Evaluation of Serum Complement Levels and Factors Affecting Treatment Resistance in Patients with Schizophrenia

There are increasing investigations about the potential role of the complement system in disorders affecting the central nervous system, including schizophrenia. Therefore, we aim to evaluate the levels of complement 3 and complement 4 and the factors affecting treatment resistance in schizophrenia patients.

This cross-sectional study was conducted between January 2020 and January 2021 and included schizophrenia patients resistant to treatment or in remission and healthy controls. The Structured Clinical Interview for Diagnostic and Statistical Manual-5 was used to confirm the diagnosis according to Diagnostic and Statistical Manual -5 criteria. We evaluated the patients with some scales and forms. The complement 3 and complement 4 levels were measured from blood samples.

In the treatment-resistant schizophrenia group, complement 3 (P = .001) and complement 4 (P = .001) levels were significantly higher compared to schizophrenia patients in remission and healthy controls. While the Brief Psychiatric Rating Scale (P < .001), the Positive and Negative Syndrome Scale-positive (P < .001), the Positive and Negative Syndrome Scale-negative (P < .001), the Positive and Negative Syndrome Scale-psychopathology (P < .001), the Positive and Negative Syndrome Scale-total (P < .001), and the Clinical Global Impression Scale-Severity (P < .001) scores were significantly higher in treatment-resistant schizophrenia patients, the General Assessment of Functioning (P < .001), and Beck Cognitive Insight Scale (P < .001) scores were significantly lower compared to the other groups. In schizophrenia patients, complement 3 levels were positively correlated with the Positive and Negative Syndrome Scale-negative (P = .046), the Positive and Negative Syndrome Scale-psychopathology (P = .001), the Positive and Negative Syndrome Scale -total (P = .025), and Clinical Global Impression Scale-Severity of Disease (P = .004). Also, complement 4 levels were positively correlated with Brief Psychiatric Rating Scale (P = .004), the Positive and Negative Syndrome Scale-positive (P = .003), the Positive and Negative Syndrome Scale -negative (P = .014), the Positive and Negative Syndrome Scale-psychopathology (P < .001), the Positive and Negative Syndrome Scale-total (P = .002), and Clinical Global Impression Scale-Severity of Disease (P = .001) in patients with schizophrenia. It was determined that a higher C4 level increased the risk of treatment resistance (odds ratio: 1.133, 95% CI: 1.012-1.268; P = .030), while a higher Beck Cognitive Insight Scale score decreased the risk of treatment resistance (odds ratio: 0.317, 95% CI: 0.191-0.526; P < .001).

In light of the analyses, it can be said that complement concentration increases in certain stages of schizophrenia, and its imbalance may be associated with symptom severity and treatment resistance.