Proposed endophenotypes of dysthymia: evolutionary, clinical and pharmacogenomic considerations

Dysthymia is highly prevalent-though underdiagnosed-occurring in at least 3 % of the population. We conceptualize it as the clinical extension of adapt ive traits that have developed during evolution to cope with stress and fai lure. A classification of dysthymias into anxious and anergic subtypes-and their putative association to bipolarity-is proposed. We further posit neur ochemical and neurophysiological substrates for the two subtypes. A better recognition and understanding of dysthymic subtypes and their respective pl ace in the affective spectrum will increase the proportion of people that m ay benefit from targeted treatments. It would also expand the pool of subje cts that may be enrolled in genetic and pharmacogenomic research studies.