15 Acute elevations of ACTH and Cortisol plasma levels have been observed immediately after ECT,16,17 and might be interpreted as a physiological stress response. However, during the course of ECT, ACTH and Cortisol plasma levels have been found to decrease, suggesting that,

a downregulation of the HPA axis18 might comprise a therapeutic effect, of ECT in major depression. In recent decades, considerable evidence has emerged that neuroactive steroids, which alter neuronal excitability via nongenomic mechanisms, might be involved in the pathophysiology Inhibitors,research,lifescience,medical of depression, and might contribute to the therapeutic effects of antidepressants.19 Although no alterations of positive GABAergic 3oc-reduced neuroactive steroids have been detected in depressed patients after treatment with ECT,20 elevated plasma, levels of dchydrocpiandrosterone sulfate (DHEAS), which Inhibitors,research,lifescience,medical is a potent negative modulator of the GABA -A receptor, have been found in psychotic depressed patients and were associated with nonresponse to ECT Inhibitors,research,lifescience,medical these patients.21 Therefore, it has been suggested that

DHEAS plasma levels might, serve as a predictive marker of nonresponsiveness to ECT.21 In a. genetic rat model of depression, DHEAS pretreatment abolished the antidepressant effects of ECS, suggesting that a pharmacologically induced decrease in DHEAS levels might serve as a Y-27632 in vivo putative intervention to restore the treatment response in depressed patients resistant, to ECT.22 Inhibitors,research,lifescience,medical Recently, growing evidence has emerged for a major role of downstream signal transduction pathways, eg, the cyclo-adenosine monophosphate

(AMP)-responsive element binding protein (CREB) cascade, and their effects on neurotrophic factors such as brain-derived neurotrophic factor (BDNF) in the pathogenesis and treatment of depressive disorders.23 Inhibitors,research,lifescience,medical In this context, in vivo and animal studies suggested that the antidepressant effects of ECS may be attributed to its putative effects on neurogenesis and neuroplasticity. Single ECS have been shown to increase BDNF mRNA24,26 and tyrosine kinase B (TrkB) mRNA, which is an effector of BDNF.25 Furthermore, comparable to the observations after pharmacological antidepressant treatment,27 BDNF mRNA and TrkB mRNA are tuclazepam continuously increased after a course of ECS.28 Moreover, several studies have indicated that ECS increase synaptic connectivity. Chronic ECS induce mossy fiber sprouting in the hippocampus29,30 and in other brain regions such as amygdala and frontal areas.31 In addition, ECS are followed by an increase in neuron formation in the hippocampus,30,32,33 an effect that was already observed after a single ECS33 but. which was even more pronounced after a. series of PX1S,32,33 suggesting a. dose-dependent mechanism of ECT on neurogenesis.