Schizoaffective disorder (SAD) is a chronic psychiatric condition characterized by psychotic and mood symptoms. Emerging evidence suggests that Leucine-Rich Repeat and Fibronectin Type-III Domain-Containing Protein 5 (LRFN5) and olfactomedin-4 (OLFM4) may play roles in synaptic organization, neurodevelopment, and neuroinflammation. However, no prior study has investigated these biomarkers in SAD. This cross-sectional case-control study aims to compare peripheral serum levels of LRFN5 and OLFM4 in subjects diagnosed with SAD in remission and healthy control subjects. The study also assessed associations between these biomarkers and clinical symptom severity, global functioning, and systemic inflammation measured by the Aggregate Index of Systemic Inflammation (AISI). The study aimed to investigate convergent synaptic and immunoinflammatory dysregulation in SAD.
Schizoaffective disorder (SAD) is a chronic psychiatric condition characterized by psychotic and mood symptoms. Leucine-rich repeat and fibronectin type III domain-containing protein 5 (LRFN5), also known as synaptic adhesion-like molecule 5 (SALM5), is a postsynaptic adhesion molecule involved in synapse formation, maturation, and stabilization, particularly within glutamatergic pathways. Olfactomedin-4 (OLFM4) is a secreted glycoprotein expressed in neutrophils and other immune cells and is involved in apoptotic regulation and inflammatory processes. Although both molecules have biological relevance to neurodevelopmental and immune mechanisms, their circulating levels in SAD have not been well characterized. This cross-sectional case-control study aims to compare peripheral serum levels of LRFN5 and OLFM4 in subjects diagnosed with SAD in remission and healthy control subjects. The study also assessed associations between these biomarkers and clinical symptom severity, global functioning, and systemic inflammation measured by the Aggregate Index of Systemic Inflammation (AISI). A total of 60 subjects with SAD (30 females, 30 males) and 60 (30 females, 30 males) age- and gender-matched healthy controls will be recruited. Blood samples will be collected after 12-hour fasting and serum levels of LRFN5 and OLFM4 will be measured using ELISA kits. The diagnosis of SAD will be made according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR). All subjects diagnosed with SAD will be included in the study during the acute manic episode phase (immediately before hospitalization).The healthy control group will consist of individuals without current or past psychiatric disorders and without significant medical illnesses. None of the participants will have chronic inflammatory, autoimmune, neurological, or systemic diseases. Venous blood samples will be collected at hospital admission prior to initiation of pharmacological treatment in the SAD group. Serum will be separated and stored at -80°C until analysis. Serum LRFN5 and OLFM4 levels will be measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits in accordance with the manufacturer's instructions. Routine complete blood count parameters will be obtained, and the Aggregate Index of Systemic Inflammation (AISI) will be calculated as: (neutrophils × monocytes × platelets) / lymphocytes. Clinical assessments in the SAD group will be include the Positive and Negative Syndrome Scale (PANSS) for psychotic symptom severity, Young Mania Rating Scale (YMRS) for manic symptom severity, and Beck Depression Inventory (BDI) for depressive symptom severity. Sociodemographic and clinical data will be recorded for all participants. The primary objective was to compare circulating LRFN5 and OLFM4 levels between SAD and healthy control groups. Secondary objectives included evaluating associations between these biomarkers and symptom severity and systemic inflammation indices, as well as assessing their potential diagnostic performance using logistic regression and receiver operating characteristic (ROC) analyses. The study was approved by the Fırat University Non-invasive Research Ethics Committee (Approval Number: 2025/09-09) and was conducted in accordance with the Declaration of Helsinki. All participants will provide written informed consent prior to participation.
Study Type
OBSERVATIONAL
Enrollment
110
Elazığ Mental Health and Diseases Hospital Psychiatry Clinic
Elâzığ, Elâzığ, Turkey (Türkiye)
Leucine-rich repeat and fibronectin type III domain-containing protein 5 (LRFN5)
Serum leucine-rich repeat and fibronectin type III domain-containing protein 5 (LRFN5) levels measured by ELISA (pg/ml)
Time frame: At hospital admission (baseline)
Olfactomedin-4 (OLFM4)
Serum olfactomedin-4 (OLFM4) levels measured by ELISA (pg/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)
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