Polygenic and Polyenvironment Interplay in Schizophrenia-Spectrum Disorder and Affective Psychosis; the EUGEI First...

Area of Science:

• Psychiatry
• Genetics
• Environmental Health

Background:

• Schizophrenia-spectrum disorders and affective psychoses share genetic and environmental risk factors.
• The combined influence of these factors on psychosis development requires further clarification.

Purpose of the Study:

• To investigate the interplay between polygenic risk scores (PRS) for schizophrenia, bipolar disorder, and depression and environmental risk factors in first-episode psychosis.
• To examine potential gene-environment interactions in the development of schizophrenia-spectrum disorders and affective psychoses.

Main Methods:

• Analysis of 573 first-episode psychosis cases and 1005 controls of European ancestry.
• Stratification of participants based on exposure to environmental factors like migration, paternal age, childhood adversity, and cannabis use.
• Regression models to assess PRS associations and test for polygenic by polyenvironment interactions.

Main Results:

• Polygenic risk score for schizophrenia (PRS-SZ) was a stronger predictor in schizophrenia-spectrum disorder, particularly in individuals with lower environmental risk exposure.
• Polygenic risk score for depression (PRS-D) showed a stronger association with affective psychosis in individuals exposed to environmental risks.
• No significant interaction was detected between any PRS and the polyenvironmental score.

Conclusions:

• Genetic liability and polyenvironmental risk appear to play independent roles in psychosis, aligning with the liability threshold model.
• Schizophrenia-spectrum disorders are primarily associated with polygenic risk for schizophrenia, with an additive effect from environmental factors.
• Affective psychosis development seems influenced by cumulative environmental exposures and heightened genetic liability for affective disorders.