The problem is that we do not know for sure how to determine the scale on which severity is measured: is it the number of episodes of MD, the length of episodes, the number of symptoms, or some other feature or combination of features? Furthermore, the severity scale needs to differentiate cases with higher genetic risk, not those cases resulting largely from environmental adversities. Alternatively, subdividing MD on the basis of one or more clinical features (e.g., typical versus atypical vegetative features, standard versus postpartum onset), sensitivity to environmental stress, or sex, might identify a rarer, or at least a more genetically homogenous, subtype. At present, deciding which features to investigate is likely to be an ad hoc enterprise. Without knowing beforehand which to use, studies will need to be comprehensive, collecting as broad a range as possible of clinical features and known or putative risk factors.
