Schizoaffective disorder (SAD) is a severe psychiatric condition characterized by the coexistence of psychotic symptoms and mood episodes. Growing evidence suggests that immune dysregulation and inflammatory processes contribute to the pathophysiology of schizophrenia-spectrum disorders, including SAD. α-N-acetylgalactosaminidase is a lysosomal enzyme involved in glycoprotein metabolism and immune regulation through its effects on Gc protein-derived macrophage activating factor. Previous studies have reported altered α-N-acetylgalactosaminidase levels in schizophrenia and bipolar disorder; however, its role in SAD has not been investigated. The aim of this cross-sectional study is to compare serum α-N-acetylgalactosaminidase levels among patients with SAD during acute exacerbation and remission phases and healthy controls. The study also examines the relationships between α-N-acetylgalactosaminidase levels, symptom severity, and systemic inflammation. Clinical assessments include the Positive and Negative Syndrome Scale, Young Mania Rating Scale, Beck Depression Inventory, and Global Assessment Scale. Systemic inflammation is evaluated using the Aggregate Index of Systemic Inflammation, derived from routine complete blood count parameters. By investigating the association of α-N-acetylgalactosaminidase with clinical and inflammatory features of SAD, this study seeks to improve understanding of the biological mechanisms underlying the disorder and to explore the potential utility of α-N-acetylgalactosaminidase as a biomarker related to disease state and symptom severity.
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. For participants in the SAD-AE group, all assessments and blood collections were performed immediately following hospital admission and prior to initiation of pharmacological treatment or other therapeutic interventions. Sociodemographic variables including age, sex, educational level, marital status, employment status, residence, smoking status, and history of suicidal behavior were recorded for all participants. Psychopathology and clinical functioning were assessed using standardized instruments. Psychotic symptoms were evaluated using the PANSS, YMRS, depressive symptoms were evaluated using the Beck Depression Inventory (BDI), and overall psychosocial functioning were assessed using the Global Assessment Scale (GAS). Venous blood samples were collected at hospital admission or study enrollment. Samples were centrifuged within 30 minutes of collection, and serum aliquots will be stored at -80°C until laboratory analyses are performed. Serum α-N-acetylgalactosaminidase concentrations were measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits according to the manufacturer's instructions. Routine complete blood count analyses were also obtained. The Aggregate Index of Systemic Inflammation (AISI) was calculated using the formula: (neutrophils × monocytes × platelets) / lymphocytes. The primary objective of the study was to compare serum α-N-acetylgalactosaminidase concentrations among SAD-AE, SAD-R, and HC groups. Secondary objectives include evaluating relationships between α-N-acetylgalactosaminidase levels and psychotic symptoms, manic symptoms, depressive symptoms, global functioning, illness duration, and systemic inflammation. Additional objectives include determining whether α-N-acetylgalactosaminidase independently predicts illness phase (acute exacerbation versus remission) using hierarchical logistic regression models and assessing its potential diagnostic utility through receiver operating characteristic curve analyses. The study hypothesis was that patients with SAD demonstrate lower serum α-N-acetylgalactosaminidase concentrations than HCs, and that α-N-acetylgalactosaminidase levels were relatively elevated during acute exacerbation compared with remission due to increased inflammatory activation. It is further hypothesized that α-N-acetylgalactosaminidase concentrations correlate positively with psychotic symptom severity, manic symptom severity, and systemic inflammatory burden. The study has been approved by the University of Health Sciences Elazığ Fethi Sekin City Hospital Non-Invasive Research Ethics Committee (Approval Number: 2025/8-15) and was conducted in accordance with the ethical principles of the Declaration of Helsinki. Written informed consent was obtained from all participants prior to enrollment.
Study Type
OBSERVATIONAL
Enrollment
93
Elazığ Mental Health and Diseases Hospital Psychiatry Clinic
Elâzığ, Elâzığ, Turkey (Türkiye)
α-N-acetylgalactosaminidase
Serum α-N-acetylgalactosaminidase levels measured by ELISA (ng/mL).
Time frame: At hospital admission (baseline)
Aggregate Index of Systemic Inflammation (AISI)
Aggregate Index of Systemic Inflammation (AISI) is calculated using the following formula: (neutrophils × monocytes × platelets) / (lymphocytes). All the parameters mentioned here are complete blood count parameters.
Time frame: At hospital admission (baseline)
Positive and Negative Syndrome Scale (PANSS) Score
Positive and Negative Syndrome Scale (PANSS) was developed to assess positive and negative symptoms and general psychopathology in patients with schizophrenia-spectrum disorder, and to measure the level of these symptoms. It is administered via a semi-structured interview, taking into account the last week. Information can also be obtained from the patient's relatives and healthcare staff. It consists of a total of 30 items: 7 items addressing positive symptoms, 7 addressing negative symptoms, and 16 addressing general psychopathology symptoms. Each item is scored from 1 to 7, and the scores are summed for the final score.
Time frame: At hospital admission (baseline)
Young Mania Rating Scale (YMRS)
YMRS comprises 11 items, each rated across five levels of severity. Items 5, 6, 8, and 9 are weighted more heavily to enhance the assessment of patients with communication difficulties. The scale is administered by an experienced clinician through a structured interview lasting approximately 15-30 minutes. Severity ratings are determined based on the patient's subjective reports over the preceding 48 hours, together with the clinician's observations of behavior during the interview.
Time frame: At hospital admission (baseline)
Beck Depression Inventory (BDI)
The questionnaire is a self-report instrument, and its outcomes are inherently relative, reflecting the respondent's answers to each item. It consists of 21 items and is among the most widely used screening tools for the identification of depressive symptoms. The measure is suitable for use in adults, adolescents, and individuals with psychiatric disorders aged 13 years and older. It is intended to capture a range of depressive symptoms experienced during the preceding week. Each item is rated on a 4-point Likert scale, with response options scored from 0 to 3.
Time frame: At hospital admission (baseline)
Global Assessment Scale (GAS)
Global Assessment Scale (GAS) is a rating scale that is administered over a short period of time and covers all aspects of changes in psychopathology (psychological, social and occupational functioning). It was developed by Endicott et al. and is scored between 0-100. Evaluation is performed by the clinician. Values between 0 and 100 are divided into 11 separate categories (such as 0, 1-10, 11-20, 21-30). There is a short text describing each category. The clinician selects just one of these categories and specifically writes a value in that range.
Time frame: At hospital admission (baseline)
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