SCHIZOPHRENIA (SZ) IS a highly debilitating illness.1,2 Standard treatments include antipsychotics, but about one-third of subjects still present significant symptoms.3 Electroconvulsive therapy (ECT) is the most effective treatment in refractory SZ, although its mechanism of action is unknown.3 Brain-derived neurotrophic factor (BDNF) is implicated in many psychiatric disorders,4,5 such as SZ. It is decreased in SZ, and increases with antipsychotic treatment,6 being suggested as a biomarker of response to treatment. We hypothesize that BDNF may play a role in the effect of ECT in patients with SZ. Thus, the aim of this pilot study is to evaluate clinical outcomes and serum BDNF levels in patients with refractory SZ before and after ECT.
Seven patients with refractory SZ were recruited from the Inpatient Psychiatric Unit, Hospital de Clinicas de Porto Alegre, Brazil. Twenty-one healthy controls matched for age and sex with the subjects with SZ were recruited from the hospital catchment area. An independent psychiatrist recommended ECT according to clinical judgment. Patients were maintained on the same drug treatment for at least 3 weeks before ECT treatment and during the entire study period (typical and atypical antipsychotics). Illness severity was measured using the Brief Psychiatry Rating Scale (BPRS)7 and the Clinical Global Impression-Severity Scale (CGI-S).8 Blood sampling and scales evaluations were performed on the day before ECT (pre-ECT), and the day after the last ECT treatment (post-ECT). Subjects were treated with standard unilateral ECT as described elsewhere.9 ECT treatment was completed on the basis of the clinical judgment of the treating physicians. The number of ECT treatments ranged from 12 to 18. BDNF serum levels were measured with sandwich-enzyme-linked immunosorbent assay. Comparisons in serum BDNF levels before and after ECT were assessed by paired t-test. The unpaired t-test was used to analyze the baseline BDNF in patients with SZ and controls. The level of significance was set at P < 0.05. The study was approved by the local ethics committee and all subjects provided written informed consent before entering the study.
The age was 35.79 ± 10.85 and 35.27 ± 10.34 for subjects with SZ and controls, respectively. Seventy percent of the subjects with SZ were male (5/7). The length of illness was 16.49 ± 3.72 years. When compared to their pre-ECT values, subjects post-ECT showed a significant improvement in psychotic features on the BPRS (40.29 ± 4.55 and 28.14 ± 9.20, respectively, P = 0.048) and on the CGI-S (6.17 ± 1.60 and 4.33 ± 1.21, respectively, P = 0.012). In the pre-ECT measurement, serum BDNF was decreased in patients with SZ when compared to controls (0.14 ± 0.05 and 0.39 ± 0.12, respectively, P = 0.036). There was no difference in BDNF between pre- and post-ECT (0.14 ± 0.05 and 0.16 ± 0.04, respectively, P = 0.53). There was no correlation between BDNF and BPRS or CGI in the pre-ECT and post-ECT treatment (data not shown).
As far are we are aware, this is the first study to verify the effect of ECT on serum BDNF levels in patients with refractory SZ. In this study, ECT was associated with symptoms improvement despite no differences in serum BDNF levels following ECT. BDNF was pointed out as a possible predictor of treatment response.9–13 Nevertheless, a difference in BDNF between pre- and post-ECT was not found in this sample.
There were some limitations in this study. First, we assessed BDNF in serum. However, a high correlation of serum and cerebrospinal fluid BDNF levels was reported.14 Second, our negative results on BDNF levels following ECT may be due to our relatively small sample. Third, an increase in BDNF serum levels (if it really occurs secondary to ECT) is not precocious but may take some time after the last ECT course, and it may follow the clinical improvement of the symptoms.10
In conclusion, our results do not support the hypothesis that improvement in SZ symptoms with ECT is associated with BDNF serum level variances. Further studies are necessary to confirm our findings.