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Mental Health Matters Journal for Psychiatrists & GP's

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NEW YORK (Reuters Health) Nov 24 - Results of a functional MRI study demonstrate that several areas of the brain associated with reward processing respond differently to stimulation in patients with major depressive disorder (MDD).

Therefore, "the brain reward system may be an excellent target for novel treatment approaches in drug development research," Dr. Usoa E. Busto and colleagues propose in their report, published in the November Archives of General Psychiatry.

The authors define the brain reward system as "a neurobiological system that consists of extensive neural pathways that mediate reward behaviors such as pleasure and motivation." They theorize that this system "may represent a key neuroanatomical substrate of anhedonia, a core symptom of depression."

To test their theory, the researchers, all based at the University of Toronto, recruited 12 individuals with MDD who were not taking any antidepressant medication and 12 healthy control subjects.

All subjects underwent functional MRI before and 90 minutes after taking a 30-mg dose of dextroamphetamine, which was used as a dopaminergic probe to isolate the neuroanatomical areas involved in the altered brain reward system response.

The investigators observed that, based on a standardized test (the Addiction Research Center Inventory, ARCI), MDD subjects had a hypersensitive, 2-fold increased response to the rewarding effects of the drug. There was a positive correlation between ARCI scores and measures of anhedonia.

MDD subjects exhibited significantly decreased activation following dextroamphetamine administration in dopamine-rich regions of the brain. Specifically, these involved the right ventrolateral prefrontal cortex, the left and right caudate and putamen, the left orbitofrontal cortex, and the supplementary motor cortex and premotor cortex. Increased activation was observed in the left and right temporal pole.

"Results of this study provide support for the involvement of dopaminergic mechanisms in the altered reward processing in MDD," Dr. Busto's group maintains.

Arch Gen Psychiatry 2005;62:1228-1236.


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