J Psychiatry Neurosci 2010;35(3):152-162
Martin Roy, MD; Philippe-Olivier Harvey, MSc; Marcelo T. Berlim, MD, MSc; Firoza Mamdani, BSc; Marie-Martine Beaulieu, MSc; Gustavo Turecki, MD, PhD; Martin Lepage, PhD
Douglas Mental Health University Institute; Roy — Centre de recherche Université Laval Robert-Giffard and École de psychologie, Laval University, Québec; Harvey, Berlim, Mamdani, Turecki, Lepage — Department of Psychiatry, McGill University; Berlim, Beaulieu, Turecki — Depressive Disorders Program and McGill Group for Suicide Studies, Douglas Mental Health University Institute, Montréal, Que.
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.
Drs. Turecki and Lepage share senior authorship of this article.
Submitted Jan. 28, 2009; Revised July 29, Nov. 25, 2009, Jan. 14, 2010; Accepted Jan. 15, 2010.
Acknowledgments: This study was supported by a Canadian Institutes of Health Research (CIHR) grant to Dr. Lepage (no. 53280) and Dr. Turecki (no. MOP-68824). Mr. Harvey was supported by fellowships from Fonds de la recherche en santé and CIHR. We thank Daniel Lalande from Laval University for proofreading earlier versions of this paper and Lisa Boucher, Maxime Plante and Thomas Howells for final linguistic revisions.
Competing interests: None declared for Drs. Roy, Turecki, Berlim and Mr. Harvey, Mr. Mamdani and Ms. Beaulieu. Dr. Lepage has received honoraria from Janssen-Ortho and Lilly. He has received payment for the development of educational presentations from CD-Pharma and has received travel/accommodations expenses from Janssen-Ortho.
Contributors: Drs. Roy and Lepage and Mr. Harvey designed the study. Dr. Berlim and Mr. Harvey, Mr. Mamdani and Ms. Beaulieu acquired the data, which Drs. Roy, Berlim, Turecki and Lepage and Mr. Harvey analyzed. Dr. Roy wrote the article, which all other authors reviewed. All authors approved the final version submitted for publication.
Correspondence to: Dr. M. Lepage, Douglas Mental Health University Institute, 6875 LaSalle Bvld., Montréal QC H4H 1R3; fax 514 888-4064; email@example.com