Definitions and factors associated with subthreshold depressive conditions:a systematic review

BACKGROUND: Subthreshold depressive disorders (minor and subthrehold depression) have been defined in a wide range of forms, varying on the number of symptoms and duration required. Disability associated with these conditions has also been reported. Our aim was to review the different definitions and to determine factors associated with these conditions in order to clarify the nosological implications of these disorders. METHODS: A Medline search was conducted of the published literature between January 2001 and September 2011. Bibliographies of the retrieved papers were also analysed. RESULTS: There is a wide heterogeneity in the definition and diagnostic criteria of minor and subthreshold depression. Minor depression was defined according to DSM-IV criteria. Regarding subthreshold depression, also called subclinical depression or subsyndromal symptomatic depression, between 2 and 5 depressive symptoms were required for the diagnosis, and a minimum duration of 2 weeks. Significant impairment associated with subthreshold depressive conditions, as well as comorbidity with other mental disorders, has been described. CONCLUSIONS: Depression as a disorder is better explained as a spectrum rather than as a collection of discrete categories. Minor and subthreshold depression are common conditions and patients falling below the diagnostic threshold experience significant difficulties in functioning and a negative impact on their quality of life. Current diagnostic systems need to reexamine the thresholds for depressive disorders and distinguish them from ordinary feelings of sadness

Role of K(+) channel opening and stimulation of cyclic GMP in the vasorelaxant effects of nicorandil in isolated piglet pulmonary and mesenteric arteries: relative efficacy and interactions between both pathways

1. The effects of the K(+) channel opener levcromakalim, the guanylate cyclase stimulant nitroprusside and the dual drug nicorandil (K(+) channel opener and guanylate cyclase stimulant) were analysed in piglet isolated endothelium-denuded pulmonary (PA) and mesenteric (MA) arteries stimulated by noradrenaline (NA) or by the thromboxane A(2) mimetic U46619. 2. Nicorandil, levcromakalim and verapamil were less potent in PA than in MA, the efficacy of levcromakalim was also reduced in PA. The effects of nicorandil and levcromakalim were similar in arteries pre-contracted by NA and U46619, whereas verapamil was more potent in arteries pre-contracted by NA. Nitroprusside was equipotent in MA pre-contracted by either NA or U46619 and in PA pre-contracted by NA whereas in PA pre-contracted by U46619, nitroprusside showed lower potency and efficacy. 3. The relaxant effects of levcromakalim and nitroprusside were inhibited by 10(−5) M glibenclamide and 10(−6) M ODQ, respectively. Nicorandil-induced relaxation was inhibited by ODQ in all experimental conditions, whereas glibenclamide had inhibitory effects in PA and MA pre-contracted by U46619, had no effect in PA pre-contracted by NA and in MA pre-contracted by NA it was only inhibitory in the presence of ODQ. 4. No apparent interactions were found between nitroprusside and levcromakalim as indicated by the lack of effects of pretreatment with one of them (producing 20–35% relaxation) on the potency of the relaxant response to the other. However, in PA pre-contracted by U46619, where nitroprusside or levcromakalim induced only partial relaxation, the combination of both mechanisms (either by combining nitroprusside plus levcromakalim or by nicorandil) was able to induce full vasodilatation. 5. In conclusion, K(+) channel opening and guanylate cyclase stimulation are independent pathways that induce additive vasorelaxation in piglet PA and MA. The mechanism of action of nicorandil is dependent on the artery and on the nature of the agonist employed to precontract the artery. The relative efficacy of K(+) channel opening vs guanylate cyclase stimulation may partially explain the preferential contribution of each mechanism to the relaxant effects of nicorandil