Up to 45% of patients with schizophrenia are treatment resistant to conventional drugs leaving clozapine as the only effective option. Its severe side-effects however limit it to a late stage option and the development of a biomarker to predict treatment response would be of high clinical utility. Our previous data demonstrate clozapine augments epidermal growth factor receptor (EGFR) signalling and hence we examined if EGF levels may be altered in treatment resistant schizophrenia (TRS) and are influenced by clozapine treatment. To determine if EGF levels are influenced by clozapine in TRS and can serve as a biomarker for clozapine response. Serum EGF levels were measured by ELISA in patients with TRS at baseline, 2, 6 and 26 weeks of clozapine treatment and in age and sexed matched healthy controls. Positive and Negative Syndrome Scale (PANSS) and CGI data were collected at baseline, 6 and 26 weeks.
In the patient group, the mean reduction in total PANSS score was 20.4 and CGI was 1.82 (n=56). Twenty-six (46%) patients responded (=20% reduction in PANSS score). Mean EGF levels at base line were 272pg/ml (±223, SD), at 2weeks 242pg/ml (±190), at 6 weeks 400pg/ml (±228) and at 26 weeks 409pg/ml (±275). These values were significantly (p<0.01) lower than that of the controls (mean 749pg/ml ±328). Mean EGF levels increased over the 26 weeks in patients by 169% (±269) and this became significant by 6 (P=0.013) and 26 weeks (P=0.019). There were no significant main correlations between EGF levels and clinical response. EGF levels were significantly decreased in people with TRS and were significantly increased with clozapine treatment indicating that clozapine is able to modulate the EGF system in patients. There was however no relationship with symptom change suggesting it is unlikely to be a suitable biomarker for clozapine response.
