This issue is more difficult, to address in clinical studies, but evidence is slowly accumulating. Brain imaging studies have been conducted to examine the influence of antidepressants on the volume of limbic brain regions. One study demonstrates that hippocampal atrophy is inversely proportional to the length of time a patient receives antidepressant

medication.67 A longitudinal study of PTSD patients before and after antidepressant treatment has found that there is a. partial Inhibitors,research,lifescience,medical reversal of hippocampal atrophy in patients receiving medication.68 The latter study demonstrated a corresponding increase in verbal declarative memory in response to antidepressant treatment. Evidence at the molecular level is also provided by postmortem studies. Levels of CREB immunoreactivity are Inhibitors,research,lifescience,medical increased in patients receiving antidepressant

treatment at the time of death relative to Everolimus manufacturer unmedicated patients.39 In addition, levels of BDNF are increased in patients taking an antidepressant at the time of death.59 Although these effects must be replicated and extended (for example, to the regulation of neurogenesis) in additional banks of postmortem tissue, the results are consistent with the hypothesis that neural plasticity is upregulatcd in patients receiving antidepressant medication. Inhibitors,research,lifescience,medical Novel targets for the treatment of depression The hypothesis that antidepressant treatment Inhibitors,research,lifescience,medical increases neural plasticity provides a number of novel targets for drug development. However, as with any fundamentally important mechanism, care

must be taken that the drugs developed for such targets do not interfere with the normal function of the brain. Nevertheless, regulation of neural plasticity is an exciting area of research for design of new drugs for a variety of indications, including learning, memory, cognition, mood, and neurodegenerative disorders. This section discusses a few of these targets in the context of the pathways regulated by antidepressants and stress. Inhibitors,research,lifescience,medical Targets for antidepressant regulation of neurogenesis Identification of the signal transduction and gene expression pathways that first are responsible for the actions of antidepressant regulation of neurogenesis is a subject, of intense investigation. Activation of the cAMP-CREB signaling cascade using either pharmacological or transgenic approaches is reported to increase both proliferation and survival of newborn neurons in the hippocampus,46,58 supporting the possibility that antidepressants increase neurogenesis via regulation of this intracellular pathway. Gene targets of CREB, as well as other neurotrophic/growfh factors that, have been shown to regulate adult neurogenesis, include BDNF, FGF-2, and insulin-like growth factor-1 , to name but. a few.