G Protein Abnormalities in Schizophrenia

Since Emil Kraepelin coined the term dementia praecox, schizophrenia has been recognized as a group of illnesses of unknown etiology sharing common symptomatology with diverse clinical courses. Family, twin, and adoption studies indicate that genetic factors contribute to the etiology of schizophrenia. There has been evidence for involvement of many neurotransmitter receptor subtypes in the pathophysiology of schizophrenia. The champion of these is the dopamine (DA) receptor because DA-D2 receptors are targets of neuroleptics and have been found to be elevated in schizophrenia. The recent cloning of genes encoding five distinct DA receptor subtypes (D1-D5) and the discovery of a functional polymorphism within each gene have made it possible to investigate linkage of each DA receptor locus with genetic susceptibility to schizophrenia. To date there appears to exist no linkage between schizophrenia and the known DA receptors (Coon et al., 1993; N�then et al., 1994). Normal density or normal structure of a certain receptor subtypes does not always mean that the downstream partners of the receptor (G proteins, effectors, protein kinases, phosphatases) are normal.