Rostral anterior cingulate cortex activity and early symptom improvement during treatment for major depressive disorder

Psychiatry Res. 2011 Jun 30;192(3):188-94. doi: 10.1016/j.pscychresns.2010.12.007. Epub 2011 May 4.


In treatment trials for major depressive disorder (MDD), early symptom improvement is predictive of eventual clinical response. Clinical response may also be predicted by elevated pretreatment theta (4-7Hz) current density in the rostral anterior cingulate (rACC) and medial orbitofrontal cortex (mOFC). We investigated the relationship between pretreatment EEG and early improvement in predicting clinical outcome in 72 MDD subjects across three placebo-controlled treatment trials. Subjects were randomized to receive fluoxetine, venlafaxine, or placebo. Theta current density in the rACC and mOFC was computed with Low-Resolution Brain Electromagnetic Tomography (LORETA). An analysis of covariance examining week-8 Hamilton Depression Rating Scale (HamD) percent change, showed a significant effect of week-2HamD percent change, and a significant three-way interaction of week-2HamD percent change×treatment×rACC. Medication subjects with robust early improvement showed almost no relationship between rACC theta current density and final clinical outcome. However, in subjects with little early improvement, rACC activity showed a strong relationship with clinical outcome. The model examining the mOFC showed a trend in the three-way interaction. A combination of pretreatment rACC activity and early symptom improvement may be useful for predicting treatment response.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Analysis of Variance
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents / therapeutic use
  • Brain Mapping
  • Cyclohexanols / pharmacology*
  • Cyclohexanols / therapeutic use
  • Depressive Disorder, Major* / drug therapy
  • Depressive Disorder, Major* / pathology
  • Depressive Disorder, Major* / physiopathology
  • Double-Blind Method
  • Electroencephalography
  • Female
  • Fluoxetine / pharmacology*
  • Fluoxetine / therapeutic use
  • Follow-Up Studies
  • Gyrus Cinguli / drug effects*
  • Gyrus Cinguli / physiopathology
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Theta Rhythm / drug effects*
  • Venlafaxine Hydrochloride


  • Antidepressive Agents
  • Cyclohexanols
  • Fluoxetine
  • Venlafaxine Hydrochloride