Phosphoinositide-specific Phospholipases C in psychiatric diseases and suicide

Mood disorders represent a major medical need requiring chronic treatment. About one million people die by suicide worldwide each year, both as a consequence of major depression or not. Multiple deficits, including cell atrophy and loss, were described in the brains of mood disorders affected patients and in experimental animal models. Numerous changes in gene expression and activity were described in limbic and cortical brain regions. Available therapies probably regulate many of these changes. Different signal transduction pathways play a role in the pathogenesis of schizoaffective disorders, namely the cyclic‐AMP, phosphoinositides (PI), mitogen‐activated protein kinase, and glycogen synthase kinase cascades. Neurobiology studies focused upon abnormalities of signalling mechanisms with special regard to the serotonin system and related PI signalling system. Involvement of PI-specific Phospholipase C (PLC) enzymes was also described. In suicide brains the overall PLC expression was altered due to a complex reorganization of the isoforms, and PLC 1 isoform was suggested to be involved in schizophrenia and bipolar disorder. The knowledge of the complex network of neurobiological molecules and interconnected signal transduction pathways in the brain might help to understand the natural history and the pathogenesis of mood disorders, as well as of the suicidal behaviour. Moreover, it might widen the panel of available therapeutic tools, also gaining prognostic suggestions in order to prevent suicide.