Associations between residential environments and late-onset schizophrenia in UK Biobank: Interaction with genetic risk factor.

Background: Environment and genes both contribute to schizophrenia. However, the impact of different natural environments surrounding residential addresses on schizophrenia in urban settings remains unknown. This study aimed to investigate the association of urbanisation, measured by residential environments, with late-onset schizophrenia and explore whether genetic risk for schizophrenia modified the associations.

Methods: We examined the associations between residential environments and late-onset schizophrenia and its interaction with genetic risk factors in UK Biobank, followed from 2006 to 2010 (baseline) to Dec 2021. Residential environments, including greenspace, domestic garden, blue space, and total natural environment, were evaluated using land use coverage percentage. The polygenic risk score (PRS) of schizophrenia was derived using a Bayesian approach and adjusted it against ancestry. Cox proportional hazard regression model was used to assess the associations between per interquartile (IQR) increase of each type of residential environments and late-onset schizophrenia. Interactive effects of PRS and residential environments on late-onset schizophrenia were assessed on both additive and multiplicative scales.

Results: A total of 393,680 participants were included in the analysis, with 844 cases of late-onset schizophrenia being observed after 12.8 years of follow-up. Within 300 m buffer surrounding the residential addresses, per interquartile increase in greenspace (31.5 %) and total natural environment (34.4 %) were both associated with an 11 % (HR = 0.89, 95 % CI 0.80, 0.99) lower risk of late-onset schizophrenia. Domestic garden and blue space did not show significant protective effects on late-onset schizophrenia. A strong dose-response relationship between schizophrenia PRS and schizophrenia was found, while no additive or multiplicative interaction effects were present between residential environments and PRS on late-onset schizophrenia.

Conclusion: Residential greenspace and total natural environment may protect against late-onset schizophrenia in older people regardless of genetic risk. These findings shed light on the prevention of schizophrenia and urban planning to optimise ecosystem benefits linked to schizophrenia.