Stuck in a rut: rethinking depression and its treatment

Abstract

The current definition of major depressive disorder (MDD) emerged from efforts to create reliable diagnostic criteria for clinical and research use. However, despite decades of research, the neurobiology of MDD is largely unknown, and treatments are no more effective today than they were 50-70 years ago. Here, we propose that the current conception of depression is misguiding basic and clinical research. Redefinition is necessary and could include a focus on a more narrowly defined set of core symptoms. However, we conclude that depression is better defined as the tendency to enter into, and inability to disengage from, a negative mood state rather than the mood state per se. We also discuss the implications of this revised definition for future clinical and basic research.

Figure 1

Milestones in the development of psychiatric treatments. DBS=deep brain stimulation; ECT=electroconvulsive therapy; TMS=transcranial magnetic stimulation; VNS=vagus nerve stimulation. Treatment categories: psychotherapy (purple), medication (green), other somatic interventions (pink).

Figure 2

Proposed model of depression: “stuck in a rut”. In response to a stressor, there is a mood reaction, i.e., a shift from the normal, euthymic state to a “down” state that includes the symptoms associated with the syndrome of depression, grief, sickness behavior, etc. The return to the normal state is achieved through mood regulation. In healthy, non-depressed individuals, the tendency to enter the down state is relatively low, and when it occurs, the return to normal is relatively quick and complete (green arrows). In individuals with Major Depressive Disorder (MDD), the pressure to enter the down state is relatively high (and may even occur in the absence of a clear stressor), but the ability to return to normal is impaired (blue arrows). During a depressive episode, the down state becomes more established, and the individual may have even greater difficulty returning to the normal state without external intervention (psychotherapy, medication, etc.). This model emphasizes that the down state itself is not abnormal. Instead, it is the tendency to enter and get stuck in this state that defines depression. Thus, the neurobiology of depression should be that of mood reaction and regulation rather than the mood state per se.