Narp Mediates Antidepressant-Like Effects of Electroconvulsive Seizures.

Growing recognition of persistent cognitive defects associated with electroconvulsive therapy (ECT), a highly effective and commonly used antidepressant treatment, has spurred interest in identifying its mechanism of action to guide development of safer treatment options. However, as repeated seizure activity elicits a bewildering array of electrophysiological and biochemical effects, this goal has remained elusive. We have examined whether deletion of Narp, an immediate early gene induced by electroconvulsive seizures (ECS), blocks its antidepressant efficacy. Based on multiple measures, we infer that Narp knockout mice undergo normal seizure activity in this paradigm, yet fail to display antidepressant-like behavioral effects of ECS. Although Narp deletion does not suppress ECS-induced proliferation in the dentate gyrus, it blocks dendritic outgrowth of immature granule cell neurons in the dentate molecular layer induced by ECS. Taken together, these findings indicate that Narp contributes to the antidepressant action of ECT and implicate the ability of ECS to induce dendritic arborization of differentiating granule cells as a relevant step in eliciting this response.

A within-subject comparison of propofol and methohexital anesthesia for electroconvulsive therapy.

OBJECTIVES: The optimal anesthetic for electroconvulsive therapy (ECT) is a frequently studied but unresolved issue. Methohexital and propofol are 2 widely used anesthetic agents for ECT. The purpose of this study was to determine which of the 2 agents was associated with superior clinical outcomes. METHODS: Records from all patients who had undergone separate ECT courses with methohexital and propofol between 1992 and 2008 (n = 48) were reviewed for a retrospective within-subject comparison of outcome measures. The clinical outcomes we examined were number of treatments required in a course of ECT, changes in the Montgomery-Åsberg Depression Rating Scale and Mini Mental Status Examination, and length of stay in the hospital after initiation of ECT. Additionally, we compared treatment delivery between methohexital and propofol treatment courses, measuring rate of restimulation for brief seizures, seizure duration, percentage of treatments that were bilateral, and average charge administered. RESULTS: Data from 1314 treatments over 155 ECT courses were reviewed. Improvement in depressive symptoms, based on the Montgomery-Åsberg Depression Rating Scale, was not affected by choice of anesthetic agent. However, when right unilateral electrode placement was used, patients receiving propofol required significantly more treatments than those receiving methohexital. Propofol was also associated with a significantly higher requirement for bilateral ECT and higher stimulus dosing. Seizure duration was significantly shorter in the propofol condition, with more patients requiring restimulation for brief seizures. Length of stay in the hospital and cognitive outcomes were not significantly different between propofol and methohexital treatments. CONCLUSIONS: We recommend methohexital as the induction agent of choice for ECT, especially with right unilateral placement.