A cannabinoid receptor gene variant predicts cognitive improvement in first-episode psychosis treatment | Research

The takeaway

The CNR1 rs7766029 CC genotype was associated with greater improvement in verbal memory over 18 months of first-episode psychosis treatment, even after controlling for cannabis use.

Psychiatric geneticists, psychosis researchers, and clinicians interested in personalized medicine.

CNR1 CC genotype linked to greater verbal memory improvement

What the researchers found

Carriers of the CNR1 rs7766029 CC genotype showed significantly greater improvement in verbal memory (Wechsler, Wechsler 30') and attention (Digit span F). The rs12720071 AG genotype was linked to improved executive function but lower language improvement. After full adjustment (age, sex, cannabis use, negative symptoms), the rs7766029 association with Wechsler 30' remained significant.

Why it matters

If cannabinoid receptor gene variants predict who will improve cognitively during psychosis treatment, this could help personalize treatment plans and identify patients who may need additional cognitive interventions.

The numbers in context

159 patients enrolled, 121 genotyped. rs7766029 CC carriers showed greater Wechsler 30' improvement (significant at FDR <15% after full adjustment). rs7766029 also associated with stress perception changes.

How the study worked

Longitudinal study of 159 first-episode psychosis patients from two Croatian hospitals (2014-2017). Neurocognitive testing at baseline and 18 months. CNR1 polymorphisms (rs7766029, rs12720071) genotyped in 121 patients. Associations adjusted for multiple covariates.

What this study cannot tell us

Moderate sample size. FDR threshold of 15% is relatively liberal. Two sites in Croatia may not generalize to other populations. Cannabis use was controlled for but may interact with genotype in complex ways.

How to read the evidence

Moderate: longitudinal design with 18-month follow-up and genotype analysis, but moderate sample size and liberal FDR threshold.

When this study was published

Published in 2019.

The bigger picture

The endocannabinoid system is increasingly recognized as a modulator of cognition in psychosis. This genetic study suggests that natural variation in cannabinoid receptor genes influences cognitive recovery trajectories.

Questions still open

Could CNR1 genotyping be used clinically to predict treatment outcomes? Do these genotypes also predict response to cannabinoid-based treatments? Would larger, multi-ethnic studies replicate these findings?

Common questions

What is the CNR1 gene?

CNR1 encodes the CB1 cannabinoid receptor, the primary target of THC in the brain. Genetic variants in CNR1 affect how this receptor functions and may influence cognitive outcomes.

Did cannabis use affect the results?

The association between CNR1 genotype and cognitive improvement remained significant after controlling for cannabis use, suggesting the genetic effect is independent of whether patients used cannabis.

Read the original research

Association of CNR1 genotypes with changes in neurocognitive performance after eighteen-month treatment in patients with first-episode psychosis.

European psychiatry : the journal of the Association of European Psychiatrists, 61, 88-96

View on PubMed ↗Publisher’s paper ↗

Citation

Rojnic Kuzman, Martina; Bosnjak Kuharic, Dina; Ganoci, Lana; Makaric, Porin; Kekin, Ivana; Rossini Gajsak, Linda; Prpic, Nikola; Bozina, Tamara; Bajic, Zarko; Bozina, Nada. (2019). Association of CNR1 genotypes with changes in neurocognitive performance after eighteen-month treatment in patients with first-episode psychosis.. European psychiatry : the journal of the Association of European Psychiatrists, 61, 88-96. https://doi.org/10.1016/j.eurpsy.2019.07.004