Stuck in a rut: rethinking depression and its treatment

Trends Neurosci. 2011 Jan;34(1):1-9. doi: 10.1016/j.tins.2010.10.004. Epub 2010 Nov 8.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidepressive Agents / therapeutic use
  • Cost of Illness
  • Depressive Disorder, Major / diagnosis*
  • Depressive Disorder, Major / epidemiology
  • Depressive Disorder, Major / physiopathology
  • Depressive Disorder, Major / therapy*
  • Diagnostic and Statistical Manual of Mental Disorders
  • Humans
  • Psychiatric Status Rating Scales


  • Antidepressive Agents