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Neurogenetic Risk Mechanism ID'ed for Bipolar Disorder

In second study, treatment-resistant depression in bipolar disorder responds quickly to ketamine

WEDNESDAY, Aug. 4 (HealthDay News) -- A genetic variant linked to bipolar disorder manifests itself as altered hippocampal brain function even in those without overt disease, according to research published in the August issue of the Archives of General Psychiatry. In a related study in the same issue, an N-methyl-D-aspartate (NMDA) receptor antagonist was found to result in rapid antidepressant effects in individuals with treatment-resistant bipolar depression.

Susanne Erk, M.D., of the University of Bonn in Germany, and colleagues investigated the neurogenetic mechanisms underlying bipolar disorder associated with the single nucleotide polymorphism rs1006737 in the CACNA1C gene. Using imaging genetics to gauge brain activation during episodic memory tasks, the researchers found that carriers of the CACNA1C risk allele showed a highly significant reduction of bilateral hippocampal activation during these tasks, a reduction that was present even without overt disease.

Nancy Diazgranados, M.D., of the National Institutes of Health in Bethesda, Md., and colleagues sought to determine if the NMDA receptor antagonist ketamine hydrochloride resulted in a rapid antidepressant effect in subjects with treatment-resistant bipolar depression. In a randomized, placebo-controlled, double blind, crossover study, patients who received ketamine had a significant improvement in depressive symptoms at 40 minutes post-infusion, which remained significant through day three, compared to those receiving placebo. Dissociative symptoms were the most common adverse effect and occurred only at 40 minutes after infusion.

"Effective treatments for preventing mood episodes in patients with bipolar disorder are urgently needed. However, it is important to note that the purpose of this study was to determine the relevance of the NMDA receptor in initial and rapid onset of antidepressant response, not in preventing relapse," Diazgranados and colleagues conclude.

Two authors of the second study are listed on a patent application for the use of ketamine in depression.

Abstract - Erk
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Abstract - Diazgranados
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