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 disord ers 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 implicate d by us in the biochemical mechanism underlying lithium action, and in the pathophysiology of mood disorders. We aimed at quantitatively and functiona lly evaluating G proteins in patients with, major mental disorders in an at tempt to unravel a differential pattern of G protein measures characterizin g each disorder. We undertook G protein functional measurements coupled to beta-adrenergic, muscarinic or dopamine receptors through bacterial toxin-s ensitive, agonist-enhanced [H-3]-Gpp(NH)p binding capacity, substantiated b y quantitative measures of G alpha(s), G alpha(i) and G beta subunit protei ns through immunoblot analysis using polyclonal anti-G subunit antibodies i n 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: m ania, depression, schizophrenia, and panic. Normalization of altered G prot ein 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 bi ochemical monitoring of the response to a specific treatment.