Introduction: Despite these efforts, the pathogenesis of schizophrenia remains unclear. Recent studies suggest that excessive synaptic pruning during adolescence may contribute to schizophrenia, potentially linking it to uncontrolled apoptosis. Given its role in inflammation and apoptosis, amphiregulin may play a key role in this process. The objective of this study was to investigate the role of the Amphiregulin/Epidermal Growth Factor Receptor (EGFR) complex in the pathogenesis of schizophrenia.
Methods: Seventy-three drug-naive patients who were admitted to our outpatient clinic or hospitalized in our clinic and diagnosed for the first time with a psychotic disorder spectrum according to Diagnostic Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), along with 77 healthy controls matched for sociodemographic characteristics and who did not have a history of psychiatric or chronic diseases were recruited for the study. The patients’ symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), administered by a skilled psychiatrist. Blood samples were collected from all participants to measure amphiregulin and EGFR levels.
Results: A statistically significant positive correlation was found between amphiregulin and EGFR levels in the patient group. However, there was no significant difference in serum amphiregulin and EGFR levels between the first-episode psychosis group and the healthy control group. Additionally, a positive correlation was observed between both age and age of onset of the disease and serum EGFR levels in the patient group, a correlation that was not present in the healthy control group.
Conclusion: The similar correlation between amphiregulin and its receptor in the central nervous system suggests that amphiregulin levels may play a stable role in the disease process rather than being a primary driver of disease development. It remains unclear whether plasma neurotrophins accurately reflect central neurotrophic activity. The presence of amphiregulin in serum, which is thought to be secreted by regulatory T cells (Tregs) in the central nervous system, may be low. Further studies using cerebrospinal fluid and brain tissue samples are particularly needed in schizophrenia research.
Keywords: Amphiregulin, biomarker, epidermal growth factor receptor,