Could low α-N-acetylgalactosaminidase plasma concentration cause schizophrenia?

Objectives: Using a neurodevelopmental approach to examine the aetiology, we predicted an enzyme deficiency to exist at the cellular level and aimed to measure α-N-acetylgalactosaminidase (α-NAGAL) blood levels.

Methods: The study included 32 patients diagnosed with schizophrenia and 30 healthy controls. The positive and negative syndrome scale (PANSS) was applied to the patients with schizophrenia. Serum α-NAGAL concentrations were measured in blood samples taken from all participants using the human alpha-N-acetylgalactosaminidase ELISA Kit.

Results: The mean α-NAGAL values of schizophrenic patients are lower than the mean α-NAGAL values of the control group ( = 0.000 < 0.001). Correlation analysis showed that there was a significant relationship between α-NAGAL values and PANSS scores of patients with schizophrenia. PANSS total ( = -0.708,  = 0.000 < 0.001), PANSS positive ( = -0.627,  = 0.000 < 0.001), PANSS negative ( = -0.386,  = 0.029 < 0.05). And a positive moderate correlation was found between the age of onset of the disease and α-NAGAL levels ( = 0.529,  = 0.002 < 0.05).

Conclusions: Based on the neurodevelopmental hypothesis, the low α-NAGAL concentrations this study found might cause accumulation of glycoproteins in the lysosomes in the central nervous system during the gestational period and then might result in the clinical symptoms of schizophrenia. α-NAGAL may be an important factor in the aetiology of schizophrenia.