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J Clin Psychiatry. 2017 Nov/Dec;78(9):1395-1401. doi: 10.4088/JCP.16m10972.

Advanced Glycation End Products in Recent-Onset Psychosis Indicate Early Onset of Cardiovascular Risk.

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Department of Psychiatry, Early Psychosis Department, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Academic Medical Centre, Department of Psychiatry, Meibergdreef 5, Amsterdam 1105 AZ, The Netherlands.
Departments of Experimental Immunology and Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Department of Community Mental Health, Mental Health Service North-Holland North, Heerhugowaard and Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands.
Contributed equally



Profoundly increased mortality rates in schizophrenia, largely caused by a higher risk and earlier onset of cardiovascular disease, remain a major challenge. During the human lifespan, advanced glycation end products (AGEs) accumulate, and their concentration is strongly linked to cardiovascular mortality. AGE accumulation can be accelerated by several pathways, including oxidative stress.


From March 2015 through January 2016, a case-control study including 111 patients with a recent-onset psychosis, 135 controls from a validation cohort, and 286 healthy controls was performed. Patients fulfilled the DSM-IV criteria for schizophrenia spectrum disorders with an illness duration shorter than 5 years. Main outcome parameters were skin autofluorescence levels of AGEs, controlled for age, gender, and smoking. Correlations of AGEs with cardiovascular risk factors and clinical variables were analyzed by hierarchical linear regression analyses.


An AGE measurement was possible in 77.4% of cases. AGEs were elevated by 15.1% in recent-onset psychosis compared to healthy controls (P < .001), corresponding to an increased accumulation of AGEs normally occurring in approximately 10 years. AGEs were not related to traditional risk factors. However, duration of illness (P = .008), duration of antipsychotic treatment (P = .009), and cumulative exposure to antipsychotics (P = .023) correlated with AGEs.


Patients with a recent onset of psychosis have increased AGE levels compared to healthy controls. These findings argue for an earlier implementation of treatment strategies aimed at preventing cardiovascular disease. Also, low-dose strategies of antipsychotics in schizophrenia could beneficially influence AGE levels.


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