806.x
- Issue published online: 10 FEB 2012
- Article first published online: 30 NOV 2011
- Accepted for publication October 31, 2011
- psychotic disorder;
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 < 0.0001), but not in controls (P = 0.68). Further examination of this interaction revealed that in patients with the MTHFR 677 T-allele, COMT Met/Met individuals displayed the largest increases in psychotic symptoms in reaction to ESM stress [χ2(2) = 29.51; P < 0.0001], whereas in patients with the MTHFR 677 C/C genotype no significant COMT Val158Met × ESM stress interaction was apparent [χ2(2) = 3.65; P = 0.16]. No moderating effect of MTHFR A1298C was found.
Conclusion: Stress reactivity associated with COMT Val158Met in patients with psychosis may crucially depend on MTHFR C677T genotype.