Commentary on Bennett and Colleagues: Differences in Cognitive Outcomes After Electroconvulsive Therapy Depending on BDNF and COMT Polymorphisms
Bennett and colleagues recently examined the effects of both the brain-derived neurotrophic factor (BDNF) Val66Met single-nucleotide polymorphism and catechol-O-methyltransferase (COMT) Val158Met single-nucleotide polymorphism cognitive and mood outcomes after electroconvulsive therapy (ECT).1 Their study included 87 depressed patients, and cognitive functioning was tested at multiple time points (pre-ECT, after 4 treatments, post-ECT, 1 month post-ECT, and 3 months post-ECT) with 2 tasks, the Mini-Mental State Examination and Spatial Recognition Memory from the CANTAB computerized battery. The authors suggested that assessing either of these polymorphisms will not be helpful for predicting cognitive outcomes after ECT in clinical practice. In a larger sample, we similarly had investigated the effects of both these polymorphisms, in addition to other potentially relevant genes, for predicting cognitive and mood outcomes after ECT.2 However, in contrast to Bennett et al,1 we administered a comprehensive neuropsychological battery, which included measures of both anterograde memory (learning and delayed recall) and retrograde autobiographical memory, the cognitive functions most affected by ECT.3,4 Our results showed effects of COMT Val158Met on change in retrograde autobiographical memory (P = 0.048, η2 = 0.055) and BDNF Val66Met on change in anterograde memory functioning (P = 0.026, η2 = 0.043) from pre- to post-ECT in unadjusted models. However, these effects were no longer statistically significant after adjustment for relevant covariates. Notwithstanding, it is possible that these effects may still hold true in a larger sample because our sample (N = 117) was modest for a gene association study, a limitation we acknowledged.
Although the Spatial Recognition Memory test used by Bennett and colleagues also assessed anterograde memory (visuospatial), it did not assess delayed recall, the anterograde memory function most affected after ECT.3 For the other task used, the Mini-Mental State Examination, their data showed improvement overall from pretreatment to posttreatment. This suggests that both tests administered may have been suboptimal for capturing the most relevant cognitive adverse effects from ECT. The potential use of the COMT and BDNF polymorphisms for predicting adverse cognitive outcomes after ECT therefore cannot be ruled out at this stage.
There currently are no known reliable pretreatment individual patient factors for predicting adverse cognitive outcomes after ECT. This continues to pose a dilemma for treating clinicians who, on a day-to-day basis, need to make judgments as to the relative cost benefits of ECT treatments for individual patients. The ability to individualize ECT treatment would be a therapeutic advantage in the age of individualized patient care. The search for interindividual factors, such as genotype, which can provide insight into an individual patient's risk for adverse outcomes, therefore is an endeavor worth pursuing.