Introduction: Bipolar disorder (BD) is largely treatable and lithium is commonly used as a first-line treatment. However, no identified biomarkers can currently reliably predict patient response to lithium. The goal of this study was to identify structural and functional brain features correlated with prospectively assessed response to lithium treatment.
Method: Participants with bipolar I disorder (N = 14) were stabilized on lithium monotherapy, followed for up to two years to determine response, and then underwent a 7 Tesla MRI scan. Healthy comparison participants (N = 21) were group-matched to BD. Local shape differences in anatomy of amygdala and hippocampus were examined from MP-RAGE images. EPI BOLD sequences during an emotional faces task and at rest were analyzed at the whole-brain level to assess differences in activation and connectivity, respectively.
Results: A patch of the ventral surface of the left hippocampus was found to be atrophied by 15% in non-responders as compared to responders (p=0.03). In response to the emotional faces task comparing fearful to neutral faces, responders exhibited less activation in parahippocampal gyrus and insula and greater activation in prefrontal and middle frontal gyrus than non-responders (peak T>7.47). Responders and non-responders displayed different patterns of resting state connectivity between hippocampus, ACC and superior temporal lobe (peak T = −6.41).
Conclusion: We identified differences in hippocampal structure and corticolimbic activation and connectivity correlated with lithium response. These preliminary findings contribute to our understanding of BD pathophysiology and highlight candidate brain features with potential to predict response to lithium treatment.