The phosphoinositide signal transduction pathway and mood disorders.

The involvement of phosphoinositides (PI) signal transduction pathway and related molecules in the pathophysiology of mood disorders is corroborated by a number of recent evidences. A multitude of pathways were involved in the pathogenesis of schizophrenia, including dopaminergic, serotoninergic, muscarinic and glutamatergic signaling. The PI signal transduction system and related Phosphoinositide-specific Phospholipase C (PI-PLC) family of enzymes seem to represent a point of convergence of different pathways during the development of selected brain regions. The existence of a susceptibility locus on the short arm of chromosome 20, where PLCB1, the gene codifying for PI- enzyme, maps, moved us to analyze possible deletions. By using interphase fluorescent in situ hybridization methodology, we analyzed PLCB1 in paraffin embedded samples of orbito-frontal cortex of 15 patients affected with bipolar disorder, 15 patients affected with schizophrenia, 15 patients affected with major depression and 15 normal controls. We found a specific deletion of one or both alleles of PLCB1 in a percentage of schizophrenia and major depression affected patients. Although significant progresses were achieved in studying the PI system and its alterations in human brain, many issues remain to be addressed with special regard to its relationship with mood disorders.