title: An explanation of why schizophrenia begins with excitotoxic damage to the hippocampus.
abstract: A recent paper by Schobel et al. provides evidence that schizophrenia begins with excitotoxic damage in the hippocampus, primarily in the CA1 subfield. MRI measurement of cerebral blood volume (CBV) was taken to be a marker of basal metabolism. High baseline CBV in the CA1 subfield of subjects at high risk for schizophrenia predicted progression to psychosis and the development of hippocampal atrophy. A mouse model of ketamine excitotoxicity reproduced the human imaging study, i.e. hypermetabolism in CA1 led to atrophy. The authors do not explain the pathophysiology of selective excitotoxicity in the hippocampus. A recently published serotonin theory of schizophrenia provides a hypothetical explanation for these findings. The serotonin theory predicts that schizophrenia begins with stress-induced overdrive of serotonergic pacemaker cells in the dorsal raphe nucleus. The overdrive is passed via the entorhinal cortex to the hippocampus, where it causes excitotoxicity. Passage through the entorhinal cortex converts a serotonergic signal into a glutamate signal, glutamate being the neurotransmitter of exicitotoxicity. The remitting-relapsing pattern of schizophrenia is explained by a balance between excitotoxicity in the hippocampus and repopulation by neurogenesis in the subgranular zone. Injury is balanced by healing.
authors.affiliation: SUNY-Downstate Medical Center, 450 Clarkson Ave., Brooklyn, NY 11203, United States; Kings County Hospital, 451 Clarkson Ave., Brooklyn, NY 11203, United States. Electronic address: eggersa@aol.com.
authors.forename: Arnold E
authors.initials: AE
authors.lastname: Eggers
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D051379:Mice; D008959:Models, Neurological; D055495:Neurogenesis / Q000502:physiology*; D009498:Neurotoxins / Q000009:adverse effects*; D012559:Schizophrenia / Q000209:etiology / Q000503:physiopathology*; D012701:Serotonin / Q000009:adverse effects*; D013315:Stress, Psychological / Q000150:complications*
chemical_list: D009498:Neurotoxins; D012701:Serotonin