Decreased serum levels of α-synuclein in patients with schizophrenia and their unaffected siblings

Early Interv Psychiatry. 2023 Jan 27. doi: 10.1111/eip.13398. Online ahead of print.


Aim: The final common pathway in the etiopathogenesis of schizophrenia is suggested that there is a defect in the presynaptic terminal in dopaminergic transmission, in which α-synuclein has an important role. Peripheral biomarker studies in schizophrenia have become crucial for better diagnoses, early interventions, and personalized therapies. This study aims to compare α-synuclein levels in patients with schizophrenia and their unaffected siblings with healthy controls, as a potential peripheral biomarker for schizophrenia.

Methods: The quantifications of α-synuclein serum concentrations were conducted by the ELISA method. PANSS and CGI-S were used to analyse the severity of the symptoms of the subjects. Data were analysed by nonparametric tests and the Receiver Operating Curve (ROC) analysis.

Results: Sixty-two patients with schizophrenia (mean age: 34,8 ± 9,9, %64,5 male), their 56 unaffected siblings (mean age: 39,4 ± 11,5, %55,4 male) and 56 healthy controls (mean age: 36,2 ± 9,8, %64,3 male) were included. α-synuclein levels were significantly lower in the patient (27,65 (12,61-46,09) pg/ml) and the unaffected sibling groups (24,62 (15,60-57,87) pg/ml) compared with healthy controls (45,58 (11,25-108,30) pg/ml) (p < .001). According to the ROC analysis, the optimal cut-off value for α-synuclein levels in distinguishing the schizophrenia group from the control group was 42.20. The sensitivity of the measurement of serum α-synuclein at this point was 93.5%, and the specificity was 60.7%.

Conclusion: Our study demonstrates that decreased levels of serum α-synuclein may be utilized as a possible peripheral biomarker of familial risk for schizophrenia in both patients and their siblings.

Keywords: biomarker; neurotransmission; presynaptic pathology; schizophrenia; siblings; α-synuclein.