Neural signatures of bipolar disorder subtypes: A comprehensive systematic review of neuroimaging studies

The neurobiological mechanisms differentiating bipolar disorder type I (BD-I) from type II (BD-II) remain poorly understood. A comprehensive synthesis systematically comparing neuroimaging findings between BD subtypes is lacking. We conducted a systematic review (PubMed, Scopus, up to March 2024), including structural MRI, functional MRI, and diffusion tensor imaging studies, to provide a comprehensive overview of the common and distinct candidate neural signatures that differentiate BD subtypes. Out of the initial 5334 references, 38 MRI studies (41 experiments) were included. Structural MRI studies showed mixed results regarding volumetric and cortical surface differences between BD subtypes. BD-I exhibited widespread gray matter (GM) volume reductions, larger lateral ventricles, and decreases in cortical thickness. Hippocampal and cerebellar volume reductions were observed in both BD subtypes but did not differentiate BD-I from BD-II. While white matter (WM) abnormalities across BD subtypes remain heterogeneous and lack consistent replication, BD-I showed a tendency toward more disrupted WM microstructure and higher WM hyperintensities rates than BD-II. Functional MRI studies revealed distinct differences in task-based and resting-state activity, suggesting differential neural patterns in reward processing and emotion regulation. BD-I displayed a greater disconnection in emotion regulation circuits. While both BD-I and BD-II share some neuroimaging characteristics, the findings suggest BD-I is characterized by more pronounced WM disruptions and emotion dysregulation. In contrast, BD-II shows more remarkable subcortical volume preservation but with distinct connectivity alterations. These results offer insights into the different and shared neurobiological mechanisms of BD subtypes, which may help refine their pathophysiology and inform tailored interventions.