Abstract
Accumulating evidence from clinical, genetic, and epidemiologic studies suggest that schizophrenia might be a neuronal development disorder. While oxysterols are important factors in neurodevelopment, it is unknown whether oxysterols might be involved in development of schizophrenia. The present study investigated the relationship between tissue-specifically originated oxysterols and risk of schizophrenia. A total of 216 individuals were recruited in this study, including 76 schizophrenia patients, 39 clinical high-risk (CHR) subjects, and 101 healthy controls (HC). We investigated the circulating levels of brain-specific oxysterol 24(S)-hydroxycholesterol (24OHC) and peripheral oxysterol 27-hydroxycholesterol (27OHC) in all participants and analyzed the potential links between the oxysterols and specific clinical symptoms in schizophrenic patients and CHR. Our data showed an elevation of 24OHC in both schizophrenia patients and CHR than that in HC, while a lower level of 27OHC in the schizophrenia group only. The ratio of 24OHC to 27OHC was only increased in the schizophrenic group compared with CHR and HC. For the schizophrenic patients, the circulating 24OHC levels are significantly associated with disease duration, positively correlated with the positive and negative syndrome total scores, while the 27OHC levels were inversely correlated with the positive symptom scores. Together, our data demonstrated the disruption of tissue-specifically originated cholesterol metabolism in schizophrenia and CHR, suggesting the circulating 24OHC or 24OHC/27OHC ratio might not only be a potential indicator for risk for schizophrenia but also be biomarkers for functional abnormalities in neuropathology of schizophrenia.
Highlights
Schizophrenia is a chronic mental disorder characterized by delusions, hallucinations, impaired cognition, behavior, or emotions
Schizophrenia is a developmental disease and alteration of circulating cholesterol levels were reported in schizophrenic patients [8,9,10,11,12], it is unclear whether brain and peripheral cholesterol metabolism are disturbanced in schizophrenia and what their relationship related to this disease
Mean plasma 24OHC levels revealed a significant increase in schizophrenia patients (Table 1; Figure 1A, p = 0.045) and an increase trend in clinical high-risk (CHR) participants (p = 0.062) relative to healthy controls (HC)
Summary
Schizophrenia is a chronic mental disorder characterized by delusions, hallucinations, impaired cognition, behavior, or emotions. While the actual causes of schizophrenia are not fully understood, recent studies support the neurodevelopmental hypothesis of schizophrenia [1]. Cholesterol is well-known for its roles in brain development, such as proper myelination, Tissue- Originated Oxysterols in Schizophrenia dendritic differentiation, and synaptic plasticity in central nervous system (CNS) [2,3,4]. Studies have shown that maining cholesterol homeostasis is essential for proper cellular and systemic functions, while disturbance cholesterol homeostasis might increase risks for many neurodevelopmental disorders [5,6,7]. Schizophrenia is a developmental disease and alteration of circulating cholesterol levels were reported in schizophrenic patients [8,9,10,11,12], it is unclear whether brain and peripheral cholesterol metabolism are disturbanced in schizophrenia and what their relationship related to this disease
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