Related Experiment Video
Updated: May 27, 2026

Rapid Fractionation and Isolation of Whole Blood Components in Samples Obtained from a Community-based Setting
Published on: November 30, 2015
Evidence that interactive effects of COMT and MTHFR moderate psychotic response to environmental stress
O Peerbooms1, B P F Rutten, D Collip
1Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, European Graduate School of Neuroscience, South Limburg Mental Health Research and Teaching Network, Maastricht University, The Netherlands.
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 [χ(2)(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 [χ(2)(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.
Related Concept Videos
Psychological and Sociocultural Causes of Schizophrenia
Human Genetics
The complex relationship between genetics and psychology is observable through common biological components such...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Gene-Environment Interactions
Causes of Social Behavior III: Biological and Environmental Influences
Stress and Mental Health
Individuals with depression often experience challenges in both their personal and professional...

