To what extent does white matter map to cognition in bipolar disorder? A systematic review of the evidence

Cognitive impairment is a prominent feature of bipolar disorder (BD), however the neural substrates underpinning it remain unclear. Several studies have explored white matter as a correlate of cognitive functioning in BD cohorts, but mixed results and varied methodologies from one to another make inferences about this relationship difficult to draw. Here we sought to systematically synthesise the findings of these studies to more clearly explicate the nature and extent of relationships between white matter and cognition in BD and determine best practice methodologies and areas for future research in this area. Using PRISMA guidelines, we identified and systematically reviewed 37 relevant studies, all of which were cross-sectional by design. There was substantial methodological heterogeneity and variability in the clinical presentations of BD cohorts encapsulated within the studies we reviewed, which complicated our synthesis of the findings. Nonetheless, there was some evidence that cognition is related to both white matter macrostructure and microstructure in people with BD. In particular, multiple microstructural studies consistently reported that higher fractional anisotropy, both globally and in the corpus callosum, associated with better complex attention skills and executive functioning. However, several reports did not identify any associations at all, and in general, associations between WM and cognition tended to only be evident in studies utilising larger samples and post-hoc selection of WM regions of interest. Further research with increased statistical power and standardised methods are required moving forward.