There is considerable evidence that depressed patients have reduced CBF and metabolism compared with normal subjects, although in some brain areas it may be increased.60,61 Some studies suggest that reduced CBF

in depression is reversed by ECT, but others report a further reduction.62,63 Reduced brain function as a consequence of ECT is consistent with the hypothesis that recruitment of endogenous inhibitory processes to terminate the seizure Inhibitors,research,lifescience,medical is important in the therapeutic action of ECT.59 A third research direction takes as its starting point the substantial endocrine effects of ECT and suggests that these effects are implicated in the therapeutic mechanism Inhibitors,research,lifescience,medical of the treatment.64 Plasma prolactin levels are acutely increased by ECT65,66 This is a consistent finding, but it has been difficult to explain how it might be related to the therapeutic action of ECT. Another focus has been on the effect of ECT on thyrotropin-releasing hormone (TRH) and TRH-receptor function.67 More recently there has been a great deal of emphasis on the effect of ECS on synaptic plasticity and neurogenesis. Adult neurogenesis, the lifelong addition

of new neurons, was first documented in rat hippocampus.68 It is now well established that neurogenesis occurs in several different species, including humans.69 The newly generated cells mature into functional neurons.70 Inhibitors,research,lifescience,medical Neurogenesis is regulated by many factors. Inhibitors,research,lifescience,medical Upregulation of neurogenesis occurs in response to enriched environment,71 exercise,72,73 and learning. Downregulation of neurogenesis occurs in response to aging74,75 and stress (psychological or environmental).76 It is well established that the volume of hippocampus is decreased in patients suffering from depression.71,72 17-AAG molecular weight Repeated stress causes atrophy of dendrites in the CA3 region, and both acute and chronic stress suppresses neurogenesis of rat dentate gyrus granule neurons. The hippocampus is an especially plastic and vulnerable region,

and a target of stress hormones Inhibitors,research,lifescience,medical (gonadal, thyroid, and adrenal hormones). This cell loss might explain the reduction in hippocampal volume observed in depression. Decreased neurogenesis might also explain some of the symptoms of depression, such as cognitive abnormalities and loss of inhibitory control of the hypothalamic-pituitary-adrenal (HPA) axis. Recently, it has been demonstrated that chronic administration of Batimastat several classes of antidepressant treatment, such as serotonin or norepinephrine selective reuptake inhibitors, monoamine oxidase inhibitors, lithium, and ECS upregulates neurogenesis in adult rodent hippocampus.79-84 ECS influences some molecular markers of neuronal plasticity; for example, ECS decreases the level of phosphorylated heavy and light neurofilament subunit (NF-H and NF-L), that may be part of the cytoskeletal remodeling.