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Symptom data reanalysis disconfirms Parker et al.'s claim that latent class analysis identifies melancholic depression

Parker et al. (1) performed a latent class analysis (LCA) to identify subtypes of depressive disorder, a much-needed undertaking given DSM-5’s heterogeneous and overly expansive category. Imposing a two-class solution, the authors find that Class I differs from Class II in several ways that Horwitz and Wakefield (2) described as characteristic of pathological depression, such as symptoms being disproportionately severe relative to the triggering stressor and symptoms lasting longer than the stressor. These variables are ignored in epidemiological surveys limited to DSM criteria, so demonstrating their importance is a unique contribution and hopefully a wake-up call for epidemiologists to go beyond DSM in their choice of variables. The authors’ primary conclusion, however, is that the LCA distinguishes depressive ‘disease’—essentially melancholic depression—from other forms of depression: ‘Depressive diseases, such as melancholia,. . .can be distinguished from nondisease clinical depressive disorders and non-clinical depressive states’ (p.1). Given the controversial history of subtyping attempts concerning melancholic depression, this would be important if true. However, further scrutiny reveals that this conclusion does not follow from – in fact, is falsified by – the symptom data the authors cite in its support. The authors observe that Class I is uniformly more severe than Class II on all the study’s variables, suggesting a ‘severity’ interpretation according to which the classes ‘might be parsimoniously interpreted as simply indicating a ‘more severe’ depressive state in those assigned to Class I’ (p. 5). The challenge is to get beyond the default severity hypothesis. The authors initially cite the ‘striking’ (p. 5) finding that 89% of Class I members had melancholic or bipolar diagnoses. However, 76% of all clinical disorders in the sample were melancholic or bipolar conditions, and 49% of Class II clinical depressions were melancholic cases, so it is unclear how striking this finding is or whether it is accounted for by the default ‘severity’ hypothesis. The authors then turn to their primary argument, which is based on the fact that melancholic depression is defined by its symptoms. If Class I has disproportionately elevated melancholic symptom rates compared to other symptoms (albeit with higher rates for all symptoms relative to Class II due to increased severity), then that would be evidence that Class I is selecting melancholic depression in addition to severe depression. Visually inspecting the percentages in each class who have each symptom (table 2, p. 5), the authors claim that Class I disproportionately elevates melancholic symptoms, thus that the LCA identified melancholic versus other depressions: ‘However, as assignment to Class I was associated most strongly with many historically weighted melancholic symptoms. . ., we suggest that Class I also weighted melancholic features and not severity alone’ (p. 5). They consider their symptom analysis to have ‘demonstrated’ their conclusion: ‘our secondary analysis demonstrated that Class I membership was over-represented with many symptoms viewed as having specificity to melancholic depression’ (p. 6). The credibility of the authors’ conclusion turns on this ‘symptom’ argument. However, visual inspection can be misleading. There is a simple way to more formally test the authors’ impression. One need only quantify the degree to which each melancholic symptom deviates from what is expectable on the severity hypothesis. If Class I melancholic symptom rates are consistently and substantially elevated from Class II rates more than the average overall increase, then the authors’ argument has some weight. If not, then no grounds exist for going beyond the ‘severity’ interpretation. A caveat is that the information provided does not suffice to perform significance tests on differences in rates, so the magnitude of differences must be subjectively assessed. To perform this analysis, I selected 15 study symptom items from table 2 corresponding to DSM-5’s list of ‘melancholic features’: diminished interest/pleasure, uninterested in people or activities, not looking forward to pleasurable things, difficulty laughing/enjoying, not cheered up by friends, depression different from grief, depression worse in mornings, waking early in the morning, being agitated, being slowed down in movements, decreased appetite, significant weight loss, excessive guilt, deserve to be punished, and inappropriate guilt. In addition, the authors mention 4 further symptoms beyond the DSM criteria that they consider melancholic symptoms: insularity, fogginess, cognitive slowing, and anergia. I thus added 4 corresponding study items (staying away from people, brain feeling foggy, diminished ability to think, and loss of energy) in a second analysis. The results were as follows. The baseline overall Class I/ Class II ratio of average number of symptoms for all 45 tested symptoms, representing Class I’s greater severity, was 1.9; the Class I/Class II ratio of average number of 15 DSM melancholic symptoms was 2.1; and the Class I/Class II ratio of average number of 19 melancholic symptoms identified either by DSM or by Parker et al. was also 2.1. So, the general severity increase approximately doubles Class I’s symptom rates for 45 depressive symptoms, and rates for the subset of melancholic symptoms (whichever list is used) are approximately doubled as well. The lack of difference falsifies the authors’ claim that Class I disproportionately elevates