Phenotype fingerprinting of bipolar disorder prodrome

Document Type

Journal Article

Publication Date



International journal of bipolar disorders








Bipolar disorder; Phenotype; Unsupervised machine learning


BACKGROUND: Detecting prodromal symptoms of bipolar disorder (BD) has garnered significant attention in recent research, as early intervention could potentially improve therapeutic efficacy and improve patient outcomes. The heterogeneous nature of the prodromal phase in BD, however, poses considerable challenges for investigators. Our study aimed to identify distinct prodromal phenotypes or "fingerprints" in patients diagnosed with BD and subsequently examine correlations between these fingerprints and relevant clinical outcomes. METHODS: 20,000 veterans diagnosed with BD were randomly selected for this study. K-means clustering analysis was performed on temporal graphs of the clinical features of each patient. We applied what we call "temporal blurring" to each patient image in order to allow clustering to focus on the clinical features, and not cluster patients based upon their varying temporal patterns in diagnosis, which lead to the desired types of clusters. We evaluated several outcomes including mortality rate, hospitalization rate, mean number of hospitalizations, mean length of stay, and the occurrence of a psychosis diagnosis within one year following the initial BD diagnosis. To determine the statistical significance of the observed differences for each outcome, we conducted appropriate tests, such as ANOVA or Chi-square. RESULTS: Our analysis yielded 8 clusters which appear to represent distinct phenotypes with differing clinical attributes. Each of these clusters also has statistically significant differences across all outcomes (p < 0.0001). The clinical features in many of the clusters were consistent with findings in the literature concerning prodromal symptoms in patients with BD. One cluster, notably characterized by patients lacking discernible prodromal symptoms, exhibited the most favorable results across all measured outcomes. CONCLUSION: Our study successfully identified distinct prodromal phenotypes in patients diagnosed with BD. We also found that these distinct prodromal phenotypes are associated with different clinical outcomes.


Clinical Research and Leadership