LRFN5 and OLFM4 in Schizoaffective Disorder

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.

• For Schizoaffective Disorder (SAD) Group:

*Inclusion Criteria:

• Diagnosis of SAD according to DSM-5-TR
• Acute manic episode
• Medication-free for at least one month prior to admission
• Age ≥ 18 years and <65 years
• Provided informed consent

For Schizoaffective Disorder (SAD) Group:

*Exclusion Criteria:

• Hypertension

• Diabetes mellitus

• Chronic kidney disease

• Rheumatoid arthritis

• Systemic lupus erythematosus

• Cardiac illness

• Severe neurological disorders

• Immunological or systemic illness

• Primary psychiatric disorders other than SAD
• Alcohol/drug/substance use
• For Healthy Control Group:

*Inclusion Criteria:

• No psychiatric diagnosis

• No systemic or immunological illness
• Medication-free for at least one month
• Age ≥ 18 years and < 65 years
• Provided informed consent

For Healthy Control Group:

*Exclusion Criteria:

• Hypertension
• Diabetes mellitus
• Chronic kidney disease
• Rheumatoid arthritis
• Systemic lupus erythematosus
• Cardiac illness
• Severe neurological disorders
• Immunological or systemic illness
• Having psychiatric disorders
• Alcohol/drug/substance use