Unveiling the Structure in Mental Disorder Presentations.

Importance: DSM criteria are polythetic, allowing for heterogeneity of symptoms among individuals with the same disorder. In empirical research, most combinations were not found or only rarely found, prompting criticism of this heterogeneity.

Objective: To elaborate how symptom-based definitions and assessments contribute to a distinct probability pattern for the occurrence of symptom combinations.

Design, setting, and participants: This cross-sectional study involved a theoretical argument, simulation, and secondary data analysis of 4 preexisting datasets, each consisting of symptoms from 1 of the following syndromes: posttraumatic stress disorder, depression, schizophrenia, and anxiety. Data were obtained from various sources, including the National Institute of Mental Health Data Archive and Department of Veteran Affairs. A total of 155 474 participants were included (individual studies were 3930 to 63 742 individuals in size). Data were analyzed between July 2021 and January 2024.

Exposure: For each participant, the presence or absence of each assessed symptom and their combination was determined. The number of all combinations and their individual frequencies were assessed.

Main outcome and measure: Probability or frequency of unique symptom combinations and their distribution.

Results: Among the 155 474 participants, the mean (SD) age was 47.5 (14.8) years; 33 933 (21.8%) self-identified as female and 121 541 (78.2%) as male. Because of the interrelation between symptoms, some symptom combinations were significantly more likely than others. The distribution of the combinations' probability was heavily skewed with most combinations having a very low probability. Across all 4 empirical samples, the 1% most common combinations were prevalent in a total of 33.1% to 78.6% of the corresponding sample. At the same time, many combinations (ranging from 41.7% to 99.8%) were reported by less than 1% of the sample.

Conclusions and relevance: This study found that within-disorder symptom heterogeneity followed a specific pattern consisting of few prevalent, prototypical combinations and numerous combinations with a very low probability of occurrence. Future discussions about the revision of diagnostic criteria should take this specific pattern into account by focusing not only on the absolute number of symptom combinations but also on their individual and cumulative probabilities. Findings from clinical populations using common diagnostic criteria may have limited generalizability to the large group of individuals with a low-probability symptom combination.