Diagnosis in Crisis: Extensive Heterogeneity Invalidates the DSM's Usefulness for Biologically Informed Research

Background
Most DSM definitions of most mental disorders are polythetic meaning that different combinations of symptoms are sufficient to obtain the same diagnosis. Although the DSM allows for vast within-disorder symptom heterogeneity, it is unclear how many of the theoretically possible symptom combinations are present in clinical practice.
Methods
We investigated the frequency of disorder-specific symptom combinations in five large samples (total N = 286,645), each assessed for symptoms of a specific disorder (posttraumatic stress disorder, depression, anxiety, schizophrenia and burnout). First, symptom ratings were binarized to indicate symptom presence or absence. Second, the specific combination of symptoms for each participant was determined. Last, we assessed the number and proportion of unique symptom combinations within each sample before obtaining formal descriptions of the found distributions.
Results
In all five samples the frequency of symptom combinations was heavily skewed. Few combinations were commonly reported, most were observed less than five times per sample. More formally, the distribution of the frequency of the combinations could be described by a power-law or a log-normal distribution.
Conclusions
Our findings demonstrate extensive symptom heterogeneity within DSM-based diagnostic categories in empirical samples challenging the validity of these categories for the identification of biomarkers as well as the development of targeted treatments. Therefore, these results provide further empirical support for the use of Research Domain Criteria (RDoc) in research in biological psychiatry.