There are 227 possible ways to meet the symptom criteria for major depressive disorder (MDD). However, symptom occurrence is not random, and some symptoms co-occur significantly beyond chance. This raises the questions of whether all of the theoretically possible different ways of meeting the MDD criteria actually occur in patients, and whether some combinations of criteria are much more common than others. More than 1500 patients who met DSM-IV criteria for MDD at the time of the evaluation were interviewed with semi-structured interviews. The patients met the MDD symptom criteria in 170 different ways. Put another way, one-quarter (57/227) of the criteria combinations did not occur. The most frequent combination was the presence of all 9 criteria (10.1%, n=157). Nine combinations (all 9 criteria, 3 of the 8-criterion combinations, 4 of the 7-criterion combinations, and one 6-criterion combination) were present in more than 2% of the patients, together accounting for more than 40% of the diagnoses. The polythetic definition of MDD, which requires a minimum number of criteria from a list, results in significant diagnostic heterogeneity because there are many different ways to meet criteria. While there is significant heterogeneity amongst patients meeting the MDD diagnostic criteria, a relatively small number of combinations could be considered as diagnostic prototypes as they account for more than 40% of the patients diagnosed with MDD.
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