1. ¹MOOD-CNS Program, Department of Psychiatry, Division of Mood and Anxiety Disorders, The University of Texas Health Science Center, San Antonio, TX, USA
2. ²South Texas Veterans Health Care System, Audie L. Murphy Division, San Antonio, TX, USA
3. ³Research Imaging Center, The University of Texas Health Science Center, San Antonio, TX, USA
4. ⁴Department of Psychiatry, University of São Paulo, São Paulo, Brazil
5. ⁵Department of Orthodontics, The University of Texas Health Science Center, San Antonio, TX, USA
6. ⁶Department of Radiology, University of Chicago, Chicago, IL, USA
7. ⁷Department of Radiology, The University of Texas Health Science Center, San Antonio, TX, USA

Correspondence: Dr JC Soares, MOOD-CNS Program, Department of Psychiatry, Division of Mood and Anxiety Disorders, The University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. E-mail: soares@uthscsa.edu

Received 17 February 2006; Revised 25 July 2006; Accepted 5 August 2006; Published online 19 September 2006.

Abstract

The prefrontal cortex, a part of the limbic-thalamic-cortical network, participates in regulation of mood, cognition and behavior and has been implicated in the pathophysiology of major depressive disorder (MDD). Many neuropsychological studies demonstrate impairment of working memory in patients with MDD. However, there are few functional neuroimaging studies of MDD patients during working memory processing, and most of the available ones included medicated patients or patients with both MDD and bipolar disorder. We used functional magnetic resonance imaging (fMRI) to measure prefrontal cortex function during working memory processing in untreated depressed patients with MDD. Fifteen untreated individuals with Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition recurrent MDD (mean ages.d.=34.311.5 years) and 15 healthy comparison subjects (37.712.1 years) matched for age, sex and race were studied using a GE/Elscint 2T MR system. An echo-planar MRI sequence was used to acquire 24 axial slices. The n-back task (0-back, 1-back and 2-back) was used to elicit frontal cortex activation. Data were analyzed with a multiple regression analysis using the FSL-FEAT software. MDD patients showed significantly greater left dorsolateral cortex activation during the n-back task compared to the healthy controls (P<0.01), although task performance was similar in the two groups. Furthermore, the patients showed significant anterior cingulate cortex activation during the task, but the comparison subjects did not (P<0.01). This study provides in vivo imaging evidence of abnormal frontolimbic circuit function during working memory processing in individuals with MDD.