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  • Academy Events

  • Treatment-Resistant Depression: Glutamate, Stress-Hormones and their Role in the Regeneration of Neurons

    Monday, March 25, 2013 | 12:00 PM - 4:00 PM
    The New York Academy of Sciences

    Presented by the Biochemical Pharmacology Discussion Group

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    Clinical depression, (major depression) is a devastating illness, which occurs in about 15% of the population, and leads frequently to death by suicide or organic consequences, such as increased cardiovascular risk. Only around one in ten patients treated with the current standard of care antidepressant medication, like SSRIs or SNRI, demonstrate clinical response that extends beyond the effects of placebo. Therefore the current paradigm, which has been in use for the past 50 years and is based on specific effects on monoamines, shows drastic limitations. A paradigm shift is on the way focusing on a completely different neurotransmitter system, namely glutamate and its receptors. A model compound, ketamine, has demonstrated unusually fast improvements in patients, who did not respond to other treatments. The molecular basis for this phenomenon has been partially characterized. The glutamatergic system is integrated in the well-established stress machinery, and the involvement of stress hormones in the regulation of this system has become apparent. Importantly, the older paradigm of the role of serotonin can also be integrated into this new perspective, which seems to be valid in a subset of patients. Astonishingly one overlap between the stress system and the glutamatergic system is the regulation of electrolytes, and in particular magnesium. Both ketamine and magnesium can lead to a sprouting of neuronal synapses in the brain and by this reverse stress-induced changes. The importance of these changes in the structure of neurons and their functional consequences for the amelioration of defective brain function and the related depressive symptoms will be highlighted.

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