Fig. 1

Neural dysfunction becomes increasingly serious in rMDD with increased numbers of depressive episodes. In health, the tendency to enter a “down state” is relatively low, and the ability to return to a “normal state” is relatively rapid and complete (green arrows). In individuals with first-episode MDD, the tendency to enter a down state is relatively high, and the ability to return to a normal state is impaired slightly (yellow arrows). This ability becomes impaired more seriously in individuals with rMDD (red arrow). The down state itself is not abnormal in this model