Remission prognosis for cognitive therapy for recurrent depression using the pupil: utility and neural correlates

Abstract

Background: Although up to 60% of people with major depressive disorder respond to cognitive therapy (CT) in controlled trials, clinicians do not routinely use standardized assessments to inform which patients should receive this treatment. Inexpensive, noninvasive prognostic indicators could aid in matching patients with appropriate treatments. Pupillary response to emotional information is an excellent candidate, reflecting limbic reactivity and executive control. This study examined 1) whether pretreatment assessment of pupillary responses to negative information were associated with remission in CT and 2) their associated brain mechanisms.

Methods: We examined whether pretreatment pupillary responses to emotional stimuli were prognostic for remission in an inception cohort of 32 unipolar depressed adults to 16 to 20 sessions of CT. Twenty patients were then assessed on the same task using functional magnetic resonance imaging. Pupillary responses were assessed in 51 never-depressed controls for reference.

Results: Remission was associated with either low initial severity or the combination of higher initial severity and low sustained pupillary responses to negative words (87% correct classification of remitters and nonremitters, 93% sensitivity, 80% specificity; 88% correct classification of high-severity participants, p < .01, 90% sensitivity, 92% specificity). Increased pupillary responses were associated with increased activity in dorsolateral prefrontal regions associated with executive control and emotion regulation.

Conclusions: For patients with higher severity, disruptions of executive control mechanisms responsible for initiating emotion regulation, which are indexed by low sustained pupil responses and targeted in therapy, may be key to remitting in this intervention. These mechanisms can be measured using inexpensive noninvasive psychophysiological assessments.

Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

CONSORT diagram of patient flow through the study. The box on the middle right displays the experimental protocol showing the time-course for the digit-sorting and alternating task. Only the alternating task was analyzed in this manuscript.

Figure 2

Pupillary responses to negative words followed by digit-sorting on the alternating task for controls, and both responders and non-responders with high-initial-severity (BDI-II> 20). Significant differences between responders and non-responders are highlighted below the x-axis; yellow=p<.1 red="p<.05." black lines show regions with enough consecutive tests to be considered significant.>

Figure 3

Scatter-plot in which final severity is on the x-axis and pupillary motility at 11.78 seconds is on the y-axis for high-initial-severity participants. Responders were defined as participants with final BDI

Figure 4

Association in 20 treated depressed patients of BOLD activity in five a priori regions with pupil dilation at 11.78 seconds – the point which maximally discriminated depressed responders from non-responders. In the second column, the Y axis represents correlation and the X axis is seconds. Scans with significant correlations are highlighted as yellow: p<.1, red: p<.05. In the third column, each participant’s data on both activity at the maximally predictive scan (X axis) and pupil dilation at 11.78 seconds (Y axis) are plotted.