Data-driven cognitive phenotypes in subjects with bipolar disorder and their clinical markers of severity.

Background: Subjects with bipolar disorder (BD) show heterogeneous cognitive profile and that not necessarily the disease will lead to unfavorable clinical outcomes. We aimed to identify clinical markers of severity among cognitive clusters in individuals with BD through data-driven methods.

Methods: We recruited 167 outpatients with BD and 100 unaffected volunteers from Brazil and Spain that underwent a neuropsychological assessment. Cognitive functions assessed were inhibitory control, processing speed, cognitive flexibility, verbal fluency, working memory, short- and long-term verbal memory. We performed hierarchical cluster analysis and discriminant function analysis to determine and confirm cognitive clusters, respectively. Then, we used classification and regression tree (CART) algorithm to determine clinical and sociodemographic variables of the previously defined cognitive clusters.

Results: We identified three neuropsychological subgroups in individuals with BD: intact (35.3%), selectively impaired (34.7%), and severely impaired individuals (29.9%). The most important predictors of cognitive subgroups were years of education, the number of hospitalizations, and age, respectively. The model with CART algorithm showed sensitivity 45.8%, specificity 78.4%, balanced accuracy 62.1%, and the area under the ROC curve was 0.61. Of 10 attributes included in the model, only three variables were able to separate cognitive clusters in BD individuals: years of education, number of hospitalizations, and age.

Conclusion: These results corroborate with recent findings of neuropsychological heterogeneity in BD, and suggest an overlapping between premorbid and morbid aspects that influence distinct cognitive courses of the disease.