Self-referential processing and the prefrontal cortex over the course of depression: A pilot study

Abstract

Background

Depressed patients exhibit cognitive biases, including maladaptive self-focus. In a previous functional magnetic resonance imaging (fMRI) study, the dorsal medial prefrontal cortex (MPFC) activation during self-referential versus semantic processing was unique to patients, as was the left dorsolateral prefrontal cortex (DLPFC) activation. The aim of this pilot study was to examine whether this pattern was stable over the course of depression.

Methods

Sixteen participants (8 depressed inpatients, 8 healthy controls) viewed personality traits during fMRI and judged whether each trait described them or not (‘self’ condition), or whether it described a socially desirable trait or not (‘general’ condition). There were 2 scanning sessions with an interval of at least 6 weeks, in which patients received an antidepressant treatment.

Results

After a mean duration of 9 weeks, depressed patients displayed a more balanced activation of the left DLPFC but a greater activation of the dorsal MPFC in ‘self’ versus ‘general’ condition remained.

Limitations

The small sample size and heterogeneous clinical features prevented subgroups analyses between responders and non-responders.

Conclusions

The change of the left DLPFC activation suggests that antidepressants are associated with a more balanced allocation of cognitive control across self-referential and non-self-referential processes. The apparent lack of effect on the dorsal MPFC activity is consistent with the specific effects of antidepressants versus cognitive behavior therapy (CBT) previously demonstrated in depression. Future studies could examine the relationships between the dorsal MPFC activity in depressed patients and the need to reduce self-focus through CBT to achieve remission and prevent relapse.

Introduction

According to the cognitive theory of depression, depressed patients suffer from cognitive biases, such as increased attention to negative stimuli or to the self (i.e. self-focus) (Clark and Beck, 1999, Mor and Winquist, 2002). Depressive self-focus is characterized by its evaluative, analytical style (i.e. ‘thinking about’ experience), rather than being a direct, intuitive, experiential awareness of experience in the moment (Watkins and Teasdale, 2004). In healthy subjects, self-referential processing (i.e. the appraisal of stimuli as strongly related to one's own person) relies mainly on the cortical midline structures, including the medial prefrontal cortex (MPFC) (Fossati et al., 2003, Amodio and Frith, 2006). Because self-focus is qualitatively distinct in depression (Mor and Winquist, 2002, Watkins and Teasdale, 2004), one could hypothesize that depressed patients would activate a different set of brain regions during self-referential processing, compared to healthy controls. However, in contrast with the neural bases of the increased attention to negative stimuli, little is known about those of depressive self-focus.

Recent functional magnetic resonance imaging (fMRI) studies addressed this issue and found an aberrant activation of the MPFC in depressed patients (Grimm et al., 2009, Sheline et al., 2009, Lemogne et al., 2009). For instance, Lemogne et al. (2009) presented depressed patients and matched healthy controls with personality traits and asked them to judge whether each trait described them or not (‘self’ condition), or whether it described a generally desirable trait or not (‘general’ condition) (Lemogne et al., 2009). Although the MPFC was activated by both patients and controls in ‘self’ versus ‘general’ condition, the activation of the dorsal part of the MPFC in ‘self’ versus ‘general’ condition was unique to patients, as was the activation of the left dorsolateral prefrontal cortex (DLPFC).

The aim of this pilot study was to examine whether this activation pattern was stable over the course of depression. Even in remitted patients, and especially in those who do not receive CBT, cognitive biases such as self-focus are pervasive (Segal et al., 2006, Bergouignan et al., 2008). Therefore, we hypothesized that the activation of the dorsal MPFC and/or the left DLPFC could persist even after several weeks of antidepressant treatment, irrespective of clinical improvement.