LACK OF EFFECT OF ANTIDEPRESSANTS ON MONONUCLEAR LEUKOCYTE G-PROTEIN LEVELS OR FUNCTION IN DEPRESSED OUTPATIENTS

Evidence from studies in animal and cultured cell models suggests that antidepressants (ADs) may enhance postreceptor signalling through the G protein coupled adenylyl cyclase (AC) pathways. To test whether thi s also occurs in patients receiving AD treatment, G-protein-activated- AC activity and the levels of alpha(s) and alpha(i) were measured in m ononuclear leukocytes (MNLs) from 12 subjects with major depressive di sorder (MDD) at baseline and after a 5 week trial of AD treatment. Alt hough no differences were found in GTP gamma S-and forskolin-stimulate d AC activity or the levels of alpha(s) and alpha(i) in MDD subjects c ompared with age- and sex-matched healthy subjects, pretreatment basal AC activity was significantly lower in treatment responders compared with healthy subjects. No significant changes were evident in any of t hese biochemical measures following 5 weeks of AD treatment in the pat ient group as a whole or stratified by response. These findings do nor support an effect of ADs on the G-protein AC pathway, at least in MNL s. Lower pretreatment basal AC activity in responders suggests some ch ange(s) in post-receptor signalling processes may be associated with a n increased likelihood of therapeutic response to ADs.