link between this main metabolite of serotonin, orbitofrontal cortex function and decision making is significant, as deficiencies in these three parameters are implicated in suicide vulnerability. Drugs with recognized antisuicidal or prosuicidal effects provide a mechanism to assess the predictive validity of a potential model. In this regard, extensive evidence indicates that lithium is effective in the prevention of suicide in patients with mood disorders.28, 79, 80, 81 Administration of lithium, compared with drugs equally effective at stabilizing mood, but less effective at reducing the risk of suicide such as valproate79, 82 can be used to provide predictive validity of promising models. Interestingly, lithium was found to modify activation of the orbitofrontal cortex in pathological gamblers.83 The endophenotypic approach may be useful for the identification of potential mechanisms underlying the antisuicidal effect of lithium.28, 84
