Fysiologföreningen: John H. Krystal
Ketamine: From probe of cortical dysfunction in schizophrenia to rapid-acting antidepressant
Dr. John H. Krystal
Chairman, Dept of Psychiatry, Yale University Medical School
This presentation reviews emerging evidence that there may be opposing disturbances in the regulation of glutamatergic neurotransmission in schizophrenia and affective disorders and that drugs with opposing effects on glutamatergic neurotransmission might be needed to treat each disorder. This presentation will begin by briefly reviewing evidence that schizophrenia is associated with glutamate synaptic deficits associated with evidence of deficits in NMDA glutamate receptor function and deficits in GABA neurotransmissions. These deficits are consistent with clinical evidence that glycine transporter 1 (GlyT1) inhibitors and drugs that attenuate glutamatergic disinhibition (mGluR2 agonists, lamotrigine) might play an adjunctive role in the treatment of schizophrenia. In contrast, depression appears to be associated with glial deficits in glutamate uptake, potentially resulting in overstimulation of presynaptic inhibitory glutamate receptors (mGluR2) and overstimulation of postsynaptic NMDA receptors. This model is consistent with the efficacy of mGluR2 antagonists in animals models of depression and the emerging efficacy of NMDA receptor antagonists, particularly ketamine, for the treatment of depression.
Host: Torgny H Svensson