A gene involved in dopamine regulation interacted with cannabis use to affect when psychosis first appeared | Research

The takeaway

In 169 first-episode psychosis patients, cannabis use was associated with earlier onset, and the COMT Val158Met gene variant's effect on onset timing was only visible in non-users.

Read this if you are interested in how genetics and cannabis interact to influence psychosis risk.

COMT gene effect on psychosis timing visible only in non-cannabis-users

What the researchers found

Researchers examined 169 patients with first-episode schizophrenia spectrum disorders, looking at how the COMT gene (which regulates dopamine) interacted with cannabis use to affect when psychosis first appeared.

Cannabis users had significantly earlier onset of psychosis compared to non-users. The Met/Met genotype of COMT was associated with later onset, but only among patients who did not use cannabis.

Among cannabis users, the COMT genotype had no effect on onset timing. The authors concluded that cannabis use may override the protective delay effect of the Met allele, essentially eliminating the genetic advantage that would otherwise delay psychosis onset.

Why it matters

This was among the first studies to demonstrate gene-environment interaction between COMT and cannabis in the timing of psychosis onset, suggesting cannabis may neutralize genetic factors that would otherwise delay disease onset.

The numbers in context

169 Caucasian patients with first-episode psychosis. Cannabis-COMT interaction was significant for both DUP and age of onset. COMT genotype differences in onset were present only in non-users.

How the study worked

Cross-sectional study of 169 Caucasian patients with first-episode schizophrenia spectrum disorder. COMT Val158Met polymorphism was typed using PCR. Cannabis use was classified as regular versus sporadic/non-user. Multivariate ANCOVA tested effects on age of onset and duration of untreated psychosis (DUP), with gender as covariate.

What this study cannot tell us

Cross-sectional design examining only patients who already developed psychosis (no healthy controls). Cannot determine whether cannabis caused earlier onset or whether earlier-onset patients were more likely to use cannabis. Self-reported cannabis use may be unreliable.

How to read the evidence

Cross-sectional study of moderate size with genetic typing, but limited by lack of healthy controls and self-reported cannabis use.

When this study was published

Published in 2010. Gene-environment interaction research in psychosis has advanced substantially.

The bigger picture

This research contributed to understanding why some people develop psychosis earlier than others, identifying cannabis use as an environmental factor that could override genetic protective factors.

Questions still open

Does cannabis accelerate psychosis onset through the dopamine pathway that COMT regulates? Would these findings replicate in larger, more diverse samples?

Common questions

What is the COMT gene?

COMT (Catechol-O-Methyltransferase) is a gene that controls an enzyme involved in breaking down dopamine in the brain. Different versions of this gene affect how quickly dopamine is cleared.

Does this mean cannabis causes earlier psychosis?

The study found an association between cannabis use and earlier psychosis onset, but the cross-sectional design could not prove causation. Other factors may explain why some patients both used cannabis and developed psychosis earlier.

Read the original research

Catechol-O-Methyltransferase (COMT) Val158Met variations and cannabis use in first-episode non-affective psychosis: clinical-onset implications.

Psychiatry research, 179(3), 291-6

View on PubMed ↗Publisher’s paper ↗

Citation

Pelayo-Terán, José María; Pérez-Iglesias, Rocío; Mata, Ignacio; Carrasco-Marín, Eugenio; Vázquez-Barquero, José Luis; Crespo-Facorro, Benedicto. (2010). Catechol-O-Methyltransferase (COMT) Val158Met variations and cannabis use in first-episode non-affective psychosis: clinical-onset implications.. Psychiatry research, 179(3), 291-6. https://doi.org/10.1016/j.psychres.2009.08.022