Rostral anterior cingulate cortex theta current density and response to antidepressants and placebo in major depression

Clin Neurophysiol. 2009 Jul;120(7):1313-9. doi: 10.1016/j.clinph.2009.05.008. Epub 2009 Jun 17.


Objective: To assess whether pretreatment theta current density in the rostral anterior cingulate (rACC) and medial orbitofrontal cortex (mOFC) differentiates responders from non-responders to antidepressant medication or placebo in a double-blinded study.

Methods: Pretreatment EEGs were collected from 72 subjects with Major Depressive Disorder (MDD) who participated in one of three placebo-controlled trials. Subjects were randomized to receive treatment with fluoxetine, venlafaxine, or placebo. Low-resolution brain electromagnetic tomography (LORETA) was used to assess theta current density in the rACC and mOFC.

Results: Medication responders showed elevated rACC and mOFC theta current density compared to medication non-responders (rACC: p=0.042; mOFC: p=0.039). There was no significant difference in either brain region between placebo responders and placebo non-responders.

Conclusions: Theta current density in the rACC and mOFC may be useful as a biomarker for prediction of response to antidepressant medication.

Significance: This is the first double-blinded treatment study to examine pretreatment rACC and mOFC theta current density in relation to antidepressant response and placebo response. Results support the potential clinical utility of this approach for predicting clinical outcome to antidepressant treatments in MDD.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use*
  • Biomarkers
  • Brain Mapping
  • Cerebral Cortex / physiopathology*
  • Cyclohexanols / pharmacology
  • Cyclohexanols / therapeutic use
  • Depression / drug therapy*
  • Depression / physiopathology*
  • Double-Blind Method
  • Electroencephalography / methods
  • Female
  • Fluoxetine / pharmacology
  • Fluoxetine / therapeutic use
  • Gyrus Cinguli / physiopathology*
  • Humans
  • Male
  • Middle Aged
  • Theta Rhythm* / drug effects
  • Treatment Outcome
  • Venlafaxine Hydrochloride
  • Young Adult


  • Antidepressive Agents
  • Biomarkers
  • Cyclohexanols
  • Fluoxetine
  • Venlafaxine Hydrochloride