Depersonalization disorder may be related to glutamate receptor activation imbalance.

Abstract

Low-dose ketamine administration mimics, both clinically and on gross neuroimaging, depersonalization disorder. The perceptual effects of ketamine may be due to secondary stimulation of glutamate release and lamotrigine, possibly by inhibited glutamate release, may reduce some of ketamine's so-called dissociative effects. However, lamotrigine does not seem to be useful in the treatment of depersonalization disorder. Glutamate release in prefrontal cortex is increased by subanaesthetic doses of ketamine, resulting in increased inhibition, possibly via intercalated GABAerg cells, of projections from amygdala, affecting structures critically involved in depersonalization. I speculate that, in depersonalization disorder, the increased glutamate activity in prefrontal cortex is due to intrinsic imbalance, resulting in long-term potentiation, at the postsynaptic glutamate receptors on the GABAerg interneurons while the same receptor abnormality at the synapses on the intercalated GABAerg cells of the amygdala result in long-term depression in the case of either normal or high glutamate release.