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The stimulatory guanine nucleotide binding protein Gs couples many cellular receptors to adenylate cyclase, and the Gsα subunit activates all 9 isoforms of the adenylate cyclase catalytic unit to produce the enzyme product cyclicAMP or cAMP. In prefrontal cortex and cerebellum of unipolar depressive suicides, Rasenick and colleagues have found increased concentrations of Gsα in membrane lipid microdomains (Donati et al, 2008), where the ensconced Gsα is less likely to activate adenylate cyclase by receptor and postreceptor pathways (Allen et al, 2005(Allen et al, & 2009.We report that a group of 7 depressed patients (DP-1) had (1) reduced activation of platelet receptor-stimulated adenylate cyclase by both prostaglandins E2 and D2 compared to controls, and (2) reduced postreceptor stimulation of adenylate cyclase by aluminum fluoride ion in both platelets and mononuclear leukocytes when compared to both another group of depressed patients (DP-2, n=17) and to controls (n=21). Our observations in the blood cells of the group DP-1 support the findings of Donati et al (2008), and they reflect the importance of this interaction between the activated Gsα subunit and membrane lipid microdomains in the pathophysiology and treatment of some major depressive disorders.