Abstract
BACKGROUND: Bipolar disorder (BD) is among the psychiatric disorders most prone to misdiagnosis, with both false positives and false negatives resulting in treatment delay. We employed a whole-brain machine learning approach focusing on gray matter volumes (GMVs) to contribute to defining objective biomarkers of BD and discriminating it from other forms of psychopathology, including subthreshold manic presentations without a BD Type I/II diagnosis. METHODS: Five support vector machine (SVM) models were used to detect differences in GMVs between inpatient adolescents aged 13-17 with BD-I/II (n = 34), other specified BD (OSB) (n = 106), other non-bipolar psychopathology (OP) (n = 52), and healthy controls (HC) (n = 27). We examined the most discriminative GMVs and tested their associations with clinical symptoms. RESULTS: Whole-brain classifiers in the model BD-I/II versus OSB achieved total accuracy of 79%, (AUC = 0.70, p = 0.002); BD versus OP 66%, (AUC = 0.61, p = 0.014); BD versus HC 66%, (AUC = 0.67, p = 0.011); OSB versus HC 77%, (AUC = 0.61, p = 0.01); OP versus HC 68%, (AUC = 0.70, p = 0.001). The most discriminative GMVs that contributed to the classification were in areas associated with movement, sensory processing, and cognitive control. Correlations between these GMVs and self-reported mania, negative affect, or anxiety were observed in all inpatient groups. CONCLUSIONS: These findings indicate that pattern recognition models focusing on GMVs in regions associated with movement, sensory processing, and cognitive control can effectively distinguish well-characterized BD-I/II from other forms of psychopathology, including other specified BD, in a pediatric population. These results may contribute to enhancing diagnostic accuracy and guiding earlier, more targeted interventions.