Acute and subsequent continuation electroconvulsive therapy elevates serum BDNF levels in patients with major depression.

INTRODUCTION: The induction of brain-derived neurotrophic factor (BDNF) release and subsequent restoration of neuroplastic homeostasis may underlie the effects of electroconvulsive therapy (ECT). OBJECTIVES: We aimed to assess serum and plasma BDNF levels during the course of acute ECT, as well as before and after subsequent continuation ECT, in patients with depression. METHODS: We included 24 patients with major depressive disorder (mean age ±â€¯SD: 54.5 ±â€¯13.7; f/m: 17/7; baseline 17-item Hamilton Depression Rating Scale score of 26.79 ±â€¯4.01). Serum and plasma BDNF (sBDNF, pBDNF) levels were assessed at nine time-points before, during, and after acute ECT series. Data were analysed using linear regression and linear mixed models, which were adjusted for multiple comparisons via Bonferroni correction. Five patients received continuation ECT subsequent to the acute ECT series. In these patients, BDNF levels were assessed before and after each two continuation ECT sessions using Wilcoxon signed-rank tests. RESULTS: Relative to baseline (mean ng/ml ±SD: 24.68 ±â€¯14.40), sBDNF levels were significantly higher 1 day (33.04 ±â€¯14.11, p = 0.013, corrected), 1 week (37.03 ±â€¯10.29, p < 0.001, corrected), and 1 month (41.05 ±â€¯10.67, p = 0.008, corrected) after the final ECT session, while pBDNF levels did not significantly differ (p > 0.1). Furthermore, our results indicated that sBDNF levels increased after each continuation ECT session. There was no significant association between sBDNF levels and clinical parameters or treatment response. CONCLUSION: The absence of an association between changes in sBDNF levels and depressive symptoms challenges the proposed concept of sBDNF/pBDNF as key markers of the effects of ECT.

The sensitivity of G protein-activated K+ channels toward halothane is essentially determined by the C terminus.

G protein-activated K(+) channels (GIRKs or Kir3.x) are targets for the volatile anesthetic, halothane. When coexpressed with the m(2) acetylcholine (ACh) receptor in Xenopus oocytes, agonist-activated GIRK1(F137S)- and GIRK2-mediated currents are inhibited by halothane, whereas in the absence of ACh, high concentrations of halothane induce GIRK1(F137S)-mediated currents. To elucidate the molecular mechanism of halothane action on GIRK currents of different subunit compositions, we constructed deletion mutants of GIRK1(F137S) (GIRK1(Delta363*)) and GIRK2 (GIRK2(Delta356)) lacking the C-terminal ends, as well as chimeric GIRK channels. Mutated GIRK channels showed normal currents when activated by ACh but exhibited different pharmacological properties toward halothane. GIRK2(Delta356) showed no sensitivity against the inhibitory action of halothane but was activated by halothane in the absence of an agonist. GIRK1(Delta363*) was activated by halothane more efficiently. Currents mediated by chimeric channels were inhibited by anesthetic concentrations that were at least 30-fold lower than those necessary to decrease GIRK2 wild type currents. Glutathione S-transferase pulldown experiments did not show displacement of bound Gbetagamma by halothane, indicating that halothane does not interfere with Gbetagamma binding. Single channel experiments revealed an influence of halothane on the gating of the channels: The agonist-induced currents of GIRK1 and GIRK2, carried mainly by brief openings, were inhibited, whereas higher concentrations of the anesthetic promoted long openings of GIRK1 channels. Because the C terminus is crucial for these effects, an interaction of halothane with the channel seems to be involved in the mechanism of current modulation.