Homer: A Genetic Factor in Schizophrenia?

The hypothesis that abnormal limbic-corticostriatal glutamate transmission underlies the pathophysiology of schizophrenia emerged from decades of neurological, brain imaging, pharmacological, genetic and biochemical research in affected individuals, as well as behavioral, molecular and neurochemical data derived from preclinical animal models of schizophrenia and related disorders (e.g., drug-induced psychosis) (Coyle 2006; Coyle and Tsai 2004; Krystal et al. 2003, 2006; MacDonald and Chafee 2006; Meador-Woodruff and Healy 2000; Moghaddam 1994; Pietraszek 2002; Tsai and Coyle 2002). In schizophrenia, pathology within the glutamatergic system is suggested by 1) reduced cortical volumes; 2) reduced glutamatergic somatic or neuropil size; 3) reduced dendritic spines; 4) a disarray of pyramidal cell orientation; 5) altered expression of subtypes of glutamate receptors; and 6) reduced expression of certain synaptic proteins within cortical areas (Coyle and Tsai 2004; Kristiansen et al. 2007; Krystal et al. 2003; Meador-Woodruff and Healy 2000; Pietraszek 2002; Tsai and Coyle 2002).