G proteins as a biochemical tool for diagnosis and monitoring treatments of mental disorders

There is a significant gap between advances in medication for mental disorders and the present static situation of diagnosis and monitoring treatments of these disorders. Heterotrimeric G proteins play a pivotal role in post-receptor information transduction. These proteins were previously implicated by us in the biochemical mechanism underlying lithium action, and in the pathophysiology of mood disorders. We aimed at quantitatively and functionally evaluating G proteins in patients with major mental disorders in an attempt to unravel a differential pattern of G protein measures characterizing each disorder. We undertook G protein functional measurements coupled to β-adrenergic, muscarinic or dopamine receptors through bacterial toxin-sensitive, agonist-enhanced [³H]-Gpp(NH)p binding capacity, substantiated by quantitative measures of Gα(s), Gα(i) and Gβ subunit proteins through immunoblot analysis using polyclonal anti-G subunit antibodies in mononuclear leukocytes obtained from patients with major mental disorders in comparison with healthy volunteers. A differential pattern of receptor-coupled G protein function and of their immunoreactive levels was detected in mononuclear leukocytes of patients for the following mental disorders: mania, depression, schizophrenia, and panic. Normalization of altered G protein measures in mood-disordered patients occurred under specific treatments. As state-dependent markers, G protein measures can potentially be used as an aid in both the biochemical diagnosis of mental disorders and in the biochemical monitoring of the response to a specific treatment.