α-N-acetylgalactosaminidase in Acute Exacerbation and Remission Stages of Schizoaffective Disorder

Schizoaffective disorder (SAD) is a severe psychiatric disorder characterized by the coexistence of psychotic symptoms and major mood episodes, resulting in substantial functional impairment, recurrent hospitalizations, and increased suicide risk. Although accumulating evidence suggests that immune dysregulation and inflammatory abnormalities contribute to the pathophysiology of schizophrenia-spectrum disorders, the biological mechanisms underlying SAD remain incompletely understood.

α-N-acetylgalactosaminidase is a lysosomal enzyme involved in glycoprotein metabolism and immune regulation. Nagalase catalyzes the removal of N-acetylgalactosamine residues from glycoproteins, thereby inhibiting the formation of Gc protein-derived macrophage activating factor, an important mediator of macrophage activation and immune function. Previous studies have demonstrated altered α-N-acetylgalactosaminidase concentrations in several neuropsychiatric disorders, including schizophrenia and bipolar disorder, suggesting a potential role for this enzyme in severe mental illnesses. However, no previous study has investigated circulating α-N-acetylgalactosaminidase levels in patients with SAD or examined whether these levels differ according to illness phase.

The present cross-sectional case-control study aims to compare serum α-N-acetylgalactosaminidase concentrations among patients with SAD during acute exacerbation (SAD-AE), patients with SAD in remission (SAD-R), and healthy control subjects (HC). The study also aims to evaluate associations between α-N-acetylgalactosaminidase levels, psychotic symptom severity, manic symptom severity, depressive symptom severity, global functioning, and systemic inflammatory burden.

A total of 51 patients diagnosed with SAD and 42 HC subjects were included in the study. SAD diagnoses will be established according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision. Participants with SAD were categorized into two groups based on clinical status. The SAD-AE group consisted of subjects experiencing a current manic episode with psychotic symptoms who have not received psychotropic medication for at least one month and have not used regular psychotropic treatment during the preceding three months. The SAD-R group consisted of clinically stable subjects receiving regular maintenance treatment, defined by sustained remission of psychotic symptoms and absence of active mood episodes. Remission status was determined using established criteria including low Positive and Negative Syndrome Scale (PANSS) symptom ratings and Young Mania Rating Scale (YMRS) scores consistent with clinical stability.

HC subjects were recruited from individuals presenting for routine medical evaluations and had no current or lifetime psychiatric disorder and no significant medical illness. Participants with hypertension, diabetes mellitus, chronic kidney disease, autoimmune disorders, systemic inflammatory diseases, severe neurological disorders, active infections, or other significant systemic diseases were excluded. All HC subjects were free of psychotropic and systemic medications for at least one month before blood sampling.