An Overview of Resting State Functional Connectivity Studies of Major Depressive Disorder

The resting state paradigm is ubiquitous in clinical neuroimaging, being convenient and practical to run, and yielding robust and theoretically salient individual differences in functional connectivity. The richness of the data, and the consequential variety of analyses that can be performed is both a blessing and a curse, providing many potential leads but few decisive observations. The problems of this complexity are compounded when the method is applied to multidimensional phenotypes such as mood disorders. In particular, I explore several potential accounts of the nature of the underlying alteration(s) of functional connectivity in major depression, including structural deficits, Hebbian mechanisms, mood and arousal-related alterations and neurotransmitter-based mechanisms. Evidence for and against each mechanism is described, with methodological heterogeneity and state-related factors being emphasized as areas of particular significance for future work. In summary, I describe the considerable progress that has been made, outlining the many challenges but also successful attempts to make progress toward the goal of identifying replicable and generalizable markers of major depression.