Genetic Risk Scores for Cannabis Use Predicted Symptom Trajectories After First-Episode Psychosis | Research

The takeaway

In 249 first-episode psychosis patients followed for 12 months, polygenic risk scores for cannabis use disorder predicted baseline cannabis consumption, while scores for cannabis initiation predicted the trajectory of negative and general symptoms over time.

Psychiatric geneticists, psychosis researchers, precision psychiatry advocates.

Genetic risk for cannabis initiation predicted psychosis symptom trajectories over 12 months

What the researchers found

Current cannabis use was associated with increased positive symptoms. Earlier age of cannabis initiation conditioned 12-month symptom progression. Higher polygenic risk for CUD (PRSCUD) predicted increased baseline cannabis use in FEP patients. Polygenic risk for cannabis initiation (PRSCI) was associated with the course of negative and general symptoms over 12 months. Cannabis initiation and CUD may have partially independent genetic factors.

Why it matters

This suggests that genetic factors influencing whether someone tries cannabis versus whether they develop problematic use are partially independent, and each influences different aspects of psychosis outcomes. This could eventually enable personalized treatment approaches.

The numbers in context

N=249 FEP patients. 12-month follow-up. PRSCUD predicted baseline cannabis use. PRSCI predicted negative and general symptom trajectories. Earlier cannabis initiation conditioned symptom progression.

How the study worked

Cohort study of 249 FEP individuals evaluated over 12 months. Symptom severity measured with PANSS. Cannabis use assessed with EuropASI. Individual polygenic risk scores constructed for lifetime cannabis initiation and cannabis use disorder.

What this study cannot tell us

Exploratory analysis with modest sample size. Polygenic risk scores explain a small fraction of variance. Single cohort without replication. Cannot determine causal direction between genetic risk, cannabis use, and symptom trajectories.

How to read the evidence

Cohort study with 12-month follow-up. Exploratory polygenic risk analysis with modest sample size.

When this study was published

Published in 2023.

The bigger picture

Precision psychiatry aims to match treatments to individual patient profiles. If genetic risk scores can identify which psychosis patients are most vulnerable to cannabis-related harm, clinicians could prioritize substance use interventions for those patients.

Questions still open

Could cannabis polygenic risk scores be used clinically to identify high-risk FEP patients?
Would cannabis-specific interventions improve outcomes for FEP patients with high genetic risk?

Common questions

Does genetics predict who will use cannabis during psychosis?

Polygenic risk scores for cannabis use disorder predicted baseline cannabis consumption in first-episode psychosis patients, suggesting genetic vulnerability plays a role.

Can genetic tests predict psychosis outcomes?

In this exploratory study, genetic risk for cannabis initiation predicted the trajectory of negative and general symptoms over 12 months, but these scores explain only a small fraction of individual variation.

Read the original research

Exploration of cannabis use and polygenic risk scores on the psychotic symptom progression of a FEP cohort.

Psychiatry research, 325, 115249

View on PubMed ↗Publisher’s paper ↗

Citation

Segura, Alex G; Mané, Anna; Prohens, Llucia; Rodriguez, Natalia; Mezquida, Gisela; Cuesta, Manuel J; Vieta, Eduard; Amoretti, Silvia; Lobo, Antonio; González-Pinto, Ana; Diaz-Caneja, Covadonga M; Bejarano, Alexandra Roldán; Jimenez, Esther; Baeza, Immaculada; Legido, Teresa; Saiz-Ruiz, Jeronimo; Bernardo, Miguel; Mas, Sergi. (2023). Exploration of cannabis use and polygenic risk scores on the psychotic symptom progression of a FEP cohort.. Psychiatry research, 325, 115249. https://doi.org/10.1016/j.psychres.2023.115249