Quantification of grey matter changes following first episode mania in bipolar I disorder : a systematic review and prospective study

Background: While there is evidence of widespread grey matter (GM) changes in bipolar I disorder (BD-I), it is unclear how early in the illness such changes emerge. However, to date there has been little systematic examination of longitudinal grey matter changes early during BD-I. We conducted a systematic review to examine the literature regarding GM changes in BD-I patients following the first episode of mania (FEM), in addition to a quantitative analysis of grey matter changes in a prospective cohort of BD-I patients in the first three years of disease. Methods: Following PRISMA guidelines, we conducted a systematic review of studies examining longitudinal changes in GM volume (GMV), cortical thickness and/or surface area in patients with BD-I following FEM. We qualitatively synthesized results regarding baseline differences between BD-I patients and HCs, and longitudinal GM changes in BD-I patients. For the longitudinal study, FEM patients and HCs were recruited and completed structural 3T MRI at pre-determined intervals. Images were analyzed using FreeSurfer’s longitudinal pipeline and linear mixed models used to examine longitudinal changes in cortical thickness, surface area and subcortical volume. Results: Fifteen studies met inclusion criteria for the systematic review, all examining changes in GMV. While results were highly heterogeneous, one replicated finding was decreased anterior cingulate cortex (ACC) volumes in first episode BD-I patients versus HC at baseline, and greater longitudinal ACC volume decrease in patients in the months following FEM. The potential impact of episode recurrence, substance use, age of onset and prior depressive episodes was inconsistently examined. In the longitudinal study, BD-I patients and HCs showed comparable reductions in cortical surface area and subcortical volumes over 3 years. No significant time*group effects were found; BD-I patients had smaller right thalamic volumes versus HCs at year 3 at trend-level significance. Limitations: The literature regarding GM changes early in BD-I is inconsistent. The sample size in our longitudinal study may have been insufficient to detect statistically significant changes. Conclusions: Evidence for longitudinal grey matter changes in the early phases of BD-I is inconsistent. Larger longitudinal studies are needed to fully understand neuroprogression in early BD-I.Medicine, Faculty ofGraduat