G protein levels and function as an objective measure of depression in patients with functional bowel disorders

Heterotrimeric G proteins play a pivotal role in postreceptor information t ransduction. These proteins have been implicated in the pathophysiology, di agnosis, and treatment of mood disorders and proposed as a state-dependent biochemical mood marker in mononuclear leukocytes. Irritable bowel syndrome (IBS) is associated with changes in mood, affecting patients' illness perc eptions and behavior. We examined whether mononuclear leukocytes of patient s with IBS have altered G protein measures. We undertook G protein function al measurements through agonist-enhanced [H-3]Gpp(NH)p binding capacity and quantitative measures by immunoblot analysis using anti-G(alpha) antibodie s in mononuclear leukocytes obtained from 19 IBS patients (Rome criteria) a nd 19 healthy matched subjects. The study groups were similar in age, gende r, and years of education. Mononuclear leukocyte functions of G, (21.3+/-8. 3%) and Gi (22.2+/-6.7%) proteins in IBS patients were similar to healthy s ubjects (24.8+/-4.7 and 25.2+/-4.0%, respectively). The relative immunoreac tivities of the G(s alpha) (98.9+/-10.2%) and the G(i alpha) ( 104.2+/-11.5 %) subunit proteins in mononuclear leukocytes of IBS patients were also si milar to those in healthy subjects. Two patients clinically diagnosed as de pressed were detected by the G protein assay. The results lend objective su pport to the contention that major depression is not a causative factor in IBS, nor associated with its severity. The G protein assay may provide an o bjective biochemical tool for detecting depression in IBS, differentiating it from psychological distress that is commonly diagnosed by subjective tes ts.