Prefrontal-subcortical circuitry abnormalities underlie MDD
By Sara Carrillo de Albornoz
23 August 2007

J Neurosci 2007; 27: 8877-8884
MedWire News: Patients with major depressive disorder (MDD) show
abnormalities in the prefrontal-subcortical circuitry that regulates
negative emotional states, reveals a study using functional magnetic
resonance imaging (fMRI).

³These findings underscore the importance of emotional regulation deficits
in depression,² Tom Johnstone (University of Wisconsin-Madison, USA) and
colleagues write in the Journal of Neuroscience.

Previous research in mentally healthy people has identified increased left
lateral prefrontal cortex (PFC) activation and decreased amygdala activation
when individuals reappraise negative stimuli as less negative.

To assess if this top-down regulation of the subcortical affective circuitry
is impaired in depression, Johnstone and team measured brain activation in
21 patients with MDD and 18 mentally healthy controls.

The participants were asked to view a series of emotionally positive and
negative images and then indicate their reaction while an fMRI scanner
detected changes in neural activity.

Four seconds after the presentation of each image, participants were asked
to either increase their emotional response, decrease it, or simply to
continue watching the image.

Results showed that MDD patients had bilateral PFC activation when
downregulating negative affect, whereas in healthy controls only the left
ventrolateral PFC was activated. This indicates a greater relative
recruitment of right PFC during reappraisal in major depression, the team
notes.

In healthy controls, activation of the left ventrolateral PFC led to the
inactivation of the amygdala, mediated by the ventromedial prefrontal cortex
(VMPFC). In depressed individuals, however, the VMPFC did not inactivate the
amygdala, and both the amygdala and VMPFC were activated in the reappraisal
process.

³Our data suggest that the role of the VMPFC as an inhibitory link between
the left ventrolateral PFC and the amygdala is compromised in depression,
likely because of the inappropriate engagement of right PFC circuitry in
depressed individuals,² the researchers say.

In controls, increased effort to reappraise negative stimuli, as reflected
by greater pupil dilation, was associated with decreased activation in
amygdala and insula, whereas in MDD patients increased pupil dilation
positively correlated with activation of these same regions, suggesting that
the attempt to reappraise negative stimuli was ineffective in the depressed
group.

³It will be essential to study the impact of cognitive therapy and other
related forms of reappraisal training on the neural circuitry of emotion
regulation,² Johnstone et al suggest.