Skin advanced glycation end products, indicating cumulative oxidative stress, associated with schizophrenia but not with psychosis-like experiences

Background: Excessive oxidative stress is one of the proposed pathophysiological mechanisms in the development of schizophrenia. As a result of oxidative stress, advanced glycation end products (AGEs) are formed. Skin autofluorescence measures of AGEs (SAF-AGEs) serve as indicator of cumulative oxidative stress and are associated with occurrence of psychotic disorders. Here, the association between SAF-AGE level as a proxy for cumulative oxidative stress and subsequent psychosis-like experiences (PLEs) in the general population is investigated. Methods: Participants of the Lifelines study, a population-based cohort study in the Netherlands, who had completed a SAF-AGE measurement at baseline and the Psychosis Screening Questionnaire (PSQ) at 10 year follow-up were included. Association between SAF-AGE level and PSQ was assessed in a linear mixed model, adjusted for family ties and sex. Sociodemographic factors and polygenic score for schizophrenia (PGS-SZ) were added to the model hierarchically. Results: Of the 30,862 included participants (59 % female, mean age of 46), 1318 (4.3 %) experienced PLEs. Age-adjusted Z-score of SAF-AGE level (n = 83,016) and self-reported schizophrenia diagnosis showed a statistically significant association (estimate = 0.65 [95 % CI 0.40, − 0.89], p < .001). SAF-AGE level was not significantly associated to PSQ (estimate = 2.88⁻³ [95 % CI -4.98⁻⁵¹, 5.81⁻³], p = .05). The adjusted model showed similar results. Conclusions: Results indicate that excessive oxidative stress is not involved in development of PLEs, as opposed to in case of clinical psychosis.