Neurotrophic factors and treatment response It has recently become appreciated that antidepressants have a stimulatory effect on BDNF, and that this action may be relevant in their therapeutic value. Essentially all treatments for depression, including antidepressants

and ECT, increase BDNF mRNA in the hippocampus and the cortex.110 Reduced brain and blood levels of BDNF are normalized by antidepressants,112,113,149 as is stress-induced reduction of BDNF.111 Furthermore, antidepressants increase the activation of the TrkB receptor.150 The benefit of stimulating BDNF may be related to this neurotrophic Inhibitors,research,lifescience,medical factor’s role in plasticity and neuronal support. In addition, BDNF is known to play a key role in neurogenesis by promoting the long-term survival of newly born neurons,151 and this action may contribute to facilitation of neurogenesis

Inhibitors,research,lifescience,medical by antidepressants. Finally, animal models of depression demonstrate that BDNF may be necessary for the behavioral effects of antidepressants, as such are reduced in animals with inhibition of TrkB signaling or reduced brain BDNF levels,150,152 and because ECT-induced increases in dendritic sprouting seen in the hippocampus are decreased in BDNF hétérozygote knockout mice.153 In the treatment of MS, GA not only decreases Inhibitors,research,lifescience,medical proinflammatory cytokines, but also increases BDNF154 Likewise, in an animal model of MS (EAE), mice exhibit reductions in BDNF that normalize upon administration of GA.155 BDNF is produced by T-helper cells that respond to GA156 and BDNF is Inhibitors,research,lifescience,medical expressed in cells in MS brain lesions.156 Thus, the therapeutic value of G

A may be related to its effect on BDNF Indeed, in one study of relapsing-remitting MS, only those people who ultimately entered remission had had increased BDNF during their relapse.157,158 Actions on BDNF may provide a mechanism by which GA administration restores neurogenesis in EAE,108 suggesting that this treatment may have specific effects on depression in MS. Chronic administration of lithium, as well as another Inhibitors,research,lifescience,medical mood stabilizer, valproate, has been reported to increase BDNF in the frontal cortex.159 These drugs also increase hippocampal neurogenesis.160 It has been suggested, therefore, that PFI-2 mw lithium and valproate may be efficacious not only for bipolar disorder, but for neurodegenerative Sodium butyrate disorder.161 Interferon treatment, depression, and treatment response A link between depression and IFN-β treatment of MS patients was suggested based on data from the pivotal IFN-β-1b (Betaseron) study in 372 subjects over 5 years, during which five patients (2%), all on active treatment, attempted suicide.162 While these differences were not statistically significant, they created initial concern about a potential causal link between IFN-β treatment of MS and depression.