One problem is, however, that the current phenotypes might be inadequate.128 It is highly unlikely that the new DSM-V classification of PDs will provide a solution. A strategy that has been proposed to increase the rate of success for molecular genetics in psychiatry is the use of endophenotypes, defined as a heritable characteristic that is along the pathway between a disorder and genotype.5 Although the strategy has not yet proven to be successful,133 it has been suggested that this approach should be applied to the study of PDs

by using clinical dimensions like for example affective instability, impulsivity, and aggression instead of diagnoses.134
Major Depressive Disorder (MDD) is Inhibitors,research,lifescience,medical common, costly,1-3 and notably heterogeneous. Unfortunately, the accurate prediction

and subsequent prevention of MDD episodes (MDEs) has been challenging. There is evidence that MDEs are variously associated Inhibitors,research,lifescience,medical with elevated psychosocial stress, the postpartum period, hypothyroidism, circadian changes, cerebrovascular disease, administration of inflammatory cytokines Inhibitors,research,lifescience,medical such as interferon-α (IFN-α), etc. check details Therefore, one approach for preventing a MDE could be to avoid stressful circumstances, pregnancy, cerebrovascular disease, and/or IFN-α therapy. However, this is often impractical. Thankfully, most people who are exposed to these various“triggers” do not develop MDD. Identifying modifiable markers of risk in specificallyvulnerable people, and then mitigating these before MDD occurs, could be a better approach for preventing MDD. However, identifying causal risk factors that Inhibitors,research,lifescience,medical pre-exist in nondepressed people requires prospective studies, and the incidence of an MDE over 1 year is less than 2%.4-6 The necessarily large epidemiologic studies have successfully identified predictive risk markers such as gender, age, cohort, family history, marital status, socioeconomic status, and stressful life events6,7 – but each of these is difficult or impossible Inhibitors,research,lifescience,medical to mitigate. Another strategy is needed for prospectively assessing nondepressed people for modifiable

Ergoloid risk factors, and a related strategy is needed for examining whether specifically alleviating these vulnerabilities prevents MDE. MDD during IFN-α therapy One approach for delineating modifiable risk factors is to examine homogeneous groups of people who are definitively known to soon be exposed to a specific MDD-evoking situation. Towards this end, patients receiving IFN-α may be ideal candidates for examining MDD vulnerability.8-12 MDD during IFN-α treatment (IFN-MDD) typically develops within the first 2 or 3 months of administration,13-17 and occurs in about 15% to 40% of patients.18 Thus, prospectively assessing IFN-MDD onset is feasible – and consequently it may be possible to determine predictive modifiable vulnerabilities in the 15% to 40% who subsequently develop IFN-MDD.