11 This issue was resolved with the help of a conditional mouse

11 This issue was resolved with the help of a conditional mouse mutant, where the CRHR1 was deleted in specific brain areas.12 These studies made it clear that CRH produces depression-like symptoms independently of its pituitary action. What is badly needed is a set of gene tests and biomarkers identifying patients who are likely to respond to CRHR1 antagonists. In search of such information, CRH overexpressing mice were studied

in a specialized sleep laboratory, and it was found that these mice have REM-sleep disinhibition, ie, increased activity of Inhibitors,research,lifescience,medical paradoxical sleep where enhanced eye movements occur. This abnormality disappears once these transgenic mice are treated with CRHR1 antagonists.13 Likewise, patients that fulfilled

the criteria for major depression but had different sleep EEG signatures responded much better to a CRHR1 antagonist if they had increased REM density. That prompts quite unexpectedly the Inhibitors,research,lifescience,medical question of whether a sleep EEG analysis might help to identify patients that would benefit from a CRHR1 antagonist.11 Such a Inhibitors,research,lifescience,medical mechanism-based approach is required to make progress in the field, which will see a departure from blockbusters and the generation of individualized treatments based on gene tests and biomarkers. This proposition is further exemplified for mifepristone, which blocks the progesterone and glucocorticoid receptors (GR). Research led by Alan Schatzberg postulated that the www.selleckchem.com/products/Axitinib.html hypercortisolemia observed in many patients with psychotic

depression is enhancing dopaminergic neuro-transmission.14 Therefore, blocking GR in dopaminoceptive Inhibitors,research,lifescience,medical neurons could be beneficial for these patients. In fact, mifepristone, by blocking GR, is a successful treatment for many, but not all patients with psychotic Inhibitors,research,lifescience,medical depression. Here again, the need for biomarkers allowing to identify GR antagonist responders is Ivacaftor EC50 obvious. Similar to the results from CRH overexpressing mice, an animal model that generates biomarkers helping the clinician to identify responders to GR antagonists is much more helpful than struggling endlessly with the generation of Dacomitinib a mouse model for psychotic depression.15 The lesson we have learned in the past is that there is no chance of developing a mouse model that fits closely to a set of diagnostic criteria for human psychiatric disorders.16 The forced swim test, for example, is not telling us anything about depression, and is even counterproductive for discovery of antidepressants beyond monoaminergic mechanisms of action. It is unlikely that complex human diseases such as schizophrenia, depression, obsessive-compulsive disorder, anorexia, or panic disorder can be modeled in a mouse, fish, or fly.

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