Medial prefrontal cortex activity during memory encoding of pictures and its relation to symptomatic improvement after citalopram treatment in patients with major depression

J Psychiatry Neurosci. 2010 May;35(3):152-62. doi: 10.1503/jpn.090010.


Background: Brain imaging studies of major depressive disorder have shown alterations in the brain regions typically involved in episodic memory, including the prefrontal cortex and medial temporal areas. Some studies of major depressive disorder have linked episodic memory performance to treatment response. In this study, we sought to identify brain regions whose activity, measured during the encoding of pictures, predicted symptomatic improvement after 8 weeks of citalopram treatment.

Methods: We included 20 unmedicated depressed patients. These patients performed an episodic recognition memory task during functional magnetic resonance imaging. During the encoding phase, 150 pictures depicting emotionally positive, negative or neutral content were presented, and the participants were required to classify each picture according to its emotional valence. The same 150 pictures were presented, along with 150 new ones, for a recognition task. We asked participants to distinguish the old pictures from the new ones. We assessed symptom severity by use of the 21-item Hamilton Rating Scale for Depression (HAM-D) at baseline and after 8 weeks of citalopram treatment. We performed subsequent memory effect analyses using SPM2 software. We explored the relation between brain activation during successful encoding of pictures and symptomatic improvement.

Results: Patients showed a mean symptomatic improvement of 54.5% on the HAM-D after 8 weeks. Symptomatic improvement was significantly and positively correlated with picture recognition memory accuracy. We also found that the activity of the ventromedial prefrontal cortex and anterior cingulate cortex during successful encoding was significantly correlated with symptomatic improvement. Finally, we found greater activation in the ventromedial prefrontal cortex during the successful encoding of positive pictures in comparison with neutral pictures.

Limitations: During the recognition memory task, 5 participants (among the best responders to treatment) were not included in the valence-specific analyses because they had very few errors. A more challenging task would have allowed the inclusion of most patients.

Conclusion: Different types of functional imaging paradigms have been used to explore whether the activity of specific brain regions measured at baseline is predictive of a better response to treatment in major depressive disorder. Among these regions, the medial prefrontal cortex and anterior cingulate cortex usually show the strongest predictive value. According to our results, the medial prefrontal cortex and anterior cingulate cortex could have an effect on treatment response in major depressive disorder by contributing to the successful encoding of positively valenced information.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Citalopram / therapeutic use*
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / physiopathology
  • Depressive Disorder, Major / psychology*
  • Emotions
  • Female
  • Gyrus Cinguli / physiopathology
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Pattern Recognition, Visual
  • Photic Stimulation / methods
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiopathology*
  • Recognition, Psychology / drug effects*
  • Temporal Lobe / physiopathology
  • Treatment Outcome
  • Young Adult


  • Antidepressive Agents, Second-Generation
  • Citalopram